bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Roadside and Urban Background Measurements of Submicron Aerosol Number Concentration and Size Distribution (in the Range 20–800 nm), along with Chemical Composition in Strasbourg, France
Authors: Chatain Mélodie , Alvarez Raphaël , Ustache Aurélien , Rivière Emmanuel , Favez Olivier , Pallares Cyril
Published: January 2021

The adverse health impact of particles and ultrafine particles (UFP) is proven, highlighting the need of measuring the particle number concentration (PNC) dominated by UFP. So far, PNC had never been measured in the Strasbourg urban area (France). The present study on particle size distribution and PNC measurements by an UFP-3031 analyzer was conducted during winter 2019 on a background and a roadside multi-instrumented sites (Black Carbon, chemical speciation, particulate matter 10 μm or less in diameter—PM10 mass). This paper shows significantly higher particle number concentrations of particles below 100 nm at the traffic site compared to the background site. The presence of a road axis thus mainly influences UFP, contrary to larger particles whose levels are more homogeneous over the agglomeration. During the measurement period, the nature of the particles (particle size contribution and chemical composition) was different between periods of high PM10 mass concentrations and periods of high PNC. High PM10 mass concentrations were associated with a high contribution of particles larger than 100 nm but they did not show specific chemical signature. On the other hand, during the periods with high PNC, the chemical composition was modified with an increase of the primary carbonaceous fraction compared to the periods with low PNC, but there was then no clear change in size distribution. Overall, this study illustrates that PM10 mass concentrations were barely representative of UFP and PNC variations, confirming that the monitoring of the latter metrics is necessary to better evaluate the particles toxicity, knowing that this toxicity also depends on the particle’s chemical composition.
Reversibility of the Hydrological Response in East Asia from CO2-Derived Climate Change Based on CMIP6 Simulation
Authors: Sun Min-Ah , Sung Hyun Min , Kim Jisun , Lee Jae-Hee , Shim Sungbo , Boo Kyung-On , Byun Young-Hwa , Marzin Charline , Kim Yeon-Hee
Published: January 2021

Understanding the response of the Earth system to CO2 removal (CDR) is crucial because the possibility of irreversibility exists. Therefore, the Carbon Dioxide Removal Model Inter-comparison Project (CDRMIP) for the protocol experiment in the Coupled Model Inter-comparison Project Phase 6 (CMIP6) has been developed. Our analysis focuses on the regional response in the hydrological cycle, especially in East Asia (EA). The peak temperature changes in EA (5.9 K) and the Korean peninsula (KO) (6.1 K) are larger than the global mean surface air temperature (GSAT) response. The precipitation changes are approximately 9.4% (EA) and 23.2% (KO) at the phase change time (130–150 years); however, the largest increase is approximately 16.6% (EA) and 36.5% (KO) in the ramp-down period (150–160 years). In addition, the differences are below 5 mm/day and 1 day for the precipitation intensity indices (Rx1day and Rx5day) and frequency indices (R95 and R99), respectively. Furthermore, the monsoon rainband of the ramp-down period moves northward as the earlier onset with high confidence compared to the ramp-up period; however, it does not move north to the KO region. The results suggest that reducing CO2 moves the rainband southward. However, a detailed interpretation in terms of the mechanism needs to be carried out in further research.
Development of an Understanding of Reactive Mercury in Ambient Air: A Review
Authors: Gustin Mae Sexauer , Dunham-Cheatham Sarrah M. , Huang Jiaoyan , Lindberg Steve , Lyman Seth N.
Published: January 2021

This review focuses on providing the history of measurement efforts to quantify and characterize the compounds of reactive mercury (RM), and the current status of measurement methods and knowledge. RM collectively represents gaseous oxidized mercury (GOM) and that bound to particles. The presence of RM was first recognized through measurement of coal-fired power plant emissions. Once discovered, researchers focused on developing methods for measuring RM in ambient air. First, tubular KCl-coated denuders were used for stack gas measurements, followed by mist chambers and annular denuders for ambient air measurements. For ~15 years, thermal desorption of an annular KCl denuder in the Tekran® speciation system was thought to be the gold standard for ambient GOM measurements. Research over the past ~10 years has shown that the KCl denuder does not collect GOM compounds with equal efficiency, and there are interferences with collection. Using a membrane-based system and an automated system—the Detector for Oxidized mercury System (DOHGS)—concentrations measured with the KCl denuder in the Tekran speciation system underestimate GOM concentrations by 1.3 to 13 times. Using nylon membranes it has been demonstrated that GOM/RM chemistry varies across space and time, and that this depends on the oxidant chemistry of the air. Future work should focus on development of better surfaces for collecting GOM/RM compounds, analytical methods to characterize GOM/RM chemistry, and high-resolution, calibrated measurement systems.
ATmospheric LIDar (ATLID): Pre-Launch Testing and Calibration of the European Space Agency Instrument That Will Measure Aerosols and Thin Clouds in the Atmosphere
Authors: do Carmo João Pereira , de Villele Geraud , Wallace Kotska , Lefebvre Alain , Ghose Kaustav , Kanitz Thomas , Chassat François , Corselle Bertrand , Belhadj Thomas , Bravetti Paolo
Published: January 2021

ATLID (ATmospheric LIDar) is the atmospheric backscatter Light Detection and Ranging (LIDAR) instrument on board of the Earth Cloud, Aerosol and Radiation Explorer (EarthCARE) mission, the sixth Earth Explorer Mission of the European Space Agency (ESA) Living Planet Programme. ATLID’s purpose is to provide vertical profiles of optically thin cloud and aerosol layers, as well as the altitude of cloud boundaries, with a resolution of 100 m for altitudes of 0 to 20 km, and a resolution of 500 m for 20 km to 40 km. In order to achieve this objective ATLID emits short duration laser pulses in the ultraviolet, at a repetition rate of 51 Hz, while pointing in a near nadir direction along track of the satellite trajectory. The atmospheric backscatter signal is then collected by its 620 mm aperture telescope, filtered through the optics of the instrument focal plane assembly, in order to separate and measure the atmospheric Mie and Rayleigh scattering signals. With the completion of the full instrument assembly in 2019, ATLID has been subjected to an ambient performance test campaign, followed by a successful environmental qualification test campaign, including performance calibration and characterization in thermal vacuum conditions. In this paper the design and operational principle of ATLID is recalled and the major performance test results are presented, addressing the main key receiver and emitter characteristics. Finally, the estimated instrument, in-orbit, flight predictions are presented; these indicate compliance of the ALTID instrument performance against its specification and that it will meet its mission science objectives for the EarthCARE mission, to be launched in 2023.
Discovery and Validation of a Novel Step Catalyzed by OsF3H in the Flavonoid Biosynthesis Pathway
Authors: Jan Rahmatullah , Asaf Sajjad , Paudel Sanjita , Lubna  , Lee Sangkyu , Kim Kyung-Min
Published: January 2021

Kaempferol and quercetin are the essential plant secondary metabolites that confer huge biological functions in the plant defense system. In this study, biosynthetic pathways for kaempferol and quercetin were constructed in Saccharomyces cerevisiae using naringenin as a substrate. OsF3H was cloned into pRS42K yeast episomal plasmid (YEp) vector and the activity of the target gene was analyzed in engineered and empty strains. We confirmed a novel step of kaempferol and quercetin biosynthesis directly from naringenin, catalyzed by the rice flavanone 3-hydroxylase (F3H). The results were confirmed through thin layer chromatography (TLC) followed by western blotting, nuclear magnetic resonance (NMR), and liquid chromatography-mass spectrometry LCMS-MS. TLC showed positive results when comparing both compounds extracted from the engineered strain with the standard reference. Western blotting confirmed the lack of OsF3H activity in empty strains and confirmed high OsF3H expression in engineered strains. NMR spectroscopy confirmed only quercetin, while LCMS-MS results revealed that F3H is responsible for the conversion of naringenin to both kaempferol and quercetin.
Functional Evaluation of a Rare Variant c.516G>C (p.Trp172Cys) in the GJB2 (Connexin 26) Gene Associated with Nonsyndromic Hearing Loss
Authors: Maslova Ekaterina A. , Orishchenko Konstantin E. , Posukh Olga L.
Published: January 2021

Mutations in the GJB2 gene encoding transmembrane protein connexin 26 (Cx26) are the most common cause for hearing loss worldwide. Cx26 plays a crucial role in the ionic and metabolic homeostasis in the inner ear, indispensable for normal hearing process. Different pathogenic mutations in the GJB2 gene can affect all stages of the Cx26 life cycle and result in nonsyndromic autosomal recessive (DFNB1) or dominant (DFNA3) deafness and syndromes associating hearing loss with skin disorders. This study aims to elucidate the functional consequences of a rare GJB2 variant c.516G>C (p.Trp172Cys) found with high frequency in deaf patients from indigenous populations of Southern Siberia (Russia). The substitution c.516G>C leads to the replacement of tryptophan at a conserved amino acid position 172 with cysteine (p.Trp172Cys) in the second extracellular loop of Cx26 protein. We analyzed the subcellular localization of mutant Cx26-p.Trp172Cys protein by immunocytochemistry and the hemichannels permeability by dye loading assay. The GJB2 knockout HeLa cell line has been generated using CRISPR/Cas9 genome editing tool. Subsequently, the HeLa transgenic cell lines stably expressing different GJB2 variants (wild type and mutations associated with hearing loss) were established based on knockout cells and used for comparative functional analysis. The impaired trafficking of mutant Cx26-p.Trp172Cys protein to the plasma membrane and reduced hemichannels permeability support the pathogenic effect of the c.516G>C (p.Trp172Cys) variant and its association with nonsyndromic hearing loss. Our data contribute to a better understanding of the role of mutations in the second extracellular loop of Cx26 protein in pathogenesis of deafness.
GABAB-Receptor Agonist-Based Immunotherapy for Type 1 Diabetes in NOD Mice
Authors: Tian Jide , Middleton Blake , Lee Victoria Seunghee , Park Hye Won , Zhang Zhixuan , Kim Bokyoung , Lowe Catherine , Nguyen Nancy , Liu Haoyuan , Beyer Ryan S. , Chao Hannah W. , Chen Ryan , Mai Davis , O’Laco Karen Anne , Song Min , Kaufman Daniel L.
Published: January 2021

Some immune system cells express type A and/or type B γ-aminobutyric acid receptors (GABAA-Rs and/or GABAB-Rs). Treatment with GABA, which activates both GABAA-Rs and GABAB-Rs), and/or a GABAA-R-specific agonist inhibits disease progression in mouse models of type 1 diabetes (T1D), multiple sclerosis, rheumatoid arthritis, and COVID-19. Little is known about the clinical potential of specifically modulating GABAB-Rs. Here, we tested lesogaberan, a peripherally restricted GABAB-R agonist, as an interventive therapy in diabetic NOD mice. Lesogaberan treatment temporarily restored normoglycemia in most newly diabetic NOD mice. Combined treatment with a suboptimal dose of lesogaberan and proinsulin/alum immunization in newly diabetic NOD mice or a low-dose anti-CD3 in severely hyperglycemic NOD mice greatly increased T1D remission rates relative to each monotherapy. Mice receiving combined lesogaberan and anti-CD3 displayed improved glucose tolerance and, unlike mice that received anti-CD3 alone, had some islets with many insulin+ cells, suggesting that lesogaberan helped to rapidly inhibit β-cell destruction. Hence, GABAB-R-specific agonists may provide adjunct therapies for T1D. Finally, the analysis of microarray and RNA-Seq databases suggested that the expression of GABAB-Rs and GABAA-Rs, as well as GABA production/secretion-related genes, may be a more common feature of immune cells than currently recognized.
Clinically Applicable Quantitative Magnetic Resonance Morphologic Measurements of Grey Matter Changes in the Human Brain
Authors: Fu Tong , Kobeleva Xenia , Bronzlik Paul , Nösel Patrick , Dadak Mete , Lanfermann Heinrich , Petri Susanne , Ding Xiao-Qi
Published: January 2021

(1) Purpose: Quantitative magnetic resonance imaging (qMRI) measurements can be used to sensitively estimate brain morphological alterations and may support clinical diagnosis of neurodegenerative diseases (ND). We aimed to establish a normative reference database for a clinical applicable quantitative MR morphologic measurement on neurodegenerative changes in patients; (2) Methods: Healthy subjects (HCs, n = 120) with an evenly distribution between 21 to 70 years and amyotrophic lateral sclerosis (ALS) patients (n = 11, mean age = 52.45 ± 6.80 years), as an example of ND patients, underwent magnetic resonance imaging (MRI) examinations under routine diagnostic conditions. Regional cortical thickness (rCTh) in 68 regions of interest (ROIs) and subcortical grey matter volume (SGMV) in 14 ROIs were determined from all subjects by using Computational Anatomy Toolbox. Those derived from HCs were analyzed to determine age-related differences and subsequently used as reference to estimate ALS-related alterations; (3) Results: In HCs, the rCTh (in 49/68 regions) and the SGMV (in 9/14 regions) in elderly subjects were less than those in younger subjects and exhibited negative linear correlations to age (p < 0.0007 for rCTh and p < 0.004 for SGMV). In comparison to age- and sex-matched HCs, the ALS patients revealed significant decreases of rCTh in eight ROIs, majorly located in frontal and temporal lobes; (4) Conclusion: The present study proves an overall grey matter decline with normal ageing as reported previously. The provided reference may be used for detection of grey matter alterations in neurodegenerative diseases that are not apparent in standard MR scans, indicating the potential of using qMRI as an add-on diagnostic tool in a clinical setting.
Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte and Monocyte-to-Lymphocyte Ratio in Bipolar Disorder
Authors: Fusar-Poli Laura , Natale Antimo , Amerio Andrea , Cimpoesu Patriciu , Grimaldi Filioli Pietro , Aguglia Eugenio , Amore Mario , Serafini Gianluca , Aguglia Andrea
Published: January 2021

Background: Several inflammatory hypotheses have been suggested to explain the etiopathogenesis of bipolar disorder (BD) and its different phases. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and monocyte-to-lymphocyte (MLR) ratios have been proposed as potential peripheral biomarkers of mood episodes. Methods: We recruited 294 patients affected by BD, of which 143 were experiencing a (hypo)manic episode and 151 were in a depressive phase. A blood sample was drawn to perform a complete blood count. NLR, PLR, and MLR were subsequently calculated. A t-test was performed to evaluate differences in blood cell counts between depressed and (hypo)manic patients and a regression model was then computed. Results: Mean values of neutrophils, platelets, mean platelet volume, NLR, PLR, and MLR were significantly higher in (hypo)manic than depressed individuals. Logistic regression showed that PLR may represent an independent predictor of (hypo)mania. Conclusions: Altered inflammatory indexes, particularly PLR, may explain the onset and recurrence of (hypo)manic episodes in patients with BD. As inflammatory ratios represent economical and accessible markers of inflammation, further studies should be implemented to better elucidate their role as peripheral biomarkers of BD mood episodes.
Are Linguistic Prediction Deficits Characteristic of Adults with Dyslexia?
Authors: Engelhardt Paul E. , Yuen Michelle K. Y. , Kenning Elise A. , Filipovic Luna
Published: January 2021

Individuals with dyslexia show deficits in phonological abilities, rapid automatized naming, short-term/working memory, processing speed, and some aspects of sensory and visual processing. There is currently one report in the literature that individuals with dyslexia also show impairments in linguistic prediction. The current study sought to investigate prediction in language processing in dyslexia. Forty-one adults with dyslexia and 43 typically-developing controls participated. In the experiment, participants made speeded-acceptability judgements in sentences with word final cloze manipulations. The final word was a high-cloze probability word, a low-cloze probability word, or a semantically anomalous word. Reaction time from the onset of the final word to participants’ response was recorded. Results indicated that individuals with dyslexia showed longer reaction times, and crucially, they showed clear differences from controls in low predictability sentences, which is consistent with deficits in linguistic prediction. Conclusions focus on the mechanism supporting prediction in language comprehension and possible reasons why individuals with dyslexia show less prediction.
Impulsivity as Early Emerging Vulnerability Factor—Prediction of ADHD by a Preschool Neuropsychological Measure
Authors: Pauli-Pott Ursula , Becker Katja
Published: January 2021

Impulsivity, comprising deviations of brain-based bottom-up and top-down control processes, has been regarded as a crucial, early emerging marker of a developmental pathway to attention-deficit/hyperactivity (ADHD) and externalizing disorders. In two independent studies (a cross-sectional study and a longitudinal study), we analyzed the concurrent and predictive validity of a task-based neuropsychological impulsivity measure for preschool children. The sample of Study 1 comprised 102 3–5-year-old children (46% boys). In Study 2, 138 children (59% boys) with elevated ADHD symptoms were recruited and assessed at the ages of 4–5 and 8 years. In both studies, preschool impulsivity was measured by a summary score of neuropsychological tasks on approach motivation and hot inhibitory control. For Study 1, the impulsivity measure was significantly associated with symptoms of ADHD and oppositional defiant disorder (ODD) (χ2(1) = 9.8, p = 0.002; χ2(1) = 8.1, p = 0.004). In Study 2, the impulsivity measure predicted the 8-year-olds’ ADHD diagnoses over and above concurrent ADHD symptoms (χ2(1) = 10.0, p = 0.002, OR = 5.0, 95% CI: 1.8–14.0). The impulsivity measure showed good concurrent and predictive validity. The measure can be useful for the early identification of children at risk for developing ADHD and externalizing disorders.
Dimensions of Craving Interact with COMT Genotype to Predict Relapse in Individuals with Alcohol Use Disorder Six Months after Treatment
Authors: Padula Claudia B. , Hansen Annika , Hughes Rachel L. , McNerney M. Windy
Published: January 2021

(1) Background: Alcohol use disorder (AUD) is associated with poor medical, psychological, and psychosocial outcomes and approximately 60% of individuals with AUD relapse six months after treatment. Craving is a core aspect of AUD and associated with high risk of relapse. One promising avenue to improve outcomes may be in understanding the relationship between COMT genotype, craving, and treatment outcomes. (2) Methods: To this end, we assessed craving, recent drinking history, and impulsivity in 70 individuals with AUD undergoing a standard course of treatment at a regional Veteran Affairs (VA) medical center. Saliva samples were collected to determine COMT genotype. In this prospective observational study, participants were followed for six months to determine who went on to relapse after treatment. (3) Results: Results revealed a significant interaction between craving and catechol-O-methyltransferse (COMT) genotype in predicting relapse. Post hoc exploratory analyses indicated that Met/Met homozygotes reported the highest levels of craving, and craving was associated with recent drinking history. Among Val/Val homozygotes, who had higher rates of relapse, craving was associated with impulsivity. (4) Conclusions: These associations highlight that specific profiles of psychological and biological factors may be important in understanding which individuals are at highest risk of relapse following treatment. Future studies that build on these findings are warranted.
New Approaches Based on Non-Invasive Brain Stimulation and Mental Representation Techniques Targeting Pain in Parkinson’s Disease Patients: Two Study Protocols for Two Randomized Controlled Trials
Authors: González-Zamorano Yeray , Fernández-Carnero Josué , Sánchez-Cuesta Francisco José , Arroyo-Ferrer Aida , Vourvopoulos Athanasios , Figueiredo Patricia , Serrano José Ignacio , Romero Juan Pablo
Published: January 2021

Pain is an under-reported but prevalent symptom in Parkinson’s Disease (PD), impacting patients’ quality of life. Both pain and PD conditions cause cortical excitability reduction and non-invasive brain stimulation. Mental representation techniques are thought to be able to counteract it, also resulting effectively in chronic pain conditions. We aim to conduct two independent studies in order to evaluate the efficacy of transcranial direct current stimulation (tDCS) and mental representation protocol in the management of pain in PD patients during the ON state: (1) tDCS over the Primary Motor Cortex (M1); and (2) Action Observation (AO) and Motor Imagery (MI) training through a Brain-Computer Interface (BCI) using Virtual Reality (AO + MI-BCI). Both studies will include 32 subjects in a longitudinal prospective parallel randomized controlled trial design under different blinding conditions. The main outcomes will be score changes in King’s Parkinson’s Disease Pain Scale, Brief Pain Inventory, Temporal Summation, Conditioned Pain Modulation, and Pain Pressure Threshold. Assessment will be performed pre-intervention, post-intervention, and 15 days post-intervention, in both ON and OFF states.
Seawater-Neutralized Bauxite Residue–Polyester Composites as Insulating Construction Materials
Authors: Adi Maissa , Abu-Jdayil Basim , Al Ghaferi Fatima , Al Yahyaee Sara , Al Jabri Maryam
Published: January 2021

Bauxite residue (BR) is one of the most commonly generated industrial wastes in the world. Thus, novel techniques for its proper utilization must be urgently developed. Herein, seawater-neutralized BR–unsaturated polyester resin (UPR) composites are presented as insulating construction materials with promising mechanical performance. Composites with different BR content (0–60 vol.%) were prepared to evaluate the influence of BR content on the compressive, tensile, and flexural strengths as well as the moduli of BR–UPR composites. Experimental results revealed that adding BR particles to the polyester matrix increased the compressive properties (strength, modulus, and strain). The composites containing 20 vol.% BR showed the maximum compressive strength (108 MPa), while the composites with 30 vol.% BR exhibited the maximum compressive modulus (1 GPa). Moreover, the reduction in tensile and flexural strengths with an increase in the BR content may be attributed to the lower efficiency of stress transfer between the BR particle–polyester interface due to weak adhesion at the interface, direct contact between particles, and presence of voids or porosity. Although the tensile strength and failure stress decreased with increasing filler content, the produced composites showed outstanding tensile strength (4.0–19.3 MPa) compared with conventional insulating materials. In addition, the composite with 40 vol.% BR demonstrated a flexural strength of 15.5 MPa. Overall, BR–UPR composites showed excellent compatibility with promising mechanical properties as potential insulating construction materials.
Ways into Understanding HIF Inhibition
Authors: Schönberger Tina , Fandrey Joachim , Prost-Fingerle Katrin
Published: January 2021

Hypoxia is a key characteristic of tumor tissue. Cancer cells adapt to low oxygen by activating hypoxia-inducible factors (HIFs), ensuring their survival and continued growth despite this hostile environment. Therefore, the inhibition of HIFs and their target genes is a promising and emerging field of cancer research. Several drug candidates target protein–protein interactions or transcription mechanisms of the HIF pathway in order to interfere with activation of this pathway, which is deregulated in a wide range of solid and liquid cancers. Although some inhibitors are already in clinical trials, open questions remain with respect to their modes of action. New imaging technologies using luminescent and fluorescent methods or nanobodies to complement widely used approaches such as chromatin immunoprecipitation may help to answer some of these questions. In this review, we aim to summarize current inhibitor classes targeting the HIF pathway and to provide an overview of in vitro and in vivo techniques that could improve the understanding of inhibitor mechanisms. Unravelling the distinct principles regarding how inhibitors work is an indispensable step for efficient clinical applications and safety of anticancer compounds.
Ruthenium Nanoparticles Intercalated in Montmorillonite (nano-Ru@MMT) Is Highly Efficient Catalyst for the Selective Hydrogenation of 2-Furaldehyde in Benign Aqueous Medium
Authors: Khan Farooq-Ahmad , Yaqoob Sana , Nasim Nourina , Wang Yan , Usman Muhammad , Isab Anvarhusein A. , Altaf Muhammad , Sun Bing , El Azab Islam H. , El-Seedi Hesham R.
Published: January 2021

Chemoselective hydrogenation of 2-furaldehyde to furfuryl alcohol using green solvents is an important research area to get eco-friendly fuels and fine chemicals. Herein, we report ruthenium nanoparticles (~1.8 nm) intercalated in montmorillonite as an efficient catalytic system, which can selectively hydrogenate 2-furaldehyde in a benign aqueous medium. The complete conversion was observed at 40 °C with 1 MPa H2, the selectivity of furfuryl alcohol being >99%, and turnover number 1165. After a catalytic run, the montmorillonite-supported ruthenium nanoparticles can be recycled and reused without losing their activity and selectivity.
Editorial: Special Issue on “Flavin Monooxygenases”
Authors: Gilardi Gianfranco , Sadeghi Sheila J.
Published: January 2021

Flavin-containing monooxygenase are a large family of enzymes involved in an array of different reactions by activating molecular oxygen and transferring one atom of oxygen to their substrates [...]
Enhanced Hydrogen Evolution Reaction in Surface Functionalized MoS2 Monolayers
Authors: Pak Sangyeon , Lim Jungmoon , Hong John , Cha SeungNam
Published: January 2021

Monolayered, semiconducting MoS2 and their transition metal dichalcogenides (TMDCs) families are promising and low-cost materials for hydrogen generation through electrolytes (HER, hydrogen evolution reaction) due to their high activities and electrochemical stability during the reaction. However, there is still a lack of understanding in identifying the underlying mechanism responsible for improving the electrocatalytic properties of theses monolayers. In this work, we investigated the significance of controlling carrier densities in a MoS2 monolayer and in turn the corresponding electrocatalytic behaviors in relation to the energy band structure of MoS2. Surface functionalization was employed to achieve p-doping and n-doping in the MoS2 monolayer that led to MoS2 electrochemical devices with different catalytic performances. Specifically, the electron-rich MoS2 surface showed lower overpotential and Tafel slope compared to the MoS2 with surface functional groups that contributed to p-doping. We attributed such enhancement to the increase in the carrier density and the corresponding Fermi level that accelerated HER and charge transfer kinetics. These findings are of high importance in designing electrocatalysts based on two-dimensional TMDCs.
The Mitochondrial Permeability Transition: Nexus of Aging, Disease and Longevity
Authors: Rottenberg Hagai , Hoek Jan B.
Published: January 2021

The activity of the mitochondrial permeability transition pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging reactive oxygen species, Ca2+ and NAD+. The various pathways that control the channel activity, directly or indirectly, can therefore either inhibit or accelerate aging or retard or enhance the progression of aging-driven degenerative diseases and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles, protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. The increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.
Usefulness of the New Hematological Parameter: Reactive Lymphocytes RE-LYMP with Flow Cytometry Markers of Inflammation in COVID-19
Authors: Rutkowska Elżbieta , Kwiecień Iwona , Kulik Katarzyna , Chełstowska Beata , Kłos Krzysztof , Rzepecki Piotr , Chciałowski Andrzej
Published: January 2021

Identification of patients with activation of the immune system which indicates the presence of infection is essential, especially in the times of the global coronavirus 2019 (COVID-19) pandemic. The aim of the present study was to evaluate the reactive lymphocytes (RE-LYMP) parameter in COVID-19 and to correlate it with activation lymphocytes markers by flow cytometry. The study group consisted of 40 patients: with COVID-19 infection (n = 20) and with others virus infections without COVID-19 (COVID-19(−) virus (n = 20)) and 20 healthy donors (HC). Blood count and flow cytometry were performed. The COVID-19(+) group had significantly lower RE-LYMP parameter than the COVID-19(−) virus group (5.45 vs. 11.05, p < 0.05). We observed higher proportion of plasmablasts in the COVID-19(+) and COVID-19(−) virus groups than HC (8.8 vs. 11.1 vs. 2.7, p < 0.05). In the COVID-19(+) there was a lower proportion of CD4+ CD38+ cells than in the other groups (significant differences between COVID-19(+) and COVID-19(−) virus groups). RE-LYMP correlated with activated T lymphocytes CD38+ and HLA-DR+ in the COVID-19(−) virus group, however in the COVID-19(+) group correlations with T lymphocytes CD25+ and CD45RO+ were observed. In summary the analysis of the RE-LYMP together with flow cytometric activation markers can be helpful in identifying and distinguishing patients with COVID-19(+) from other viruses and HC.
Keap1-Nrf2 Pathway Regulates ALDH and Contributes to Radioresistance in Breast Cancer Stem Cells
Authors: Kamble Dinisha , Mahajan Megharani , Dhat Rohini , Sitasawad Sandhya
Published: January 2021

Tumor recurrence after radiotherapy due to the presence of breast cancer stem cells (BCSCs) is a clinical challenge, and the mechanism remains unclear. Low levels of ROS and enhanced antioxidant defenses are shown to contribute to increasing radioresistance. However, the role of Nrf2-Keap1-Bach1 signaling in the radioresistance of BCSCs remains elusive. Fractionated radiation increased the percentage of the ALDH-expressing subpopulation and their sphere formation ability, promoted mesenchymal-to-epithelial transition and enhanced radioresistance in BCSCs. Radiation activated Nrf2 via Keap1 silencing and enhanced the tumor-initiating capability of BCSCs. Furthermore, knockdown of Nrf2 suppressed ALDH+ population and stem cell markers, reduced radioresistance by decreasing clonogenicity and blocked the tumorigenic ability in immunocompromised mice. An underlying mechanism of Keap1 silencing could be via miR200a, as we observed a significant increase in its expression, and the promoter methylation of Keap1 or GSK-3β did not change. Our data demonstrate that ALDH+ BCSC population contributes to breast tumor radioresistance via the Nrf2-Keap1 pathway, and targeting this cell population with miR200a could be beneficial but warrants detailed studies. Our results support the notion that Nrf2-Keap1 signaling controls mesenchymal–epithelial plasticity, regulates tumor-initiating ability and promotes the radioresistance of BCSCs.
Altered TGFβ/SMAD Signaling in Human and Rat Models of Pulmonary Hypertension: An Old Target Needs Attention
Authors: Sanada Takayuki Jujo , Sun Xiao-Qing , Happé Chris , Guignabert Christophe , Tu Ly , Schalij Ingrid , Bogaard Harm-Jan , Goumans Marie-José , Kurakula Kondababu
Published: January 2021

Recent translational studies highlighted the inhibition of transforming growth factor (TGF)-β signaling as a promising target to treat pulmonary arterial hypertension (PAH). However, it remains unclear whether alterations in TGF-β signaling are consistent between PAH patients and animal models. Therefore, we compared TGF-β signaling in the lungs of PAH patients and rats with experimental PAH induced by monocrotaline (MCT) or SU5416+hypoxia (SuHx). In hereditary PAH (hPAH) patients, there was a moderate increase in both TGFβR2 and pSMAD2/3 protein levels, while these were unaltered in idiopathic PAH (iPAH) patients. Protein levels of TGFβR2 and pSMAD2/3 were locally increased in the pulmonary vasculature of PAH rats under both experimental conditions. Conversely, the protein levels of TGFβR2 and pSMAD2/3 were reduced in SuHx while slightly increased in MCT. mRNA levels of plasminogen activator inhibitor (PAI)-1 were increased only in MCT animals and such an increase was not observed in SuHx rats or in iPAH and hPAH patients. In conclusion, our data demonstrate considerable discrepancies in TGFβ-SMAD signaling between iPAH and hPAH patients, as well as between patients and rats with experimental PAH.
Effect of Plating Current Density on the Ball-On-Disc Wear of Sn-Plated Ni Coatings on Cu Foils
Authors: Sharma Ashutosh , Ahn Byungmin
Published: January 2021

Metallic and alloyed coatings are used widely in several decorative and technology-based applications. In this work, we selected Sn coatings plated on Cu substrates for joining applications. We employed two different plating baths for the fabrication of Sn and Ni coatings: acidic stannous sulfate for Sn and Watts bath for Ni layer. The plating current densities were varied from 100–500 mA/cm2. Further, the wear and friction behavior of the coatings were studied using a ball-on-disc apparatus under dry sliding conditions. The impact of current density was studied on the morphology, wear, and coefficient of friction (COF) of the resultant coatings. The wear experiments were done at various loads from 2–10 N. The sliding distance was fixed to 7 m. The wear loss was quantified in terms of the volume of the track geometry (width and depth of the tracks). The results indicate that current density has an important role in tailoring the composition and morphology of coatings, which affects the wear properties. At higher loads (8–10 N), Sn coatings on Ni/Cu had higher volume loss with a stable COF due to a mixed adhesive and oxidative type of wear mechanism.
Improvement of Wear, Pitting Corrosion Resistance and Repassivation Ability of Mg-Based Alloys Using High Pressure Cold Sprayed (HPCS) Commercially Pure-Titanium Coatings
Authors: Daroonparvar Mohammadreza , Kasar Ashish K. , Farooq Khan Mohammad Umar , L. Menezes Pradeep , Kay Charles M. , Misra Manoranjan , Gupta Rajeev K.
Published: January 2021

In this study, a compact cold sprayed (CS) Ti coating was deposited on Mg alloy using a high pressure cold spray (HPCS) system. The wear and corrosion behavior of the CS Ti coating was compared with that of CS Al coating and bare Mg alloy. The Ti coating yielded lower wear rate compared to Al coating and Mg alloy. Electrochemical impedance spectroscopy (EIS) and cyclic potentiodynamic polarization (CPP) tests revealed that CS Ti coating can substantially reduce corrosion rate of AZ31B in chloride containing solutions compared to CS Al coating. Interestingly, Ti-coated Mg alloy demonstrated negative hysteresis loop, depicting repassivation of pits, in contrast to AZ31B and Al-coated AZ31B with positive hysteresis loops where corrosion potential (Ecorr) > repassivation potential (Erp); indicating irreversible growth of pits. AZ31B and Al-coated AZ31B were most susceptible to pitting corrosion, while Ti-coated Mg alloy indicated noticeable resistance to pitting in 3.5 wt % NaCl solution. In comparison to Al coating, Ti coating considerably separated the AZ31BMg alloy surface from the corrosive electrolyte during long term immersion test for 11 days.
Molecular Dynamics Investigation of Phenolic Oxidative Coupling Protein Hyp-1 Derived from Hypericum perforatum
Authors: Smietanska Joanna , Kozik Tomasz , Strzalka Radoslaw , Buganski Ireneusz , Wolny Janusz
Published: January 2021

Molecular dynamics (MD) simulations provide a physics-based approach to understanding protein structure and dynamics. Here, we used this intriguing tool to validate the experimental structural model of Hyp-1, a pathogenesis-related class 10 (PR-10) protein from the medicinal herb Hypericum perforatum, with potential application in various pharmaceutical therapies. A nanosecond MD simulation using the all-atom optimized potentials for liquid simulations (OPLS–AA) force field was performed to reveal that experimental atomic displacement parameters (ADPs) underestimate their values calculated from the simulation. The average structure factors obtained from the simulation confirmed to some extent the relatively high compliance of experimental and simulated Hyp-1 models. We found, however, many outliers between the experimental and simulated side-chain conformations within the Hyp-1 model, which prompted us to propose more reasonable energetically preferred rotameric forms. Therefore, we confirmed that MD simulation may be applicable for the verification of refined, experimental models and the explanation of their structural intricacies.
Preoperative Evaluation of Coronary Artery Disease in Liver Transplant Candidates: Many Unanswered Questions in Clinical Practice
Authors: Bonou Maria , Mavrogeni Sophie , Kapelios Chris J. , Skouloudi Marina , Aggeli Constantina , Cholongitas Evangelos , Papatheodoridis George , Barbetseas John
Published: January 2021

Cardiovascular (CV) complications represent the first non-graft-related cause of death and the third overall cause of death among patients undergoing liver transplantation (LT). History of coronary artery disease is related to increased CV mortality following LT. Although it is of paramount importance to stratify CV risk in pre-LT patients, there is no consensus regarding the choice of the optimal non-invasive cardiac imaging test. Algorithms proposed by scientific associations include non-traditional risk factors, which are associated with increased cardiac risk profiles. Thus, an individualized pre-LT evaluation protocol should be followed. As the average age of patients undergoing LT and the number of candidates continue to rise, the “3 W” questions still remain unanswered, Who, Which and When? Who should be screened for coronary artery disease (CAD), which screening modality should be used and when should the asymptomatic waitlisted patients repeat cardiac evaluation? Prospective studies with large sample sizes are warranted to define an algorithm that can provide better risk stratification and more reliable survival prediction.
Multimodal Diagnostics of Microrheologic Alterations in Blood of Coronary Heart Disease and Diabetic Patients
Authors: Maslianitsyna Anastasia , Ermolinskiy Petr , Lugovtsov Andrei , Pigurenko Alexandra , Sasonko Maria , Gurfinkel Yury , Priezzhev Alexander
Published: January 2021

Coronary heart disease (CHD) has serious implications for human health and needs to be diagnosed as early as possible. In this article in vivo and in vitro optical methods are used to study blood properties related to the aggregation of red blood cells in patients with CHD and comorbidities such as type 2 diabetes mellitus (T2DM). The results show not only a significant difference of the aggregation in patients compared to healthy people, but also a correspondence between in vivo and in vitro parameters. Red blood cells aggregate in CHD patients faster and more numerously; in particular the aggregation index increases by 20 ± 7%. The presence of T2DM also significantly elevates aggregation in CHD patients. This work demonstrates multimodal diagnostics and monitoring of patients with socially significant pathologies.
Comparison of Five Serological Assays for the Detection of SARS-CoV-2 Antibodies
Authors: Dörschug Anja , Schwanbeck Julian , Hahn Andreas , Hillebrecht Anke , Blaschke Sabine , Mese Kemal , Groß Uwe , Dierks Sascha , Frickmann Hagen , Zautner Andreas E.
Published: January 2021

Serological assays can contribute to the estimation of population proportions with previous immunologically relevant contact with the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) virus. In this study, we compared five commercially available diagnostic assays for the diagnostic identification of SARS-CoV-2-specific antibodies. Depending on the assessed immunoglobulin subclass, recorded sensitivity ranged from 17.0% to 81.9% with best results for immunoglobulin G. Specificity with blood donor sera ranged from 90.2% to 100%, with sera from EBV patients it ranged from 84.3% to 100%. Agreement from fair to nearly perfect was recorded depending on the immunoglobulin class between the assays, the with best results being found for immunoglobulin G. Only for this immunoglobulin class was the association between later sample acquisition times (about three weeks after first positive PCR results) and positive serological results in COVID-19 patients confirmed. In conclusion, acceptable and comparable reliability for the assessed immunoglobulin G-specific assays could be shown, while there is still room for improvement regarding the reliability of the assays targeting the other immunoglobulin classes.
Genomic Characterization of VIM and MCR Co-Producers: The First Two Clinical Cases, in Italy
Authors: Marchetti Vittoria Mattioni , Bitar Ibrahim , Sarti Mario , Fogato Elena , Scaltriti Erika , Bracchi Chiara , Hrabak Jaroslav , Pongolini Stefano , Migliavacca Roberta
Published: January 2021

Background: the co-production of carbapenemases and mcr-genes represents a worrisome event in the treatment of Enterobacteriaceae infections. The aim of the study was to characterize the genomic features of two clinical Enterobacter cloacae complex (ECC) isolates, co-producing VIM and MCR enzymes, in Italy. Methods: species identification and antibiotic susceptibility profiling were performed using MALDI-TOF and broth microdilution methods, respectively. Transferability of the blaVIM- and mcr- type genes was verified through conjugation experiment. Extracted DNA was sequenced using long reads sequencing technology on the Sequel I platform (PacBio). Results: the first isolate showed clinical resistance against ertapenem yet was colistin susceptible (EUCAST 2020 breakpoints). The mcr-9.2 gene was harbored on a conjugative IncHI2 plasmid, while the blaVIM-1 determinant was harbored on a conjugative IncN plasmid. The second isolate, resistant to both carbapenems and colistin, harbored: mcr-9 gene and its two component regulatory genes for increased expression on the chromosome, mcr-4.3 on non-conjugative (yet co-transferable) ColE plasmid, and blaVIM-1 on a non-conjugative IncA plasmid. Conclusions: to our knowledge, this is the first report of co-production of VIM and MCR in ECC isolates in Italy.
Comparison of Two Different Semiquantitative Urinary Dipstick Tests with Albumin-to-Creatinine Ratio for Screening and Classification of Albuminuria According to KDIGO. A Diagnostic Test Study
Authors: Hodel Nikolai C. , Hamad Ali , Reither Klaus , Kasella Irene Mndala , Abdulla Salim , Schoetzau Andreas , Hatz Christoph F. R. , Mayr Michael
Published: January 2021

Background: Semiquantitative dipstick tests are utilized for albuminuria screening. Methods: In a prospective cross-sectional survey, we analyzed the diagnostic test validity of the semiquantitative colorimetric indicator-dye-based Combur9-Test® and the albumin-specific immunochromatographic assay Micral-Test® for the detection of albuminuria, the distribution of the semiquantitative measurements within the albuminuria stages according to KDIGO, and the utility for albuminuria screening compared with an albumin-to-creatinine ratio (ACR) in a walk-in population. Results: In 970 subjects, albuminuria (≥30 mg/g) was detected in 12.7% (95% CI 85.6–96.3%) with the ACR. Sensitivity was 82.9% (95% CI 75.1–89.1%) and 91.9% (95% CI 88.7–96.9%) and specificity 71.5% (95% CI 68.4–74.6%) and 17.5% (95% CI 15.0–20.2%) for the Combur9-Test® and Micral-Test®, respectively. Correct classification to KDIGO albuminuria stages A2/A3 with the Combur9-Test® was 15.4%, 51.4%, and 87.9% at cut-offs of 30, 100, and ≥300 mg/dL, and with the Micral-Test® it was 1.8%, 10.5%, and 53.6% at cut-offs of 2, 5, and 10 mg/dL, respectively. Overall, disagreement to KDIGO albuminuria was seen in 27% and 73% with the Combur9-Test® and Micral-Test®, respectively. From the total population, 62.5% and 15.3% were correctly ruled out and 2.2% and 1% were missed as false-negatives by the Combur9-Test® and Micral-Test®, respectively. Conclusion: Compared to the Combur9-Test®, the utility of the Micral-Test® is limited, because the fraction of correctly ruled out patients is small and a large proportion with a positive Micral-Test® require a subsequent ACR conformation test.
Enhanced Methods of Seasonal Adjustment
Authors: Pollock D. Stephen G.
Published: January 2021

The effect of the conventional model-based methods of seasonal adjustment is to nullify the elements of the data that reside at the seasonal frequencies and to attenuate the elements at the adjacent frequencies. It may be desirable to nullify some of the adjacent elements instead of merely attenuating them. For this purpose, two alternative sets of procedures are presented that have been implemented in a computer program named SEASCAPE. In the first set of procedures, a basic seasonal adjustment filter is augmented by additional filters that are targeted at the adjacent frequencies. In the second set of procedures, a Fourier transform of the data is exploited to allow the elements in the vicinities of the seasonal frequencies to be eliminated or attenuated at will. The question is raised of whether an estimated trend-cycle trajectory that is devoid of high-frequency noise can serve in place of the seasonally adjusted data.