bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced Mrp2 surface availability as PI3Kγ-mediated hepatocytic dysfunction reflecting a hallmark of cholestasis in sepsis
Authors: Beer Anne J. , Hertz David , Seemann Eric , Beretta Martina , Westermann Martin , Bauer Reinhard , Bauer Michael , Kessels Michael M. , Qualmann Britta
Published: August 2020

Sepsis-associated liver dysfunction manifesting as cholestasis is common during multiple organ failure. Three hepatocytic dysfunctions are considered as major hallmarks of cholestasis in sepsis: impairments of microvilli covering canalicular membranes, disruptions of tight junctions sealing bile-collecting canaliculae and disruptions of Mrp2-mediated hepatobiliary transport. PI3Kγ loss-of-function was suggested as beneficial in early sepsis. Yet, the PI3Kγ-regulated cellular processes in hepatocytes remained largely unclear. We analysed all three sepsis hallmarks for responsiveness to massive PI3K/Akt signalling and PI3Kγ loss-of-function, respectively. Surprisingly, neither microvilli nor tight junctions were strongly modulated, as shown by electron microscopical studies of mouse liver samples. Instead, quantitative electron microscopy proved that solely Mrp2 surface availability, i.e. the third hallmark, responded strongly to PI3K/Akt signalling. Mrp2 plasma membrane levels were massively reduced upon PI3K/Akt signalling. Importantly, Mrp2 levels at the plasma membrane of PI3Kγ KO hepatocytes remained unaffected upon PI3K/Akt signalling stimulation. The effect explicitly relied on PI3Kγ’s enzymatic ability, as shown by PI3Kγ kinase-dead mice. Keeping the surface availability of the biliary transporter Mrp2 therefore is a cell biological process that may underlie the observation that PI3Kγ loss-of-function protects from hepatic excretory dysfunction during early sepsis and Mrp2 should thus take center stage in pharmacological interventions.
Unravelling molecular interactions in uracil clusters by XPS measurements assisted by ab initio and tight-binding simulations
Authors: Mattioli Giuseppe , Avaldi Lorenzo , Bolognesi Paola , Bozek John D. , Castrovilli Mattea C. , Chiarinelli Jacopo , Domaracka Alicja , Indrajith Suvasthika , Maclot Sylvain , Milosavljević Aleksandar R. , Nicolafrancesco Chiara , Nicolas Christophe , Rousseau Patrick
Published: August 2020

The C, N and O 1s XPS spectra of uracil clusters in the gas phase have been measured. A new bottom-up approach, which relies on computational simulations starting from the crystallographic structure of uracil, has been adopted to interpret the measured spectra. This approach sheds light on the different molecular interactions (H-bond, π-stacking, dispersion interactions) at work in the cluster and provides a good understanding of the observed XPS chemical shifts with respect to the isolated molecule in terms of intramolecular and intermolecular screening occurring after the core–hole ionization. The proposed bottom-up approach, reasonably expensive in terms of computational resources, has been validated by finite-temperature molecular dynamics simulations of clusters composed of up to fifty molecules.
The perception threshold of the panda illusion, a particular form of 2D pulse-width-modulated halftone, correlates with visual acuity
Authors: Straßer Torsten , Kurtenbach Anne , Langrová Hana , Kuehlewein Laura , Zrenner Eberhart
Published: August 2020

To call attention to the danger of extinction of the panda bear, the Lithuanian artist Ilja Klemencov created the artwork “They can disappear”. The illustration is composed of black-and-white zigzagged lines, which form the famous panda logo of the World Wild Fund For Nature (WWF) when seen from a distance. If one is too close to the artwork, it is difficult to spot the bear, however, if one steps back or takes off one’s glasses the panda suddenly appears. This led us to ask if the ability to see the panda is related to the visual acuity of the observer and if therefore, the panda illusion can be used to assess the spatial resolution of the eye. Here we present the results of the comparison between visual acuity determined using the Landolt C and that predicted from the panda illusion in 23 healthy volunteers with artificially reduced visual acuity. Furthermore, we demonstrate that the panda illusion is based on a 2D pulse-width modulation, explain its technical history, and provide the equations required to create the illusion. Finally, we explain why the illusion indeed can be used to predict visual acuity and discuss the neural causes of its perception with best-corrected visual acuity.
Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus
Authors: Friberg Cathrine , Haaber Jakob Krause , Vestergaard Martin , Fait Anaëlle , Perrot Veronique , Levin Bruce R. , Ingmer Hanne
Published: August 2020

Antimicrobial peptides (AMPs) are central components of the innate immune system providing protection against pathogens. Yet, serum and tissue concentrations vary between individuals and with disease conditions. We demonstrate that the human AMP LL-37 lowers the susceptibility to vancomycin in the community-associated methicillin-resistant S. aureus (CA-MRSA) strain FPR3757 (USA300). Vancomycin is used to treat serious MRSA infections, but treatment failures occur despite MRSA strains being tested susceptible according to standard susceptibility methods. Exposure to physiologically relevant concentrations of LL-37 increased the minimum inhibitory concentration (MIC) of S. aureus towards vancomycin by 75%, and resulted in shortened lag-phase and increased colony formation at sub-inhibitory concentrations of vancomycin. Computer simulations using a mathematical antibiotic treatment model indicated that a small increase in MIC might decrease the efficacy of vancomycin in clearing a S. aureus infection. This prediction was supported in a Galleria mellonella infection model, where exposure of S. aureus to LL-37 abolished the antimicrobial effect of vancomycin. Thus, physiological relevant concentrations of LL-37 reduce susceptibility to vancomycin, indicating that tissue and host specific variations in LL-37 concentrations may influence vancomycin susceptibility in vivo.
Prognostic value of neutrophil-to-lymphocyte ratio in human epidermal growth factor receptor 2-negative breast cancer patients who received neoadjuvant chemotherapy
Authors: Bae Soong June , Cha Yoon Jin , Yoon Changik , Kim Dooreh , Lee Janghee , Park Soeun , Cha Chihwan , Kim Jee Ye , Ahn Sung Gwe , Park Hyung Seok , Park Seho , Kim Seung Il , Jeong Joon
Published: August 2020

We aimed to investigate the correlation between neutrophil-to-lymphocyte ratio (NLR) and pathologic complete response (pCR) and survival outcomes in human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who received neoadjuvant chemotherapy. The baseline NLR was evaluated in non-metastatic, HER2-negative breast cancer patients who received neoadjuvant chemotherapy. Baseline NLR was calculated as absolute neutrophil per lymphocyte count from pre-treatment blood samples. Any value ≥ 2.74 was considered to be a high NLR. In the 1,097 patients studied, 272 (24.4%) had high NLR and 825 (75.6%) had low NLR. The high NLR was an independent factor for pCR (OR 0.595; 95% CIs 0.398–0.890; P = 0.011). Furthermore, high NLR was a significant independent parameter affecting DFS (HR 2.298; 95% CIs 1.691–3.124; P < 0.001) and OS (HR 1.905; 95% CIs 1.167–3.108; P = 0.010). Regardless of the baseline NLR, survival outcomes were excellent in patients who achieved pCR, but high NLR was associated with worse survival for patients with residual invasive disease. Our study showed that NLR was predictive for treatment response and a prognostic factor in patients with HER2-negative breast cancer who received neoadjuvant chemotherapy. Moreover, we identified that high NLR was associated with poor survival outcomes in patients who did not achieve pCR.
A preliminary study of the concentration of metallic elements in the blood of patients with multiple sclerosis as measured by ICP-MS
Authors: de Oliveira Marcela , Gianeti Thiago Marcelo Ribeiro , da Rocha Fernando Coronetti Gomes , Lisboa-Filho Paulo Noronha , Piacenti-Silva Marina
Published: August 2020

It is estimated that multiple sclerosis (MS) affects 35,000 Brazilians and 2.5 million individuals worldwide. Many studies have suggested a possible role of metallic elements in the etiology of MS, but their concentration in the blood of MS patients is nonetheless little investigated in Brazil. In this work, these elements were studied through Inductively Coupled Plasma Mass Spectrometry (ICP-MS), whose analysis provides a tool to quantify the concentrations of metal elements in the blood samples of individuals with neurodegenerative disorders. This study aimed to compare the concentration of metallic elements in blood samples from patients with MS and healthy individuals. Blood was collected from 30 patients with multiple sclerosis and compared with the control group. Blood samples were digested in closed vessels using a microwave and ICP-MS was used to determine the concentrations of 12 metallic elements (Ba, Be, Ca, Co, Cr, Cu, Fe, Mg, Mo, Ni, Pb and Zn). In MS patients, we observed a reduction in the concentrations of beryllium, copper, chromium, cobalt, nickel, magnesium and iron. The mean concentration of lead in blood was significantly elevated in the MS group. However, no difference was observed in the concentrations of Mo, Ba, Ca and Zn in blood samples from MS patients and the control group. According to our data, there is a possible role for the concentrations of 8 of the 12 evaluated metallic elements in multiple sclerosis. Abnormalities in transition metals levels in biological matrices have been reported in several neurological diseases.
Reduction of focal sweating by lipid nanoparticle-delivered myricetin
Authors: Ban Choongjin , Park Joon-Bum , Cho Sora , Kim Hye Rin , Kim Yong Joon , Choi Young Jin , Chung Woo-Jae , Kweon Dae-Hyuk
Published: August 2020

Myricetin—a flavonoid capable of inhibiting the SNARE complex formation in neurons—reduces focal sweating after skin-application when delivers as encapsulated in lipid nanoparticles (M-LNPs). The stability of M-LNP enables efficient delivery of myricetin to sudomotor nerves located underneath sweat glands through transappendageal pathways while free myricetin just remained on the skin. Furthermore, release of myricetin from M-LNP is accelerated through lipase-/esterase-induced lipolysis in the skin-appendages, enabling uptake of myricetin by the surrounding cells. The amount of sweat is reduced by 55% after application of M-LNP (0.8 mg kg−1) on the mouse footpad. This is comparable to that of subcutaneously injected anticholinergic agents [0.25 mg kg−1 glycopyrrolate; 0.8 U kg−1 botulinum neurotoxin-A-type (BoNT/A)]. M-LNP neither shows a distal effect after skin-application nor induced cellular/ocular toxicity. In conclusion, M-LNP is an efficient skin-applicable antiperspirant. SNARE-inhibitory small molecules with suitable delivery systems have the potential to replace many BoNT/A interventions for which self-applications are preferred.
Single-nucleotide polymorphism rs4664308 in PLA2R1 gene is associated with the risk of idiopathic membranous nephropathy: a meta-analysis
Authors: Yoshikawa Masahiro , Asaba Kensuke
Published: August 2020

Although many studies investigated the associations between single-nucleotide polymorphisms (SNPs) in the M-type phospholipase A2 receptor-1 (PLA2R1) gene and susceptibility to idiopathic membranous nephropathy (IMN), some showed inconsistent results. Here, we conducted a meta-analysis examining the associations between PLA2R1 SNPs and IMN susceptibility after systematic searches in the PubMed and Web of Science databases. Our meta-analysis for rs4664308 A>G including 2,542 IMN patients and 4,396 controls in seven studies showed a significant association between the G allele and a lower risk of IMN, as determined using an allelic model (odds ratio, 0.45; 95% confidence interval [0.41–0.50]), an additive model (for GG vs. AA: 0.26; [0.21–0.33]; for AG vs. AA: 0.40; [0.36–0.45]), a dominant model (0.37; [0.34–0.42]) and a recessive model (0.38; [0.31–0.48]). Our meta-analysis also suggested associations between rs3828323, rs35771982, rs3749117 and rs3749119 and IMN susceptibility although high heterogeneities and/or publication biases were observed. We did not study in our meta-analysis, but other studies indicated that high-risk genotype combinations of rs2187668 in the human leucocyte antigen-DQ a-chain 1 gene and rs4664308 in the PLA2R1 gene had even stronger associations and could affect the formation of anti-PLA2R1 antibodies, suggesting these SNPs could be novel therapeutic targets.
The AAA + ATPase valosin-containing protein (VCP)/p97/Cdc48 interaction network in Leishmania
Authors: Aguiar Bruno Guedes , Dumas Carole , Maaroufi Halim , Padmanabhan Prasad K. , Papadopoulou Barbara
Published: August 2020

Valosin‐containing protein (VCP)/p97/Cdc48 is an AAA + ATPase associated with many ubiquitin-dependent cellular pathways that are central to protein quality control. VCP binds various cofactors, which determine pathway selectivity and substrate processing. Here, we used co-immunoprecipitation and mass spectrometry studies coupled to in silico analyses to identify the Leishmania infantum VCP (LiVCP) interactome and to predict molecular interactions between LiVCP and its major cofactors. Our data support a largely conserved VCP protein network in Leishmania including known but also novel interaction partners. Network proteomics analysis confirmed LiVCP-cofactor interactions and provided novel insights into cofactor-specific partners and the diversity of LiVCP complexes, including the well-characterized VCP-UFD1-NPL4 complex. Gene Ontology analysis coupled with digitonin fractionation and immunofluorescence studies support cofactor subcellular compartmentalization with either cytoplasmic or organellar or vacuolar localization. Furthermore, in silico models based on 3D homology modeling and protein–protein docking indicated that the conserved binding modules of LiVCP cofactors, except for NPL4, interact with specific binding sites in the hexameric LiVCP protein, similarly to their eukaryotic orthologs. Altogether, these results allowed us to build the first VCP protein interaction network in parasitic protozoa through the identification of known and novel interacting partners potentially associated with distinct VCP complexes.
Optimisation of Tet-On inducible systems for Sleeping Beauty-based chimeric antigen receptor (CAR) applications
Authors: Ali Hosseini Rad S. M. , Poudel Aarati , Tan Grace Min Yi , McLellan Alexander D.
Published: August 2020

Regulated expression of genetic elements that either encode polypeptides or various types of functional RNA is a fundamental goal for gene therapy. Inducible expression may be preferred over constitutive promoters to allow clinician-based control of gene expression. Existing Tet-On systems represent one of the tightest rheostats for control of gene expression in mammals. However, basal expression in absence of tetracycline compromises the widespread application of Tet-controlled systems in gene therapy. We demonstrate that the order of P2A-linked genes of interest was critical for maximal response and tightness of a chimeric antigen receptor (CAR)-based construct. The introduction of G72V mutation in the activation region of the TetR component of the rtTA further improved the fold response. Although the G72V mutation resulted in a removal of a cryptic splice site within rtTA, additional removal of this splice site led to only a modest improvement in the fold-response. Selective removal of key promoter elements (namely the BRE, TATA box, DPE and the four predicted Inr) confirmed the suitability of the minimal CMV promoter and its downstream sequences for supporting inducible expression. The results demonstrate marked improvement of the rtTA based Tet-On system in Sleeping Beauty for applications such as CAR T cell therapy.
High-mobility junction field-effect transistor via graphene/MoS2 heterointerface
Authors: Kim Taesoo , Fan Sidi , Lee Sanghyub , Joo Min-Kyu , Lee Young Hee
Published: August 2020

Monolayer molybdenum disulfide (MoS2) possesses a desirable direct bandgap with moderate carrier mobility, whereas graphene (Gr) exhibits a zero bandgap and excellent carrier mobility. Numerous approaches have been suggested for concomitantly realizing high on/off current ratio and high carrier mobility in field-effect transistors, but little is known to date about the effect of two-dimensional layered materials. Herein, we propose a Gr/MoS2 heterojunction platform, i.e., junction field-effect transistor (JFET), that enhances the carrier mobility by a factor of ~ 10 (~ 100 cm2 V−1 s−1) compared to that of monolayer MoS2, while retaining a high on/off current ratio of ~ 108 at room temperature. The Fermi level of Gr can be tuned by the wide back-gate bias (VBG) to modulate the effective Schottky barrier height (SBH) at the Gr/MoS2 heterointerface from 528 meV (n-MoS2/p-Gr) to 116 meV (n-MoS2/n-Gr), consequently enhancing the carrier mobility. The double humps in the transconductance derivative profile clearly reveal the carrier transport mechanism of Gr/MoS2, where the barrier height is controlled by electrostatic doping.
Uncovering a possible role of reactive oxygen species in magnetogenetics
Authors: Brier Matthew I. , Mundell Jordan W. , Yu Xiaofei , Su Lichao , Holmann Alexander , Squeri Jessica , Zhang Baolin , Stanley Sarah A. , Friedman Jeffrey M. , Dordick Jonathan S.
Published: August 2020

Recent reports have shown that intracellular, (super)paramagnetic ferritin nanoparticles can gate TRPV1, a non-selective cation channel, in a magnetic field. Here, we report the effects of differing field strength and frequency as well as chemical inhibitors on channel gating using a Ca2+-sensitive promoter to express a secreted embryonic alkaline phosphatase (SEAP) reporter. Exposure of TRPV1-ferritin-expressing HEK-293T cells at 30 °C to an alternating magnetic field of 501 kHz and 27.1 mT significantly increased SEAP secretion by ~ 82% relative to control cells, with lesser effects at other field strengths and frequencies. Between 30–32 °C, SEAP production was strongly potentiated 3.3-fold by the addition of the TRPV1 agonist capsaicin. This potentiation was eliminated by the competitive antagonist AMG-21629, the NADPH oxidase assembly inhibitor apocynin, and the reactive oxygen species (ROS) scavenger N-acetylcysteine, suggesting that ROS contributes to magnetogenetic TRPV1 activation. These results provide a rational basis to address the heretofore unknown mechanism of magnetogenetics.
Zonisamide ameliorates progression of cervical spondylotic myelopathy in a rat model
Authors: Kanbara Shunsuke , Ohkawara Bisei , Nakashima Hiroaki , Ohta Kyotaro , Koshimizu Hiroyuki , Inoue Taro , Tomita Hiroyuki , Ito Mikako , Masuda Akio , Ishiguro Naoki , Imagama Shiro , Ohno Kinji
Published: August 2020

Cervical spondylotic myelopathy (CSM) is caused by chronic compression of the spinal cord and is the most common cause of myelopathy in adults. No drug is currently available to mitigate CSM. Herein, we made a rat model of CSM by epidurally implanting an expanding water-absorbent polymer underneath the laminae compress the spinal cord. The CSM rats exhibited progressive motor impairments recapitulating human CSM. CSM rats had loss of spinal motor neurons, and increased lipid peroxidation in the spinal cord. Zonisamide (ZNS) is clinically used for epilepsy and Parkinson's disease. We previously reported that ZNS protected primary spinal motor neurons against oxidative stress. We thus examined the effects of ZNS on our rat CSM model. CSM rats with daily intragastric administration of 0.5% methylcellulose (n = 11) and ZNS (30 mg/kg/day) in 0.5% methylcellulose (n = 11). Oral administration of ZNS ameliorated the progression of motor impairments, spared the number of spinal motor neurons, and preserved myelination of the pyramidal tracts. In addition, ZNS increased gene expressions of cystine/glutamate exchange transporter (xCT) and metallothionein 2A in the spinal cord in CSM rats, and also in the primary astrocytes. ZNS increased the glutathione (GSH) level in the spinal motor neurons of CSM rats. ZNS potentially ameliorates loss of the spinal motor neurons and demyelination of the pyramidal tracts in patients with CSM.
Betatrophin is downregulated in pregnant women with a history of RYGB operation and a high risk of postprandial hypoglycaemia
Authors: Leutner Michael , Matzhold Caspar , Bellach Luise , Deischinger Carola , Thurner Stefan , Klimek Peter , Kautzky-Willer Alexandra
Published: August 2020

Betatrophin is a liver and adipose tissue-derived protein which has recently been linked to glucose metabolism. So far, no data exist about the role of betatrophin in pregnant women with a history of Roux-En-Y gastric bypass (RYGB) operation with a high risk of postprandial hypoglycaemia. In this prospective clinical study, an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed between the 24th and 28th week of pregnancy and 3–6 months post-partum in a cohort of obese and normal-weight pregnant women, as well as in women with a history of RYGB operation. In the cohort of pregnant women with RYGB and exaggerated risk of postprandial hypoglycaemic events, basal and dynamic betatrophin levels during the OGTT were lower than in the obese or normal-weight pregnant women (basal levels: 13.66 ± 5.88 vs. 19.03 ± 4.15 vs. 15.68 ± 6.48, p = 0.016; OGTT 60′: 13.33 ± 5.40 vs. 17.37 ± 3.16 vs. 15.84 ± 4.99, p = 0.030). During the OGTT, basal and dynamic betatrophin levels at 60′ were positively associated with glucose levels at 60 min (r = 0.55, p = 0.01 and r = 0.45, p = 0.039). This positive association was followed by significant hypoglycaemic events in the RYGB group. It was only in the RYGB group that betatrophin was negatively related to the disposition index (rho = -0.53, p = 0.014). After pregnancy there was a decrease in basal and stimulated betatrophin levels during the OGTT in all three patient groups. In comparison to normal-weight and obese pregnant women, women with a history of RYGB operation and a high risk of postprandial hypoglycaemic events have lower levels of betatrophin. This indicate a mechanistic role in order to decrease the risk of postprandial hypoglycaemia in this specific cohort.
Influence of flicker noise and nonlinearity on the frequency spectrum of spin torque nano-oscillators
Authors: Wittrock Steffen , Talatchian Philippe , Tsunegi Sumito , Crété Denis , Yakushiji Kay , Bortolotti Paolo , Ebels Ursula , Fukushima Akio , Kubota Hitoshi , Yuasa Shinji , Grollier Julie , Cibiel Gilles , Galliou Serge , Rubiola Enrico , Cros Vincent
Published: August 2020

The correlation of phase fluctuations in any type of oscillator fundamentally defines its spectral shape. However, in nonlinear oscillators, such as spin torque nano-oscillators, the frequency spectrum can become particularly complex. This is specifically true when not only considering thermal but also colored 1/f flicker noise processes, which are crucial in the context of the oscillator’s long term stability. In this study, we address the frequency spectrum of spin torque oscillators in the regime of large-amplitude steady oscillations experimentally and as well theoretically. We particularly take both thermal and flicker noise into account. We perform a series of measurements of the phase noise and the spectrum on spin torque vortex oscillators, notably varying the measurement time duration. Furthermore, we develop the modelling of thermal and flicker noise in Thiele equation based simulations. We also derive the complete phase variance in the framework of the nonlinear auto-oscillator theory and deduce the actual frequency spectrum. We investigate its dependence on the measurement time duration and compare with the experimental results. Long term stability is important in several of the recent applicative developments of spin torque oscillators. This study brings some insights on how to better address this issue.
Best period to replace or change plastic stents with self-expandable metallic stents using multivariate competing risk regression analysis
Authors: Chiba Masafumi , Kato Masayuki , Kinoshita Yuji , Shimamoto Nana , Tomita Youichi , Abe Takahiro , Kawahara Yosuke , Koyama Seita , Kanazawa Keisuke , Takakura Kazuki , Tsukinaga Shintaro , Nakano Masanori , Torisu Yuichi , Toyoizumi Hirobumi , Ikeda Keiichi , Arakawa Hiroshi , Sumiyama Kazuki
Published: August 2020

In endoscopic biliary drainage (EBD) for various benign and malignant biliary disorders, the appropriate timing to replace or change a plastic stent (PS) with a self-expandable metallic stent (SEMS) remains unclear. This study aimed to define the best period to replace or change a PS with a SEMS. Between January 1, 2012, and December 31, 2018, 1,887 consecutive EBD procedures, including 170 SEMS placements, were retrospectively identified. The period to recurrent biliary obstruction (PRBO) was estimated and compared between the malignant and benign groups and according to each disease using time to event analysis and competing risk analysis. Compared with the benign group, the malignant group had significantly shorter median PRBO with interquartile range (IQR) after PS placement [108 (39 – 270) vs. 613 (191 – 1,329) days, P < 0.001], even on multivariate analysis, with a subdistribution hazard ratio (SHR) of 3.58 (P < 0.001). The shortest PRBO distribution from the first quartile of the non-RBO period was seen in Mirizzi syndrome cases (25 days, P = 0.030, SHR = 3.32) in the benign group and in cases of pancreatic cancer (32 days, P = 0.041, SHR = 2.06); perihilar bile duct cancer (27 days, P = 0.006, SHR = 2.69); and ampullary cancer (22 days, P = 0.001, SHR = 3.78) in the malignant group. Our study supports that stent replacement for the benign group is feasible after 6 months, and the best period to replace or change a PS with a SEMS should be decided on the basis of the underlying disease to prevent RBO.
A novel Monte Carlo simulation procedure for modelling COVID-19 spread over time
Authors: Xie Gang
Published: August 2020

The coronavirus disease 2019 (COVID-19) has now spread throughout most countries in the world causing heavy life losses and damaging social-economic impacts. Following a stochastic point process modelling approach, a Monte Carlo simulation model was developed to represent the COVID-19 spread dynamics. First, we examined various expected performances (theoretical properties) of the simulation model assuming a number of arbitrarily defined scenarios. Simulation studies were then performed on the real COVID-19 data reported (over the period of 1 March to 1 May) for Australia and United Kingdom (UK). Given the initial number of COVID-19 infection active cases were around 10 for both countries, the model estimated that the number of active cases would peak around 29 March in Australia (≈ 1,700 cases) and around 22 April in UK (≈ 22,860 cases); ultimately the total confirmed cases could sum to 6,790 for Australia in about 75 days and 206,480 for UK in about 105 days. The results of the estimated COVID-19 reproduction numbers were consistent with what was reported in the literature. This simulation model was considered an effective and adaptable decision making/what-if analysis tool in battling COVID-19 in the immediate need, and for modelling any other infectious diseases in the future.
Development of digital breast tomosynthesis and diffuse optical tomography fusion imaging for breast cancer detection
Authors: Chae Eun Young , Kim Hak Hee , Sabir Sohail , Kim Yejin , Kim Hyeongseok , Yoon Sungho , Ye Jong Chul , Cho Seungryong , Heo Duchang , Kim Kee Hyun , Bae Young Min , Choi Young-Wook
Published: August 2020

Diffuse optical tomography (DOT) non-invasively measures the functional characteristics of breast lesions using near infrared light to probe tissue optical properties. This study aimed to evaluate a new digital breast tomosynthesis (DBT)/DOT fusion imaging technique and obtain preliminary data for breast cancer detection. Twenty-eight women were prospectively enrolled and underwent both DBT and DOT examinations. DBT/DOT fusion imaging was created after acquisition of both examinations. Two breast radiologists analyzed DBT and DOT images independently, and then finally evaluated the fusion images. The diagnostic performance of each reading session was compared and interobserver agreement was assessed. The technical success rate was 96.4%, with one failure due to an error during DOT data storage. Among the 27 women finally included in the analysis, 13 had breast cancer. The areas under the receiver operating characteristic curve (AUCs) for DBT were 0.783 and 0.854 for readers 1 and 2, respectively. DOT showed comparable diagnostic performance to DBT for both readers. The AUCs were significantly improved (P = 0.004) when the DBT/DOT fusion images were used. Interobserver agreements were highest for the DBT/DOT fusion images. In conclusion, this study suggests that DBT/DOT fusion imaging technique appears to be a promising tool for breast cancer diagnosis.
Biomarkers of neutrophil extracellular traps (NETs) and nitric oxide-(NO)-dependent oxidative stress in women who miscarried
Authors: Omeljaniuk Wioleta Justyna , Jabłońska Ewa , Garley Marzena , Pryczynicz Anna , Ratajczak-Wrona Wioletta , Socha Katarzyna , Borawska Maria Halina , Charkiewicz Angelika Edyta
Published: August 2020

Pregnancy loss is a multidisciplinary problem which concerns researchers from the fields of medicine, epidemiology, psychology, and public health. The primary objective of the present study was to explain the potential role of neutrophil extracellular traps (NETs) in the process of spontaneous miscarriage. Enzyme-linked immunosorbent assay to assess the levels of biomarkers of NETs in the serum of examined women was conducted. Furthermore, levels of nitric oxide (NO) and late markers of its action were measured in serum samples. Analyses results demonstrated the existence of NETs in the placental tissue of women who miscarried as well as a simultaneous increase in the levels of myeloperoxidase and pentraxin 3. This clearly confirms the participation of NETs in the course of pregnancy loss. Women who have had a miscarriage but did not show the presence of NETs in their placenta exhibited the highest contents of NO, nitrotyrosine, and malondialdehyde suggesting a different pathway leading to pregnancy loss associated with disturbed oxidative–antioxidative processes. Although study results demonstrate new aspects associated with the formation of NETs they are not, however, sufficient to unambiguously determine the role of NETs in the course of miscarriage.
The schizophrenia risk locus in SLC39A8 alters brain metal transport and plasma glycosylation
Authors: Mealer Robert G. , Jenkins Bruce G. , Chen Chia-Yen , Daly Mark J. , Ge Tian , Lehoux Sylvain , Marquardt Thorsten , Palmer Christopher D. , Park Julien H. , Parsons Patrick J. , Sackstein Robert , Williams Sarah E. , Cummings Richard D. , Scolnick Edward M. , Smoller Jordan W.
Published: August 2020

A common missense variant in SLC39A8 is convincingly associated with schizophrenia and several additional phenotypes. Homozygous loss-of-function mutations in SLC39A8 result in undetectable serum manganese (Mn) and a Congenital Disorder of Glycosylation (CDG) due to the exquisite sensitivity of glycosyltransferases to Mn concentration. Here, we identified several Mn-related changes in human carriers of the common SLC39A8 missense allele. Analysis of structural brain MRI scans showed a dose-dependent change in the ratio of T2w to T1w signal in several regions. Comprehensive trace element analysis confirmed a specific reduction of only serum Mn, and plasma protein N-glycome profiling revealed reduced complexity and branching. N-glycome profiling from two individuals with SLC39A8-CDG showed similar but more severe alterations in branching that improved with Mn supplementation, suggesting that the common variant exists on a spectrum of hypofunction with potential for reversibility. Characterizing the functional impact of this variant will enhance our understanding of schizophrenia pathogenesis and identify novel therapeutic targets and biomarkers.
Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy
Authors: Montaldo Paolo , Cunnington Aubrey , Oliveira Vania , Swamy Ravi , Bandya Prathik , Pant Stuti , Lally Peter J. , Ivain Phoebe , Mendoza Josephine , Atreja Gaurav , Padmesh Vadakepat , Baburaj Mythili , Sebastian Monica , Yasashwi Indiramma , Kamalarathnam Chinnathambi , Chandramohan Rema , Mangalabharathi Sundaram , Kumaraswami Kumutha , Kumar Shobha , Benakappa Naveen , Manerkar Swati , Mondhkar Jayashree , Prakash Vinayagam , Sajjid Mohammed , Seeralar Arasar , Jahan Ismat , Moni Sadeka Choudhury , Shahidullah Mohammod , Sujatha Radhika , Chandrasekaran Manigandan , Ramji Siddarth , Shankaran Seetha , Kaforou Myrsini , Herberg Jethro , Thayyil Sudhin
Published: August 2020

A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth, predicts adverse neurodevelopmental outcome eighteen months after neonatal encephalopathy. We performed next generation sequencing on whole blood ribonucleic acid obtained within six hours of birth from the first 47 encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX) trial. Two infants with blood culture positive sepsis were excluded, and the data from remaining 45 were analysed. A total of 855 genes were significantly differentially expressed between the good and adverse outcome groups, of which RGS1 and SMC4 were the most significant. Biological pathway analysis adjusted for gender, trial randomisation allocation (cooling therapy versus usual care) and estimated blood leukocyte proportions revealed over-representation of genes from pathways related to melatonin and polo-like kinase in babies with adverse outcome. These preliminary data suggest that transcriptomic profiling may be a promising tool for rapid risk stratification in neonatal encephalopathy. It may provide insights into biological mechanisms and identify novel therapeutic targets for neuroprotection.
SpiFoG: an efficient supervised learning algorithm for the network of spiking neurons
Authors: Hussain Irshed , Thounaojam Dalton Meitei
Published: August 2020

There has been a lot of research on supervised learning in spiking neural network (SNN) for a couple of decades to improve computational efficiency. However, evolutionary algorithm based supervised learning for SNN has not been investigated thoroughly which is still in embryo stage. This paper introduce an efficient algorithm (SpiFoG) to train multilayer feed forward SNN in supervised manner that uses elitist floating point genetic algorithm with hybrid crossover. The evidence from neuroscience claims that the brain uses spike times with random synaptic delays for information processing. Therefore, leaky-integrate-and-fire spiking neuron is used in this research introducing random synaptic delays. The SpiFoG allows both excitatory and inhibitory neurons by allowing a mixture of positive and negative synaptic weights. In addition, random synaptic delays are also trained with synaptic weights in an efficient manner. Moreover, computational efficiency of SpiFoG was increased by reducing the total simulation time and increasing the time step since increasing time step within the total simulation time takes less iteration. The SpiFoG is benchmarked on Iris and WBC dataset drawn from the UCI machine learning repository and found better performance than state-of-the-art techniques.
Hepatopancreas immune response during molt cycle in the mud crab, Scylla paramamosain
Authors: Xu Zhanning , Liu An , Li Shengkang , Wang Guizhong , Ye Haihui
Published: August 2020

Molt is a critical developmental process in crustaceans. Recent studies have shown that the hepatopancreas is an important source of innate immune molecules, yet hepatopancreatic patterns of gene expression during the molt cycle which may underlie changes in immune mechanism are unknown. In this study, we performed Illumina sequencing for the hepatopancreas of the mud crab,Scylla paramamosainduring molt cycle (pre-molt stage, post-molt stage, and inter-molt stage). A total of 44.55 Gb high-quality reads were obtained from the normalized cDNA of hepatopancreas. A total of 70,591 transcripts were assembled; 55,167 unigenes were identified. Transcriptomic comparison revealed 948 differentially expressed genes (DEGs) in the hepatopancreas from the three molt stages. We found that genes associated with immune response patterns changed in expression during the molt cycle. Antimicrobial peptide genes, inflammatory response genes, Toll signaling pathway factors, the phenoloxidase system, antioxidant enzymes, metal-binding proteins and other immune related genes are significantly up-regulated at the post-molt stage and inter-molt stage compared with the pre-molt stage, respectively. These genes are either not expressed or are expressed at low levels at the pre-molt stage. To our knowledge, this is the first systematic transcriptome analysis of genes capable of mobilizing a hepatopancreas immune response during the molt cycle in crustaceans, and this study will contribute to a better understanding of the hepatopancreas immune system and mud crab prophylactic immune mechanisms at the post-molt stage.
In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication
Authors: Touret Franck , Gilles Magali , Barral Karine , Nougairède Antoine , van Helden Jacques , Decroly Etienne , de Lamballerie Xavier , Coutard Bruno
Published: August 2020

A novel coronavirus, named SARS-CoV-2, emerged in 2019 in China and rapidly spread worldwide. As no approved therapeutics exists to treat COVID-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time-consuming stages of drug development. In this study, we screened the PRESTWICK CHEMICAL LIBRARY composed of 1,520 approved drugs in an infected cell-based assay. The robustness of the screen was assessed by the identification of drugs that already demonstrated in vitro antiviral effect against SARS-CoV-2. Thereby, 90 compounds were identified as positive hits from the screen and were grouped according to their chemical composition and their known therapeutic effect. Then EC50 and CC50 were determined for a subset of 15 compounds from a panel of 23 selected drugs covering the different groups. Eleven compounds such as macrolides antibiotics, proton pump inhibitors, antiarrhythmic agents or CNS drugs emerged showing antiviral potency with 2 < EC50 ≤ 20 µM. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study provides information for the selection of drugs to be further validated in vivo. Disclaimer: This study corresponds to the early stages of antiviral development and the results do not support by themselves the use of the selected drugs to treat SARS-CoV-2 infection.
Publisher Correction: Pyroglutamic acidosis as a cause for high anion gap metabolic acidosis: a prospective study
Authors: Raibman Spector Shir , Mayan Haim , Loebstein Ronen , Markovits Noa , Priel Eldar , Massalha Eias , Shafir Yuval , Gueta Itai
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Photocatalytic radical defluoroalkylation of unactivated alkenes via distal heteroaryl ipso-migration
Authors: Yuan Xin , Zhuang Kai-Qiang , Cui Yu-Sheng , Qin Long-Zhou , Sun Qi , Duan Xiu , Chen Lin , Zhu Ning , Li Guigen , Qiu Jiang-Kai , Guo Kai
Published: August 2020

Currently, the selective activation of C(sp3)–F bonds and C–C bonds constitute one of the most widely used procedures for the synthesis of high-value products that range from pharmaceuticals to agrochemical applications. While numerous examples of these two methods have been reported in their respective fields, the processes which merge the activation of both single C(sp3)-F bonds and C–C bonds in one step still remain elusive. Here, we demonstrate the controllable defluoroalkylation–distal functionalization of trifluoromethylarenes with unactivated alkenes via distal heteroaryl migration. This is proposed to proceed via tandem C(sp3)–F and C–C bond cleavage using visible-light photoredox catalysis combined with Lewis acid activation. This strategy provides facile and flexible access to multiply functionalizedα,α-difluorobenzylic ketones in useful yields (up to 88%) under mild conditions. The products can be further transformed into other valuable compounds, demonstrating the method’s utility.
A theoretical model of laser-driven ion acceleration from near-critical double-layer targets
Authors: Pazzaglia Andrea , Fedeli Luca , Formenti Arianna , Maffini Alessandro , Passoni Matteo
Published: August 2020

Laser-driven ion sources are interesting for many potential applications, from nuclear medicine to material science. A promising strategy to enhance both ion energy and number is given by Double-Layer Targets (DLTs), i.e. micrometric foils coated by a near-critical density layer. Optimization of DLT parameters for a given laser setup requires a deep and thorough understanding of the physics at play. In this work, we investigate the acceleration process with DLTs by combining analytical modeling of pulse propagation and hot electron generation together with Particle-In-Cell (PIC) simulations in two and three dimensions. Model results and predictions are confirmed by PIC simulations—which also provide numerical values to the free model parameters—and compared to experimental findings from the literature. Finally, we analytically find the optimal values for near-critical layer thickness and density as a function of laser parameters; this result should provide useful insights for the design of experiments involving DLTs.
The one-step transformation of fructose to 2,5-diformylfuran over Ru metal supported on montmorillonite
Authors: Raut Amol B. , Shende Vaishali S. , Bhanage Bhalchandra M.
Published: August 2020

Ruthenium metal supported on a montmorillonite (2 wt% Ru-MMT) catalyst have been synthesized and characterized. Catalyst found to be effective for the one-pot transformation of fructose to DFF showing an excellent yield with good recyclability.
Breaking the scaling relationship via dual metal doping in a cobalt spinel for the OER: a computational prediction
Authors: Kang Yikun , Zhang Feiran , Liu Bowen , Sun Yuanqing , Zhang Xiao , Song Weiyu , Wei Yuechang , Zhao Zhen , Liu Jian
Published: August 2020

The scaling relationship in the OER is found to be broken on a reconstructed Co3O4(110) surface via dual metal doping.
Solution combustion synthesis, characterization, magnetic, and dielectric properties of CoFe2O4 and Co0.5M0.5Fe2O4 (M = Mn, Ni, and Zn)
Authors: Bera Parthasarathi , Lakshmi R. V. , Prakash B. H. , Tiwari Khushubo , Shukla Ashish , Kundu Asish K. , Biswas Krishanu , Barshilia Harish C.
Published: August 2020

Co0.5Zn0.5Fe2O4 (CZF) shows the highest Ms value compared to CoFe2O4 (CF), Co0.5Mn0.5Fe2O4 (CMF), and Co0.5Ni0.5Fe2O4 (CNF) as Zn2+ would prefer to occupy tetrahedral sites with a consequent increase of the Fe3+ concentration in octahedral sites.
Vibronic optical spectroscopy of cryogenic flavin ions: the O2+ and N1 tautomers of protonated lumiflavin
Authors: Müller David , Dopfer Otto
Published: August 2020

The electronic structure of cryogenic protonated lumiflavin ions probed by photodissociation spectroscopy and density functional theory calculations reveals the presence of the two most stable tautomers protonated at the O2+ and N1 positions.
How to complete the tautomerization and substrate-assisted activation prior to C–C bond fission by meta-cleavage product hydrolase LigY?
Authors: Wang Junjie , Tang Xiaowen , Zhang Yixin , Li Yanwei , Zhu Ledong , Zhang Qingzhu , Wang Wenxing
Published: August 2020

Two feasible binding modes could complete the C–C bond fission of the substrate. One is the bidentate mode and five-coordination, and the other is the monodentate mode and five-coordination.
Enhanced production of H2 under visible light via co-deposited Pt and Ir species on g-C3N4
Authors: Chen Chen , Zhao Jianjun , Xu Yiming
Published: August 2020

Synergism between PtO-mediated electron transfer and IrO2-mediated hole transfer enhanced the photocatalytic hydrogen evolution of g-C3N4.
Color tuning of intrinsic white-light emission in anthracene-linker coordination networks
Authors: Yu Chengfeng , Wang Xiaoling , Wu Ting , Gu Xiangwei , Huang Wei , Kirillov Alexander M. , Wu Dayu
Published: August 2020

We present two new Zn(ii) anthracene-linker-driven coordination polymers that exhibit intrinsic white-light emission, which can be tuned under external stimuli, including thermal and mechanical grinding.
Triphosphenium salts: air-stable precursors for phosphorus(i) chemistry
Authors: Dionisi Erica M. , Binder Justin F. , LaFortune James H. W. , Macdonald Charles L. B.
Published: August 2020

This Perspective summarizes the use of air- and moisture-stable triphosphenium salts of [dppeP]+ as sources of P+ ions to generate low-coordinate P-containing species. The electronic structure and subsequent reactivity of these species is emphasized.
Understanding KOtBu in atomic layer deposition – in situ mechanistic studies of the KNbO3 growth process
Authors: Sønsteby Henrik H. , Killi Veronica A.-L. K. , Storaas Thomas A. , Choudhury Devika , Elam Jeffrey W. , Fjellvåg Helmer , Nilsen Ola
Published: August 2020

Providing a deeper understanding of alkali metal-containing ternary processes in ALD by in situ FT-IR and QCM mechanistic studies.
Magnesium hydrides bearing sterically demanding amidinate ligands: synthesis, reactivity and catalytic application
Authors: Bakewell Clare
Published: August 2020

The synthesis, characterisation and reactivity of a series of magnesium complexes bearing sterically demanding amidinate ligands is reported; this includes magneisum amides, hydrides and alkyl complexes.
Cissus quadrangularis(veldt grape) attenuates disease progression and anatomical changes in mono sodium iodoacetate (MIA)-induced knee osteoarthritis in the rat model
Authors: Lakshmanan Dinesh Kumar , Ravichandran Guna , Elangovan Abbirami , Jeyapaul Preethi , Murugesan Selvakumar , Thilagar Sivasudha
Published: August 2020

TheCissus quadrangularis(CQ) stem has interesting nutritional and pharmacological properties to promote the health of the skeletal system.
Stimuli-responsive hydrogel consisting of hydrazide-functionalized poly(oligo(ethylene glycol)methacrylate) and dialdehyde cellulose nanocrystals
Authors: Nasseri Rasool , Tam Kam C.
Published: August 2020

This graphical abstract depicts our hydrogel consisting of hydrazide-functionalized poly(oligo(ethylene glycol) methacrylate) and dialdehyde cellulose nanocrystals and its thermoresponsive and self-healing properties.
Machine-learning-assisted search for functional materials over extended chemical space
Authors: Korolev Vadim , Mitrofanov Artem , Eliseev Artem , Tkachenko Valery
Published: August 2020

New computational framework has extended an inverse materials design over all the possible stoichiometric compounds.
Rational structural design and manipulation advance SnSe thermoelectrics
Authors: Shi Xiao-Lei , Chen Wen-Yi , Tao Xinyong , Zou Jin , Chen Zhi-Gang
Published: August 2020

This review aims to comprehensively summarize the significant developments in nanostructural manipulations that benefit SnSe thermoelectrics.
Facile green synthesis of silicon nanoparticles from Equisetum arvense for fluorescence based detection of Fe(iii) ions
Authors: Adinarayana T. V. S. , Mishra Ayushi , Singhal Ishu , Koti Reddy D. V. Rama
Published: August 2020

Fluorescent silicon nanoparticles (SiNPs) might be one of the excellent candidates for use as optical markers in optical sensing, biological profiling, and diagnostic applications.