bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of a biomarker tool capable of measuring the absorbed dose soon after exposure to ionizing radiation
Authors: Giovanetti Anna , Marconi Raffaella , Awad Noha , Abuzied Hala , Agamy Neveen , Barakat Mohamed , Bartoleschi Cecilia , Bossi Gianluca , Canfora Marco , Elsaid Amr A. , Ioannilli Laura , Ismail Horeya M. , Issa Yasmine Amr , Novelli Flavia , Pardini Maria Chiara , Pioli Claudio , Pinnarò Paola , Sanguineti Giuseppe , Tahoun Mohamed M. , Turchi Riccardo , Strigari Lidia
Published: April 2021

A radiological or nuclear attack could involve such a large number of subjects as to overwhelm the emergency facilities in charge. Resources should therefore be focused on those subjects needing immediate medical attention and care. In such a scenario, for the triage management by first responders, it is necessary to count on efficient biological dosimetry tools capable of early detection of the absorbed dose. At present the validated assays for measuring the absorbed dose are dicentric chromosomes and micronuclei counts, which require more than 2–3 days to obtain results. To overcome this limitation the NATO SPS Programme funded an Italian–Egyptian collaborative project aimed at validating a fast, accurate and feasible tool for assessing the absorbed dose early after radiation exposure. Biomarkers as complete blood cell counts, DNA breaks and radio-inducible proteins were investigated on blood samples collected before and 3 h after the first fraction of radiotherapy in patients treated in specific target areas with doses/fraction of about: 2, 3.5 or > 5 Gy and compared with the reference micronuclei count. Based on univariate and multivariate multiple linear regression correlation, our results identify five early biomarkers potentially useful for detecting the extent of the absorbed dose 3 h after the exposure.
The role of salivary vesicles as a potential inflammatory biomarker to detect traumatic brain injury in mixed martial artists
Authors: Matuk Rani , Pereira Mandy , Baird Janette , Dooner Mark , Cheng Yan , Wen Sicheng , Rao Shyam , Quesenberry Peter , Raukar Neha P.
Published: April 2021

Traumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.
Evaluating the association between extreme heat and mortality in urban Southwestern Ontario using different temperature data sources
Authors: Clemens Kristin K. , Ouédraogo Alexandra M. , Li Lihua , Voogt James A. , Gilliland Jason , Krayenhoff E. Scott , Leroyer Sylvie , Shariff Salimah Z.
Published: April 2021

Urban areas have complex thermal distribution. We examined the association between extreme temperature and mortality in urban Ontario, using two temperature data sources: high-resolution and weather station data. We used distributed lag non-linear Poisson models to examine census division-specific temperature–mortality associations between May and September 2005–2012. We used random-effect multivariate meta-analysis to pool results, adjusted for air pollution and temporal trends, and presented risks at the 99th percentile compared to minimum mortality temperature. As additional analyses, we varied knots, examined associations using different temperature metrics (humidex and minimum temperature), and explored relationships using different referent values (most frequent temperature, 75th percentile of temperature distribution). Weather stations yielded lower temperatures across study months. U-shaped associations between temperature and mortality were observed using both high-resolution and weather station data. Temperature–mortality relationships were not statistically significant; however, weather stations yielded estimates with wider confidence intervals. Similar findings were noted in additional analyses. In urban environmental health studies, high-resolution temperature data is ideal where station observations do not fully capture population exposure or where the magnitude of exposure at a local level is important. If focused upon temperature–mortality associations using time series, either source produces similar temperature–mortality relationships.
Combining genotypic and phenotypic variation in a geospatial framework to identify sources of mussels in northern New Zealand
Authors: Gardner Jonathan P. A. , Silva Catarina N. S. , Norrie Craig R. , Dunphy Brendon J.
Published: April 2021

The New Zealand green-lipped mussel aquaculture industry is largely dependent on the supply of young mussels that wash up on Ninety Mile Beach (so-called Kaitaia spat), which are collected and trucked to aquaculture farms. The locations of source populations of Kaitaia spat are unknown and this lack of knowledge represents a major problem because spat supply may be irregular. We combined genotypic (microsatellite) and phenotypic (shell geochemistry) data in a geospatial framework to determine if this new approach can help identify source populations of mussels collected from two spat-collecting and four non-spat-collecting sites further south. Genetic analyses resolved differentiated clusters (mostly three clusters), but no obvious source populations. Shell geochemistry analyses resolved six differentiated clusters, as did the combined genotypic and phenotypic data. Analyses revealed high levels of spatial and temporal variability in the geochemistry signal. Whilst we have not been able to identify the source site(s) of Kaitaia spat our analyses indicate that geospatial testing using combined genotypic and phenotypic data is a powerful approach. Next steps should employ analyses of single nucleotide polymorphism markers with shell geochemistry and in conjunction with high resolution physical oceanographic modelling to resolve the longstanding question of the origin of Kaitaia spat.
Maternal lipidomic signatures in relation to spontaneous preterm birth and large-for-gestational age neonates
Authors: Aung Max T. , Ashrap Pahriya , Watkins Deborah J. , Mukherjee Bhramar , Rosario Zaira , Vélez-Vega Carmen M. , Alshawabkeh Akram N. , Cordero José F. , Meeker John D.
Published: April 2021

Lipidome-wide metabolites may be useful biomarkers of pregnancy outcomes. We sought to characterize maternal lipidomic signatures associated with preterm birth and neonatal anthropometric parameters. Plasma samples were collected 24–28 weeks gestation, and lipidomic profiling was quantified using high-performance liquid chromatography tandem mass spectrometry. Lipid metabolites were analyzed individually and as whole lipid classes and subgroups based on degree of hydrocarbon chain saturation. Associations were estimated using linear and logistic regression. After false discovery adjustment (q < 0.15), four plasmenyl-phosphatidylethanolamines and three free fatty acids associated with increased risk for spontaneous preterm birth. Five phosphatidylinositols, two phosphatidylglycerols, and one phosphatidic acid were associated with large for gestational age neonates. The saturated plasmenyl-phosphatidylethanolamines held the association with increased risk for spontaneous preterm birth. Both the mono- and poly-unsaturated free fatty acids held the association for increased risk for spontaneous preterm birth. Mono- and poly-unsaturated phosphatidylinositols were associated with large for gestational age neonates. Whole lipid classes (plasmenyl-phophatidylcholines and plasmenyl-phosphatidylethanolamines) were associated with increased risk for large for gestational age at delivery. This study provides evidence that finer omics-scale analysis of the maternal lipidome may be more informative biomarkers of pregnancy outcomes compared to whole class level lipid analysis.
Accuracy of heart rate variability estimated with reflective wrist-PPG in elderly vascular patients
Authors: Hoog Antink Christoph , Mai Yen , Peltokangas Mikko , Leonhardt Steffen , Oksala Niku , Vehkaoja Antti
Published: April 2021

Optical heart rate monitoring (OHR) with reflective wrist photoplethysmography is a technique mainly used in the wellness application domain for monitoring heart rate levels during exercise. In the absence of motion, OHR technique is also able to estimate individual beat-to-beat intervals relatively well and can therefore also be used, for example, in monitoring of cardiac arrhythmias, stress, or sleep quality through heart rate variability (HRV) analysis. HRV analysis has also potential in monitoring the recovery of patients, e.g. after a medical intervention. However, in order to detect subtle changes, the calculated HRV parameters should be sufficiently accurate and very few studies exist that asses the accuracy of OHR derived HRV in non-healthy subjects. In this paper, we present a method to estimate beat-to-beat-intervals (BBIs) from reflective wrist PPG signal and evaluated the accuracy of the proposed method in estimating BBIs in a cross-sectional study with 29 hospitalized patients (mean age 70.6 years) in 24-h recordings performed after peripheral vascular surgery or endovascular interventions. Finally, we evaluate the accuracy of more than 30 commonly used HRV parameters and find that the accuracy of certain metrics, for example SDNN and triangular index, shown in the literature to be associated with the deterioration of the status of the patients during recovery from surgical intervention, could be adequate for patient monitoring. On the other hand, the parameters more affected by the high-frequency content of the HRV and especially the LF/HF-ratio should be used with caution.
Rapid weight loss in free ranging pygmy killer whales (Feresa attenuata) and the implications for anthropogenic disturbance of odontocetes
Authors: Currie Jens J. , van Aswegen Martin , Stack Stephanie H. , West Kristi L. , Vivier Fabien , Bejder Lars
Published: April 2021

Understanding the impacts of foraging disruptions to odontocete body condition is fundamental to quantifying biological effects of human disturbance and environmental changes on cetacean populations. Here, reductions in body volume of free-ranging pygmy killer whales (Feresa attenuata) were calculated using repeated measurements of the same individuals obtained through Unoccupied Aerial System (UAS)-photogrammetry during a prolonged disruption in foraging activity arising from a 21-day stranding event. Stranded individuals were used to verify UAS-derived volume and length estimates through 3D-imaging, water displacement, and post-mortem measurements. We show that (a) UAS estimates of length were within 1.5% of actual body length and UAS volume estimates were within 10–13% of actual volume, (b) foraging disruption resulted in a daily decrease of 2% of total body mass/day, and (c) pygmy killer whales can lose up to 27% of their total body weight within 17 days. These findings highlight the use of UAS as a promising new method to remotely monitor changes in body condition and animal health, which can be used to determine the potential effects of anthropogenic disturbance and environmental change on free-ranging odontocetes.
In vitro expression of precore proteins of hepatitis B virus subgenotype A1 is affected by HBcAg, and can affect HBsAg secretion
Authors: Deroubaix Aurélie , Kramvis Anna
Published: April 2021

HBeAg, a non-particulate protein of hepatitis B virus (HBV), is translated from the precore/core region as a precursor, which is post-translationally modified. Subgenotype A1 of HBV, which is a risk factor for hepatocellular carcinoma (HCC), has unique molecular characteristics in the basic core promoter/precore regions. Carriers of A1 exhibit early HBeAg loss. We sought to further characterize the precore proteins of A1 in vitro. HuH-7 cells were transfected with subgenomic constructs expressing individual precore proteins. Western blot analysis using DAKO anti-core antibody showed the expected sizes and a 1 kDa larger band for P22, P20 and P17. Using confocal microscopy, a cytoplasmic accumulation of HBeAg and precursors was observed with P25-expressing plasmid, whereas P22 localized both in the cytoplasm and nucleus. P20 and P17, which lack the carboxy end of P22 showed strong nuclear accumulation, implicating a nuclear localization signal in the N-terminal 10 amino acids. G1862T, unique to subgenotype A1, is frequently found in HBV from HCC patients. P25 with G1862T showed delayed and reduced HBeAg expression/secretion. Knock-out of core in the replication competent clones led to precore protein accumulation in the cytoplasm/perinuclear region, and decreased HBeAg secretion. Knock-out of precore proteins increased HBsAg secretion but intracellular HBsAg expression was unaffected. Over-expression of precore proteins intransled to decreased HBsAg expression and secretion. Intracellular trafficking of HBV A1 precore proteins was followed. This was unaffected by the CMV promoter and different cell types. In the viral context, precore protein expression was affected by absence of core, and affected HBsAg expression, suggesting an interrelationship between precore proteins, HBcAg and HBsAg. This modulatory role of HBeAg and its precursors may be important in viral persistence and ultimate development of HCC.
Controlling the breakup of toroidal liquid films on solid surfaces
Authors: Edwards Andrew M. J. , Ruiz-Gutiérrez Élfego , Newton Michael I. , McHale Glen , Wells Gary G. , Ledesma-Aguilar Rodrigo , Brown Carl V.
Published: April 2021

The breakup of a slender filament of liquid driven by surface tension is a classical fluid dynamics stability problem that is important in many situations where fine droplets are required. When the filament is resting on a flat solid surface which imposes wetting conditions the subtle interplay with the fluid dynamics makes the instability pathways and mode selection difficult to predict. Here, we show how controlling the static and dynamic wetting of a surface can lead to repeatable switching between a toroidal film of an electrically insulating liquid and patterns of droplets of well-defined dimensions confined to a ring geometry. Mode selection between instability pathways to these different final states is achieved by dielectrophoresis forces selectively polarising the dipoles at the solid-liquid interface and so changing both the mobility of the contact line and the partial wetting of the topologically distinct liquid domains. Our results provide insights into the wetting and stability of shaped liquid filaments in simple and complex geometries relevant to applications ranging from printing to digital microfluidic devices.
Delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb in freely behaving rats
Authors: Mofleh Rola , Kocsis Bernat
Published: April 2021

Respiratory rhythm (RR) during sniffing is known to couple with hippocampal theta rhythm. However, outside of the short sniffing bouts, a more stable ~ 2 Hz RR was recently shown to rhythmically modulate non-olfactory cognitive processes, as well. The underlying RR coupling with wide-spread forebrain activity was confirmed using advanced techniques, creating solid premise for investigating how higher networks use this mechanism in their communication. Here we show essential differences in the way prefrontal cortex (PFC) and hippocampus (HC) process the RR signal from the olfactory bulb (OB) that may support dynamic, flexible PFC-HC coupling utilizing this input. We used inter-regional coherences and their correlations in rats, breathing at low rate (~ 2 Hz), outside of the short sniffing bouts. We found strong and stable OB-PFC coherence in wake states, contrasting OB-HC coherence which was low but highly variable. Importantly, this variability was essential for establishing PFC-HC synchrony at RR, whereas variations of RRO in OB and PFC had no significant effect. The findings help to understand the mechanism of rhythmic modulation of non-olfactory cognitive processes by the on-going regular respiration, reported in rodents as well as humans. These mechanisms may be impaired when nasal breathing is limited or in OB-pathology, including malfunctions of the olfactory epithelium due to infections, such as in Covid-19.
Novel humidity sensors based on nanomodified Portland cement
Authors: Buasiri Thanyarat , Habermehl-Cwirzen Karin , Krzeminski Lukasz , Cwirzen Andrzej
Published: April 2021

Commonly used humidity sensors are based on metal oxides, polymers or carbon. Their sensing accuracy often deteriorates with time, especially when exposed to higher temperatures or very high humidity. An alternative solution based on the utilization of Portland cement-based mortars containing in-situ grown carbon nanofibers (CNFs) was evaluated in this study. The relationship between the electrical resistivity, CNF content and humidity were determined. The highest sensitivity was observed for samples containing 10 wt.% of the nanomodified cement which corresponded to 0.27 wt.% of CNFs. The highest calculated sensitivity was approximately 0.01024 per 1% change in relative humidity (RH). The measured electrical resistivity is a linear function of the RH in the humidity range between 11 and 97%. The percolation threshold value was estimated to be at around 7 wt.% of the nanomodified cement, corresponding to ~ 0.19 wt.% of CNFs.
Detecting network anomalies using Forman–Ricci curvature and a case study for human brain networks
Authors: Chatterjee Tanima , Albert Réka , Thapliyal Stuti , Azarhooshang Nazanin , DasGupta Bhaskar
Published: April 2021

We analyze networks of functional correlations between brain regions to identify changes in their structure caused by Attention Deficit Hyperactivity Disorder (adhd). We express the task for finding changes as a network anomaly detection problem on temporal networks. We propose the use of a curvature measure based on the Forman–Ricci curvature, which expresses higher-order correlations among two connected nodes. Our theoretical result on comparing this Forman–Ricci curvature with another well-known notion of network curvature, namely the Ollivier–Ricci curvature, lends further justification to the assertions that these two notions of network curvatures are not well correlated and therefore one of these curvature measures cannot be used as an universal substitute for the other measure. Our experimental results indicate nine critical edges whose curvature differs dramatically in brains of adhd patients compared to healthy brains. The importance of these edges is supported by existing neuroscience evidence. We demonstrate that comparative analysis of curvature identifies changes that more traditional approaches, for example analysis of edge weights, would not be able to identify.
Mushroom data creation, curation, and simulation to support classification tasks
Authors: Wagner Dennis , Heider Dominik , Hattab Georges
Published: April 2021

Predicting if a set of mushrooms is edible or not corresponds to the task of classifying them into two groups—edible or poisonous—on the basis of a classification rule. To support this binary task, we have collected the largest and most comprehensive attribute based data available. In this work, we detail the creation, curation and simulation of a data set for binary classification. Thanks to natural language processing, the primary data are based on a text book for mushroom identification and contain 173 species from 23 families. While the secondary data comprise simulated or hypothetical entries that are structurally comparable to the 1987 data, it serves as pilot data for classification tasks. We evaluated different machine learning algorithms, namely, naive Bayes, logistic regression, and linear discriminant analysis (LDA), and random forests (RF). We found that the RF provided the best results with a five-fold Cross-Validation accuracy and F2-score of 1.0 ($$\mu =1$$

μ
=
1

, $$\sigma =0$$

σ
=
0

), respectively. The results of our pilot are conclusive and indicate that our data were not linearly separable. Unlike the 1987 data which showed good results using a linear decision boundary with the LDA. Our data set contains 23 families and is the largest available. We further provide a fully reproducible workflow and provide the data under the FAIR principles.
Shortened key growth periods of soybean observed in China under climate change
Authors: Tan Qinghua , Liu Yujie , Dai Liang , Pan Tao
Published: April 2021

Phenology is an important indicator of global climate change. Revealing the spatiotemporal characteristics of crop phenology is vital for ameliorating the adverse effects of climate change and guiding regional agricultural production. This study evaluated the spatiotemporal variability of soybean’s phenological stages and key growth periods, and assessed their sensitivity to key climatic factors, utilizing a long-term dataset (1992–2018) of soybean phenology and associated meteorological data collected at 51 stations across China. The results showed that (1) during the soybean growing seasons from 1992 to 2018, the average temperature (0.34 ± 0.09 ℃ decade−1) and cumulative precipitation (6.66 ± 0.93 mm decade−1) increased, but cumulative sunshine hours (− 33.98 ± 1.05 h decade−1) decreased. (2) On a national scale, dates of sowing, emergence, trifoliate, anthesis, and podding of soybean were delayed, while the maturity date showed an advancing trend. The vegetative growth period (− 0.52 ± 0.24 days decade−1) and whole growth period (− 1.32 ± 0.30 days decade−1) of soybean were shortened, but the reproductive growth period (0.05 ± 0.26 days decade−1) was slightly extended. Trends in soybean phenological stages and key growth periods diverged in regions. Soybean phenological stages were delayed in Huang-Huai-Hai soybean zone, whereas advanced in southern soybean zone. Moreover, the key growth periods were greatly shortened in northern soybean zone. (3) In general, the sensitivity of soybean key growth periods to temperature was negative, whereas those to precipitation and sunshine hours differed among regions. In particular, most phenological stages were negatively sensitive to sunshine hours. Our results will provide scientific support for decision-making in agricultural production practices.
Olive leaf extract supplementation improves the vascular and metabolic alterations associated with aging in Wistar rats
Authors: González-Hedström Daniel , García-Villalón Ángel Luís , Amor Sara , de la Fuente-Fernández María , Almodóvar Paula , Prodanov Marin , Priego Teresa , Martín Ana Isabel , Inarejos-García Antonio Manuel , Granado Miriam
Published: April 2021

Olive leaves are rich in bioactive substances which exert anti-inflammatory, antioxidant, insulin-sensitizing and antihypertensive effects. The aim of this study was to analyze the possible beneficial effects of an olive leaf extract (OLE) rich in secoiridoids and phenolic compounds on the aging-induced metabolic and vascular alterations. Three experimental groups of rats were used: 3-month-old rats, 24-month-old rats and 24-month-old rats supplemented 21 days with OLE (100 mg/kg). Administration of OLE to aged rats decreased the weight of adrenal glands and prevented the aging-induced loss of body weight and muscle mass. In the serum, OLE reduced the circulating levels of LDL-cholesterol and IL-6 and increased the concentrations of leptin and adiponectin. In the liver OLE attenuated the decreased gene expression of SOD-1, GSR, GCK and GSK-3β and reduced the aging-induced overexpression of NOX-4, Alox-5, iNOS and TNF-α. In aorta segments, OLE prevented endothelial dysfunction and vascular insulin resistance and improved vasoconstriction in response to KCl and NA. Improvement in vascular function was associated with the attenuation of the alterations in the gene expression of COX-2, IL-6, GPx, NOX-1 and IL-10. In conclusion, OLE exerts anti-inflammatory and antioxidant effects in aged rats and attenuates the alterations in vascular function associated with aging.
H3K4me2 ChIP-Seq reveals the epigenetic landscape during mushroom formation and novel developmental regulators of Schizophyllum commune
Authors: Vonk Peter Jan , Ohm Robin A.
Published: April 2021

Mushroom formation represents the most complex multicellular development in fungi. In the model mushroom Schizophyllum commune, comparative genomics and transcriptomics have previously resulted in a regulatory model of mushroom development. However, little is known about the role of epigenetic regulation. We used chromatin immunoprecipitation sequencing (ChIP-Seq) to determine the distribution of dimethylation of lysine 4 on histone H3 (H3K4me2), a mark for transcriptionally active genes, during monokaryotic and dikaryotic development. We identified a total of 6032 and 5889 sites during monokaryotic and dikaryotic development, respectively. The sites were strongly enriched near translation initiation sites of genes. Although the overall epigenetic landscape was similar between both conditions, we identified 837 sites of differential enrichment during monokaryotic or dikaryotic development, associated with 965 genes. Six transcription factor genes were enriched in H3K4me2 during dikaryotic development, indicating that these are epigenetically regulated during development. Deletion of two of these genes (fst1 and zfc7) resulted in arrested development of fruiting bodies, resulting in immature mushrooms. Together these results indicate that H3K4me2 ChIP-Seq is a powerful new tool to map the restructuring of the epigenetic landscape during mushroom development. Moreover, it can be used to identify novel developmental regulators.
Diamond formation from methane hydrate under the internal conditions of giant icy planets
Authors: Kadobayashi Hirokazu , Ohnishi Satoka , Ohfuji Hiroaki , Yamamoto Yoshitaka , Muraoka Michihiro , Yoshida Suguru , Hirao Naohisa , Kawaguchi-Imada Saori , Hirai Hisako
Published: April 2021

Hydrocarbon chemistry in the C–O–H system at high pressure and high temperature is important for modelling the internal structure and evolution of giant icy planets, such as Uranus and Neptune, as their interiors are thought to be mainly composed of water and methane. In particular, the formation of diamond from the simplest hydrocarbon, i.e., methane, under the internal conditions of these planets has been discussed for nearly 40 years. Here, we demonstrate the formation of diamond from methane hydrate up to 3800 K and 45 GPa using a CO2 laser-heated diamond anvil cell combined with synchrotron X-ray diffraction, Raman spectroscopy, and scanning electron microscopy observations. The results show that the process of dissociation and polymerisation of methane molecules to produce heavier hydrocarbons while releasing hydrogen to ultimately form diamond proceeds at milder temperatures (~ 1600 K) and pressures (13–45 GPa) in the C–O–H system than in the C–H system due to the influence of water. Our findings suggest that diamond formation can also occur in the upper parts of the icy mantles of giant icy planets.
Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1
Authors: Dallas Mark L. , Al-Owais Moza M. , Hettiarachchi Nishani T. , Vandiver Matthew Scott , Jarosz-Griffiths Heledd H. , Scragg Jason L. , Boyle John P. , Steele Derek , Peers Chris
Published: April 2021

Hydrogen sulfide (H2S) is gaining interest as a mammalian signalling molecule with wide ranging effects. S-sulfhydration is one mechanism that is emerging as a key post translational modification through which H2S acts. Ion channels and neuronal receptors are key target proteins for S-sulfhydration and this can influence a range of neuronal functions. Voltage-gated K+ channels, including Kv2.1, are fundamental components of neuronal excitability. Here, we show that both recombinant and native rat Kv2.1 channels are inhibited by the H2S donors, NaHS and GYY4137. Biochemical investigations revealed that NaHS treatment leads to S-sulfhydration of the full length wild type Kv2.1 protein which was absent (as was functional regulation by H2S) in the C73A mutant form of the channel. Functional experiments utilising primary rat hippocampal neurons indicated that NaHS augments action potential firing and thereby increases neuronal excitability. These studies highlight an important role for H2S in shaping cellular excitability through S-sulfhydration of Kv2.1 at C73 within the central nervous system.
Single neonatal dexamethasone administration has long-lasting outcome on depressive-like behaviour, Bdnf, Nt-3, p75ngfr and sorting receptors (SorCS1-3) stress reactive expression
Authors: Lanshakov D. A. , Sukhareva E. V. , Bulygina V. V. , Bannova A. V. , Shaburova E. V. , Kalinina T. S.
Published: April 2021

Elevated glucocorticoid level in the early postnatal period is associated with glucocorticoid therapy prescribed at preterm delivery most often has severe long-lasting neurodevelopmental and behavioural effects. Detailed molecular mechanisms of such programming action of antenatal glucocorticoids on behaviour are still poorly understood. To address this question we studied neurotrophins: Bdnf, Nt-3, Ngf and their receptors: p75ngfr, Sorcs3 expression changes after subcutaneous dexamethasone (DEX) 0.2 mg/kg injection to P2 rat pups. Neurotrophins expression level was studied in the hippocampus (HPC). Disturbances in these brain regions have been implicated in the emergence of multiple psychopathologies. p75ngfr and Sorcs3 expression was studied in the brainstem—region where monoamine neurons are located. Immunohistochemically P75NTR protein level changes after DEX were investigated in the brainstem Locus Coereleus norepinephrine neurons (NE). In the first hours after DEX administration elevation of neurotrophins expression in HPC and decline of receptor’s expression in the NE brainstem neurons were observed. Another critical time point during maturation is adolescence. Impact of elevated glucocorticoid level in the neonatal period and unpredictable stress (CMUS) at the end of adolescence on depressive-like behaviour was studied. Single neonatal DEX injection leads to decrease in depressive-like behaviour, observed in FST, independently from chronic stress. Neonatal DEX administration decreased Ntf3 and SorCS1 expression in the brainstem. Also Bdnf mRNA level in the brainstem of these animals didn’t decrease after FST. CMUS at the end of adolescence changed p75ngfr and SorCS3 expression in the brainstem in the animals that received single neonatal DEX administration.
SIRT1 promotes lipid metabolism and mitochondrial biogenesis in adipocytes and coordinates adipogenesis by targeting key enzymatic pathways
Authors: Majeed Yasser , Halabi Najeeb , Madani Aisha Y. , Engelke Rudolf , Bhagwat Aditya M. , Abdesselem Houari , Agha Maha V. , Vakayil Muneera , Courjaret Raphael , Goswami Neha , Hamidane Hisham Ben , Elrayess Mohamed A. , Rafii Arash , Graumann Johannes , Schmidt Frank , Mazloum Nayef A.
Published: April 2021

The NAD+-dependent deacetylase SIRT1 controls key metabolic functions by deacetylating target proteins and strategies that promote SIRT1 function such as SIRT1 overexpression or NAD+ boosters alleviate metabolic complications. We previously reported that SIRT1-depletion in 3T3-L1 preadipocytes led to C-Myc activation, adipocyte hyperplasia, and dysregulated adipocyte metabolism. Here, we characterized SIRT1-depleted adipocytes by quantitative mass spectrometry-based proteomics, gene-expression and biochemical analyses, and mitochondrial studies. We found that SIRT1 promoted mitochondrial biogenesis and respiration in adipocytes and expression of molecules like leptin, adiponectin, matrix metalloproteinases, lipocalin 2, and thyroid responsive protein was SIRT1-dependent. Independent validation of the proteomics dataset uncovered SIRT1-dependence of SREBF1c and PPARα signaling in adipocytes. SIRT1 promoted nicotinamide mononucleotide acetyltransferase 2 (NMNAT2) expression during 3T3-L1 differentiation and constitutively repressed NMNAT1 and 3 levels. Supplementing preadipocytes with the NAD+ booster nicotinamide mononucleotide (NMN) during differentiation increased expression levels of leptin, SIRT1, and PGC-1α and its transcriptional targets, and reduced levels of pro-fibrotic collagens (Col6A1 and Col6A3) in a SIRT1-dependent manner. Investigating the metabolic impact of the functional interaction of SIRT1 with SREBF1c and PPARα and insights into how NAD+ metabolism modulates adipocyte function could potentially lead to new avenues in developing therapeutics for obesity complications.
Panels and models for accurate prediction of tumor mutation burden in tumor samples
Authors: Martínez-Pérez Elizabeth , Molina-Vila Miguel Angel , Marino-Buslje Cristina
Published: April 2021

Immune checkpoint blockade (ICB) is becoming standard-of-care in many types of human malignancies, but patient selection is still imperfect. Tumor mutation burden (TMB) is being evaluated as a biomarker for ICB in clinical trials, but most of the sequencing panels used to estimate it are inadequately designed. Here, we present a bioinformatics-based method to select panels and mathematical models for accurate TMB prediction. Our method is based on tumor-specific, forward-step selection of genes, generation of panels using a linear regression algorithm, and rigorous internal and external validation comparing predicted with experimental TMB. As a result, we propose cancer-specific panels for 14 malignancies which can offer reliable, clinically relevant estimates of TMBs. Our work facilitates a better prediction of TMB that can improve the selection of patients for ICB therapy.
Enhanced visible-light photodegradation of fluoroquinolone-based antibiotics and E. coli growth inhibition using Ag–TiO2 nanoparticles
Authors: Wang Jiao , Svoboda Ladislav , Němečková Zuzana , Sgarzi Massimo , Henych Jiří , Licciardello Nadia , Cuniberti Gianaurelio
Published: April 2021

Ag nanoparticles decorated-TiO2 P25 are a viable alternative for the degradation, through a rutile-mediated mechanism, of fluoroquinolone-based antibiotics under visible light irradiation and, at the same time, for bacteria inactivation in water.
A facile and efficient route to one-pot synthesis of new cyclophanes using vinamidinium salts
Authors: Golzar Nooshin , Mehranpour Abdolmohammad , Nowrouzi Najmeh
Published: April 2021

New cyclophane derivatives are synthesized from the reaction of γ-substituted vinamidinium salts with 1,4-phenylenedimethanamine and 2,3,5,6-tetramethylbenzene-1,4-diamine in the presence of acetic acid and acetonitrile as solvent.
A flexible and highly sensitive pressure sensor based on three-dimensional electrospun carbon nanofibers
Authors: Cai Chuan , Gong He , Li Weiping , Gao Feng , Jiang Qiushi , Cheng Zhiqiang , Han Zhaolian , Li Shijun
Published: April 2021

A three-dimensional electrospun carbon nanofiber network was used to measure press strains with high sensitivity.
Rh particles in N-doped porous carbon materials derived from ZIF-8 as an efficient bifunctional electrocatalyst for the ORR and HER
Authors: Sun Can , Duan Xinde , Song Jiajun , Zhang Mengxian , Jin Yachao , Zhang Mingdao , Song Li , Cao Hui
Published: April 2021

ZIF-derived RhNC-900 bifunctional electrocatalysts for the oxygen reduction reaction and hydrogen evolution reaction have been prepared via a simple and scalable method, exhibiting excellent catalytic activity and promising performance.
An integrated console for capsule-based, automated organic synthesis
Authors: Jiang Tuo , Bordi Samuele , McMillan Angus E. , Chen Kuang-Yen , Saito Fumito , Nichols Paula L. , Wanner Benedikt M. , Bode Jeffrey W.
Published: April 2021

Using a combination of reagent design, hardware engineering, and a simple operating system we provide an instrument capable of executing complex organic reactions using prepacked capsules with minimal user involvement.
Code-Switching and Language Proficiency in Bilingual Children With and Without Developmental Language Disorder
Authors: Kapantzoglou Maria , Brown Julie Esparza , Cycyk Lauren M. , Fergadiotis Gerasimos
Published: April 2021

Purpose

This study examined the frequency of code-switching by Spanish–English-speaking children as a function of language proficiency in each language and diagnosis (developmental language disorder [DLD] or typical language development [TLD]).

Method

Sixty-two Spanish–English-speaking children, 5–7 years of age, participated in this study (24 with DLD and 38 with TLD). Language samples were used to determine the level of language proficiency in each language as a continuum of performance. Correlational analyses were conducted to evaluate the relationship between Spanish and English language proficiency and the frequency of code-switching considering the total number of code-switched words, intrasentential code-switching (i.e., number of sentences/C-units with code-switched parts), and intersentential code-switching (i.e., code-switched sentences/C-units). Negative binomial and zero-inflated Poisson regressions were conducted to evaluate whether the frequency of code-switched words, code-switched parts, and code-switched sentences is different across children with DLD and their peers with TLD, controlling for Spanish and English proficiency.

Results

When Spanish was the target language, lower proficiency in Spanish was associated with higher frequency of code-switches to English for the group with DLD, but not for their peers with TLD who code-switched to English regardless of their Spanish and English proficiency. There were no statistically significant effects of diagnosis on the frequency of code-switches.

Conclusion

Results indicate that code-switching occurs similarly across children with DLD and their peers with TLD; therefore, the frequency and type of code-switches should not be used as an indicator of DLD.
A Modeling-Guided Case Study of Disordered Speech in Minimally Verbal Children With Autism Spectrum Disorder
Authors: Chenausky Karen V. , Brignell Amanda , Morgan Angela T. , Norton Andrea C. , Tager-Flusberg Helen B. , Schlaug Gottfried , Guenther Frank H.
Published: April 2021

Purpose

Understanding what limits speech development in minimally verbal (MV) children with autism spectrum disorder (ASD) is important for providing highly effective targeted therapies. This preliminary investigation explores the extent to which developmental speech deficits predicted by Directions Into Velocities of Articulators (DIVA), a computational model of speech production, exemplify real phenotypes.

Method

Implementing a motor speech disorder in DIVA predicted that speech would become highly variable within and between tokens, while implementing a motor speech plus an auditory processing disorder predicted that DIVA's speech would become highly centralized (schwa-like). Acoustic analyses of DIVA's output predicted that acoustically measured phoneme distortion would be similar between the two cases, but that in the former case, speech would show more within- and between-token variability than in the latter case. We tested these predictions quantitatively on the speech of children with MV ASD. In Study 1, we tested the qualitative predictions using perceptual analysis methods. Speech pathologists blinded to the purpose of the study tallied the signs of childhood apraxia of speech that appeared in the speech of 38 MV children with ASD. K-means clustering was used to create two clusters from the group of 38, and analysis of variance was used to determine whether the clusters differed according to perceptual features corresponding to within- and between-token variability. In Study 2, we employed acoustic analyses on the speech of the child from each cluster who produced the largest number of analyzable tokens to test the predictions of differences in within-token variability, between-token variability, and vowel space area.

Results

Clusters produced by k-means analysis differed by perceptual features that corresponded to within-token variability. Nonsignificant differences between clusters were found for features corresponding to between-token variability. Subsequent acoustic analyses of the selected cases revealed that the speech of the child from the high-variability cluster showed significantly more quantitative within- and between-token variability than the speech of the child from the low-variability cluster. The vowel space of the child from the low-variability cluster was more centralized than that of typical children and that of the child from the high-variability cluster.

Conclusions

Results provide preliminary evidence that subphenotypes of children with MV ASD may exist, characterized by (a) comorbid motor speech disorder and (b) comorbid motor speech plus auditory processing disorder. The results motivate testable predictions about how these comorbidities affect speech.

Supplemental Material

https://doi.org/10.23641/asha.14384432
La mécanique dissipative des géo-matériaux granulaires et ses applications pratiques en Génie Civil
Authors: Frossard Etienne
Published: April 2021

L’article, résultant d’un travail de long terme sur la physique des géo-matériaux granulaires et la pratique du génie civil de grandes infrastructures, synthétise une vision nouvelle du comportement mécanique de ces matériaux, à partir d’approches dissipatives micromécaniques originales. Après le contexte et les hypothèses-clé, il présente les aspects essentiels des structures dissipatives induites par la friction de contact élémentaire, associée à des spécificités de mécanique statistique dans ces matériaux en mouvement quasi-statique, et leur expression multi-échelle par des relations tensorielles fortes : les équations de la dissipation d’énergie résultant de la friction. Sur cette base, est ensuite établi un large ensemble de propriétés pratiques d’usage général en génie civil, incluant : le critère de rupture, le couplage résistance au cisaillement/variations de volume, la compaction cyclique, l’équilibre géostatique « au repos »… Bien que l’essentiel de l’article soit focalisé sur les caractères induits par la friction de contact, une dernière section présente d’autres propriétés-clé induites par la rupture des granulats, autre processus dissipatif après la friction de contact. Ces propriétés incluent des incidences explicites sur les effets d’échelle dans le comportement structural d’ouvrages, vérifiées sur de grands ouvrages.
Wear assessment model for cylinder liner of internal combustion engine under fuzzy uncertainty
Authors: Kang Jianxiong , Lu Yanjun , Luo Hongbo , Li Jie , Hou Yutao , Zhang Yongfang
Published: April 2021

The wear of the piston ring-cylinder system is inevitable in the operation of the internal combustion engines (ICEs). If wear exceeds the maximum, the piston ring-cylinder system will be failure. A novel wear assessment model is proposed based on the support vector regression, and the fuzzy uncertainty is modeled to describe the random behavior under small sample. To verify the proposed model, the sample data of cylinder liner wear is applied. For best results, the particle swarm optimization (PSO) algorithm is used to optimize the model parameters. A back propagation neural network (BPNN) is employed to verify the effectiveness of the proposed model. The results show that the novel support vector regression has better prediction accuracy than other methods for cylinder wear in this paper, the proposed model can evaluate the cylinder liner wear of the ICEs effectively. The work provides a technical support for evaluating the service performance of the piston ring-cylinder liner and a reference for regular maintenance of the ships.
Sessile serrated lesion detection rates during average risk screening colonoscopy: A systematic review and meta-analysis of the published literature
Authors: Desai Madhav , Anderson Joseph C. , Kaminski Michael , Thoguluva Chandrasekar Viveksandeep , Fathallah Jihan , Hassan Cesare , Lieberman David , Sharma Prateek
Published: April 2021

Background and study aims Sessile serrated lesion (SSL) detection rate has been variably reported and unlike adenoma detection rate (ADR) is not currently a quality indicator for screening colonoscopy. Composite detection rates of SSL in patients undergoing average risk screening colonoscopy are not available.

Methods Electronic database search (Medline, Embase and Cochrane) was conducted for studies reporting detection rates of serrated polyps (SSL, Hyperplastic polyp, traditional serrated adenoma) among average risk subjects undergoing screening colonoscopy. Primary outcomes were pooled SDR (SSL detection rate) and proximal serrated polyp detection rate (PSPDR). Pooled proportion rates were calculated with 95 %CI with assessment of heterogeneity (I2). Publication bias, regression test and 95 %prediction interval were calculated.

Results A total of 280,370 screening colonoscopies among average risk subjects that were eligible with 48.9 % males and an average age of 58.7 years (± 3.2). The pooled SDR was available from 16 studies: 2.5 % (1.8 %–3.4 %) with significant heterogeneity (I2 = 98.66 %) and the 95 % prediction interval ranging from 0.6 % to 9.89 %. When analysis was restricted to large (n > 1000) and prospective studies (n = 4), SDR was 2 % (1.1 %–3.3 %). Pooled PSPDR was 10 % (8.5 %–11.8 %; 12 studies). There was evidence of publication bias (P < 0.01).

Conclusion Definitions of SSL have been varying over years and there exists significant heterogeneity in prevalence reporting of serrated polyps during screening colonoscopy. Prevalence rate of 2 % for SSL and 10 % for proximal serrated polyps could serve as targets while robust high-quality data is awaited to find a future benchmark showing reduction in colorectal cancer arising from serrated pathway.