bluuebunny/crossref_metadata_2025 huggingface dataset:
Depression and Cognitive Impairment in a Spanish Sample of Psychoactive Substance Users Receiving Mental Health Care
Authors: Luque Bárbara , García Victoriana , Tabernero Carmen
Published: May 2022

(1) Background: Numerous studies state that the abuse of psychoactive substances produces cognitive, emotional and behavioral disorders. The aim of this study is to analyze the relationship between the consumption of different psychoactive substances with cognitive performance and depression. (2) Methods: The sample was composed of 254 individuals (M = 41.81; SD = 10.74, from 18 to 69; 76% male) who received psychological treatment related to the use of substances. Participants were classified according to the main substance consumed: alcohol (42.9%), cannabis (20.5%), cocaine (15.4%), heroin (13%) and benzodiazepines (8.3%). The Montreal Cognitive Assessment and the Beck’s Depression Inventory were administrated. (3) The results indicated no statistically significant differences between levels of depression depending on the substance consumed. Regarding cognitive impairment, it was found that cocaine consumers have the worst level of cognitive impairment, while cannabis consumers have the best level of cognitive functioning. Finally, it was found that participants with severe depression have higher cognitive impairment than those who were diagnosed with moderate depression. (4) Conclusions: Given the high prevalence of depression and cognitive impairment with the abuse of psychoactive substances, early treatment is recommended to avoid a higher cognitive and emotional affectation.
A Novel Approach to the Authentication of Apricot Seed Cultivars Using Innovative Models Based on Image Texture Parameters
Authors: Ropelewska Ewa , Sabanci Kadir , Aslan Muhammet Fatih , Azizi Afshin
Published: May 2022

The different cultivars of apricot seeds may differ in their properties. To ensure economical and efficient seed processing, knowledge of the cultivars’ composition and physical properties may be necessary. Therefore, the correct identification of the cultivar of the apricot seeds may be very important. The objective of this study was to develop models based on selected textures of apricot seed images to distinguish different cultivars. The images of four cultivars of apricot seeds were acquired using a flatbed scanner. For each seed, approximately 1600 textures from the image, converted to the different color channels R, G, B, L, a, b, X, Y, and Z, were calculated. The models were built separately for the individual color channels; the color spaces Lab, RGB, XYZ; and all color channels combined based on selected texture parameters using different classifiers. The average accuracy of the classification of apricot seeds reached 99% (with an accuracy of 100% for the seeds of the cultivars ‘Early Orange’, ‘Bella’, and ‘Harcot’, and 96% for ‘Taja’) in the case of the set of textures selected from the color space Lab for the model built using the Multilayer Perceptron classifier. The same classifier produced high average accuracies for the color spaces RGB (90%) and XYZ (86%). For the set of textures selected from all color channels, i.e., R, G, B, L, a, b, X, Y, and Z, the average accuracy reached 96% (Multilayer Perceptron and Random Forest classifiers). In the case of individual color channels, the highest average accuracy was up to 91% for the models built based on a set of textures selected from color channel b (Multilayer Perceptron). The results proved the possibility of distinguishing apricot seed cultivars with a high probability using a non-destructive, inexpensive, and objective procedure involving image analysis.
MRI and Adenomyosis: What Can Radiologists Evaluate?
Authors: Celli Veronica , Dolciami Miriam , Ninkova Roberta , Ercolani Giada , Rizzo Stefania , Porpora Maria , Catalano Carlo , Manganaro Lucia
Published: May 2022

Uterine adenomyosis is a common benign condition defined by the presence of heterotopic endometrial glands and stroma within the myometrium. Adenomyosis is often related to infertility and other adverse pregnancy outcomes. Modern imaging techniques allow the non-invasive diagnosis of adenomyosis and, in this framework, Magnetic Resonance Imaging (MRI) has assumed a central role due to its high diagnostic accuracy in the detection of adenomyosis. Currently, there is still a lack of international consensus on adenomyosis diagnostic criteria and classification, despite the fact that an agreed reporting system would promote treatment outcomes and research. This review aims to emphasize the important contribution of MRI to the diagnosis of adenomyosis and to highlight how, thanks to the great tissue differentiation provided by MRI, it is possible to identify the main direct (cystic component) and indirect (junctional zone features) signs of adenomyosis and to distinguish its various subtypes according to different MRI-based classifications. We also explored the main MRI criteria to identify the most common pitfalls and differential diagnoses of adenomyosis, whose features should be considered to avoid misdiagnosis.
Comparative Study of Algae-Based Measurements of the Toxicity of 14 Manufactured Nanomaterials
Authors: Lee Seung-Hun , Jung Kiyoon , Chung Jinwook , Lee Yong-Woo
Published: May 2022

With the increasing use of nanomaterials in recent years, determining their comparative toxicities has become a subject of intense research interest. However, the variety of test methods available for each material makes it difficult to compare toxicities. Here, an accurate and reliable method is developed to evaluate the toxicity of manufactured nanomaterials, such as Al2O3, carbon black, single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), CeO2, dendrimers, fullerene, gold, iron, nanoclays, silver, SiO2, TiO2, and ZnO. A series of 72 h chronic and 8 h acute toxicity tests was performed using cell counting, chlorophyll, and delayed fluorescence methods. Comparable toxicities using the chlorophyll and delayed fluorescence methods were impossible to determine because the EC50 of some of the nanomaterials could not be measured. All three test methods were successfully applied to the chronic toxicity tests of manufactured nanomaterials, and cell counting was the only method applicable to acute toxicity tests. The toxicity data and the proposal of measurement method for manufactured nanomaterials obtained in this study can be helpful for preparing exposure standards and investigating the toxicities of other nanomaterials in the future.
Space—Time Surveillance of COVID-19 Seasonal Clusters: A Case of Sweden
Authors: Aturinde Augustus , Mansourian Ali
Published: May 2022

While COVID-19 is a global pandemic, different countries have experienced different morbidity and mortality patterns. We employ retrospective and prospective space–time permutation analysis on COVID-19 positive records across different municipalities in Sweden from March 2020 to February 2021, using data provided by the Swedish Public Health Agency. To the best of our knowledge, this is the first study analyzing nationwide COVID-19 space–time clustering in Sweden, on a season-to-season basis. Our results show that different municipalities within Sweden experienced varying extents of season-dependent COVID-19 clustering in both the spatial and temporal dimensions. The reasons for the observed differences could be related to the differences in the earlier exposures to the virus, the strictness of the social restrictions, testing capabilities and preparedness. By profiling COVID-19 space–time clusters before the introduction of vaccines, this study contributes to public health efforts aimed at containing the virus by providing plausible evidence in evaluating which epidemiologic interventions in the different regions could have worked and what could have not worked.
Transplantation of Brown Adipose Tissue with the Ability of Converting Omega-6 to Omega-3 Polyunsaturated Fatty Acids Counteracts High-Fat-Induced Metabolic Abnormalities in Mice
Authors: Tsuji Tadataka , Bussberg Valerie , MacDonald Allison M. , Narain Niven R. , Kiebish Michael A. , Tseng Yu-Hua
Published: May 2022

A balanced omega (ω)-6/ω-3 polyunsaturated fatty acids (PUFAs) ratio has been linked to metabolic health and the prevention of chronic diseases. Brown adipose tissue (BAT) specializes in energy expenditure and secretes signaling molecules that regulate metabolism via inter-organ crosstalk. Recent studies have uncovered that BAT produces different PUFA species and circulating oxylipin levels are correlated with BAT-mediated energy expenditure in mice and humans. However, the impact of BAT ω-6/ω-3 PUFAs on metabolic phenotype has not been fully elucidated. The Fat-1 transgenic mice can convert ω-6 to ω-3 PUFAs. Here, we demonstrated that mice receiving Fat-1 BAT transplants displayed better glucose tolerance and higher energy expenditure. Expression of genes involved in thermogenesis and nutrient utilization was increased in the endogenous BAT of mice receiving Fat-1 BAT, suggesting that the transplants may activate recipients’ BAT. Using targeted lipidomic analysis, we found that the levels of several ω-6 oxylipins were significantly reduced in the circulation of mice receiving Fat-1 BAT transplants than in mice with wild-type BAT transplants. The major altered oxylipins between the WT and Fat-1 BAT transplantation were ω-6 arachidonic acid-derived oxylipins via the lipoxygenase pathway. Taken together, these findings suggest an important role of BAT-derived oxylipins in combating obesity-related metabolic disorders.
Antiviral Characterization of Advanced Materials: Use of Bacteriophage Phi 6 as Surrogate of Enveloped Viruses Such as SARS-CoV-2
Authors: Serrano-Aroca Ángel
Published: May 2022

The bacteriophage phi 6 is a virus that belongs to a different Baltimore group than SARS-CoV-2 (group III instead of IV). However, it has a round-like shape and a lipid envelope like SARS-CoV-2, which render it very useful to be used as a surrogate of this infectious pathogen for biosafety reasons. Thus, recent antiviral studies have demonstrated that antiviral materials such as calcium alginate hydrogels, polyester-based fabrics coated with benzalkonium chloride (BAK), polyethylene terephthalate (PET) coated with BAK and polyester-based fabrics coated with cranberry extracts or solidified hand soap produce similar log reductions in viral titers of both types of enveloped viruses after similar viral contact times. Therefore, researchers with no access to biosafety level 3 facilities can perform antiviral tests of a broad range of biomaterials, composites, nanomaterials, nanocomposites, coatings and compounds against the bacteriophage phi 6 as a biosafe viral model of SARS-CoV-2. In fact, this bacteriophage has been used as a surrogate of SARS-CoV-2 to test a broad range of antiviral materials and compounds of different chemical natures (polymers, metals, alloys, ceramics, composites, etc.) and forms (films, coatings, nanomaterials, extracts, porous supports produced by additive manufacturing, etc.) during the current pandemic. Furthermore, this biosafe viral model has also been used as a surrogate of SARS-CoV-2 and other highly pathogenic enveloped viruses such as Ebola and influenza in a wide range of biotechnological applications.
Chitosan-Based Materials Featuring Multiscale Anisotropy for Wider Tissue Engineering Applications
Authors: Vlăsceanu George Mihail , Ioniță Mariana , Popescu Corina Cristiana , Giol Elena Diana , Ionescu Irina , Dumitrașcu Andrei-Mihai , Floarea Mădălina , Boerasu Iulian , Necolau Mădălina Ioana , Olăreț Elena , Ghițman Jana , Iovu Horia
Published: May 2022

We designed graphene oxide composites with increased morphological and structural variability using fatty acid-coupled polysaccharide co-polymer as the continuous phase. The matrix was synthesized by N, O-acylation of chitosan with palmitic and lauric acid. The obtained co-polymer was crosslinked with genipin and composited with graphene oxide. FTIR spectra highlighted the modification and multi-components interaction. DLS, SEM, and contact angle tests demonstrated that the conjugation of hydrophobic molecules to chitosan increased surface roughness and hydrophilicity, since it triggered a core-shell macromolecular structuration. Nanoindentation revealed a notable durotaxis gradient due to chitosan/fatty acid self-organization and graphene sheet embedment. The composited building blocks with graphene oxide were more stable during in vitro enzymatic degradation tests and swelled less. In vitro viability, cytotoxicity, and inflammatory response tests yielded promising results, and the protein adsorption test demonstrated potential antifouling efficacy. The robust and stable substrates with heterogeneous architecture we developed show promise in biomedical applications.
A MLR-Based Approach to Analyze Regulators of T Lymphocyte Activation In Vivo
Authors: Koutník Jiří , Klepsch Victoria , Pommermayr Maria , Thuille Nikolaus , Baier Gottfried , Siegmund Kerstin
Published: May 2022

Depending on the context, robust and durable T lymphocyte activation is either desirable, as in the case of anti-tumor responses, or unwanted, in cases of autoimmunity when chronic stimulation leads to self-tissue damage. Therefore, reliable in vivo models are of great importance to identify and validate regulatory pathways of T lymphocyte activation. Here, we describe an in vivo mixed-lymphocyte-reaction (MLR) approach, which is based on the so-called parent-into-F1 (P → F1) mouse model in combination with the congenic marker CD45.1/2 and cell proliferation dye-labeling. This setup allows us to track adoptively transferred allogenic CD4+ and CD8+ T lymphocytes and analyze their phenotype as well as the proliferation by flow cytometry in the blood and spleen. We could show hypo-reactive responses of T lymphocytes isolated from knockout mice with a known defect in T lymphocyte activation. Thus, this MLR-based in vivo model provides the opportunity to analyze positive regulators of T cell responses under physiological conditions of polyclonal T lymphocyte activation in vivo.
Carbon Dots Boost dsRNA Delivery in Plants and Increase Local and Systemic siRNA Production
Authors: Delgado-Martín Josemaría , Delgado-Olidén Alejo , Velasco Leonardo
Published: May 2022

In this work, we obtained carbon dots from glucose or saccharose as the nucleation source and passivated them with branched polyethylenimines for developing dsRNA nanocomposites. The CDs were fully characterized using hydrodynamic analyses, transmission electron microscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The ζ potential determined that the CDs had positive charges, good electrophoretic mobility and conductivity, and were suitable for obtaining dsRNA nanocomposites. DsRNA naked or coated with the CDs were delivered to leaves of cucumber plants by spraying. Quantitation of the dsRNA that entered the leaves showed that when coated with the CDs, 50-fold more dsRNA was detected than when naked dsRNA. Moreover, specific siRNAs derived from the sprayed dsRNAs were 13 times more abundant when the dsRNA was coated with the CDs. Systemic dsRNAs were determined in distal leaves and showed a dramatic increase in concentration when delivered as a nanocomposite. Similarly, systemic siRNAs were significantly more abundant in distal leaves when spraying with the CD-dsRNA nanocomposite. Furthermore, FITC-labeled dsRNA was shown to accumulate in the apoplast and increase its entry into the plant when coated with CDs. These results indicate that CDs obtained by hydrothermal synthesis are suitable for dsRNA foliar delivery in RNAi plant applications.
Comparison of Cytotoxic, Genotoxic, and DNA-Protective Effects of Skyrin on Cancerous vs. Non-Cancerous Human Cells
Authors: Zajičková Terézia , Horváthová Eva , Kyzek Stanislav , Šályová Eva , Túryová Eva , Ševčovičová Andrea , Gálová Eliška
Published: May 2022

Secondary metabolites as a potential source of anticancer therapeutics have been the subject of many studies. Since hypericin, a metabolite isolated from Hypericum perforatum L., shows several biomedical properties applicable in oncology, the aim of our study was to investigate its potential precursor skyrin in terms of genotoxic and DNA-protective effects. These skyrin effects were analyzed by cell-free methods, and cytotoxicity was estimated by an MTT assay and by a trypan blue exclusion test, while the genotoxic/antigenotoxic potential was examined by comet assay using non-cancerous human lymphocytes and the HepG2 cancer cell line. Skyrin did not show DNA-damaging effects but rather exhibited DNA-protectivity using a DNA-topology assay. However, we observed only weak antioxidant and chelating skyrin properties in other cell-free methods. Regarding the cytotoxic activity of skyrin, HepG2 cells were more prone to skyrin-induced death in comparison to human lymphocytes. Skyrin in non-cytotoxic concentrations did not exhibit elevated genotoxicity in both cell types. On the other hand, skyrin displayed moderate DNA-protective effects that were more noticeable in the case of non-cancerous human lymphocytes. The potential genotoxic effects of skyrin were not observed, and its DNA-protective capacity was more prominent in non-cancerous cells. Therefore, skyrin might be a promising agent used in anticancer therapy.
Overexpression of Sugarcane ScDIR Genes Enhances Drought Tolerance in Nicotiana benthamiana
Authors: Li Xiufang , Liu Zongling , Zhao Haiyun , Deng Xingli , Su Yizu , Li Ru , Chen Baoshan
Published: May 2022

Dirigent proteins (DIRs) are known to function in lignin biogenesis and to be involved in stress resistance in plants. However, the sugarcane DIRs have not been functionally characterized. In this study, we investigated the DIR−protein−encoding genes in Saccharum spp. (ScDIR) by screening collections of sugarcane databases, monitoring the responses of these genes to drought stress by real−time quantitative PCR, and identifying their heterologous expression in tobacco. Of the 64 ScDIRs identified, four belonging to the DIR−b/d (ScDIR5 and ScDIR11) and DIR−c (ScDIR7 and ScDIR40) subfamilies showed a significant transcriptional response when subjected to drought stress. ScDIR5, ScDIR7, and ScDIR11 are localized in the cell membrane, whereas ScDIR40 is found in the cell wall. The overexpression of these ScDIR genes in tobacco generally increased the drought tolerance of the transgenic lines, with ScDIR7 conferring the highest degree of drought tolerance. The characterization of the physiological and biochemical indicators (superoxide dismutase, catalase, malondialdehyde, and H2O2) confirmed that the ScDIR−overexpressing lines outperformed the wild type. These results demonstrated that specific ScDIRs in sugarcane respond and contribute to tolerance of drought stress, shedding light on potential means of improving drought tolerance in this crop.
CARS Imaging Advances Early Diagnosis of Cardiac Manifestation of Fabry Disease
Authors: Tolstik Elen , Ali Nairveen , Guo Shuxia , Ebersbach Paul , Möllmann Dorothe , Arias-Loza Paula , Dierks Johann , Schuler Irina , Freier Erik , Debus Jörg , Baba Hideo A. , Nordbeck Peter , Bocklitz Thomas , Lorenz Kristina
Published: May 2022

Vibrational spectroscopy can detect characteristic biomolecular signatures and thus has the potential to support diagnostics. Fabry disease (FD) is a lipid disorder disease that leads to accumulations of globotriaosylceramide in different organs, including the heart, which is particularly critical for the patient’s prognosis. Effective treatment options are available if initiated at early disease stages, but many patients are late- or under-diagnosed. Since Coherent anti-Stokes Raman (CARS) imaging has a high sensitivity for lipid/protein shifts, we applied CARS as a diagnostic tool to assess cardiac FD manifestation in an FD mouse model. CARS measurements combined with multivariate data analysis, including image preprocessing followed by image clustering and data-driven modeling, allowed for differentiation between FD and control groups. Indeed, CARS identified shifts of lipid/protein content between the two groups in cardiac tissue visually and by subsequent automated bioinformatic discrimination with a mean sensitivity of 90–96%. Of note, this genotype differentiation was successful at a very early time point during disease development when only kidneys are visibly affected by globotriaosylceramide depositions. Altogether, the sensitivity of CARS combined with multivariate analysis allows reliable diagnostic support of early FD organ manifestation and may thus improve diagnosis, prognosis, and possibly therapeutic monitoring of FD.
Plant Defense Responses to a Novel Plant Elicitor Candidate LY5-24-2
Authors: Qi Xin , Li Kun , Chen Lei , Zhang Yue , Zhang Nailou , Gao Wei , Li Yuedong , Liu Xingzhong , Fan Zhijin
Published: May 2022

Plant elicitors enhance plant defense against pathogen attacks by inducing systemic acquired resistance (SAR) with no or low direct fungicidal activity. Here we report the synthesis of a novel plant elicitor candidate LY5-24-2 [3,4-dichloro-N-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)isothiazole-5-carboxamide] and evaluation of its SAR inducing activity. Bioassays indicated that LY5-24-2 did not show significant anti-fungal activity but provided long-lasting resistance in Arabidopsis thaliana (A. thaliana) through promoting the accumulation of lignin, cellulose and pectin by 60.1%, 82.4% and 305.6%, respectively, at a concentration of 100 µM. LY5-24-2 also facilitated the closure of leaf stomata and increased the intracellular free Ca2+ by 47.8%, induced reactive oxygen species (ROS) accumulation, and inhibited the activity of ascorbate peroxidase (APX, EC 1.11.1.11) and catalase (CAT, EC 1.11.1.6) by 38.9% and 34.0%, respectively, as compared with the control at a concentration of 100 µM. LY5-24-2 induced SAR in plants and was dependent on the NPR1-mediated SA pathway by up-regulating expression of 2273 genes in A. thaliana. Meanwhile, LY5-24-2 also improved cucumber (Cucumis sativus L.) defense against Pseudoperonospora cubensis (P. cubensis) through promoting ROS accumulation and inhibiting activity of APX and CAT by 30.7% and 23.1%, respectively. Its expression of SA signaling genes CsNPR1, CsPR4 and CsPR5 was enhanced by 10.8, 5.8 and 6.6 times, respectively. These results demonstrated that LY5-24-2 is a novel elicitor candidate for plant protection via inducing SAR.
The Development of Hindlimb Postural Asymmetry Induced by Focal Traumatic Brain Injury Is Not Related to Serotonin 2A/C Receptor Expression in the Spinal Cord
Authors: Andersen Marlene Storm , Güler Dilârâ Bedriye , Larsen Jonas , Rich Karen Kalhøj , Svenningsen Åsa Fex , Zhang Mengliang
Published: May 2022

Brain injury and stroke are leading causes of adult disability. Motor deficits are common problems, and their underlying pathological mechanisms remain poorly understood. The serotoninergic system is implicated in both functional recovery from and the occurrence of spasticity after injuries to the central nervous system. This study, which was conducted on rats, investigated the development of limb postural changes and their relationship to the expression of serotonin (5-HT) 2A and 2C receptors in the spinal cord in the 4 weeks after focal traumatic brain injury (TBI) to the right hindlimb sensorimotor cortex. The limb motor deficits were assessed by measuring gait pattern changes during walking and hindlimb postural asymmetry at different time intervals (3–28 days) after surgery. The expressions of the 5-HT2A and 2C receptors in the lumbar spinal cord were investigated using immunohistochemistry. The results showed that all the rats with TBI, independently of the duration of the interval, displayed postural asymmetry with flexion on the contralateral (left) side (>2 mm), while the sham-operated rats showed no apparent postural asymmetry. The TBI rats also had longer stride lengths during walking in both their hindlimbs and their forelimbs compared with the sham rats. For both the TBI and the sham rats, the hind-paw placement angles were larger on the contralateral side in some of the groups. Compared to the sham-operated rats, the 5-HT2A and 2C receptor expression did not significantly change on either side of the lumbar spinal cords of the TBI rats in any of the groups. These results suggest that focal TBI can induce motor deficits lasting a relatively long time, and that these deficits are not related to the expression of the 5-HT2A and 2C receptors in the spinal cord.
Raman Spectroscopy of Oral Candida Species: Molecular-Scale Analyses, Chemometrics, and Barcode Identification
Authors: Pezzotti Giuseppe , Kobara Miyuki , Nakaya Tamaki , Imamura Hayata , Miyamoto Nao , Adachi Tetsuya , Yamamoto Toshiro , Kanamura Narisato , Ohgitani Eriko , Marin Elia , Zhu Wenliang , Nishimura Ichiro , Mazda Osam , Nakata Tetsuo , Makimura Koichi
Published: May 2022

Oral candidiasis, a common opportunistic infection of the oral cavity, is mainly caused by the following four Candida species (in decreasing incidence rate): Candida albicans, Candida glabrata, Candida tropicalis, and Candida krusei. This study offers in-depth Raman spectroscopy analyses of these species and proposes procedures for an accurate and rapid identification of oral yeast species. We first obtained average spectra for different Candida species and systematically analyzed them in order to decode structural differences among species at the molecular scale. Then, we searched for a statistical validation through a chemometric method based on principal component analysis (PCA). This method was found only partially capable to mechanistically distinguish among Candida species. We thus proposed a new Raman barcoding approach based on an algorithm that converts spectrally deconvoluted Raman sub-bands into barcodes. Barcode-assisted Raman analyses could enable on-site identification in nearly real-time, thus implementing preventive oral control, enabling prompt selection of the most effective drug, and increasing the probability to interrupt disease transmission.
Regulation and Role of Neuron-Derived Hemoglobin in the Mouse Hippocampus
Authors: Lu Yujiao , Wang Jing , Tang Fulei , Pratap Uday P. , Sareddy Gangadhara R. , Dhandapani Krishnan M. , Capuano Ana , Arvanitakis Zoe , Vadlamudi Ratna K. , Brann Darrell W.
Published: May 2022

Hemoglobin (Hb) is the oxygen transport protein in erythrocytes. In blood, Hb is a tetramer consisting of two Hb-alpha (Hb-α) chains and two Hb-beta (Hb-β) chains. A number of studies have also shown that Hb-α is also expressed in neurons in both the rodent and human brain. In the current study, we examined for age-related regulation of neuronal Hb-α and hypoxia in the hippocampus and cerebral cortex of intact male and female mice. In addition, to confirm the role and functions of neuronal Hb-α, we also utilized lentivirus CRISPR interference-based Hb-α knockdown (Hb-α CRISPRi KD) in the non-ischemic and ischemic mouse hippocampus and examined the effect on neuronal oxygenation, as well as induction of hypoxia-inducible factor-1α (HIF-1α) and its downstream pro-apoptotic factors, PUMA and NOXA, and on neuronal survival and neurodegeneration. The results of the study revealed an age-related decrease in neuronal Hb-α levels and correlated increase in hypoxia in the hippocampus and cortex of intact male and female mice. Sex differences were observed with males having higher neuronal Hb-α levels than females in all brain regions at all ages. In vivo Hb-α CRISPRi KD in the mouse hippocampus resulted in increased hypoxia and elevated levels of HIF-1α, PUMA and NOXA in the non-ischemic and ischemic mouse hippocampus, effects that were correlated with a significant decrease in neuronal survival and increased neurodegeneration. As a whole, these findings indicate that neuronal Hb-α decreases with age in mice and has an important role in regulating neuronal oxygenation and neuroprotection.
Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation
Authors: Yang Shaobin , Du Yaqin , Zhao Xiaoqian , Tang Qi , Su Wei , Hu Yuemeng , Yu Peng
Published: May 2022

Alzheimer’s disease (AD) is associated with the accumulation and aggregation of amyloid in the brain. The cation channel TRPV2 may mediate the pathological changes in mild cognitive impairment. A high-affinity agonist of TRPV2 named cannabidiol is one of the candidate drugs for AD. However, the molecular mechanism of cannabidiol via TRPV2 in AD remains unknown. The present study investigated whether cannabidiol enhances the phagocytosis and clearance of microglial Aβ via the TRPV2 channel. We used a human dataset, mouse primary neuron and microglia cultures, and AD model mice to evaluate TRPV2 expression and the ability of microglial amyloid-β phagocytosis in vivo and in vitro. The results revealed that TRPV2 expression was reduced in the cortex and hippocampus of AD model mice and AD patients. Cannabidiol enhanced microglial amyloid-β phagocytosis through TRPV2 activation, which increased the mRNA expression of the phagocytosis-related receptors, but knockdown of TRPV2 or Trem2 rescued the expression. TRPV2-mediated effects were also dependent on PDK1/Akt signaling, a pathway in which autophagy was indispensable. Furthermore, cannabidiol treatment successfully attenuated neuroinflammation while simultaneously improving mitochondrial function and ATP production via TRPV2 activation. Therefore, TRPV2 is proposed as a potential therapeutic target in AD, while CBD is a promising drug candidate for AD.
Ganglioside GM3 Synthase Deficiency in Mouse Models and Human Patients
Authors: Inamori Kei-ichiro , Inokuchi Jin-ichi
Published: May 2022

Gangliosides (glycosphingolipids containing one or more sialic acids) are highly expressed in neural tissues in vertebrates, and four species (GM1a, GD1a, GD1b, GT1b) are predominant in mammalian brains. GM3 is the precursor of each of these four species and is the major ganglioside in many nonneural tissues. GM3 synthase (GM3S), encoded by ST3GAL5 gene in humans, is a sialyltransferase responsible for synthesis of GM3 from its precursor, lactosylceramide. ST3GAL5 mutations cause an autosomal recessive form of severe infantile-onset neurological disease characterized by progressive microcephaly, intellectual disability, dyskinetic movements, blindness, deafness, intractable seizures, and pigment changes. Some of these clinical features are consistently present in patients with ST3GAL5 mutations, whereas others have variable expression. GM3S knockout (KO) mice have deafness and enhanced insulin sensitivity, but otherwise do not display the above-described neurological defects reported in ST3GAL5 patients. The authors present an overview of physiological functions and pathological aspects of gangliosides based on findings from studies of GM3S KO mice and discuss differential phenotypes of GM3S KO mice versus human GM3S-deficiency patients.
Hydroxyapatite-Integrated, Heparin- and Glycerol-Functionalized Chitosan-Based Injectable Hydrogels with Improved Mechanical and Proangiogenic Performance
Authors: Kocak Fatma Z. , Yar Muhammad , Rehman Ihtesham U.
Published: May 2022

The investigation of natural bioactive injectable composites to induce angiogenesis during bone regeneration has been a part of recent minimally invasive regenerative medicine strategies. Our previous study involved the development of in situ-forming injectable composite hydrogels (Chitosan/Hydroxyapatite/Heparin) for bone regeneration. These hydrogels offered facile rheology, injectability, and gelation at 37 °C, as well as promising pro-angiogenic abilities. In the current study, these hydrogels were modified using glycerol as an additive and a pre-sterile production strategy to enhance their mechanical strength. These modifications allowed a further pH increment during neutralisation with maintained solution homogeneity. The synergetic effect of the pH increment and further hydrogen bonding due to the added glycerol improved the strength of the hydrogels substantially. SEM analyses showed highly cross-linked hydrogels (from high-pH solutions) with a hierarchical interlocking pore morphology. Hydrogel solutions showed more elastic flow properties and incipient gelation times decreased to just 2 to 3 min at 37 °C. Toluidine blue assay and SEM analyses showed that heparin formed a coating at the top layer of the hydrogels which contributed anionic bioactive surface features. The chick chorioallantoic membrane (CAM) assay confirmed significant enhancement of angiogenesis with chitosan-matrixed hydrogels comprising hydroxyapatite and small quantities of heparin (33 µg/mL) compared to basic chitosan hydrogels.
Distinct Effects of Cannabidiol on Sphingolipid Metabolism in Subcutaneous and Visceral Adipose Tissues Derived from High-Fat-Diet-Fed Male Wistar Rats
Authors: Berk Klaudia , Konstantynowicz-Nowicka Karolina , Charytoniuk Tomasz , Harasim-Symbor Ewa , Chabowski Adrian
Published: May 2022

Available data suggest that cannabidiol (CBD) may ameliorate symptoms of insulin resistance by modulating the sphingolipid concentrations in particular organs. However, it is not entirely clear whether its beneficial actions also involve adipose tissues in a state of overnutrition. The aim of the study was to evaluate the effect of CBD on sphingolipid metabolism pathways and, as a result, on the development of insulin resistance in subcutaneous (SAT) and visceral (VAT) adipose tissues of an animal model of HFD-induced insulin resistance. Our experiment was performed on Wistar rats that were fed with a high-fat diet and/or received intraperitoneal CBD injections. We showed that CBD significantly lowered the ceramide content in VAT by reducing its de novo synthesis and increasing its catabolism. However, in SAT, CBD decreased the ceramide level through the inhibition of salvage and de novo synthesis pathways. All of these changes restored adipose tissues’ sensitivity to insulin. Our study showed that CBD sensitized adipose tissue to insulin by influencing the metabolism of sphingolipids under the conditions of increased availability of fatty acids in the diet. Therefore, we believe that CBD use may be considered as a potential therapeutic strategy for treating or reducing insulin resistance, T2DM, and metabolic syndrome.
Introducing Newborn Screening for Severe Combined Immunodeficiency—The New Zealand Experience
Authors: Heather Natasha , de Hora Mark , Brothers Shannon , Grainger Pippa , Knoll Detlef , Webster Dianne
Published: May 2022

Screening for severe combined immunodeficiency (SCID) was added to the New Zealand national newborn screening programme in December 2017. Documentation pertaining to the application to add SCID to the panel and screening results over the first three years were reviewed. Screening evaluation metrics were shown to differ according to site of collection (babies in a neonatal intensive care unit vs. the community), definition of a positive test (out-of-range result vs. result leading to a further action on baby), and screening target/case definition (primary SCID vs. non-SCID T-cell lymphopenia). Our experience demonstrates both the value of close clinical involvement during the implementation phase of SCID screening and that the use of standard definitions will facilitate international comparison.
Improving English-to-Indian Language Neural Machine Translation Systems
Authors: Kandimalla Akshara , Lohar Pintu , Maji Souvik Kumar , Way Andy
Published: May 2022

Most Indian languages lack sufficient parallel data for Machine Translation (MT) training. In this study, we build English-to-Indian language Neural Machine Translation (NMT) systems using the state-of-the-art transformer architecture. In addition, we investigate the utility of back-translation and its effect on system performance. Our experimental evaluation reveals that the back-translation method helps to improve the BLEU scores for both English-to-Hindi and English-to-Bengali NMT systems. We also observe that back-translation is more useful in improving the quality of weaker baseline MT systems. In addition, we perform a manual evaluation of the translation outputs and observe that the BLEU metric cannot always analyse the MT quality as well as humans. Our analysis shows that MT outputs for the English–Bengali pair are actually better than that evaluated by BLEU metric.
Global Translation of Classification Models
Authors: Al-Merri Mohammad , Ben Miled Zina
Published: May 2022

The widespread and growing usage of machine learning models, particularly for critical areas such as law, predicate the need for global interpretability. Models that cannot be audited are vulnerable to biases inherited from the datasets that were used to develop them. Moreover, locally interpretable models are vulnerable to adversarial attacks. To address this issue, the present paper proposes a new methodology that can translate any existing machine learning model into a globally interpretable one. MTRE-PAN is a hybrid SVM-decision tree architecture that leverages the interpretability of linear hyperplanes by creating a set of polygons that delimit the decision boundaries of the target model. Moreover, the present paper introduces two new metrics: certain and boundary model parities. These metrics can be used to accurately evaluate the performance of the interpretable model near the decision boundaries. These metrics are used to compare MTRE-PAN to a previously proposed interpretable architecture called TRE-PAN. As in the case of TRE-PAN, MTRE-PAN aims at providing global interpretability. The comparisons are performed over target models developed using three benchmark datasets: Abalone, Census and Diabetes data. The results show that MTRE-PAN generates interpretable models that have a lower number of leaves and a higher agreement with the target models, especially around the most important regions in the feature space, namely the decision boundaries.
The C2G Framework to Convert Infrastructure Data from Computer-Aided Design (CAD) to Geographic Information Systems (GIS)
Authors: Badhrudeen Mohamed , Boria Eric Sergio , Fonteix Guillemette , Siciliano Michael D. , Derrible Sybil
Published: May 2022

Making smart and informed decisions often requires the integration and analysis of large amounts of data. However, integrating these data is rarely straightforward, mainly because of heterogeneities in data structure and format. In this study, we focus on two widely used data formats by municipalities to store digital maps of their infrastructure: Computer-Aided Design (CAD) and Geographic Information Systems (GIS). While most municipalities still maintain infrastructure data in CAD format, many have started converting them to GIS since GIS includes geographical coordinates. However, the inherent differences between these two formats pose challenges to accurately converting information from CAD to GIS. The main goal of this study is to develop a procedure to help municipalities to perform CAD-to-GIS conversion. To that end, potential problems in CAD-to-GIS conversion were first identified through interviews with practitioners at different U.S. municipalities and through a literature review. Taken together, we propose the C2G framework to streamline the conversion process while minimizing information loss. The framework consists of five stages, and the execution of this framework and tasks involved in each stage are explained. Moreover, we apply the framework to real-world underground stormwater infrastructure data obtained from the University of Illinois at Chicago (UIC) to illustrate the framework’s applicability. The case study explains details about the technical difficulties we encountered in the process and provides recommendations to circumvent those difficulties. The results from the case study showed that the C2G framework was able to successfully convert CAD data to GIS data. Although the framework is developed specific to the needs of CAD/GIS practitioners in the US municipalities, it can be adopted in most CAD-to-GIS conversion situations. The information learned during the interviews supports the need for a standard CAD-to-GIS conversion process. The contribution of this study is to fill this gap by developing a generalized framework to carry out CAD-to-GIS conversion which only requires basic knowledge of CAD and GIS.
Antibiotic Administration within Two Days after Successful Endoscopic Retrograde Cholangiopancreatography Is Sufficient for Mild and Moderate Acute Cholangitis
Authors: Masuda Sakue , Koizumi Kazuya , Makazu Makomo , Uojima Haruki , Kubota Jun , Kimura Karen , Nishino Takashi , Sumida Chihiro , Ichita Chikamasa , Sasaki Akiko , Shionoya Kento
Published: May 2022

To prevent the increase of resistant bacteria, it is important to minimize the use of antimicrobial agents. Studies have found that administration for ≤3 days after successful endoscopic retrograde cholangiopancreatography (ERCP) is appropriate. Therefore, the present study aimed to verify if administration of antimicrobial agents can be further shortened to ≤2 days after ERCP. We divided 390 patients with mild and moderate cholangitis who underwent technically successful ERCP from January 2018 to June 2020 and had positive blood or bile cultures into two groups: antibiotic therapy within two days of ERCP (short-course therapy, SCT; n = 59, 15.1%), and for >3 days (long-course therapy, LCT; n = 331, 84.9%). The increased severity after admission and other outcomes were compared between the two groups, and the risk factors for increased severity were verified. There were no between-group differences in patient characteristics. Total length of hospital stay was shorter in SCT than in LCT, and other outcomes in SCT were not significantly different from those in LCT. Being 80 or older was a risk factor for increased severity; however, SCT was not associated with increased severity. Antimicrobial therapy for ≤2 days after successful ERCP is adequate in patients with mild and moderate acute cholangitis.
Dry Eye Parameters and Lid Geometry in Adults Born Extremely, Very, and Moderately Preterm with and without ROP: Results from the Gutenberg Prematurity Eye Study
Authors: Fieß Achim , Hufschmidt-Merizian Clara , Gißler Sandra , Hampel Ulrike , Mildenberger Eva , Urschitz Michael S. , Zepp Fred , Stoffelns Bernhard , Pfeiffer Norbert , Schuster Alexander K.
Published: May 2022

Background/Aims: This study aimed to analyze the effects of perinatal history on tear film properties and lid geometry in adults born preterm. Methods: The Gutenberg Prematurity Eye Study (GPES) is a German prospective examination of adults born preterm and term aged 18 to 52 years with Keratograph® 5M and Schirmer test I. Main outcome measures were first non-invasive tear film break-up time (F-NITBUT), bulbar redness (BR), Schirmer test, and nasal palpebral angle measurement. The associations with gestational age (GA), birth weight (BW), and BW percentile, retinopathy of prematurity (ROP), ROP treatment, and other perinatal factors were evaluated using regression analyses. Results: 489 eyes of 255 preterm and 277 eyes of 139 full-term individuals (aged 28.6 +/− 8.8 years, 220 females) were included. Of these, 33 participants (56 eyes) had a history of spontaneously regressed ROP and 9 participants (16 eyes) had a history of ROP treatment. After adjustment for age and sex, lower F-NITBUT (<20 s) was associated with ROP treatment (OR = 4.42; p = 0.025). Lower GA correlated with increased bulbar redness (B = −0.02; p = 0.011) and increased length of wetting in the Schirmer test (B = −0.69; p = 0.003). Furthermore, low GA was associated with narrowing of the nasal palpebral angle (B = 0.22; p = 0.011) adjusted for age and sex, but not when considering ROP in the multivariable model. Conclusion: Our analyses indicate that perinatal history affects ocular surface properties, tear production and lid geometry in adults born term and preterm. This might indicate that affected persons have a predisposition to diseases of the corneal surface such as the dry eye disease.
Implementing and Evaluating the Impact of BoneRx: A Healthy Bone Prescription for Men with Prostate Cancer Initiating Androgen Deprivation Therapy
Authors: Jones Jennifer M. , Tsang Derek S. , Zheng Shiyu , Yeheskel Ariel , Catton Charles N. , Cheung Angela M. , Hamilton Robert , Alibhai Shabbir M. H.
Published: May 2022

Background: The initiation of Androgen Deprivation Therapy (ADT) results in rapid and profound hypogonadism, resulting in significant bone and muscle loss, increasing the risk for osteoporosis (OP), falls, and fractures. Despite this, there exist very low rates of guideline adherent care regarding bone health in this population. We developed and implemented a healthy bone prescription tool entitled BoneRx to facilitate the uptake of guideline-concordant bone health care into practice and increase patient awareness and promote the uptake of health bone behaviours (HBBs). Methods: We conducted a cross-sectional pre-BoneRx implementation (n = 143) vs. post-implementation (n = 149) cohort study to evaluate the impact on (i) bone health care, patient engagement in HBB, and patient knowledge and health beliefs regarding OP. Results: There was a significant difference pre- vs. post BoneRx implementation on receipt of baseline BMD (34.7% vs. 59.5%, p < 0.0001) and bone health counselling (32.4% vs. 59.9%, p < 0.0001). More participants in the post-BoneRx implementation cohort reported taking vitamin D supplements 57% vs. 81% (p < 0.001) and calcium supplements 39% vs. 61% (p < 0.001). Physical activity levels also significantly increased (p = 0.021). No differences were detected in OP knowledge or feelings of OP susceptibility, seriousness, or health motivation. Conclusion: BoneRx is a simple, cost-effective, and acceptable strategy that could improve the care of PCa survivors receiving ADT.
Left Atrial Thrombus in Atrial Fibrillation/Flutter Patients in Relation to Anticoagulation Strategy: LATTEE Registry
Authors: Kapłon-Cieślicka Agnieszka , Gawałko Monika , Budnik Monika , Uziębło-Życzkowska Beata , Krzesiński Paweł , Starzyk Katarzyna , Gorczyca-Głowacka Iwona , Daniłowicz-Szymanowicz Ludmiła , Kaufmann Damian , Wójcik Maciej , Błaszczyk Robert , Hiczkiewicz Jarosław , Łojewska Katarzyna , Mizia-Stec Katarzyna , Wybraniec Maciej T , Kosmalska Katarzyna , Fijałkowski Marcin , Szymańska Anna , Dłużniewski Mirosław , Haberka Maciej , Kucio Michał , Michalski Błażej , Kupczyńska Karolina , Tomaszuk-Kazberuk Anna , Wilk-Śledziewska Katarzyna , Wachnicka-Truty Renata , Koziński Marek , Burchardt Paweł , Scisło Piotr , Piątkowski Radosław , Kochanowski Janusz , Opolski Grzegorz , Grabowski Marcin
Published: May 2022

Background: Atrial fibrillation (AF) and flutter (AFl) increase the risk of thromboembolism. The aim of the study was to assess the prevalence of left atrial thrombus (LAT) in AF/AFl in relation to oral anticoagulation (OAC). Methods: LATTEE (NCT03591627) was a multicenter, prospective, observational study enrolling consecutive patients with AF/AFl referred for transesophageal echocardiography before cardioversion or ablation. Results: Of 3109 patients enrolled, 88% were on chronic, 1.5% on transient OAC and 10% without OAC. Of patients on chronic OAC, 39% received rivaroxaban, 30% dabigatran, 14% apixaban and 18% vitamin K antagonists (VKA). Patients on apixaban were oldest, had the worst renal function and were highest in both bleeding and thromboembolic risk, and more often received reduced doses. Prevalence of LAT was 8.0% (7.3% on chronic OAC vs. 15% without OAC; p < 0.01). In patients on VKA, prevalence of LAT was doubled compared to patients on non-VKA-OACs (NOACs) (13% vs. 6.0%; p < 0.01), even after propensity score weighting (13% vs. 7.5%; p < 0.01). Prevalence of LAT in patients on apixaban was higher (9.8%) than in those on rivaroxaban (5.7%) and dabigatran (4.7%; p < 0.01 for both comparisons), however, not after propensity score weighting. Conclusions: The prevalence of LAT in AF is non-negligible even on chronic OAC. The risk of LAT seems higher on VKA compared to NOAC, and similar between different NOACs.