bluuebunny/crossref_metadata_2025 huggingface dataset:
APOBEC SBS13 Mutational Signature—A Novel Predictor of Radioactive Iodine Refractory Papillary Thyroid Carcinoma
Authors: Siraj Sarah , Masoodi Tariq , Siraj Abdul K. , Azam Saud , Qadri Zeeshan , Parvathareddy Sandeep K. , Bu Rong , Siddiqui Khawar S. , Al-Sobhi Saif S. , AlDawish Mohammed , Al-Kuraya Khawla S.
Published: March 2022

Standard surgery followed by radioactive iodine (131I, RAI) therapy are not curative for 5–20% of papillary thyroid carcinoma (PTC) patients with RAI refractory disease. Early predictors indicating therapeutic response to RAI therapy in PTC are yet to be elucidated. Whole-exome sequencing was performed (at median depth 198x) on 66 RAI-refractory and 92 RAI-avid PTCs with patient-matched germline. RAI-refractory tumors were significantly associated with distinct aggressive clinicopathological features, including positive surgical margins (p = 0.016) and the presence of lymph node metastases at primary diagnosis (p = 0.012); higher nonsilent tumor mutation burden (p = 0.011); TERT promoter (TERTp) mutation (p < 0.0001); and the enrichment of the APOBEC-related single-base substitution (SBS) COSMIC mutational signatures 2 (p = 0.030) and 13 (p < 0.001). Notably, SBS13 (odds ratio [OR] 30.4, 95% confidence intervals [CI] 1.43–647.22) and TERTp mutation (OR 41.3, 95% CI 4.35–391.60) were revealed to be independent predictors of RAI refractoriness in PTC (p = 0.029 and 0.001, respectively). Although SBS13 and TERTp mutations alone highly predicted RAI refractoriness, when combined, they significantly increased the likelihood of predicting RAI refractoriness in PTC. This study highlights the APOBEC SBS13 mutational signature as a novel independent predictor of RAI refractoriness in a distinct subgroup of PTC.
Immune Landscape and an RBM38-Associated Immune Prognostic Model with Laboratory Verification in Malignant Melanoma
Authors: Liu Jinfang , Xu Jun , Luo Binlin , Tang Jian , Hou Zuoqiong , Zhu Zhechen , Zhu Lingjun , Yao Gang , Li Chujun
Published: March 2022

Background: Current studies have revealed that RNA-binding protein RBM38 is closely related to tumor development, while its role in malignant melanoma remains unclear. Therefore, this research aimed to investigate the function of RBM38 in melanoma and the prognosis of the disease. Methods: Functional experiments (CCK-8 assay, cell colony formation, transwell cell migration/invasion experiment, wound healing assay, nude mouse tumor formation, and immunohistochemical analysis) were applied to evaluate the role of RBM38 in malignant melanoma. Immune-associated differentially expressed genes (DEGs) on RBM38 related immune pathways were comprehensively analyzed based on RNA sequencing results. Results: We found that high expression of RBM38 promoted melanoma cell proliferation, invasion, and migration, and RBM38 was associated with immune infiltration. Then, a five-gene (A2M, NAMPT, LIF, EBI3, and ERAP1) model of RBM38-associated immune DEGs was constructed and validated. Our signature showed superior prognosis capacity compared with other melanoma prognostic signatures. Moreover, the risk score of our signature was connected with the infiltration of immune cells, immune-regulatory proteins, and immunophenoscore in melanoma. Conclusions: We constructed an immune prognosis model using RBM38-related immune DEGs that may help evaluate melanoma patient prognosis and immunotherapy modalities.
The Role of Catecholamines in Pathophysiological Liver Processes
Authors: Lelou Elise , Corlu Anne , Nesseler Nicolas , Rauch Claudine , Mallédant Yannick , Seguin Philippe , Aninat Caroline
Published: March 2022

Over the last few years, the number of research publications about the role of catecholamines (epinephrine, norepinephrine, and dopamine) in the development of liver diseases such as liver fibrosis, fatty liver diseases, or liver cancers is constantly increasing. However, the mechanisms involved in these effects are not well understood. In this review, we first recapitulate the way the liver is in contact with catecholamines and consider liver implications in their metabolism. A focus on the expression of the adrenergic and dopaminergic receptors by the liver cells is also discussed. Involvement of catecholamines in physiological (glucose metabolism, lipids metabolism, and liver regeneration) and pathophysiological (impact on drug-metabolizing enzymes expression, liver dysfunction during sepsis, fibrosis development, or liver fatty diseases and liver cancers) processes are then discussed. This review highlights the importance of understanding the mechanisms through which catecholamines influence liver functions in order to draw benefit from the adrenergic and dopaminergic antagonists currently marketed. Indeed, as these molecules are well-known drugs, their use as therapies or adjuvant treatments in several liver diseases could be facilitated.
The Emerging Significance of Histone Lysine Demethylases as Prognostic Markers and Therapeutic Targets in Head and Neck Cancers
Authors: Dorna Dawid , Paluszczak Jarosław
Published: March 2022

Epigenetic aberrations, associated with altered DNA methylation profiles and global changes in the level of histone modifications, are commonly detected in head and neck squamous cell carcinomas (HNSCC). Recently, histone lysine demethylases have been implicated in the pathogenesis of HNSCC and emerged as potential molecular targets. Histone lysine demethylases (KDMs) catalyze the removal of methyl groups from lysine residues in histones. By affecting the methylation of H3K4, H3K9, H3K27, or H3K36, these enzymes take part in transcriptional regulation, which may result in changes in the level of expression of tumor suppressor genes and protooncogenes. KDMs are involved in many biological processes, including cell cycle control, senescence, DNA damage response, and heterochromatin formation. They are also important regulators of pluripotency. The overexpression of most KDMs has been observed in HNSCC, and their inhibition affects cell proliferation, apoptosis, cell motility, invasiveness, and stemness. Of all KDMs, KDM1, KDM4, KDM5, and KDM6 proteins are currently regarded as the most promising prognostic and therapeutic targets in head and neck cancers. The aim of this review is to present up-to-date knowledge on the significance of histone lysine demethylases in head and neck carcinogenesis and to discuss the possibility of using them as prognostic markers and pharmacological targets in patients’ treatment.
Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease
Authors: Lim Jung Yeon , Lee Jung Eun , Park Soon A , Park Sang In , Yon Jung-Min , Park Jeong-Ah , Jeun Sin-Soo , Kim Seung Joon , Lee Hong Jun , Kim Sung Won , Yang Seung Ho
Published: March 2022

The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer’s disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electrophysiological features, and then evaluated the protective effect of hNTSCs against amyloid-β peptide (Aβ1–42) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aβ1–42 induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aβ1–42 exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aβ1–42. Silencing OPN via siRNA suppressed Aβ-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD.
DHEA Protects Human Cholangiocytes and Hepatocytes against Apoptosis and Oxidative Stress
Authors: Kilanczyk Ewa , Ruminkiewicz Dagmara , Banales Jesus M. , Milkiewicz Piotr , Milkiewicz Małgorzata
Published: March 2022

Primary biliary cholangitis (PBC) is a rare chronic cholestatic and immune-mediated liver disease of unknown aetiology that targets intrahepatic bile duct cells (cholangiocytes) and primarily affects postmenopausal women, when their estrogen levels sharply decrease. An impaired cholangiocyte response to estrogen characterizes the terminal stage of the disease, as this is when an inefficiency of cholangiocyte proliferation, in balancing the loss of intrahepatic bile ducts, is observed. Here, we report that the estrogen precursor dehydroepiandrosterone (DHEA) and its sulfate metabolites, DHEA-S and 17 β-estradiol, enhance the proliferation of cholangiocytes and hepatocytes in vitro. Flow cytometry analysis showed that DHEA and DHEA-S decreased glyco-chenodeoxycholic acid (GCDC)-driven apoptosis in cholangiocytes. Cell viability assay (MTT) indicated that ER-α, -β, and the G-protein-coupled estrogen receptor, are involved in the protection of DHEA against oxidative stress in cholangiocytes. Finally, immunoblot analysis showed an elevated level of steroid sulfatase and a reduced level of sulfotransferase 1E1 enzymes, involved in the desulfation/sulfation process of estrogens in cirrhotic PBC, and primary sclerosis cholangitis (PSC) liver tissues, another type of chronic cholestatic and immune-mediated liver disease. Taken together, these results suggest that DHEA can prevent the deleterious effects of certain potentially toxic bile acids and reactive oxygen species, delaying the onset of liver disease.
Tumor Cell Glycolysis—At the Crossroad of Epithelial–Mesenchymal Transition and Autophagy
Authors: Marcucci Fabrizio , Rumio Cristiano
Published: March 2022

Upregulation of glycolysis, induction of epithelial–mesenchymal transition (EMT) and macroautophagy (hereafter autophagy), are phenotypic changes that occur in tumor cells, in response to similar stimuli, either tumor cell-autonomous or from the tumor microenvironment. Available evidence, herein reviewed, suggests that glycolysis can play a causative role in the induction of EMT and autophagy in tumor cells. Thus, glycolysis has been shown to induce EMT and either induce or inhibit autophagy. Glycolysis-induced autophagy occurs both in the presence (glucose starvation) or absence (glucose sufficiency) of metabolic stress. In order to explain these, in part, contradictory experimental observations, we propose that in the presence of stimuli, tumor cells respond by upregulating glycolysis, which will then induce EMT and inhibit autophagy. In the presence of stimuli and glucose starvation, upregulated glycolysis leads to adenosine monophosphate-activated protein kinase (AMPK) activation and autophagy induction. In the presence of stimuli and glucose sufficiency, upregulated glycolytic enzymes (e.g., aldolase or glyceraldehyde 3-phosphate dehydrogenase) or decreased levels of glycolytic metabolites (e.g., dihydroxyacetone phosphate) may mimic a situation of metabolic stress (herein referred to as “pseudostarvation”), leading, directly or indirectly, to AMPK activation and autophagy induction. We also discuss possible mechanisms, whereby glycolysis can induce a mixed mesenchymal/autophagic phenotype in tumor cells. Subsequently, we address unresolved problems in this field and possible therapeutic consequences.
Mitochondrial Phenotypes in Genetically Diverse Neurodegenerative Diseases and Their Response to Mitofusin Activation
Authors: Dang Xiawei , Walton Emily K. , Zablocka Barbara , Baloh Robert H. , Shy Michael E. , Dorn Gerald W.
Published: March 2022

Mitochondrial fusion is essential to mitochondrial fitness and cellular health. Neurons of patients with genetic neurodegenerative diseases often exhibit mitochondrial fragmentation, reflecting an imbalance in mitochondrial fusion and fission (mitochondrial dysdynamism). Charcot–Marie–Tooth (CMT) disease type 2A is the prototypical disorder of impaired mitochondrial fusion caused by mutations in the fusion protein mitofusin (MFN)2. Yet, cultured CMT2A patient fibroblast mitochondria are often reported as morphologically normal. Metabolic stress might evoke pathological mitochondrial phenotypes in cultured patient fibroblasts, providing a platform for the pre-clinical individualized evaluation of investigational therapeutics. Here, substitution of galactose for glucose in culture media was used to redirect CMT2A patient fibroblasts (MFN2 T105M, R274W, H361Y, R364W) from glycolytic metabolism to mitochondrial oxidative phosphorylation, which provoked characteristic mitochondrial fragmentation and depolarization and induced a distinct transcriptional signature. Pharmacological MFN activation of metabolically reprogrammed fibroblasts partially reversed the mitochondrial abnormalities in CMT2A and CMT1 and a subset of Parkinson’s and Alzheimer’s disease patients, implicating addressable mitochondrial dysdynamism in these illnesses.
Long-Range Supramolecular Synthon Isomerism: Insight from a Case Study of Vinylic Tellurium Trihalides Cl(Ph)C=C(Ph)TeX3 (X = Cl, I)
Authors: Torubaev Yury V. , Samigullina Aida S.
Published: March 2022

A slight modification of the synthetic procedure resulted in a new (Cc) polymorph of vinylic tellurium-trichloride Z-Cl(Ph)C=C(Ph)TeCl3 (1, β-form) which is stabilized by Te⋯Cl chalcogen bonds, assembling its molecules into the zigzag chains. Such a packing motive is in contrast to the known (Pca21) polymorph of Z-Cl(Ph)C=C(Ph)TeCl3 (1, α-form, CCDC refcode: BESHOW), which is built upon Te⋯π(Ph) chalcogen bonded chains. We noted a similar case of [Te⋯halogen] vs. [Te⋯π(Ph)] supramolecular synthon polymorphism in its triiodide congener Z-Cl(Ph)C=CPh(TeI3) (2, α and β-polymorphic forms). Quantum chemical calculations of the intermolecular interaction and lattice energies for 1α–β and 2α–β supported the assumption that α is thermodynamic while β is a kinetic form. Kinetic forms 1β and 2β are isostructural (Cc), while the thermodynamic forms 1α (Pca21) and 2α (P21/c) are not and feature an unusual example of long-range supramolecular synthon module isomerism. In other words, 1α–2α pairs demonstrate very similarly to isostructural Te⋯πPh ChB stabilized chains, which are further packed differently relative to each other, following different angular geometry of type-I Cl⋯Cl and type-II I⋯I halogen bonding. These structural considerations are backed by quantum chemical calculations that support the proposed hierarchy of primary and secondary supramolecular synthons and the assignment of α and β as thermodynamic and kinetic forms, respectively.
Dynamic Potentiometry with an Ion-Selective Electrode: A Tool for Qualitative and Quantitative Analysis of Inorganic and Organic Cations
Authors: González-Franco José Antonio , Ruiz Alberto , Ortuño Joaquín Ángel
Published: March 2022

A study of the transient potential signals obtained with a cation-selective electrode based on an ion-exchanger was carried out for solutions of the following individual cations at different concentrations: H+, Li+, Na+, K+, Rb+, Mg2+, Ca2+, choline (Ch+), acetylcholine (AcCh+), and procaine (Pr+). Three different general types of transient signals were distinguished depending on the value of the selectivity coefficient of the corresponding ion. A principal component analysis (PCA) was performed on the signals, finding that the qualitative identification of the corresponding ion from the scores of two principal components is possible. The study was extended to the transient signals of solutions containing an analyte in the presence of an interfering ion. The PCA of the corresponding signal allows for the detection of the presence of interfering ions, thus avoiding biased results in the determination of the analyte. Moreover, the two principal components of the transient signals obtained for each of the ions at different concentrations allow for the construction of calibration graphs for the quantitative determination of the corresponding ion. All the transient signals obtained experimentally in this work can be reconstructed accurately from principal components and their corresponding scores.
A Review on the Use of Biochar Derived Carbon Quantum Dots Production for Sensing Applications
Authors: Lo Bello Giovanni , Bartoli Mattia , Giorcelli Mauro , Rovere Massimo , Tagliaferro Alberto
Published: March 2022

Since their discovery, carbon dots have attracted a great deal of interest for their perspective biological applications. Nevertheless, the quenching of carbon dots photoluminescence represents an interesting feature for quantitative analysis in very low concentration of many species. A particular approach for the production of carbon dots is the use of biochar, a carbonized biomass, as a precursor. In this work, we overview the main achievements accomplished by using biochar-derived carbon dots for detecting and quantifying inorganic and organic species. We also provide background knowledge of the main properties, production and purification routes of carbon dots.
Assessing over Time Performance of an eNose Composed of 16 Single-Type MOX Gas Sensors Applied to Classify Two Volatiles
Authors: Palacín Jordi , Clotet Eduard , Rubies Elena
Published: March 2022

This paper assesses the over time performance of a custom electronic nose (eNose) composed of an array of commercial low-cost and single-type miniature metal-oxide (MOX) semiconductor gas sensors. The eNose uses 16 BME680 versatile sensor devices, each including an embedded non-selective MOX gas sensor that was originally proposed to measure the total volatile organic compounds (TVOC) in the air. This custom eNose has been used previously to detect ethanol and acetone, obtaining initial promising classification results that worsened over time because of sensor drift. The current paper assesses the over time performance of different classification methods applied to process the information gathered from the eNose. The best classification results have been obtained when applying a linear discriminant analysis (LDA) to the normalized conductance of the sensing layer of the 16 MOX gas sensors available in the eNose. The LDA procedure by itself has reduced the influence of drift in the classification performance of this single-type eNose during an evaluation period of three months.
Incidence, Predictors and Outcomes of Noninvasive Ventilation Failure in Very Preterm Infants
Authors: Fernandez-Gonzalez Sara M. , Sucasas Alonso Andrea , Ogando Martinez Alicia , Avila-Alvarez Alejandro
Published: March 2022

Non-invasive ventilation (NIV) is now considered the first-line treatment for respiratory distress syndrome in preterm infants. We aimed to evaluate the rates of non-invasive ventilation failure rate in very preterm infants, as well as to identify its predictors and associated outcomes. We designed a single-center retrospective cohort study including infants ≤32 weeks gestational age and ≤1500 g. The NIV failure was defined as the need for intubation at <72 h of life. After applying inclusion and exclusion criteria, 154 patients were included in the study, with a mean GA of 29.7 ± two weeks. The NIV failure rate was 16.2% (n = 25) and it was associated with lower bronchopulmonary dysplasia (BPD)-free survival (OR 0.08; 95% CI 0.02–0.32) and higher incidence of intraventricular hemorrhage > II (OR 6.22; 95% CI 1.36–28.3). These infants were significantly smaller in GA and weight. Higher FiO2 during resuscitation (OR 1.14; 95% CI 1.06–1.22) and after surfactant administration (OR 1.17; 95% CI 1.05–1.31) represented independent risk factors for NIV failure. In conclusion, NIV failure is frequent and it could be predicted by a higher oxygen requirement during resuscitation and a modest response to surfactant therapy. Importantly, this NIV failure is associated with worse clinical outcomes.
Internet Gaming Disorder in Children and Adolescents with Attention Deficit Hyperactivity Disorder
Authors: Berloffa Stefano , Salvati Andrea , D’Acunto Giulia , Fantozzi Pamela , Inguaggiato Emanuela , Lenzi Francesca , Milone Annarita , Muratori Pietro , Pfanner Chiara , Ricci Federica , Ruglioni Laura , Tacchi Annalisa , Tessa Chiara , Villafranca Arianna , Masi Gabriele
Published: March 2022

Although Attention Deficit Hyperactivity Disorder (ADHD) has been related to an increased risk for behavioral addictions, the relationship between ADHD and Internet Gaming Disorder (IGD) is still debated. The aim of this study is to address this topic by exploring the prevalence of IGD in a consecutive sample of ADHD youth, compared to a normal control group, and by assessing selected psychopathological and cognitive features in ADHD patients with and without IGD. One hundred and eight patients with ADHD (mean age 11.7 ± 2.6 years, 96 males) and 147 normal controls (NC) (mean age 13.9 ± 3.0 years, 114 males) were included in the study and received structured measures for IGD. In the ADHD group, 44% of the sample were above the IGD cut-off, compared to 9.5% in the NC group. ADHD patients with IGD presented with greater severity and impairment, more severe ADHD symptomatology, more internalizing symptoms, particularly withdrawal/depression and socialization problems, and more prominence of addiction and evasion dimensions. A binary logistic regression showed that the degree of inattention presented a greater weight in determining IGD. These findings may be helpful for identifying, among ADHD patients, those at higher risk for developing a superimposed IGD.
Correlation between Language Development and Motor Skills, Physical Activity, and Leisure Time Behaviour in Preschool-Aged Children
Authors: Mulé Daniela , Jeger Ilka , Dötsch Jörg , Breido Florian , Ferrari Nina , Joisten Christine
Published: March 2022

Sedentary behaviour has a negative impact on children’s physical and mental health. However, limited data are available on language development. Therefore, this pilot study aimed to analyse the associations between language development and possible predictors such as motor skills and leisure time behaviour in preschool-aged children. Methods: In this cross-sectional analysis, motor skills and speech development status were assessed in 49 healthy preschool children. Physical activity and screen time were assessed via a parental questionnaire. Results: On average, physical activity was 8.2 ± 6.5 h/week; mean screen time was 154.2 ± 136.2 min/week. A positive relationship between the results in the item ‘One-leg stand’ and ‘Phonological working memory for nonwords’ (β-coefficient −0.513; p < 0.001) resp. ‘Formation of morphological rules’ (β-coefficient −0.626; p = 0.004) was shown within backward stepwise regression. ‘Lateral jumping’, resp. ‘Sit and Reach’ were positively associated with ‘Understanding sentences’ (β-coefficient 0.519; p = 0.001 resp. β-coefficient 0.735; p = 0.002). ‘Physical inactivity’ correlated negatively with all language development subtests (each p < 0.05). Media consumption had a negative predictive effect on the subdomain ‘Understanding Sentences’ (β-coefficient −0.530, p = 0.003). Conclusions: An inactive lifestyle correlated negatively with selected subtests of language development in early childhood. These results should be verified in larger groups and longitudinally but support the need for early health promotion.
Differential Diagnosis of Cyclic Vomiting and Periodic Headaches in a Child with Ventriculoperitoneal Shunt: Case Report of Chronic Shunt Overdrainage
Authors: Mauritz Maximilian , Hasan Carola , Schreiber Lutz , Wegener-Panzer Andreas , Barth Sylvia , Zernikow Boris
Published: March 2022

Fourteen months after the implantation of a ventriculoperitoneal shunt catheter, a six-year-old boy developed recurrent, severe headaches and vomiting every three weeks. The attacks were of such severity that hospitalizations for analgesic and antiemetic therapies and intravenous rehydration and electrolyte substitution were repeatedly required. The patient was asymptomatic between the attacks. After an extensive diagnostic workup—including repeated magnetic resonance imaging (MRI) and neurosurgical examinations—common differential diagnoses, including shunt overdrainage, were ruled out. The patient was transferred to a specialized pediatric pain clinic with suspected cyclic vomiting syndrome (CVS). Despite intensive and in part experimental prophylactic and abortive pharmacological treatment, there was no improvement in his symptoms. Consecutive MRI studies reinvestigating the initially excluded shunt overdrainage indicated an overdrainage syndrome. Subsequently, the symptoms disappeared after disconnecting the shunt catheter. This case report shows that even if a patient meets CVS case definitions, other differential diagnoses must be carefully reconsidered to avoid fixation error.
hERG1 Potassium Channel Expression in Colorectal Adenomas: Comparison with Other Preneoplastic Lesions of the Gastrointestinal Tract
Authors: Lastraioli Elena , Iorio Jessica , Petrelli Federica , Tomezzoli Anna , Battista Serena , Ambrosio Maria Raffaella , Chiudinelli Mariella , De Salvatore Federica , Messerini Luca , Villanacci Vincenzo , Saragoni Luca , Arcangeli Annarosa
Published: March 2022

Preneoplastic lesions represent a useful target for early diagnosis and follow-up of gastrointestinal malignancies. hERG1 channel expression was tested by immunohistochemistry (IHC) in a cohort of colorectal adenoma samples belonging to Italian subjects. Overall, hERG1 was expressed in 56.5% of cases with both high staining intensity and a high percentage of positive cells. Moreover, hERG1 was expressed in a higher percentage of dysplastic adenomas with respect to hyperplastic lesions, and the proportion of positive samples further increased in patients with high-grade dysplasia. Comparing hERG1 expression in other preneoplastic lesions of the GI tract (gastric dysplasia and Barrett’s esophagus), it emerged that in all the conditions, hERG1 was expressed with a diffused pattern, throughout the cell, with variable staining intensity within the samples. The highest expression was detected in gastric dysplasia samples and the lowest in Barrett’s esophagus at similar levels observed in colorectal adenomas. Our results show that hERG1 is aberrantly expressed in human preneoplastic lesions of the gastrointestinal tract and has a different pattern of expression and role in the different sites. Overall, the detection of hERG1 expression in preneoplastic lesions could represent a novel diagnostic or prognostic marker of progression in the gastrointestinal tract.
Putative Mechanisms Underlying the Beneficial Effects of Polyphenols in Murine Models of Metabolic Disorders in Relation to Gut Microbiota
Authors: Niwano Yoshimi , Kohzaki Hidetsugu , Shirato Midori , Shishido Shunichi , Nakamura Keisuke
Published: March 2022

The beneficial effects of polyphenols on metabolic disorders have been extensively reported. The interaction of these compounds with the gut microbiota has been the focus of recent studies. In this review, we explored the fundamental mechanisms underlying the beneficial effects of polyphenols in relation to the gut microbiota in murine models of metabolic disorders. We analyzed the effects of polyphenols on three murine models of metabolic disorders, namely, models of a high-fat diet (HFD)-induced metabolic disorder, dextran sulfate sodium (DSS)-induced colitis, and a metabolic disorder not associated with HFD or DSS. Regardless of the model, polyphenols ameliorated the effects of metabolic disorders by alleviating intestinal oxidative stress, improving inflammatory status, and improving intestinal barrier function, as well as by modulating gut microbiota, for example, by increasing the abundance of short-chain fatty acid-producing bacteria. Consequently, polyphenols reduce circulating lipopolysaccharide levels, thereby improving inflammatory status and alleviating oxidative imbalance at the lesion sites. In conclusion, polyphenols likely act by regulating intestinal functions, including the gut microbiota, and may be a safe and suitable therapeutic agent for various metabolic disorders.
Potential Sea Level Rise Impacts in Acapulco Diamante, Mexico
Authors: Gómez-Villerías Ramiro Salvador , Tejeda-Martínez Adalberto , Conde Álvarez Ana Cecilia , Reyes Umaña Maximino , Rosas-Acevedo José Luis , Ruz Vargas Manuel Ignacio , Galán Castro Erick Alfonso
Published: March 2022

The potential impacts of sea level in the study region are presented using the Integrated Procedure for Estimate Sea Level Impacts (IPESLI), made up of Landsat images, official databases, and design software for geographic information systems. IPESLI is useful in areas with little georeferenced and validated information. The sea level projections are based on the climate projections, which incorporate the possible attenuation of the ice sheet near the upper end of Antarctica. Flood risk statistics were used to simulate the frequency of extreme flooding across the planet. The IPESLI was calibrated using seven field visits to compare the height values generated by the digital elevation model against the in situ data. The inundation maps generated in the study can be used to find the most vulnerable areas and initiate decision making for coastal adaptation. The IPESLI procedure has the potential to contribute to the formation of a communication bridge between climate change science and policy makers. The projection is profound for all scenarios, but it is particularly devastating for the Acapulco Diamante area if we start with the worst future climate scenario (SSP5-RCP8.5).
Local Potential Functional Embedding Theory: A Self-Consistent Flavor of Density Functional Theory for Lattices without Density Functionals
Authors: Sekaran Sajanthan , Saubanère Matthieu , Fromager Emmanuel
Published: March 2022

Quantum embedding is a divide and conquer strategy that aims at solving the electronic Schrödinger equation of sizeable molecules or extended systems. We establish in the present work a clearer and in-principle-exact connection between density matrix embedding theory (DMET) and density-functional theory (DFT) within the simple but nontrivial one-dimensional Hubbard model. For that purpose, we use our recent reformulation of single-impurity DMET as a Householder transformed density-matrix functional embedding theory (Ht-DMFET). On the basis of well-identified density-functional approximations, a self-consistent local potential functional embedding theory (LPFET) is formulated and implemented. Combining both LPFET and DMET numerical results with our formally exact density-functional embedding theory reveals that a single statically embedded impurity can in principle describe the density-driven Mott–Hubbard transition, provided that a complementary density-functional correlation potential (which is neglected in both DMET and LPFET) exhibits a derivative discontinuity (DD) at half filling. The extension of LPFET to multiple impurities (which would enable to circumvent the modeling of DDs) and its generalization to quantum chemical Hamiltonians are left for future work.
Mind Your Outcomes: The ΔQSD Paradigm for Quality-Centric Systems Development and Its Application to a Blockchain Case Study
Authors: Haeri Seyed , Thompson Peter , Davies Neil , Van Roy Peter , Hammond Kevin , Chapman James
Published: March 2022

This paper directly addresses a long-standing issue that affects the development of many complex distributed software systems: how to establish quickly, cheaply, and reliably whether they can deliver their intended performance before expending significant time, effort, and money on detailed design and implementation. We describe ΔQSD, a novel metrics-based and quality-centric paradigm that uses formalised outcome diagrams to explore the performance consequences of design decisions, as a performance blueprint of the system. The distinctive feature of outcome diagrams is that they capture the essential observational properties of the system, independent of the details of system structure and behaviour. The ΔQSD paradigm derives bounds on performance expressed as probability distributions encompassing all possible executions of the system. The ΔQSD paradigm is both effective and generic: it allows values from various sources to be combined in a rigorous way so that approximate results can be obtained quickly and subsequently refined. ΔQSD has been successfully used by a small team in Predictable Network Solutions for consultancy on large-scale applications in a number of industries, including telecommunications, avionics, and space and defence, resulting in cumulative savings worth billions of US dollars. The paper outlines the ΔQSD paradigm, describes its formal underpinnings, and illustrates its use via a topical real-world example taken from the blockchain/cryptocurrency domain. ΔQSD has supported the development of an industry-leading proof-of-stake blockchain implementation that reliably and consistently delivers blocks of up to 80 kB every 20 s on average across a globally distributed network of collaborating block-producing nodes operating on the public internet.
Representation Learning for EEG-Based Biometrics Using Hilbert–Huang Transform
Authors: Svetlakov Mikhail , Kovalev Ilya , Konev Anton , Kostyuchenko Evgeny , Mitsel Artur
Published: March 2022

A promising approach to overcome the various shortcomings of password systems is the use of biometric authentication, in particular the use of electroencephalogram (EEG) data. In this paper, we propose a subject-independent learning method for EEG-based biometrics using Hilbert spectrograms of the data. The proposed neural network architecture treats the spectrogram as a collection of one-dimensional series and applies one-dimensional dilated convolutions over them, and a multi-similarity loss was used as the loss function for subject-independent learning. The architecture was tested on the publicly available PhysioNet EEG Motor Movement/Imagery Dataset (PEEGMIMDB) with a 14.63% Equal Error Rate (EER) achieved. The proposed approach’s main advantages are subject independence and suitability for interpretation via created spectrograms and the integrated gradients method.
Occurrence of Allergens in Cosmetics for Sensitive Skin
Authors: Martins Márcia S. , Ferreira Marta S. , Almeida Isabel F. , Sousa Emília
Published: March 2022

Sensitive skin is characterized by symptoms such as stinging and tingling in response to stimuli that usually do not cause unpleasant sensations. Epidemiological studies show that individuals with sensitive skin are more prone to developing skin allergies, although the link between both conditions is unknown. Aiming to evaluate the presence of allergens in facial-skin products for sensitive skin, a pool of 88 cosmetic products from international brands marketed in pharmacies and parapharmacies was analyzed. A list of allergens identified in product labels was compiled and grouped according to their function. Fragrances were the most common allergens, followed by skin-conditioning agents, surfactants, and preservatives. Fragrances presenting the highest use percentages were linalool, benzyl alcohol, geraniol, and citronellol. Overall, the majority of cosmetic formulations were absent of fragrance allergens, being present only in 7% of products. Other allergens were found in most products (95%). This finding should be interpreted with caution, since many of these compounds are rare sensitizers and studies demonstrating their risk for individuals with sensitive skin are lacking. With this study, useful information for health professionals is provided to support their advice and to help consumers choosing cosmetic products.
Storage Effect on Phenolic Compounds and Antioxidant Activity of Nephelium lappaceum L. Extract
Authors: Thitilertdecha Nont
Published: March 2022

Preparation of potential antioxidant extracts with less process for storing in a long period is preferable. N. lappaceum rind, well known as a promising source of phenolic antioxidants agricultural residue, was employed to prepare crude extracts by different solvents. The phenolic content, flavonoid content, antioxidant, and anti-tyrosinase activities of the extracts were evaluated. The stability of the potential extract was then assessed for phenolic content and antioxidant activity under various storage conditions. The extractive yields of crude phenolic extract ranged from 16.61 to 28.78%. The ethanolic extract of N. lappaceum rind exhibited potential antioxidant activities and contained a high amount of phenolics and flavonoid contents. The extract remained with a high amount of the phenolic content (up to 88.79%) and retained its antioxidant property under various temperatures (4, 25, and 45 °C) after the first week of the storage period. The results suggest that phenolic content and antioxidant activity of N. lappaceum rind extract, as a nutraceutical or anti-aging ingredients in cosmetics, could be stored at a temperature from 4 °C to 45 °C with or without oxygen exposure at least for 16 weeks.
Nonself Mutations in the Spike Protein Suggest an Increase in the Antigenicity and a Decrease in the Virulence of the Omicron Variant of SARS-CoV-2
Authors: Otaki Joji M. , Nakasone Wataru , Nakamura Morikazu
Published: March 2022

Despite extensive worldwide vaccination, the current COVID-19 pandemic caused by SARS-CoV-2 continues. The Omicron variant is a recently emerged variant of concern and is now overtaking the Delta variant. To characterize the potential antigenicity of the Omicron variant, we examined the distributions of SARS-CoV-2 nonself mutations (in reference to the human proteome) as five amino acid stretches of short constituent sequences (SCSs) in the Omicron and Delta proteomes. The number of nonself SCSs did not differ much throughout the Omicron, Delta, and reference sequence (RefSeq) proteomes but markedly increased in the receptor binding domain (RBD) of the Omicron spike protein compared to those of the Delta and RefSeq proteins. In contrast, the number of nonself SCSs decreased in non-RBD regions in the Omicron spike protein, compensating for the increase in the RBD. Several nonself SCSs were tandemly present in the RBD of the Omicron spike protein, likely as a result of selection for higher binding affinity to the ACE2 receptor (and, hence, higher infectivity and transmissibility) at the expense of increased antigenicity. Taken together, the present results suggest that the Omicron variant has evolved to have higher antigenicity and less virulence in humans despite increased infectivity and transmissibility.
On the IND-CCA1 Security of FHE Schemes
Authors: Fauzi Prastudy , Hovd Martha Norberg , Raddum Håvard
Published: March 2022

Fully homomorphic encryption (FHE) is a powerful tool in cryptography that allows one to perform arbitrary computations on encrypted material without having to decrypt it first. There are numerous FHE schemes, all of which are expanded from somewhat homomorphic encryption (SHE) schemes, and some of which are considered viable in practice. However, while these FHE schemes are semantically (IND-CPA) secure, the question of their IND-CCA1 security is much less studied, and we therefore provide an overview of the IND-CCA1 security of all acknowledged FHE schemes in this paper. To give this overview, we grouped the SHE schemes into broad categories based on their similarities and underlying hardness problems. For each category, we show that the SHE schemes are susceptible to either known adaptive key recovery attacks, a natural extension of known attacks, or our proposed attacks. Finally, we discuss the known techniques to achieve IND-CCA1-secure FHE and SHE schemes. We concluded that none of the proposed schemes were IND-CCA1-secure and that the known general constructions all had their shortcomings.
Green Synthesis of Silver Nanoparticles Using Juniperus procera Extract: Their Characterization, and Biological Activity
Authors: Khan Merajuddin , Karuppiah Ponmurugan , Alkhathlan Hamad Z. , Kuniyil Mufsir , Khan Mujeeb , Adil Syed Farooq , Shaik Mohammed Rafi
Published: March 2022

Plant extract-based green synthesis of metal nanoparticles (NPs) has become a popular approach in the field of nanotechnology. In this present investigation, silver nanoparticles were prepared by an efficient and facile approach using Juniperus procera extract as a bioreducing and stabilizing agent. The as-synthesized silver nanoparticles (JP-AgNPs) were characterized by several characterization techniques such as UV–Vis, XRD, FT-IR, HR-TEM, and EDX analysis. The XRD analysis evidently confirms that the as-synthesized Ag nanoparticles (NPs) from Juniperus procera plant extract (JP-AgNPs) are crystalline in nature. FT-IR analysis confirms that the plant extract plays a dual role as a bioreducing and capping agent, while HR-TEM revealed the spherical morphology of as-synthesized JP-AgNPs with the size of ~23 nm. Furthermore, the synthesized JP-AgNPs were evaluated for antibacterial properties against several bacterial and fungal strains such as Staphylococcus aureus (ATCC 12228), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Proteus mirabilis (ATCC 4753), Cryptococcus neoformans (ATCC 16620), and Candida albicans (ATCC 885-653). The JP-AgNPs displayed an efficient mean zone of inhibition (MZI) at 50.00 µL for bacterial associated with fungal pathogens than the plant extract. Mainly, MZI values against microbial pathogens were as follows; E. coli (17.17 ± 0.72 mm), P. mirabilis (14.80 ± 0.17 mm), and C. albicans (14.30 ± 0.60 mm), whereas JP-AgNPs showed moderate activity against P. aeruginosa (11.50 ± 0.29 mm) and C. neoformans (9.83 ± 0.44 mm). Notably, the tested JP-AgNPs have displayed almost similar antimicrobial activities with that of standard antimicrobial drugs, such as streptomycin and nystatin. The enhanced antimicrobial activity of JP-AgNPs can be ascribed to the quality of resultant NPs including, uniform size, shape, and aqueous colloidal stability of nanoparticles.
Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration’s RWE Data Working Group
Authors: Dai Wei , de Oliveira Claire , Blommaert Scott , Pataky Reka , Tran David , Aurangzeb Zeb , Kendell Cynthia , Folkins Chris , Somayaji Chandy , Dowden Jeff , Cheung Winson , Strumpf Erin , Beca Jaclyn , McClure Carol , Urquhart Robin , McDonald James , Alvi Riaz , Turner Donna , Peacock Stuart , Denburg Avram , Mercer Rebecca , Muñoz Caroline , Parmar Ambica , Tadrous Mina , Takhar Pam , Chan Kelvin ,   on behalf of the CanREValue Collaboration
Published: March 2022

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8–11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration’s Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.
Not All Canadian Cancer Patients Are Equal—Disparities in Public Cancer Drug Funding across Canada
Authors: MacPhail Ceilidh , Snow Stephanie
Published: March 2022

Canada lacks a national drug insurance plan. The home province or territory of a patient determines which cancer drugs are available on the public formulary, who is eligible for public coverage and what portion of the financial burden of cancer care falls to the individual. This narrative review describes the current interprovincial disparities in access to cancer drugs across Canada. Health technology assessment (HTA) of drugs at a provincial and territory level is a closed process, does not necessarily follow the recommendations of national HTA and leads to further delays in drug access. The public coverage of take-home cancer drugs (THCDs) in Ontario and the Atlantic provinces is often fragmented, unnecessarily complex and a barrier to cancer drug access. Policy solutions to address inter-provincial formulary variation and poor access to THCDs are discussed.
Evaluation of Patient-Reported Outcome Differences by Radiotherapy Techniques for Bone Metastases in A Population-Based Healthcare System
Authors: Olson Robert A. , LaPointe Vincent , Benny Alex , Chan Matthew , Lefresne Shilo , McKenzie Michael
Published: March 2022

We assessed whether advanced RT techniques were associated with differences in patient-reported outcomes (PROs). Patients with bone metastases who completed the brief pain inventory (BPI) before and after RT were identified, and RT technique was categorized as simple (e.g., parallel opposed pair) or advanced (e.g., 3D-conformal RT (3DCRT), intensity-modulated RT (IMRT), or stereotactic ablative RT (SABR)). Pain response and patient-reported interference on quality of life secondary to pain was compared. A total of 1712 patients completed the BPI. From 2017–2021, the rate of advanced RT technique increased significantly (p < 0.001; 2.4%, 2.4%, 9.7%, 5.5%, 9.3%), with most advanced techniques consisting of IMRT, and only 7% of advanced techniques were SABR. Comparing simple vs. advanced technique, neither the complete pain response (12.3% vs. 11.4%; p = 0.99) nor the partial pain response (50.0% vs. 51.8%; p = 0.42) was significantly different. There was no significant patient-reported difference in pain interfering with general activity, mood, walking ability, normal work, relationships, sleep, or enjoyment of life. Given that there is increasing utilization of advanced RT techniques, there is further need for randomized trials to assess their benefits given the increased cost and inconvenience to patients.