bluuebunny/crossref_metadata_2025 huggingface dataset:
Eruption Pattern of Permanent Canines and Premolars in Polish Children
Authors: Cieślińska Katarzyna , Zaborowicz Katarzyna , Buchwald Zuzanna , Biedziak Barbara
Published: July 2022

Eruption is a complex and dynamic process determined by both genetic and epigenetic factors. This process involves a number of changes in the tissues surrounding the tooth and in tooth morphology. The aim of this study was to analyze the eruption sequence of permanent canines and premolars on the basis of pantomographic images. The study material consisted of 300 digital pantomographic images of children in the developmental period. The study group consisted of 165 boys and 135 girls. Images of patients of Polish nationality, aged 6–10 years, without diagnosed systemic diseases and local disorders were used in the study. Results: The study has shown that the most common pattern of tooth eruption in the lateral zones is type A positioning of the lateral teeth, which is 4-5-3. This pattern is characteristic of both girls and boys. This pattern also occurs most frequently in the maxilla in both boys and girls. In the mandible, on the contrary, two patterns of lateral tooth eruption were predominant. In girls, types A and E/4-5-3 and 3-4-5/occurred in the mandible, while in boys, types A and C/4-5-3 and 5-4-3/were observed in the mandible. The process of tooth eruption is a recognized measure of a child’s physical development, and pantomographic images are an effective and common diagnostic tool.
Work–Life Balance and Teleworking: Lessons Learned during the Pandemic on Gender Role Transformation and Self-Reported Well-Being
Authors: González Ramos Ana M. , García-de-Diego José María
Published: July 2022

Lockdown during COVID-19 forced the emergence of a new scenario, with men and women teleworkers spending all their time at home. The purpose of this study is to address whether this situation has triggered a transformation in gender roles and self-reported well-being, comparing the responses of male and female respondents to the EUROFOUND April to July 2020 survey. The analysis addresses cultural differences across European regions related to diverse gender regimes, employment status, and the possibility of teleworking. It explores male and female well-being through life satisfaction, the distance between happiness and life satisfaction, and rates their feelings about work–life balance. Findings on life satisfaction display a low transformation of social roles, with women still worrying about work–life balance, while men were more affected by the health crisis. Men self-report high life satisfaction across Europe compared to women, although unexpectedly, female freelancers in Northern and Southern European had a higher life satisfaction ratio than men. Both men and women teleworkers reported difficulties with managing work–life balance at home, despite women handling core care and household tasks. These findings suggest that women would have received more support from men, as they worked harder and longer hours during the lockdown, despite their weak position in the labor market. This would seem to be a propitious setting for men to have assumed more responsibility at home, resulting in a more equal distribution of roles at home.
Multi-Level System to Assess Toxicity in Water Distribution Plants
Authors: Magara Gabriele , Varello Katia , Pastorino Paolo , Francese Danila Raffaella , Arsieni Paola , Pezzolato Marzia , Masoero Loretta , Messana Erika , Caldaroni Barbara , Abete Maria Cesarina , Pederiva Sabina , Squadrone Stefania , Elia Antonia Concetta , Prearo Marino , Bozzetta Elena
Published: July 2022

The toxicity of water samples from water distribution plants needs to be investigated further. Indeed, studies on the pro-oxidant effects driven by tap water are very limited. In this study, the water quality, pro-oxidant effects, and potential health risks driven by exposure to groundwater samples from two water plants (sites A and B) located in Northwestern Italy were investigated in a multi-level system. Physicochemical parameters and the absence of pathogens, cyanotoxins, and endocrine active substances indicated a good water quality for both sites. The 25 metals analyzed were found under the limit of quantification or compliant with the maximum limits set by national legislation. Water samples were concentrated by the solid-phase extraction system in order to assess the aquatic toxicity on Epithelioma papulosum cyprini (EPC) cell line. Levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase were evaluated through the Integrated Biomarkers Response (IBRv2) index. EPC cell line was found a sensible model for assessing the antioxidant responses driven by both water concentrates. A similar antioxidant response was shown by plots and IBRv2 suggesting a muted risk for the two sampling sites.
Mental Health Problems and Associated Factors among High School Students in Shandong Province of China: A Cross-Sectional Study
Authors: Xiu Xiaolei , Qian Qing , Wu Sizhu
Published: July 2022

Background: Although many studies have analyzed the mental health problems (MHP) of Chinese adolescents, the associations of Chinese high school students’ MHP with personal and family circumstances, parents’ educational level, physical activity, and school adaptation are rarely discussed. Methods: The participants were 9398 students who were randomly recruited from 30 high schools in Shandong, China. Self-reported questionnaires were used to collect data. Multivariate logistic regression models were used to investigate associations between MHP and related factors. Results: The positive rate of MHP among high school students was 27.0%. Female, intimate friends of the opposite sex, poor family economic status, father’s educational level of primary school or below, low social competence, and high antisocial behavior were significantly associated with higher odds of having MHP (p < 0.05). Students’ self-reported odds of having obsessive–compulsive disorder, interpersonal sensitivity, and depression were inversely related to their mother’s educational level. Compared with students who did not exercise, students who engaged in more than 30 min of physical activity 5–6 times per week had 60% lower self-reported odds of depression. Conclusions: We recommend strengthening the prevention, early detection, and treatment of MHP in high school students, especially those whose parents have low educational attainment, inactivity, and high disruptive behaviors.
Effects of the COVID-19 Restrictions on Eating Behaviour and Eating Disorder Symptomology in Female Adolescents
Authors: Muth Lois , Leven Karl-Heinz , Moll Gunther , Kratz Oliver , Horndasch Stefanie
Published: July 2022

Confinement due to the COVID-19 pandemic imposes a burden on adolescents worldwide and may seriously impact patients with an eating disorder (ED). The current FRanconian Anorexia Nervosa during COVID-19 (FRANCO) study explored (1) perceived change of depressive and ED symptomology during lockdown, (2) the role of social media, and (3) coping strategies of anorexia nervosa (AN) patients and clinical as well as healthy comparison groups. From June 2021 to September 2021, 222 female adolescents (19 with AN, 20 with depression, 45 with a self-reported psychiatric disorder (SRPD), and 138 controls) aged 11.2 to 18.9 years completed a one-time anonymous survey retrospectively reporting back on ED and depressive symptomology before and during the pandemic, the impact of social media, and coping strategies. A reduced quality of life (QoL) due to confinement was observed in almost half of female adolescents. All groups reported a significant perceived increase of disordered eating, overeating, anxiety, and depressive symptoms and emotion-regulation problems. In AN patients, significantly higher percentual deterioration of disordered eating and anxiety and depressive symptoms was found. For controls, a younger age and higher susceptibility of the sociocultural body image significantly correlated with increased disordered eating. Large-scale media literacy interventions are recommended.
COVID-19 Pandemic Consequences among Individuals with Eating Disorders on a Clinical Sample in Poland—A Cross-Sectional Study
Authors: Kasiak Przemysław Seweryn , Adamczyk Natalia , Jodczyk Alicja Monika , Kaproń Aleksandra , Lisowska Anna , Mamcarz Artur , Śliż Daniel
Published: July 2022

The COVID-19 pandemic and imposed restrictions had negative consequences on overall health among many populations. This study aimed to investigate the influence of the pandemic on eating disorders (ED) and mental health (MH) of individuals with confirmed ED diagnoses. A survey consisting of questions related to (1) diagnosis of COVID-19, (2) changes in ED symptoms and onset of new symptoms, (3) psychological and MH aspects regarding to the pandemic, (4) lifestyle changes, and (5) social media (SM) usage was distributed between April–June 2021. One hundred and ninety-eight individuals met all of the inclusion criteria (nfemales = 195, 98.48%; nother gender = 3, 1.52%). Of the participants, 78.79% reported worsening of their ED symptoms, 42.93% of them noticed an onset of new ED symptoms, and 57.58% believed that the pandemic had a negative impact on their ED treatment. Negative changes due to the pandemic on MH were reported by 88.89%. Of the participants, 91.92% increased their time spent on SM and 54.04% of them declared that it had a negative impact on their MH. Medical professionals should consider results while providing comprehensive psychological care, which can be crucial information in the application of the appropriate treatment strategy.
Background Level of Unstable Chromosome Aberrations in the Kazakhstan Population: A Human Biomonitoring Study
Authors: Kenzhina Laura B. , Mamyrbayeva Aigul N. , Lukashenko Sergey N. , Baigazinov Zhanat A. , Biyakhmetova Dina B. , Panitskiy Andrey V. , Polivkina Elena , Zhamaldinov Fail F. , Patrono Clarice , Palma Valentina , Testa Antonella
Published: July 2022

Kazakhstan is known as a country with a complex radioecological situation resulting from different sources such as a natural radiation background, extensive activities of the industrial system of the former Soviet Union and a well-known testing of nuclear power weapons occurred in the Semipalatinsk Test Site (STS) area. The present study focuses on the assessment of the background of dicentric chromosomes in Kazakhstan’s population, which is the starting point in the dose assessment of irradiated people, since the baseline level of spontaneous dicentrics can vary significantly in different populations. In this context, aiming to determine the background frequency of chromosome aberrations in the population of Kazakhstan, considering the heterogeneity of natural radiation background levels of its large territory, a selection of 40 control subjects living in four cities of North, South, West and East Kazakhstan was performed. The cytogenetic study on the selected groups showed fairly low background frequency values of chromosome aberrations (0.84 ± 0.83 per 1000 cells), comparable with other data in the literature on general populations, reporting background frequency values between 0.54 and 2.99 per 1000 cells. The obtained results should be taken into account when constructing the dose–effect calibration curve used in cytogenetic biodosimetry, as a “zero” dose point, which will reduce the uncertainty in quantifying the individual absorbed dose in emergency radiological situations.
The Mediating Role of Psychological Well-Being in the Relationship between Self-Care Knowledge and Disease Self-Management in Patients with Hypertensive Nephropathy
Authors: Chen Wen-Chun , Wu Shu-Fang Vivienne , Sun Juo-Hsiang , Tai Chun-Yi , Lee Mei-Chen , Chu Chun-Hua
Published: July 2022

Objective: This study aimed to investigate the correlation between self-care knowledge, psychological well-being, and disease self-management in patients with hypertensive nephropathy, and to assess the effect of psychological well-being as a mediator of self-care knowledge and disease self-management. Methods: This is a cross-sectional study. The 220 patients with hypertensive nephropathy were recruited from a teaching hospital in Taiwan using purposive sampling. The average age was 70.14 (SD = 11.96) years old. Among them, 128 (58.2%) were male and 92 (41.8%) were female. Instruments included a hypertensive nephropathy self-care knowledge scale, the World Health Organization-5 Well-Being Index, and the chronic kidney disease self-management instrument. The mediating effect was determined with linear regression models and the Sobel test. Results: The total explanatory variation of age, systolic blood pressure, psychological well-being, and self-care knowledge on the disease self-management was 27.7%. Psychological well-being was the most important explanatory factor and alone explains 16%. Psychological well-being was a partial mediator of self-care knowledge and quality of life in patients with hypertensive nephropathy, with a total effect of 23.2%. Conclusions: This study showed that older patients with hypertensive nephropathy and those with a higher systolic blood pressure had lower levels of disease self-management. The higher the patients’ self-care knowledge and psychological well-being, the better their disease self-management.
MG-Pe: A Novel Galectin-3 Ligand with Antimelanoma Properties and Adjuvant Effects to Dacarbazine
Authors: Biscaia Stellee M. P. , Pires Cassiano , Lívero Francislaine A. R. , Bellan Daniel L. , Bini Israel , Bustos Silvina O. , Vasconcelos Renata O. , Acco Alexandra , Iacomini Marcello , Carbonero Elaine R. , Amstalden Martin K. , Kubata Fábio R. , Cummings Richard D. , Dias-Baruffi Marcelo , Simas Fernanda F. , Oliveira Carolina C. , Freitas Rilton A. , Franco Célia Regina Cavichiolo , Chammas Roger , Trindade Edvaldo S.
Published: July 2022

Melanoma is a highly metastatic and rapidly progressing cancer, a leading cause of mortality among skin cancers. The melanoma microenvironment, formed from the activity of malignant cells on the extracellular matrix and the recruitment of immune cells, plays an active role in the development of drug resistance and tumor recurrence, which are clinical challenges in cancer treatment. These tumoral metabolic processes are affected by proteins, including Galectin-3 (Gal-3), which is extensively involved in cancer development. Previously, we characterized a partially methylated mannogalactan (MG-Pe) with antimelanoma activities. In vivo models of melanoma were used to observe MG-Pe effects in survival, spontaneous, and experimental metastases and in tissue oxidative stress. Analytical assays for the molecular interaction of MG-Pe and Gal-3 were performed using a quartz crystal microbalance, atomic force microscopy, and contact angle tensiometer. MG-Pe exhibits an additive effect when administered together with the chemotherapeutic agent dacarbazine, leading to increased survival of treated mice, metastases reduction, and the modulation of oxidative stress. MG-Pe binds to galectin-3. Furthermore, MG-Pe antitumor effects were substantially reduced in Gal-3/KO mice. Our results showed that the novel Gal-3 ligand, MG-Pe, has both antitumor and antimetastatic effects, alone or in combination with chemotherapy.
Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice
Authors: Ono Masanori , Toyoda Natsumi , Kagami Kyosuke , Hosono Takashi , Matsumoto Takeo , Horike Shin-ichi , Yamazaki Rena , Nakamura Mitsuhiro , Mizumoto Yasunari , Fujiwara Tomoko , Ando Hitoshi , Fujiwara Hiroshi , Daikoku Takiko
Published: July 2022

Recently, it was demonstrated that the expression of BMAL1 was decreased in the endometrium of women suffering from recurrent spontaneous abortion. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found that cKO mice could receive embryo implantation but not sustain pregnancy. Gene ontology analysis of microarray suggested that uterine NK (uNK) cell function was suppressed in cKO mice. Histological examination revealed the poor formation of maternal vascular spaces in the placenta. In contrast to WT mice, uNK cells in the spongiotrophoblast layer, where maternal uNK cells are directly in contact with fetal trophoblast, hardly expressed an immunosuppressive NK marker, CD161, in cKO mice. By progesterone supplementation, pregnancy could be sustained until the end of pregnancy in some cKO mice. Although this treatment did not improve the structural abnormalities of the placenta, it recruited CD161-positive NK cells into the spongiotrophoblast layer in cKO mice. These findings indicate that the uterine clock system may be critical for pregnancy maintenance after embryo implantation.
Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages, Driving Them toward Gaucher Cells
Authors: Dupuis Lucie , Chauvet Margaux , Bourdelier Emmanuelle , Dussiot Michaël , Belmatoug Nadia , Le Van Kim Caroline , Chêne Arnaud , Franco Mélanie
Published: July 2022

Gaucher disease (GD) is caused by glucocerebrosidase deficiency leading to the accumulation of sphingolipids in macrophages named “Gaucher’s Cells”. These cells are characterized by deregulated expression of cell surface markers, abnormal secretion of inflammatory cytokines, and iron sequestration. These cells are known to infiltrate tissues resulting in hematological manifestations, splenomegaly, and bone diseases. We have already demonstrated that Gaucher red blood cells exhibit altered properties suggesting their key role in GD clinical manifestations. We hypothesized that Gaucher’s erythrocytes could be prone to premature destruction by macrophages contributing to the formation of altered macrophages and Gaucher-like cells. We conducted in vitro experiments of erythrophagocytosis using erythrocytes from Gaucher’s patients or healthy donors. Our results showed an enhanced erythrophagocytosis of Gaucher red blood cells compared to healthy red blood cells, which is related to erythrocyte sphingolipids overload and reduced deformability. Importantly, we showed elevated expression of the antigen-presenting molecules CD1d and MHC-II and of the iron-regulator hepcidin in macrophages, as well as enhanced secretion of the pro-inflammatory cytokine IL-1β after phagocytosis of GD erythrocytes. These results strongly suggested that erythrophagocytosis in GD contribute to phenotypic modifications in macrophages. This present study shows that erythrocytes-macrophages interactions may be crucial in GD pathophysiology and pathogenesis.
Transcriptional Analysis on Resistant and Susceptible Kiwifruit Genotypes Activating Different Plant-Immunity Processes against Pseudomonas syringae pv. actinidiae
Authors: Qin Xiaobo , Zhang Min , Li Qiaohong , Chen Dalei , Sun Leiming , Qi Xiujuan , Cao Ke , Fang Jinbao
Published: July 2022

Pseudomonas syringae pv. actinidiae (Psa), a bacterial pathogen, is a severe threat to kiwifruit production. To elucidate the species-specific interaction between Psa and kiwifruit, transcriptomic-profiles analyses were conducted, under Psa-infected treatment and mock-inoculated control, on shoots of resistant Maohua (MH) and susceptible Hongyang (HY) kiwifruit varieties. The plant hormone-signal transduction and plant–pathogen interaction were significantly enriched in HY compared with MH. However, the starch and sucrose metabolism, antigen processing and presentation, phagosome, and galactose metabolism were significantly enriched in MH compared with HY. Interestingly, the MAP2 in the pathogen/microbe-associated molecular patterns (PAMPs)-triggered immunity (PTI) was significantly up-regulated in MH. The genes RAR1, SUGT1, and HSP90A in the effector-triggered immunity (ETI), and the NPR1 and TGA genes involved in the salicylic acid signaling pathway as regulatory roles of ETI, were significantly up-regulated in HY. Other important genes, such as the CCRs involved in phenylpropanoid biosynthesis, were highly expressed in MH, but some genes in the Ca2+ internal flow or involved in the reactive oxygen metabolism were obviously expressed in HY. These results suggested that the PTI and cell walls involved in defense mechanisms were significant in MH against Psa infection, while the ETI was notable in HY against Psa infection. This study will help to understand kiwifruit bacterial canker disease and provide important theoretical support in kiwifruit breeding.
Establishment of Stem Cell-like Cells of Sida hermaphrodita (L.) Rusby from Explants Containing Cambial Meristems
Authors: Kaňuková Šarlota , Gubišová Marcela , Klčová Lenka , Mihálik Daniel , Kraic Ján
Published: July 2022

The in vitro cultures of plant stem cells and stem cell-like cells can be established from tissues containing meristematic cells. Chemical compounds—as well as their production potential—is among the emerging topics of plant biotechnology. We induced the callus cell biomass growth and characterized the parameters indicating the presence of stem cells or stem cell-like cells. Four types of explants (stem, petiole, leaf, root) from Sida hermaphrodita (L.) Rusby and various combinations of auxins and cytokinins were tested for initiation of callus, growth of sub-cultivated callus biomass, and establishment of stem cells or stem cell-like cells. Induction of callus and its growth parameters were significantly affected both by the explant type and the combination of used plant growth hormones and regulators. The responsibility for callus initiation and growth was the highest in stem-derived explants containing cambial meristematic cells. Growth parameters of callus biomass and specific characteristics of vacuoles confirmed the presence of stem cells or stem cell-like cells in sub-cultivated callus cell biomass. Establishment of in vitro stem cell or stem cell-like cell cultures in S. hermaphrodita can lead to the development of various applications of in vitro cultivation systems as well as alternative applications of this crop.
The Capillary Morphogenesis Gene 2 Triggers the Intracellular Hallmarks of Collagen VI-Related Muscular Dystrophy
Authors: Castroflorio Enrico , Pérez Berná Ana Joaquina , López-Márquez Arístides , Badosa Carmen , Loza-Alvarez Pablo , Roldán Mónica , Jiménez-Mallebrera Cecilia
Published: July 2022

Collagen VI-related disorders (COL6-RD) represent a severe form of congenital disease for which there is no treatment. Dominant-negative pathogenic variants in the genes encoding α chains of collagen VI are the main cause of COL6-RD. Here we report that patient-derived fibroblasts carrying a common single nucleotide variant mutation are unable to build the extracellular collagen VI network. This correlates with the intracellular accumulation of endosomes and lysosomes triggered by the increased phosphorylation of the collagen VI receptor CMG2. Notably, using a CRISPR-Cas9 gene-editing tool to silence the dominant-negative mutation in patients’ cells, we rescued the normal extracellular collagen VI network, CMG2 phosphorylation levels, and the accumulation of endosomes and lysosomes. Our findings reveal an unanticipated role of CMG2 in regulating endosomal and lysosomal homeostasis and suggest that mutated collagen VI dysregulates the intracellular environment in fibroblasts in collagen VI-related muscular dystrophy.
Current Insights into the Molecular Mode of Action of Seaweed-Based Biostimulants and the Sustainability of Seaweeds as Raw Material Resources
Authors: Sujeeth Neerakkal , Petrov Veselin , Guinan Kieran J. , Rasul Fiaz , O’Sullivan John T. , Gechev Tsanko S.
Published: July 2022

Natural biostimulants, such as seaweed extracts, can stimulate plant growth and development in both model and crop plants. Due to the increasing demands for their use in agriculture, it is crucial to ensure the sustainability of the sources from which they are produced. Furthermore, some seaweed extracts were recently shown to prime and protect from adverse environmental factors such as drought, salinity and extreme temperatures, as well as from oxidative stress. The molecular mode of action of these biostimulants has still not been fully elucidated, but there has been significant progress in this direction in the last years. Firstly, this review examines the sustainability aspects of harvesting seaweed resources as raw materials for manufacturing biostimulants and provides an overview of the regulatory landscape pertaining to seaweed-based biostimulants. The review then summarises the recent advances in determining the genetic and molecular mechanisms activated by seaweed-based biostimulants, their influence on transcriptome reconfiguration, metabolite adjustment, and ultimately stress protection, improved nutrient uptake, and plant growth and performance. This knowledge is important for deciphering the intricate stress signalling network modulated by seaweed-based biostimulants and can aid in designing molecular priming technologies for crop improvement.
Proteomic Investigation of the Role of Nucleostemin in Nucleophosmin-Mutated OCI-AML 3 Cell Line
Authors: Cela Ilaria , Cufaro Maria Concetta , Fucito Maurine , Pieragostino Damiana , Lanuti Paola , Sallese Michele , Del Boccio Piero , Di Matteo Adele , Allocati Nerino , De Laurenzi Vincenzo , Federici Luca
Published: July 2022

Nucleostemin (NS; a product of the GNL3 gene) is a nucleolar–nucleoplasm shuttling GTPase whose levels are high in stem cells and rapidly decrease upon differentiation. NS levels are also high in several solid and hematological neoplasms, including acute myeloid leukaemia (AML). While a role in telomere maintenance, response to stress stimuli and favoring DNA repair has been proposed in solid cancers, little or no information is available as to the role of nucleostemin in AML. Here, we investigate this issue via a proteomics approach. We use as a model system the OCI-AML 3 cell line harboring a heterozygous mutation at the NPM1 gene, which is the most frequent driver mutation in AML (approximately 30% of total AML cases). We show that NS is highly expressed in this cell line, and, contrary to what has previously been shown in other cancers, that its presence is dispensable for cell growth and viability. However, proteomics analysis of the OCI-AML 3 cell line before and after nucleostemin (NS) silencing showed several effects on different biological functions, as highlighted by ingenuity pathway analysis (IPA). In particular, we report an effect of down-regulating DNA repair through homologous recombination, and we confirmed a higher DNA damage rate in OCI-AML 3 cells when NS is depleted, which considerably increases upon stress induced by the topoisomerase II inhibitor etoposide. The data used are available via ProteomeXchange with the identifier PXD034012.
Endothelium-Dependent Induction of Vasculogenic Mimicry in Human Triple-Negative Breast Cancer Cells Is Inhibited by Calcitriol and Curcumin
Authors: Morales-Guadarrama Gabriela , Méndez-Pérez Edgar A. , García-Quiroz Janice , Avila Euclides , García-Becerra Rocío , Zentella-Dehesa Alejandro , Larrea Fernando , Díaz Lorenza
Published: July 2022

In highly aggressive tumors, cancer cells may form channel-like structures through a process known as vasculogenic mimicry (VM). VM is generally associated with metastasis, mesenchymal phenotype, and treatment resistance. VM can be driven by antiangiogenic treatments and/or tumor microenvironment-derived factors, including those from the endothelium. Curcumin, a turmeric product, inhibits VM in some tumors, while calcitriol, the most active vitamin D metabolite, exerts potent antineoplastic effects. However, the effect of these natural products on VM in breast cancer remains unknown. Herein, we studied the effect of both compounds on triple-negative breast cancer (TNBC) VM-capacity in a co-culture model. The process of endothelial cell-induced VM in two human TNBC cell lines was robustly inhibited by calcitriol and partially by curcumin. Calcitriol promoted TNBC cells’ morphological change from spindle-like to cobblestone-shape, while curcumin diminished VM 3D-structure. Notably, the treatments dephosphorylated several active kinases, especially those involved in the PI3K/Akt pathway. In summary, calcitriol and curcumin disrupted endothelium-induced VM in TNBC cells partially by PI3K/Akt inactivation and mesenchymal phenotype inhibition. Our results support the possible use of these natural compounds as adjuvants for VM inactivation in patients with malignant tumors inherently capable of forming VM, or those with antiangiogenic therapy, warranting further in vivo studies.
Bile Duct Ligation Impairs Function and Expression of Mrp1 at Rat Blood–Retinal Barrier via Bilirubin-Induced P38 MAPK Pathway Activations
Authors: Li Ping , Yang Yiting , Lin Zijin , Hong Shijin , Jiang Ling , Zhou Han , Yang Lu , Zhu Liang , Liu Xiaodong , Liu Li
Published: July 2022

Liver injury is often associated with hepatic retinopathy, resulting from accumulation of retinal toxins due to blood–retinal barrier (BRB) dysfunction. Retinal pigment epithelium highly expresses MRP1/Mrp1. We aimed to investigate whether liver injury affects the function and expression of retinal Mrp1 using bile duct ligation (BDL) rats. Retinal distributions of fluorescein and 2,4-dinitrophenyl-S-glutathione were used for assessing Mrp1 function. BDL significantly increased distributions of the two substrates and bilirubin, downregulated Mrp1 protein, and upregulated phosphorylation of p38 and MK2 in the retina. BDL neither affected the retinal distribution of FITC-dextran nor expressions of ZO-1 and claudin-5, demonstrating intact BRB integrity. In ARPE-19 cells, BDL rat serum or bilirubin decreased MRP1 expression and enhanced p38 and MK2 phosphorylation. Both inhibiting and silencing p38 significantly reversed the bilirubin- and anisomycin-induced decreases in MRP1 protein. Apparent permeability coefficients of fluorescein in the A-to-B direction (Papp, A-to-B) across the ARPE-19 monolayer were greater than Papp, B-to-A. MK571 or bilirubin significantly decreased Papp, A-to-B of fluorescein. Bilirubin treatment significantly downregulated Mrp1 function and expression without affecting integrity of BRB and increased bilirubin levels and phosphorylation of p38 and MK2 in rat retina. In conclusion, BDL downregulates the expression and function of retina Mrp1 by activating the p38 MAPK pathway due to increased bilirubin levels.
Probiotic Supplementation Suppresses Tumor Growth in an Experimental Colorectal Cancer Liver Metastasis Model
Authors: Jakubauskas Matas , Jakubauskiene Lina , Leber Bettina , Horvath Angela , Strupas Kestutis , Stiegler Philipp , Schemmer Peter
Published: July 2022

Colorectal cancer (CRC) ranks third in incidence and second in mortality of all cancers worldwide. At the time of primary diagnosis, around 20% of patients already have metastatic CRC and only around 20% are candidates for radical resection. Thus, most of the patients have to undergo chemotherapy (CTx). Due to chemoresistance and side effects, novel treatment additives are crucial for controlling the disease and prolonging patient survival. The aim of this study was to evaluate probiotic supplementation and its antitumorigenic effects in an experimental CRC liver metastasis model. Six-week-old male Wistar rats received either a multispecies probiotic (1.2 × 109 CFU/daily) or placebo mixture. On day 14 of the experiment, rat CRC cells (CC531) were implanted under the liver capsule later treated by FOLFOX CTx. Change in tumor volume was measured by performing micro computed tomography (micro-CT) scanning on experimental days 28 and 34. Additionally, immunohistochemical staining with anti-MPO, anti-Ki67, and anti-CD31 were performed. Tumor apoptosis was evaluated using TUNEL staining. Micro-CT image analysis indicates that probiotic supplementation significantly inhibits tumor growth. No synergistic effects between probiotic supplementation and FOLFOX CTx was observed. Reduced tumor volume was achieved by inhibiting angiogenesis, as tumor microvascular density was significantly lower in rats receiving probiotic supplementation. This study shows that a multispecies probiotic mixture significantly reduces angiogenesis and inhibits CRC liver metastasis growth in an experimental rat model.
A Reinforcement Learning Approach to Speech Coding
Authors: Gibson Jerry , Oh Hoontaek
Published: July 2022

Speech coding is an essential technology for digital cellular communications, voice over IP, and video conferencing systems. For more than 25 years, the main approach to speech coding for these applications has been block-based analysis-by-synthesis linear predictive coding. An alternative approach that has been less successful is sample-by-sample tree coding of speech. We reformulate this latter approach as a multistage reinforcement learning problem with L step lookahead that incorporates exploration and exploitation to adapt model parameters and to control the speech analysis/synthesis process on a sample-by-sample basis. The minimization of the spectrally shaped reconstruction error to finite depth manages complexity and serves as an effective stand in for the overall subjective evaluation of reconstructed speech quality and intelligibility. Different control policies that attempt to persistently excite the system states and that encourage exploration are studied and evaluated. The resulting methods produce reconstructed speech quality competitive with the most popular speech codec utilized today. This new reinforcement learning formulation provides new insights and opens up new directions for system design and performance improvement.
REDfly: An Integrated Knowledgebase for Insect Regulatory Genomics
Authors: Keränen Soile V. E. , Villahoz-Baleta Angel , Bruno Andrew E. , Halfon Marc S.
Published: July 2022

We provide here an updated description of the REDfly (Regulatory Element Database for Fly) database of transcriptional regulatory elements, a unique resource that provides regulatory annotation for the genome of Drosophila and other insects. The genomic sequences regulating insect gene expression—transcriptional cis-regulatory modules (CRMs, e.g., “enhancers”) and transcription factor binding sites (TFBSs)—are not currently curated by any other major database resources. However, knowledge of such sequences is important, as CRMs play critical roles with respect to disease as well as normal development, phenotypic variation, and evolution. Characterized CRMs also provide useful tools for both basic and applied research, including developing methods for insect control. REDfly, which is the most detailed existing platform for metazoan regulatory-element annotation, includes over 40,000 experimentally verified CRMs and TFBSs along with their DNA sequences, their associated genes, and the expression patterns they direct. Here, we briefly describe REDfly’s contents and data model, with an emphasis on the new features implemented since 2020. We then provide an illustrated walk-through of several common REDfly search use cases.
Using Minimum Redundancy Maximum Relevance Algorithm to Select Minimal Sets of Heart Rate Variability Parameters for Atrial Fibrillation Detection
Authors: Buś Szymon , Jędrzejewski Konrad , Guzik Przemysław
Published: July 2022

Heart rate is quite regular during sinus (normal) rhythm (SR) originating from the sinus node. In contrast, heart rate is usually irregular during atrial fibrillation (AF). Complete atrioventricular block with an escape rhythm, ventricular pacing, or ventricular tachycardia are the most common exceptions when heart rate may be regular in AF. Heart rate variability (HRV) is the variation in the duration of consecutive cardiac cycles (RR intervals). We investigated the utility of HRV parameters for automated detection of AF with machine learning (ML) classifiers. The minimum redundancy maximum relevance (MRMR) algorithm, one of the most effective algorithms for feature selection, helped select the HRV parameters (including five original), best suited for distinguishing AF from SR in a database of over 53,000 60 s separate electrocardiogram (ECG) segments cut from longer (up to 24 h) ECG recordings. HRV parameters entered the ML-based classifiers as features. Seven different, commonly used classifiers were trained with one to six HRV-based features with the highest scores resulting from the MRMR algorithm and tested using the 5-fold cross-validation and blindfold validation. The best ML classifier in the blindfold validation achieved an accuracy of 97.2% and diagnostic odds ratio of 1566. From all studied HRV features, the top three HRV parameters distinguishing AF from SR were: the percentage of successive RR intervals differing by at least 50 ms (pRR50), the ratio of standard deviations of points along and across the identity line of the Poincare plots, respectively (SD2/SD1), and coefficient of variation—standard deviation of RR intervals divided by their mean duration (CV). The proposed methodology and the presented results of the selection of HRV parameters have the potential to develop practical solutions and devices for automatic AF detection with minimal sets of simple HRV parameters. Using straightforward ML classifiers and the extremely small sets of simple HRV features, always with pRR50 included, the differentiation of AF from sinus rhythms in the 60 s ECGs is very effective.
The Impact of Surgical Waiting Time on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy: A Systematic Review
Authors: Nowak Łukasz , Krajewski Wojciech , Łaszkiewicz Jan , Małkiewicz Bartosz , Chorbińska Joanna , Del Giudice Francesco , Mori Keiichiro , Moschini Marco , Kaliszewski Krzysztof , Rajwa Paweł , Laukhtina Ekaterina , Shariat Shahrokh F. , Szydełko Tomasz ,   on behalf of European Association of Urology EAU-Young Academic Urologists YAU Urothelial Cancer Working Party
Published: July 2022

Radical nephroureterectomy (RNU) with bladder cuff excision is a standard of care in patients with high-risk upper tract urothelial carcinoma (UTUC). Although several recommendations and guidelines on the delayed treatment of urologic cancers exist, the evidence on UTUC is scarce and ambiguous. The present systematic review aimed to summarize the available evidence on the survival outcomes after deferred RNU in patients with UTUC. A systematic literature search of the three electronic databases (PubMed, Embase, and Cochrane Library) was conducted until 30 April 2022. Studies were found eligible if they reported the oncological outcomes of patients treated with deferred RNU compared to the control group, including those patients treated with RNU without delay. Primary endpoints were cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS). In total, we identified seven eligible studies enrolling 5639 patients. Significant heterogeneity in the definition of “deferred RNU” was found across the included studies. Three out of five studies reporting CSS showed that deferring RNU was associated with worse CSS. Furthermore, three out of four studies reporting OS found a negative impact of delay in RNU on OS. One out of three studies reporting RFS found a negative influence of delayed RNU on RFS. While most studies reported a 3 month interval as a significant threshold for RNU delay, some subgroup analyses showed that a safe delay for RNU was less than 1 month in patients with ureteral tumors (UT) or less than 2 months in patients with hydronephrosis. In conclusion, long surgical waiting time for RNU (especially more than 3 months after UTUC diagnosis) could be considered as an important risk factor having a negative impact on oncological outcomes in patients with UTUC; however, the results of the particular studies are still inconsistent. The safe delay for RNU might be shorter in specific subsets of high-risk patients, such as those with UT and/or hydronephrosis at the time of diagnosis. High-quality additional studies are required to establish evidence for valid recommendations.
Association of Serum Lipid Level with Meibum Biosynthesis and Meibomian Gland Dysfunction: A Review
Authors: Yoo Young-Sik , Park Sun-Kyoung , Hwang Ho-Sik , Kim Hyun-Seung , Arita Reiko , Na Kyung-Sun
Published: July 2022

The primary role of meibomian glands (MGs) is to actively synthesize and secret lipids and proteins spread onto the tear film, and the glandular lipids promote tear stability, prevent evaporation, and reduce friction. Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease and one of the most common ophthalmic problems worldwide. MGs are densely innervated and regulated by hormones and growth factors. However, since the polar and nonpolar lipids are produced through processes in MGs that are not completely understood, a relevant question has been raised: Would the altered systemic lipids metabolism affect the physiology and structure of MGs? This review introduces the recent update regarding the relationships between serum lipid and MGD in clinical and basic research while providing answers to this question. A causal relationship remains to be established; however, serum lipid level or dyslipidemia may be related to MGD directly or indirectly, or both. Further studies are warranted to establish the role of serum lipid level and meibocyte differentiation/maturation and lipid synthesis.
Vital Pulp Therapy of Permanent Teeth with Reversible or Irreversible Pulpitis: An Overview of the Literature
Authors: Iaculli Flavia , Rodríguez-Lozano Francisco Javier , Briseño-Marroquín Benjamín , Wolf Thomas Gerhard , Spagnuolo Gianrico , Rengo Sandro
Published: July 2022

Vital pulp therapy (VPT) has been recently proposed as an alternative approach even in symptomatic mature permanent teeth with deep caries’ lesions, aiming to maintain the pulp vitality over time and/or to avoid non-surgical root canal therapy (NSRCT). However, to date, the diagnosis of reversible or irreversible pulpitis is only based on clinical pain quantity and quality, without precisely reflecting the pulp inflammation status. Therefore, the aim of the present study was to provide an overview based on the current scientific literature to demonstrate the clinical effectiveness of VPT on mature permanent teeth, validating the use of hydraulic calcium silicate-based cements and their role in pain management. VPT may be successfully applied not only in mature permanent teeth diagnosed with reversible pulpitis, but also in permanent dental elements with signs and symptoms of irreversible pulpitis. Hydraulic cements showed favorable outcomes in terms of decrease of pro-inflammatory mediators and of post-operative pain. Pain plays a central role in the chance to perform VPT in mature permanent teeth, since it may be considered as a pre-operative diagnostic criterion as well as a treatment success parameter. In addition, proper assessment of pulp inflammation and choice of appropriate materials are key factors in enhancing VPT success.
Employing the Multivariate Edmonton Scale in the Assessment of Frailty Syndrome in Heart Failure
Authors: Studzińska Karolina , Wąż Piotr , Frankiewicz Anna , Stopczyńska Iwona , Studnicki Rafał , Hansdorfer-Korzon Rita
Published: July 2022

Background: Frailty syndrome (FS) is a syndrome characterized by a reduction in the body’s physiological reserves as a result of the accumulation of reduced efficiency of many organs and systems. Experts of the Heart Failure Association of the European Society of Cardiology (ECS) emphasize the need to assess frailty in all patients with heart failure (HF). There is no specific scale dedicated to this group of patients. The aim of the study was to assess the occurrence of the frailty syndrome in heart failure using the multidimensional Edmonton Frailty Scale (EFS). Methods: The study included 106 patients diagnosed with heart failure with reduced left ventricular ejection fraction (LVEF < 40%). The average age was 62.6 ± 9.7 years. Most of the patients (84%) studied were men. In 70 people (66%), the cause of heart failure was coronary artery disease. The study group included patients admitted to hospital on a scheduled basis and with exacerbation of heart failure. Frailty was measured using the EFS before discharge from the hospital. Demographic, sociodemographic and clinical data were obtained. A 12-month follow-up period was included in the project. The number of readmissions after 6 and 12 months was assessed. Results: A correlation was observed between the New York Heart Association (NYHA) functional class and the occurrence of frailty—this applies to the assessment at the beginning and at the end of hospitalization. When analyzing the age of the patients in relation to frailty, a statistically significant difference was obtained. The youngest group in terms of age were non-frail patients. Hospitalization of people prone to development of the frailty syndrome and diagnosed with the FS was significantly more often associated with the occurrence of complications during hospital stays. Rehospitalizations for exacerbation of heart failure were much more frequent in patients with frailty. Conclusions: Assessment and monitoring of the state of increased sensitivity to the development of frailty or FS in patients with heart failure should influence the differentiation of clinical management. The Edmonton Questionnaire may be a helpful tool for the assessment of frailty in hospitalized patients with HF.
A Systematic Review to Assess the Relationship between Disseminated Cerebral Aspergillosis, Leukemias and Lymphomas, and Their Respective Therapeutics
Authors: Sullivan Brianne N. , Baggett Mia A. , O’Connell Samantha S. , Pickett Keith M. , Steele Chad
Published: July 2022

Disseminated disease following invasive pulmonary aspergillosis (IPA) remains a significant contributor to mortality amongst patients with hematologic malignancies (HMs). At the highest risk of mortality are those with disseminated disease to the central nervous system, known as cerebral aspergillosis (CA). However, little is known about the risk factors contributing to disease amongst HM patients. A systematic review using PRISMA guidelines was undertaken to define HM patient subgroups, preventative measures, therapeutic interventions, and outcomes of patients with disseminated CA following IPA. The review resulted in the identification of 761 records, of which 596 articles were screened, with the final inclusion of 47 studies and 76 total patients. From included articles, the proportion of CA was assessed amongst HM patient subgroups. Further, pre-and post-infection characteristics, fungal species, and mortality were evaluated for the total population included and HM patient subgroups. Patients with acute myeloid leukemia and acute lymphoid lymphoma, patients receiving corticosteroids as a part of their HM therapeutic regimen, and anti-fungal prophylaxis constitute the top identified patient populations at risk for disseminated CA. Overall, information presented here indicates that measures for the prevention of IPA should be taken in higher-risk HM patient subgroups. Specifically, the type of anti-fungal therapy used should be carefully considered for those patients with IPA and increased risk for cerebral dissemination. Additional reports detailing patient characteristics are needed to define further the risk of developing disseminated CA from IPA in patients with HMs.