bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary and genomic analysis of four SARS-CoV-2 isolates circulating in March 2020 in Sri Lanka; Additional evidence on multiple introduction and further transmission
Authors: Satharasinghe Dilan Amila , Parakatawella Parakatawella Mudiyanselage Shalini Daupadi Kumari , Premarathne Jayasekara Mudiyanselage Krishanthi Jayarukshi Kumari , Jayasooriya L. J. P. Anura P. , Prathapasinghe Gamika A. , Yeap Swee Keong
Published: March 2021

The molecular epidemiology of the virus and mapping helps understand the epidemics' evolution and apply quick control measures. This study provides genomic evidence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introductions into Sri Lanka and virus evolution during circulation. Whole-genome sequences of four SARS-CoV-2 strains obtained from coronavirus disease 2019 (COVID-19) positive patients reported in Sri Lanka during March 2020 were compared with sequences from Europe, Asia, Africa, Australia and North America. The phylogenetic analysis revealed that the sequence of the sample of the first local patient collected on 10 March, who contacted tourists from Italy, was clustered with SARS-CoV-2 strains collected from Italy, Germany, France and Mexico. Subsequently, the sequence of the isolate obtained on 19 March also clustered in the same group with the samples collected in March and April from Belgium, France, India and South Africa. The other two strains of SARS-CoV-2 were segregated from the main cluster, and the sample collected from 16 March clustered with England and the sample collected on 30 March showed the highest genetic divergence to the isolate of Wuhan, China. Here we report the first molecular epidemiological study conducted on circulating SARS-CoV-2 in Sri Lanka. The finding provides the robustness of molecular epidemiological tools and their application in tracing possible exposure in disease transmission during the pandemic.
A unified approach to some non-Hausdorff topological properties
Authors: Li Qingguo , Yuan Zhenzhu , Zhao Dongsheng
Published: March 2021

Sobriety, well-filteredness, and monotone convergence are three of the most important properties of topological spaces extensively studied in domain theory. Some other weak forms of sobriety and well-filteredness have also been investigated by some authors. In this paper, we introduce the notion of Θ-fine spaces, which provides a unified approach to such properties. In addition, this general approach leads to the definitions of some new topological properties.
Acute and short-term haemodynamic impact of transcatheter pulmonary valve implantation on left ventricular systolic and diastolic function
Authors: Romans Ryan A. , Whiteside Wendy , Yu Sunkyung , Harris Lori , Dottermann Veronika , Zampi Jeffrey D.
Published: March 2021

Objectives:

Assess the acute and short-term haemodynamic impact of transcatheter pulmonary valve implantation on left ventricular systolic and diastolic function stratified by pre-transcatheter pulmonary valve implantation physiology.

Background:

Transcatheter pulmonary valve implantation is a widely available option to treat residual or recurrent pulmonary stenosis and pulmonary insufficiency. Transcatheter pulmonary valve implantation acutely increases pulmonary artery size and diastolic pressure in patients with pulmonary insufficiency and acute pulmonary edema has been reported after transcatheter pulmonary valve implantation, possibly related to acute left ventricular volume loading. However, the impact of transcatheter pulmonary valve implantation on left ventricular diastolic function has not been established.

Methods:

Patients who underwent transcatheter pulmonary valve implantation from 2010 to 2017 at our centre were grouped by indication for transcatheter pulmonary valve implantation as pulmonary stenosis, pulmonary insufficiency, or mixed disease. Separate analysis was performed on those who underwent transcatheter pulmonary valve implantation for pulmonary stenosis versus pulmonary insufficiency or mixed disease. Intracardiac haemodynamics immediately before and after transcatheter pulmonary valve implantation and echocardiographic assessment of left ventricular systolic and diastolic function at baseline, 1-day post transcatheter pulmonary valve implantation, and 1-year post transcatheter pulmonary valve implantation were compared between groups.

Results:

In 102 patients who underwent transcatheter pulmonary valve implantation, the indication was pulmonary stenosis in 29 (28%), pulmonary insufficiency in 28 (29%), and mixed disease in 44 (43%). There were no significant differences in left ventricular systolic or diastolic function between groups at baseline, immediately after transcatheter pulmonary valve implantation, or 1-year post implantation. The mean pulmonary artery wedge pressure increased equally across groups.

Conclusions:

While patients with pulmonary insufficiency likely have acute left ventricular volume loading following transcatheter pulmonary valve implantation, this does not appear to be haemodynamically significant as transcatheter pulmonary valve implantation was not associated with measurable changes in left ventricular systolic or diastolic function acutely or 1-year post implantation.
GENETIC, CULTURAL, AND HISTORICAL DETERMINANTS OF KNOWLEDGE CREATION
Authors: Gören Erkan
Published: March 2021

Knowledge creation has been a pivotal ingredient of endogenous growth theory to understand differences in standards of living across countries. Yet, the identification of key drivers explaining cross-country differences in knowledge creation still remains a topic of central interest in this research field. In this paper, I provide a framework to hypothesize and empirically test the persistent effects of novelty-seeking traits on cross-country differences in scientific knowledge creation. The results suggest a positive and statistically significant relationship between both outcomes that is consistent with the hypothesis that the prevalence of novelty-seeking traits in society facilitates scientific knowledge creation through beneficial human behaviors related to risk-taking and explorative behavior. The empirical findings remain qualitatively unaffected when controlling for additional historical, biogeographical, and socioeconomic factors that appear as additional important determinants in the creation of scientific knowledge in society.
Personality Associations With WhatsApp Usage and Usage of Alternative Messaging Applications to Protect One’s Own Data
Authors: Sindermann Cornelia , Lachmann Bernd , Elhai Jon D. , Montag Christian
Published: March 2021

Abstract. Data protection became an increasingly important topic in today’s digital society. With regard to messaging applications, WhatsApp especially has been at the center of discussion. Despite the existence of alternative messaging applications seemingly protecting one’s data more than WhatsApp does, individuals seem to rarely use these alternatives. The present study, therefore, investigated personality differences between individuals using WhatsApp versus alternative messaging applications which are deemed more protective of one’s data. A total of N = 7,874 individuals ( n = 3,992 men) participated in the present online survey. All of them provided information on whether they used WhatsApp and/or an alternative messaging application because WhatsApp was deemed to be non-data-protective. Additionally, they completed the Big Five Inventory. Most participants (69.27%) reported using WhatsApp but no alternative messaging application due to data protection concerns. This group showed the lowest scores on Openness. The group using neither WhatsApp nor another messaging application due to data protection concerns regarding WhatsApp showed the lowest scores on Extraversion. The highest scores on Agreeableness were found in the group using WhatsApp and at least one alternative messaging application due to WhatsApp-related data protection concerns. These results reveal initial insights into who is using seemingly data protective versus non-data-protective messaging applications. Personality may not be the only factor influencing the decisions about data protective messaging application use.
Investigation of UV Absorbers on Venus Using the 283 and 365 nm Phase Curves Obtained From Akatsuki
Authors: Lee Y. J. , García Muñoz A. , Yamazaki A. , Yamada M. , Watanabe S. , Encrenaz T.
Published: March 2021

The so‐called unknown absorber in the clouds of Venus is an important absorber of solar energy, but its vertical distribution remains poorly quantified. We analyze the 283 and 365 nm phase curves of the disk‐integrated albedo measured by Akatsuki. Based on our models, we find that the unknown absorber can exist either well mixed over the entire upper cloud or within a thin layer. The necessary condition to explain the 365 nm phase curve is that the unknown absorber must absorb efficiently within the cloud scale height immediately below the cloud top. Using this constraint, we attempt to extract the SO2 abundance from the 283 nm phase curve. However, we cannot disentangle the absorption by SO2 and by the unknown absorber. Considering previous SO2 abundance measurements at midinfrared wavelengths, the required absorption coefficient of the unknown absorber at 283 nm must be more than twice that at 365 nm.
Spectral Signature of Landscape Channelization
Authors: Hooshyar Milad , Katul Gabriel , Porporato Amilcare
Published: March 2021

Channel networks increase in complexity as the importance of erosion grows compared to diffusion by soil creep, giving rise to a channelization cascade. Simulations, laboratory experiments, and data from a natural landscape are used to uncover the signature of such a cascade in the wavenumber spectrum of elevation fluctuations. Power spectra at intermediate distances from the boundaries are characterized by a peak wavenumber that is related to the quasi‐cyclic valleys superimposed on a power‐law scaling with exponent (α) at smaller scales. Dimensional analysis and self‐similarity arguments show that α is uniquely linked to the power‐law relation (with exponent m) between erosion potential and the specific drainage area via α = 2m − 3. This finding connects the spectral behavior of erosional surfaces to the exponent m that distinguishes between the steep landscapes with debris‐flow‐dominated channels and relatively flat fluvial landscapes and directly controls the shape of the channel profile.
The Ocean Carbon Response to COVID‐Related Emissions Reductions
Authors: Lovenduski Nicole S. , Swart Neil C. , Sutton Adrienne J. , Fyfe John C. , McKinley Galen A. , Sabine Christopher , Williams Nancy L.
Published: March 2021

The decline in global emissions of carbon dioxide due to the COVID‐19 pandemic provides a unique opportunity to investigate the sensitivity of the global carbon cycle and climate system to emissions reductions. Recent efforts to study the response to these emissions declines has not addressed their impact on the ocean, yet ocean carbon absorption is particularly susceptible to changing atmospheric carbon concentrations. Here, we use ensembles of simulations conducted with an Earth system model to explore the potential detection of COVID‐related emissions reductions in the partial pressure difference in carbon dioxide between the surface ocean and overlying atmosphere (ΔpCO2), a quantity that is regularly measured. We find a unique fingerprint in global‐scale ΔpCO2 that is attributable to COVID, though the fingerprint is difficult to detect in individual model realizations unless we force the model with a scenario that has four times the observed emissions reduction.
The First Angstrom-Scale View of Weathering
Authors: Wheeling Kate
Published: March 2021

Researchers observe how water vapor and liquid alter sedimentary rocks through physical and chemical processes.
5G mobile networks and health—a state-of-the-science review of the research into low-level RF fields above 6 GHz
Authors: Karipidis Ken , Mate Rohan , Urban David , Tinker Rick , Wood Andrew
Published: March 2021

The increased use of radiofrequency (RF) fields above 6 GHz, particularly for the 5 G mobile phone network, has given rise to public concern about any possible adverse effects to human health. Public exposure to RF fields from 5 G and other sources is below the human exposure limits specified by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). This state-of-the science review examined the research into the biological and health effects of RF fields above 6 GHz at exposure levels below the ICNIRP occupational limits. The review included 107 experimental studies that investigated various bioeffects including genotoxicity, cell proliferation, gene expression, cell signalling, membrane function and other effects. Reported bioeffects were generally not independently replicated and the majority of the studies employed low quality methods of exposure assessment and control. Effects due to heating from high RF energy deposition cannot be excluded from many of the results. The review also included 31 epidemiological studies that investigated exposure to radar, which uses RF fields above 6 GHz similar to 5 G. The epidemiological studies showed little evidence of health effects including cancer at different sites, effects on reproduction and other diseases. This review showed no confirmed evidence that low-level RF fields above 6 GHz such as those used by the 5 G network are hazardous to human health. Future experimental studies should improve the experimental design with particular attention to dosimetry and temperature control. Future epidemiological studies should continue to monitor long-term health effects in the population related to wireless telecommunications.
Recognition of high-specificity hERG K+ channel inhibitor-induced arrhythmia in cardiomyocytes by automated template matching
Authors: Wang Hao , Li Hongbo , Wei Xinwei , Zhang Tao , Xiang Yuting , Fang Jiaru , Wu Peiran , Xie Xi , Wang Ping , Hu Ning
Published: March 2021

Cardiovascular disease (CVD) is the number one cause of death in humans. Arrhythmia induced by gene mutations, heart disease, or hERG K+ channel inhibitors is a serious CVD that can lead to sudden death or heart failure. Conventional cardiomyocyte-based biosensors can record extracellular potentials and mechanical beating signals. However, parameter extraction and examination by the naked eye are the traditional methods for analyzing arrhythmic beats, and it is difficult to achieve automated and efficient arrhythmic recognition with these methods. In this work, we developed a unique automated template matching (ATM) cardiomyocyte beating model to achieve arrhythmic recognition at the single beat level with an interdigitated electrode impedance detection system. The ATM model was established based on a rhythmic template with a data length that was dynamically adjusted to match the data length of the target beat by spline interpolation. The performance of the ATM model under long-term astemizole, droperidol, and sertindole treatment at different doses was determined. The results indicated that the ATM model based on a random rhythmic template of a signal segment obtained after astemizole treatment presented a higher recognition accuracy (100% for astemizole treatment and 99.14% for droperidol and sertindole treatment) than the ATM model based on arrhythmic multitemplates. We believe this highly specific ATM method based on a cardiomyocyte beating model has the potential to be used for arrhythmia screening in the fields of cardiology and pharmacology.
Psychosocial care and support in the field of intersex/diverse sex development (dsd): counselling experiences, localisation and needed improvements
Authors: Lampalzer Ute , Briken Peer , Schweizer Katinka
Published: March 2021

From different sides, there is a call for better psychosocial care and counselling in the field of diverse sex development (dsd). However, studies on the specific demands, deficits and needed improvements regarding those services are rare. This exploratory online study aimed at investigating counselling experiences and the ideas that different groups of participants have concerning the localisation of counselling structures and improving care. Quantitative and qualitative data (N = 630) were analysed within a mixed methods framework. The participants included experts of experience resp. patients with different intersex/dsd conditions (n = 40), parents of children with dsd (n = 27), professional psychosocial counsellors (n = 321) and experts in the field including medical practitioners, psychologists, natural and social scientists as well as others involved, e.g., students or relatives (n = 56). The results show a gap between receiving psychosocial and medical care in the group of adult lived-experience experts, who had received less psychosocial care than medical interventions. The findings also reveal important tasks of psychosocial care. A focus was set on parental experiences. Helpful aspects reported were talking with other parents of children with intersex/dsd, aspects missed were assistance in supporting the individual development of their children. The majority of all participants (58%) held the view that, apart from multidisciplinary competence centres, there also have to be easily accessible counselling services which offer support in everyday life. The participants named increasing quality and quantity as necessary improvements in counselling structures for children and adults with intersex/dsd and their families. Implications are drawn for the specific tasks and target groups of psychosocial care and needed research in intersex healthcare over life span.
Publisher Correction: Author Correction: A patient-centric dataset of images and metadata for identifying melanomas using clinical context
Authors: Rotemberg Veronica , Kurtansky Nicholas , Betz-Stablein Brigid , Caffery Liam , Chousakos Emmanouil , Codella Noel , Combalia Marc , Dusza Stephen , Guitera Pascale , Gutman David , Halpern Allan , Helba Brian , Kittler Harald , Kose Kivanc , Langer Steve , Lioprys Konstantinos , Malvehy Josep , Musthaq Shenara , Nanda Jabpani , Reiter Ofer , Shih George , Stratigos Alexander , Tschandl Philipp , Weber Jochen , Soyer H. Peter
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41597-021-00879-x.
Genomics and transcriptomics of the green mussel explain the durability of its byssus
Authors: Inoue Koji , Yoshioka Yuki , Tanaka Hiroyuki , Kinjo Azusa , Sassa Mieko , Ueda Ikuo , Shinzato Chuya , Toyoda Atsushi , Itoh Takehiko
Published: March 2021

Mussels, which occupy important positions in marine ecosystems, attach tightly to underwater substrates using a proteinaceous holdfast known as the byssus, which is tough, durable, and resistant to enzymatic degradation. Although various byssal proteins have been identified, the mechanisms by which it achieves such durability are unknown. Here we report comprehensive identification of genes involved in byssus formation through whole-genome and foot-specific transcriptomic analyses of the green mussel, Perna viridis. Interestingly, proteins encoded by highly expressed genes include proteinase inhibitors and defense proteins, including lysozyme and lectins, in addition to structural proteins and protein modification enzymes that probably catalyze polymerization and insolubilization. This assemblage of structural and protective molecules constitutes a multi-pronged strategy to render the byssus highly resistant to environmental insults.
Genome-wide identification and characterization of circular RNA in resected hepatocellular carcinoma and background liver tissue
Authors: Sunagawa Yuki , Yamada Suguru , Sonohara Fuminori , Kurimoto Keisuke , Tanaka Nobutake , Suzuki Yunosuke , Inokawa Yoshikuni , Takami Hideki , Hayashi Masamichi , Kanda Mitsuro , Tanaka Chie , Nakayama Goro , Koike Masahiko , Kodera Yasuhiro
Published: March 2021

Circular RNA (circRNA) is a type of non-coding RNA known to affect cancer-related micro RNAs and various transcription factors. circRNA has promise as a cancer-related biomarker because its circular structure affords high stability. We found using high-throughput sequencing that seven candidate circRNAs (hsa_circ_0041150, hsa_circ_0025624, hsa_circ_0001020, hsa_circ_0028129, hsa_circ_0008558, hsa_circ_0036683, hsa_circ_0058087) were downregulated in HCC. The expression of these circRNAs was examined by quantitative PCR in 233 sets of HCC and matched background normal liver tissues, and correlations between candidate circRNA expression and prognosis were evaluated. The results of quantitative PCR showed that expression of hsa_circ_0041150, hsa_circ_0001020 and hsa_circ_0008558 was significantly lower in HCC than in background normal liver tissues. Kaplan–Meier analysis revealed that low expression of hsa_circ_0001020, hsa_circ_0036683, and hsa_circ_0058087 was associated with poor recurrence-free (RFS) and overall survival (OS) in HCC. Additionally, multivariate analysis revealed that low hsa_circ_0036683 expression was a significant prognostic factor, independent from other clinicopathological features, for inferior RFS and OS. There was no significant association between the expression of these circRNAs and hepatitis B/C status or cirrhosis. This study therefore identified circRNAs as potential prognostic markers for patients who undergo curative surgery for HCC and highlighted hsa_circ_0036683 as the most useful biomarker.
Evaluation of Indonesian mangrove Xylocarpus granatum leaves ethyl acetate extract as potential anticancer drug
Authors: Darmadi Jason , Batubara Razethy Rahayu , Himawan Sandiego , Azizah Norma Nur , Audah Hilyatushalihah Kholis , Arsianti Ade , Kurniawaty Evi , Ismail Intan Safinar , Batubara Irmanida , Audah Kholis Abdurachim
Published: March 2021

Local Xylocarpus granatum leaves were extracted by ethyl acetate solvent and characterized by TLC fingerprinting and 2D 1H NMR spectroscopy to contain phenolic compounds as well as several organic and amino acids as metabolic byproducts, such as succinic acid and acetic acid. Traces of flavonoids and other non-categorized phenolic compounds exhibited intermediate antioxidant activity (antioxidant IC50 84.93 ppm) as well as anticancer activity against HeLa, T47D, and HT-29 cell lines; which the latter being most effective against HT-29 with Fraction 5 contained the strongest activity (anticancer IC50 23.12 ppm). Extracts also behaved as a natural growth factor and nonlethal towards brine shrimps as well as human adipose-derived stem cell hADSC due to antioxidative properties. A stability test was performed to examine how storage conditions factored in bioactivity and phytochemical structure. Extracts were compared with several studies about X. granatum leaves extracts to evaluate how ethnogeography and ecosystem factored on biologically active compounds. Further research on anticancer or antioxidant mechanism on cancer cells is needed to determine whether the extract is suitable as a candidate for an anticancer drug.
A facile colorimetric method for the quantification of labile iron pool and total iron in cells and tissue specimens
Authors: Abbasi Usama , Abbina Srinivas , Gill Arshdeep , Bhagat Vriti , Kizhakkedathu Jayachandran N.
Published: March 2021

Quantification of iron is an important step to assess the iron burden in patients suffering from iron overload diseases, as well as tremendous value in understanding the underlying role of iron in the pathophysiology of these diseases. Current iron determination of total or labile iron, requires extensive sample handling and specialized instruments, whilst being time consuming and laborious. Moreover, there is minimal to no overlap between total iron and labile iron quantification methodologies—i.e. requiring entirely separate protocols, techniques and instruments. Herein, we report a unified-ferene (u-ferene) assay that enables a 2-in-1 quantification of both labile and total iron from the same preparation of a biological specimen. We demonstrate that labile iron concentrations determined from theu-ferene assay is in agreement with confocal laser scanning microscopy techniques employed within the literature. Further, this assay offers the same sensitivity as the current gold standard, inductively coupled plasma mass spectrometry (ICP-MS), for total iron measurements. The newu-ferene assay will have tremendous value for the wider scientific community as it offers an economic and readily accessible method for convenient 2-in-1 measurement of total and labile iron from biological samples, whilst maintaining the precision and sensitivity, as compared to ICP-MS.
Prediction of urine culture results by automated urinalysis with digital flow morphology analysis
Authors: Kim Dokyun , Oh Seoung Chul , Liu Changseung , Kim Yoonjung , Park Yongjung , Jeong Seok Hoon
Published: March 2021

To investigate the association between the results of urinalysis and those of concurrent urine cultures, and to construct a prediction model for the results of urine culture. A total of 42,713 patients were included in this study. Patients were divided into two independent groups including training and test datasets. A novel prediction algorithm, designated the UTOPIA value, was constructed with the training dataset, based on an association between the results of urinalysis and those of concurrent urine culture. The diagnostic performance of the UTOPIA value was validated with the test dataset. Six variables were selected for the equation of the UTOPIA value: age of higher UTI risk [odds ratio (OR), 2.069125], female (OR, 1.400648), nitrite (per 1 grade; OR, 3.765457), leukocyte esterase (per 1 grade; OR, 1.701586), the number of WBCs (per 1 × 106/L; OR, 1.000121), and the number of bacteria (per 1 × 106/L; OR, 1.004195). The UTOPIA value exhibited an area under the curve value of 0.837 when validated with the independent test dataset. The UTOPIA value displayed good diagnostic performance for predicting urine culture results, which would help to reduce unnecessary culture. Different cutoffs can be used according to the clinical indication.
Comparison of penetrating keratoplasty outcomes with or without microwave thermokeratoplasty
Authors: Hieda Osamu , Wakimasu Koichi , Kinoshita Shigeru , Sotozono Chie
Published: March 2021

Microwave thermokeratoplasty (MTK) is a surgical procedure for the correction of pathologic corneal steepening. The purpose of this study was to examine the postoperative outcomes of eyes with advanced keratoconus that underwent femtosecond-laser zig-zag penetrating keratoplasty (z-PK) following MTK for reshaping of the central cornea. This study involved 32 eyes of 32 consecutive advanced keratoconus patients; i.e., 25 eyes of 25 patients who underwent MTK prior to z-PK (MTK + z-PK group), and 7 eyes of 7 patients who underwent z-PK alone (z-PK group). In all treated eyes, visual acuity (VA) and corneal topography were measured before surgery and at 6-months postoperative. At 6-months postoperative, the mean uncorrected distance VA (logarithm of the minimum angle of resolution) and surface regularity index (SRI) of the MTK + z-PK group was 0.62 ± 0.39 (mean ± standard deviation) and 1.26 ± 0.45, respectively, while that in the z-PK group was 1.02 ± 0.18 and 7.64 ± 3.22, respectively. Both variables were significantly better in the MTK + z-PK group than in the z-PK group (P < 0.05). The findings in this study reveal that MTK prior to z-PKP is effective for improving UDVA and reducing the irregularity of corneal topography in patients with advanced keratoconus.
Nanoimprinted multifunctional nanoprobes for a homogeneous immunoassay in a top-down fabrication approach
Authors: Brueckl Hubert , Shoshi Astrit , Schrittwieser Stefan , Schmid Barbara , Schneeweiss Pia , Mitteramskogler Tina , Haslinger Michael J. , Muehlberger Michael , Schotter Joerg
Published: March 2021

Multifunctional nanoparticles are discussed as versatile probes for homogeneous immunoassays for in-vitro diagnostics. Top-down fabrication allows to combine and tailor magnetic and plasmonic anisotropic properties. The combination of nanoimprint lithography, thin film deposition, and lift-off processing provides a top-down fabrication platform, which is both flexible and reliable. Here, we discuss the material compositions and geometrical designs of monodisperse multicomponent nanoparticles and their consequences on optical and magnetic properties. The rotational hydrodynamics of nanoparticles is measured and considered under the influence of magnetic shape anisotropy in the framework of the Stoner-Wohlfarth theory. The plasmon-optical properties are explained by discrete-dipole finite-element simulations. Rotational dynamical measurements of imprinted nanoprobes for two test proteins demonstrate the applicability as highly sensitive biomolecular nanoprobes.
The multi-target small-molecule inhibitor SB747651A shows in vitro and in vivo anticancer efficacy in glioblastomas
Authors: Knudsen Arnon Møldrup , Boldt Henning Bünsow , Jakobsen Elisabeth Victoria , Kristensen Bjarne Winther
Published: March 2021

Glioblastoma multiforme is the most common primary brain tumor and among the most lethal types of cancer. Several mono-target small molecule-inhibitors have been investigated as novel therapeutics, thus far with poor success. In this study we investigated the anticancer effects of SB747651A, a multi-target small-molecule inhibitor, in three well characterized patient-derived glioblastoma spheroid cultures and a murine orthotopic xenograft model. Concentrations of 5–10 µM SB747651A reduced cell proliferation, spheroid formation, migration and chemoresistance, while apoptotic cell death increased. Investigation of oncogenic kinase signaling showed decreased phosphorylation levels of mTOR, CREB, GSK3 and GYS1 leading to altered glycogen metabolism and formation of intracellular reactive oxygen species. Expression levels of cancer stemness marker SOX2 were reduced in treated tumor cells and SB747651A treatment significantly prolonged survival of mice with intracranial glioblastoma xenografts, while no adverse effects were observed in vivo at doses of 25 mg/kg administered 5 days/week for 8 weeks. These findings suggest that SB747651A has anticancer effects in glioblastoma. The cancer-related pathophysiological mechanisms targeted by SB747651A are shared among many types of cancer; however, an in-depth clarification of the mechanisms of action in cancer cells is important before further potential application of SB747651A as an anticancer agent can be considered.
Single-copy detection of somatic variants from solid and liquid biopsy
Authors: Silva Ana-Luisa , Powalowska Paulina Klaudyna , Stolarek Magdalena , Gray Eleanor Ruth , Palmer Rebecca Natalie , Herman Bram , Frayling Cameron Alexander , Balmforth Barnaby William
Published: March 2021

Accurate detection of somatic variants, against a background of wild-type molecules, is essential for clinical decision making in oncology. Existing approaches, such as allele-specific real-time PCR, are typically limited to a single target gene and lack sensitivity. Alternatively, next-generation sequencing methods suffer from slow turnaround time, high costs, and are complex to implement, typically limiting them to single-site use. Here, we report a method, which we term Allele-Specific PYrophosphorolysis Reaction (ASPYRE), for high sensitivity detection of panels of somatic variants. ASPYRE has a simple workflow and is compatible with standard molecular biology reagents and real-time PCR instruments. We show that ASPYRE has single molecule sensitivity and is tolerant of DNA extracted from plasma and formalin fixed paraffin embedded (FFPE) samples. We also demonstrate two multiplex panels, including one for detection of 47EGFRvariants. ASPYRE presents an effective and accessible method that simplifies highly sensitive and multiplexed detection of somatic variants.
Shear wave elastography of the lateral abdominal muscles in C-shaped idiopathic scoliosis: a case–control study
Authors: Linek Paweł , Pałac Małgorzata , Wolny Tomasz
Published: March 2021

Considering that knowledge about lateral abdominal muscles (LAM) in idiopathic scoliosis (IS) is still very limited, the aims of this study were: (a) to compare LAM thickness and elasticity between C-shaped IS and non-scoliotic population; and (b) to compare LAM thickness and elasticity between C-shaped thoracic, thoracolumbar, and lumbar IS. A total of 259 adolescents were included in the final analysis; among these, 108 were IS and 151 were non-IS. LAM thickness and elasticity were measured at rest and during isometric contraction by an Aixplorer ultrasound scanner. Out of all LAM, only OE thickness was higher on the convex body side compared to the concave side in lumbar and thoracolumbar scoliosis. It may be related with muscle’s atrophy/hypertrophy or other tissues displacement rather than different force generated by the muscle on both body sides, because an asymmetry in the elasticity of the LAM between the convex and concave side was not presented. The only TrA was stiffer in lumbar scoliosis compared to thoracolumbar and thoracic scoliosis. LAM elasticity was similar in IS and non-IS adolescents.
Reopening businesses and risk of COVID-19 transmission
Authors: O’Donoghue Ashley , Dechen Tenzin , Pavlova Whitney , Boals Michael , Moussa Garba , Madan Manvi , Thakkar Aalok , DeFalco Frank J. , Stevens Jennifer P.
Published: March 2021

The true risk of a COVID-19 resurgence as states reopen businesses is unknown. In this paper, we used anonymized cell-phone data to quantify the potential risk of COVID-19 transmission in business establishments by building a Business Risk Index that measures transmission risk over time. The index was built using two metrics, visits per square foot and the average duration of visits, to account for both density of visits and length of time visitors linger in the business. We analyzed trends in traffic patterns to 1,272,260 businesses across eight states from January 2020 to June 2020. We found that potentially risky traffic behaviors at businesses decreased by 30% by April. Since the end of April, the risk index has been increasing as states reopen. There are some notable differences in trends across states and industries. Finally, we showed that the time series of the average Business Risk Index is useful for forecasting future COVID-19 cases at the county-level (P < 0.001). We found that an increase in a county’s average Business Risk Index is associated with an increase in positive COVID-19 cases in 1 week (IRR: 1.16, 95% CI: (1.1–1.26)). Our risk index provides a way for policymakers and hospital decision-makers to monitor the potential risk of COVID-19 transmission from businesses based on the frequency and density of visits to businesses. This can serve as an important metric as states monitor and evaluate their reopening strategies.
Elucidation of transient protein-protein interactions within carrier protein-dependent biosynthesis
Authors: Bartholow Thomas G. , Sztain Terra , Patel Ashay , Lee D. John , Young Megan A. , Abagyan Ruben , Burkart Michael D.
Published: March 2021

Fatty acid biosynthesis (FAB) is an essential and highly conserved metabolic pathway. In bacteria, this process is mediated by an elaborate network of protein•protein interactions (PPIs) involving a small, dynamic acyl carrier protein that interacts with dozens of other partner proteins (PPs). These PPIs have remained poorly characterized due to their dynamic and transient nature. Using a combination of solution-phase NMR spectroscopy and protein-protein docking simulations, we report a comprehensive residue-by-residue comparison of the PPIs formed during FAB in Escherichia coli. This technique describes and compares the molecular basis of six discrete binding events responsible for E. coli FAB and offers insights into a method to characterize these events and those in related carrier protein-dependent pathways.
Spatiotemporal dynamics of single cell stiffness in the early developing ascidian chordate embryo
Authors: Fujii Yuki , Koizumi Wataru C. , Imai Taichi , Yokobori Megumi , Matsuo Tomohiro , Oka Kotaro , Hotta Kohji , Okajima Takaharu
Published: March 2021

During the developmental processes of embryos, cells undergo massive deformation and division that are regulated by mechanical cues. However, little is known about how embryonic cells change their mechanical properties during different cleavage stages. Here, using atomic force microscopy, we investigated the stiffness of cells in ascidian embryos from the fertilised egg to the stage before gastrulation. In both animal and vegetal hemispheres, we observed a Rho kinase (ROCK)-independent cell stiffening that the cell stiffness exhibited a remarkable increase at the timing of cell division where cortical actin filaments were organized. Furthermore, in the vegetal hemisphere, we observed another mechanical behaviour, i.e., a ROCK-associated cell stiffening, which was retained even after cell division or occurred without division and propagated sequentially toward adjacent cells, displaying a characteristic cell-to-cell mechanical variation. The results indicate that the mechanical properties of embryonic cells are regulated at the single cell level in different germ layers.
Cell wall N-glycan of Candida albicans ameliorates early hyper- and late hypo-immunoreactivity in sepsis
Authors: Kawakita Masataka , Oyama Taiki , Shirai Ikuma , Tanaka Shuto , Akaki Kotaro , Abe Shinya , Asahi Takuma , Cui Guangwei , Itoh Fumie , Sasaki Masato , Shibata Nobuyuki , Ikuta Koichi , Hatakeyama Tomomitsu , Takahara Kazuhiko
Published: March 2021

Severe infection often causes a septic cytokine storm followed by immune exhaustion/paralysis. Not surprisingly, many pathogens are equipped with various anti-inflammatory mechanisms. Such mechanisms might be leveraged clinically to control septic cytokine storms. Here we show that N-glycan from pathogenicC. albicansameliorates mouse sepsis through immunosuppressive cytokine IL-10. In a sepsis model using lipopolysaccharide (LPS), injection of the N-glycan upregulated serum IL-10, and suppressed pro-inflammatory IL-1β, TNF-α and IFN-γ. The N-glycan also improved the survival of mice challenged by LPS. Analyses of structurally defined N-glycans from several yeast strains revealed that the mannose core is key to the upregulation of IL-10. Knocking out the C-type lectin Dectin-2 abrogated the N-glycan-mediated IL-10 augmentation. Furthermore,C. albicansN-glycan ameliorated immune exhaustion/immune paralysis after acute inflammation. Our results suggest a strategy where the immunosuppressive mechanism of one pathogen can be applied to attenuate a severe inflammation/cytokine storm caused by another pathogen.
Mutations in hik26 and slr1916 lead to high-light stress tolerance in Synechocystis sp. PCC6803
Authors: Yoshikawa Katsunori , Ogawa Kenichi , Toya Yoshihiro , Akimoto Seiji , Matsuda Fumio , Shimizu Hiroshi
Published: March 2021

Increased tolerance to light stress in cyanobacteria is a desirable feature for their applications. Here, we obtained a high light tolerant (Tol) strain of Synechocystis sp. PCC6803 through an adaptive laboratory evolution, in which the cells were repeatedly sub-cultured for 52 days under high light stress conditions (7000 to 9000 μmol m−2 s−1). Although the growth of the parental strain almost stopped when exposed to 9000 μmol m−2 s−1, no growth inhibition was observed in the Tol strain. Excitation-energy flow was affected because of photosystem II damage in the parental strain under high light conditions, whereas the damage was alleviated and normal energy flow was maintained in the Tol strain. The transcriptome data indicated an increase in isiA expression in the Tol strain under high light conditions. Whole genome sequence analysis and reverse engineering revealed two mutations in hik26 and slr1916 involved in high light stress tolerance in the Tol strain.
Adiponectin-expressing Treg facilitate T lymphocyte development in thymic nurse cell complexes
Authors: Zhang Yiwei , Cao Handi , Chen Jie , Li Yuanxin , Xu Aimin , Wang Yu
Published: March 2021

Adiponectin is a well-known insulin sensitizer and anti-inflammatory molecule, possessing therapeutic potentials in cardiovascular, metabolic and cancer diseases. Results of the present study demonstrate that adiponectin is expressed in a population of regulatory T-cells (Treg) resided within the thymic nurse cell (TNC) complexes. Adoptive transfer of adiponectin-expressing Treg precursors effectively attenuated obesity, improved glucose and insulin tolerance, prevented fatty liver injuries in wild-type mice fed a high-fat diet, and significantly inhibited breast cancer development in MMTV-PyVT transgenic mice. Within the TNC complexes, locally produced adiponectin bound to and regulated the expression as well as the distribution of CD100, a transmembrane lymphocyte semaphorin, in turn modulating the lymphoepithelial interactions to facilitate T-cell development and maturation. In summary, adiponectin plays an important role in the selection and development of T lymphocytes within the TNC complexes. Adiponectin-expressing Treg represent a promising candidate for adoptive cell immunotherapy against obesity-related metabolic and cancer diseases.
A water-stable molecular cadmium phosphonate bearing 2-(2-pyridyl)benzimidazole as a highly sensitive luminescence sensor for the selective detection of bisphenol AF and bisphenol B
Authors: Wu Jing-Yun , Hu Zhi-Jia , Sung Hui-Ling
Published: March 2021

A highly water-stable molecular cadmium phosphonate bearing 2-(2-pyridyl)benzimidazole has been used as a sensor platform for the luminescence detection of bisphenol AF (BPAF) and bisphenol B (BPB) in water with good sensitivity and selectivity.
Macroplastics in rivers: present knowledge, issues and challenges
Authors: Al-Zawaidah Hadeel , Ravazzolo Diego , Friedrich Heide
Published: March 2021

The contextualization of macroplastics in a budget framework can help to improve our understanding of the physical processes determining macroplastic behaviour and impacts in rivers. Hence, better management practices can be adopted.
Mechanotransduction-on-chip: vessel-chip model of endothelial YAP mechanobiology reveals matrix stiffness impedes shear response
Authors: Walther Brandon K. , Rajeeva Pandian Navaneeth Krishna , Gold Karli A. , Kiliç Ecem S. , Sama Vineeth , Gu Jianhua , Gaharwar Akhilesh K. , Guiseppi-Elie Anthony , Cooke John P. , Jain Abhishek
Published: March 2021

Walther et al. employed vessel-chip technology to study how matrix stiffness and shear stress combine to influence endothelial cell YAP mechanobiology, discovering that stiff matrices impede the protective effects of physiologic shear stress.
Symmetric cytotoxic trimeric and dimeric indole alkaloids isolated from Bousigonia angustifolia
Authors: Shi Bao-Bao , Lu Jing-Song , Wu Jing , Bao Mei-Fen , Cai Xiang-Hai
Published: March 2021

Symmetric trimeric and dimeric indole alkaloids were isolated for the first time from Bousigonia angustifolia, and they could be constructed through Friedel–Crafts and free radical reactions, respectively.
A novel molecularly imprinted electrochemiluminescence sensor based on cobalt nitride nanoarray electrode for the sensitive detection of bisphenol S
Authors: Cheng Rongqi , Ding Yulong , Wang Yaoguang , Wang Huan , Zhang Yong , Wei Qin
Published: March 2021

Sensitive molecularly imprinted ECL sensor for the determination of BPS based on the CoN nanoarray electrode directly used as the ECL sensing platform was fabricated for the first time.
Electrochemical bubble generation via hydrazine oxidation for the in situ control of an electrodeposited conducting polymer micro/-nanostructure
Authors: Possetto David , Fernández Luciana , Marzari Gabriela , Fungo Fernando
Published: March 2021

An electrochemical method to manipulate the size and density of electrodeposited polypyrrole structures at the micro-nanoscale by the discharge of hydrazine.
HERs in an acidic medium over MoS2nanosheets: from fundamentals to synthesis and the recent progress
Authors: Mansingh Sriram , Das Kundan Kumar , Parida Kulamani
Published: March 2021

Electrocatalytic hydrogen evolution reactions on 2D MoS2in an acidic medium.
Hybrid carbon spherogels: carbon encapsulation of nano-titania
Authors: Salihovic Miralem , Schoiber Jürgen , Cherevan Alexey , Rameshan Christoph , Fritz-Popovski Gerhard , Ulbricht Maike , Arnold Stefanie , Presser Volker , Paris Oskar , Musso Maurizio , Hüsing Nicola , Elsaesser Michael S.
Published: March 2021

Extraordinarily homogeneous, freestanding titania-loaded carbon spherogels can be obtained using Ti(acac)2(OiPr)2 in the polystyrene sphere templated resorcinol-formaldehyde gelation.
Cyclodextrins: a new and effective class of co-modulators for aqueous zirconium-MOF syntheses
Authors: Hoyez Guillaume , Rousseau Jolanta , Rousseau Cyril , Saitzek Sébastien , King James , Szilágyi Petra Ágota , Volkringer Christophe , Loiseau Thierry , Hapiot Frédéric , Monflier Eric , Ponchel Anne
Published: March 2021

Zr-MOFs exhibiting superior textural properties with BET surface area as high as 1451 m2 g−1 were successfully synthesized under hydrothermal conditions using native α-CD and β-CD as macromolecular additives.
A novel copper(i) metal–organic framework as a highly efficient and ultrasensitive electrochemical platform for detection of Hg(ii) ions in aqueous solution
Authors: Wang Xiao-Qing , Tang Jing , Ma Xuehui , Wu Dan , Yang Jie
Published: March 2021

A novel copper(i) metal–organic framework was constructed and used to modify a glassy carbon electrode, and exhibits excellent electrochemical sensing of Hg(ii) ions.
Molecular-scale origins of solution nanostructure and excess thermodynamic properties in a water/amphiphile mixture
Authors: Servis Michael J. , Piechowicz Marek , Skanthakumar S. , Soderholm L.
Published: March 2021

The molecular and nanoscale origins of nonideality in excess thermodynamic properties are essential to understanding cosolvent mixtures, yet they remain challenging to determine.
Substance and shadow of formamidinium lead triiodide based solar cells
Authors: Haris Muhammed P. U. , Kazim Samrana , Pegu Meenakshi , Deepa M. , Ahmad Shahzada
Published: March 2021

We shed light on the compositional, surface engineering and crystallization kinetics manipulations for FAPbI3 followed by a proposition for unified testing protocols in order to scale-up the solar cells from the lab to the market.
Few-nm-sized, phase-pure Au5Sn intermetallic nanoparticles: synthesis and characterization
Authors: Osugi Satoshi , Takano Shinjiro , Masuda Shinya , Harano Koji , Tsukuda Tatsuya
Published: March 2021

Few-nm-sized, phase-pure Au5Sn intermetallic nanoparticles (IMNPs) were synthesized by co-reduction of Au3+ and Sn2+ precursors with the ratio of 6 : 4 in the presence of oleylamine. Optical and catalytic properties of the Au5Sn IMNPs were compared to those of pure Au NPs.
A thermoresponsive crosslinker for reversible micelle stabilization
Authors: Tolentino Mark Q. , Rouge Jessica L.
Published: March 2021

Herein we report a thermoresponsive crosslinker that can be utilized to stabilize the surface of micelles through “click” reaction and to trigger the disassembly via retro Diels Alder (rDA) mechanism.
The Piancatelli rearrangement of non-symmetrical furan-2,5-dicarbinols for the synthesis of highly functionalized cyclopentenones
Authors: Cacheux Fanny , Le Goff Géraldine , Ouazzani Jamal , Bignon Jérôme , Retailleau Pascal , Marinetti Angela , Voituriez Arnaud , Betzer Jean-François
Published: March 2021

Piancatelli rearrangement on substituted non-symmetrical furan-2,5-dicarbinols has been developed using an effective combination of microwave activation and Lewis acid catalyst.
A smart diagnostic tool based on deep kernel learning for on-site determination of phosphate, calcium, and magnesium concentration in a hydroponic system
Authors: Tuan Vu Ngoc , Dinh Trinh Dinh , Zhang Wenxin , Khattak Abdul Mateen , Le Anh Tuan , Saeed Iftikhar Ahmed , Gao Wanlin , Wang Minjuan
Published: March 2021

A smart diagnostic tool based on deep kernel learning for on-site determining phosphate, calcium, and magnesium concentration in a hydroponic system.