bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychopathology, Protective Factors, and COVID-19 among Adolescents: A Structural Equation Model
Authors: Scheiner Christin , Seis Christian , Kleindienst Nikolaus , Buerger Arne
Published: January 2023

Since the outbreak of the COVID-19 pandemic in December 2019 and the associated restrictions, mental health in children and adolescents has been increasingly discussed in the media. Negative impacts of the pandemic, including a sharp increase in psychopathology and, consequently, reduced quality of life, appear to have particularly affected children and young people, who may be especially vulnerable to the adverse effects of isolation. Nevertheless, many children and adolescents have managed to cope well with the restrictions, without deterioration of their mental health. The present study therefore explored the links between COVID-19 infection (in oneself or a family member, as well as the death of a family member due to the virus), protective factors such as self-efficacy, resilience, self-esteem, and health-related quality of life, and measures of psychopathology such as depression scores, internalizing/externalizing problems, emotion dysregulation, and victimization. For this purpose, we examined data from 2129 adolescents (mean age = 12.31, SD = 0.67; 51% male; 6% born outside of Germany) using a structural equation model. We found medium to high loadings of the manifest variables with the latent variables (COVID-19, protective factors, and psychopathology). Protective factors showed a significant negative correlation with psychopathology. However, COVID-19 had a weak connection with psychopathology in our sample. External pandemic-related factors (e.g., restrictions) and their interaction with existing psychopathology or individual protective factors appear to have a greater influence on young people’s mental health than the impact of the virus per se. Sociopolitical efforts should be undertaken to foster prevention and promote individual resilience, especially in adolescence.
Affectivity and Sexuality in Adolescents with Autism Spectrum Disorder from the Perspective of Education and Healthcare Professionals: A Qualitative Study
Authors: Torralbas-Ortega Jordi , Valls-Ibáñez Victoria , Roca Judith , Sastre-Rus Meritxell , Campoy-Guerrero Carme , Sala-Corbinos Dolores , Sánchez-Fernández María
Published: January 2023

People with autism spectrum disorder (ASD) present several different characteristics that predispose them to greater difficulties with intimate emotional and sexual relationships. This qualitative study uncovers the perspective of education and healthcare professionals on the affective and sexual needs of young people with ASD by analysing their narratives in semi-structured focus group sessions. Professionals highlight the inadequate training they receive in this aspect of health. They consider it should be commonplace for professionals working with autistic people as it would aid their collaborative efforts when treating children and adolescents with ASD. They show that, by working together with the families to establish joint objectives, these professionals can appropriately address sex and affective education, preventing risky behaviours among young people with ASD, and improving the interactions these individuals have with others. Sex and affective education is described as an indispensable tool at this stage of development and should be specially adapted for those with ASD.
The Relationship between Social Support and Mental Health Problems of Peri- and Postmenopausal Women during the SARS-CoV-2 Pandemic
Authors: Cybulska Anna Maria , Głębicka Katarzyna , Stanisławska Marzanna , Cymbaluk-Płoska Aneta , Grochans Elżbieta , Rachubińska Kamila
Published: January 2023

The COVID-19 pandemic affects women’s mental health, because they are more predisposed to vulnerabilities and adverse impacts. Therefore, is important to find strategies for preventing and treating these mental health consequences in the female population. The main purposes of our study were to determine the level of social support received by peri- and postmenopausal women during the SARS-CoV-2 pandemic, as well as factors related to this level with reference to health status and sociodemographic variables. A total of 218 women in peri- and postmenopausal status participated in the study. The study assessed depression (Beck Depression Inventory), anxiety (the Spielberg State-Trait Anxiety Scale), climacteric symptoms (the Blatt–Kupperman Index), social support (the Inventory of Social Supportive Behaviors). The majority of the respondents had a moderate level of anxiety as a state (40.8%), a low level of anxiety as a trait (51.4%), no depressive symptoms (75.2%) and no climacteric symptoms (52.3%). Age was found to significantly correlate with anxiety as a state (p = 0.036). The anxiety as state was significantly stronger in people with higher education than in people with secondary education (p = 0.019). Professionally inactive women had more emotional (p = 0.05) and appraisal (p = 0.014) support than women who work. The analysis demonstrated no statistically significant correlation between social support and depression, anxiety or climacteric symptoms (p > 0.05). The majority of peri- and postmenopausal women had no depressive symptoms and/or anxiety symptoms. Professionally inactive women had more emotional and appraisal support than women who work. The analysis demonstrated no statistically significant correlation between social support and depression, anxiety or climacteric symptoms.
Testosterone and Suicidal Behavior in Bipolar Disorder
Authors: Sher Leo
Published: January 2023

Bipolar disorder is associated with suicidal behavior. The risk of suicide for individuals with bipolar disorder is up to 20–30 times larger than that of the general population. Considerable evidence suggests that testosterone may play a role in the pathophysiology of suicidal behavior in both men and women with bipolar disorder and other psychiatric conditions. Testosterone has complex effects on psychological traits. It affects mood and behavior, including interactions with other people. Testosterone regulates pro-active and re-active aspects of aggression. Probably, both high and low levels of testosterone may contribute to the neurobiology of suicide in various patient populations. The effects of endogenous and exogenous testosterone on suicidality in patients with bipolar disorder need further investigation. The aim of this commentary article is to provide a commentary on the author’s work on the topic, summarize the literature on testosterone, bipolar disorder, and suicide, and encourage future research on this poorly studied topic.
Training for Food Handlers at Production Level in Italian Regions
Authors: Pattono Daniele , Petey Matteo , Covarino Anna Maria , Gea Marta , Schilirò Tiziana
Published: January 2023

Food safety has always been a public health challenge. Globally, food safety control is supported by laws and preventive measures, such as inspections conducted from primary production to market, “from farm to fork” as emphasized by the European Union and training of Food Handlers (FHs). This latter preventive measure plays a very important role, and for this reason a review of training courses regulations provided in the different Italian regions was conducted. Analysis of the results shows that the Italian regions approach this issue in different ways: some regions provide only general guidelines, while others offer detailed instructions. The most significant differences concern the topics dealt with, the stakeholders, the staff training and the verification of results; topics such as allergens and gluten are often absent. More detailed guidelines tailored to fit the local scenario could provide better support to FHs, thus leading to real changes in their behaviors and mindsets and promoting the development of an actual “prevention culture”.
Implementation of GIS Tools in the Quality of Life Assessment of Czech Municipalities
Authors: Macků Karel , Burian Jaroslav , Vodička Hynek
Published: January 2023

Although quality of life is a phenomenon with a significant geographical component, its assessment is often only based on non-spatial statistical data. In Czechia, there are currently several assessments of quality of life at the level of municipalities, yet they do not consider the spatial aspect of the input indicators. This study uses the existing quality of life index compiled by the research agencies Median and the Aspen Institute, whose input indicators related to the accessibility of services and facilities have been redesigned to capture real-world phenomena more appropriately with GIS (Geographic Information Systems) tools using network analysis. In accordance with the original methodology, an adjusted index of quality of life was compiled. An update of indicators resulted in a more accurate description of quality of life. The differences between the original and the adjusted index were mainly seen in the areas around the larger cities, where quality of life has significantly risen. On the other hand, rural/rather rural areas experienced a slight decrease in quality of life with the change of inputs. The mapping of the resulting index documents the disparities in quality of life across Czechia and contributes to the discussions on the topic of quality of life in Czechia with new up-to-date reference data.
Transcriptional Insights of Oxidative Stress and Extracellular Traps in Lung Tissues of Fatal COVID-19 Cases
Authors: Hosseini Aref , Stojkov Darko , Fettrelet Timothée , Bilyy Rostyslav , Yousefi Shida , Simon Hans-Uwe
Published: January 2023

Neutrophil extracellular traps (NETs) and oxidative stress are considered to be beneficial in the innate immune defense against pathogens. However, defective clearance of NETs in the lung of acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients could lead to severe respiratory syndrome infection, the so-called coronavirus disease 2019 (COVID-19). To elucidate the pathways that are related to NETs within the pathophysiology of COVID-19, we utilized RNA sequencing (RNA-seq) as well as immunofluorescence and immunohistochemistry methods. RNA-seq analysis provided evidence for increased oxidative stress and the activation of viral-related signaling pathways in post-mortem lungs of COVID-19 patients compared to control donors. Moreover, an excess of neutrophil infiltration and NET formation were detected in the patients’ lungs, where the extracellular DNA was oxidized and co-localized with neutrophil granule protein myeloperoxidase (MPO). Interestingly, staining of the lipid peroxidation marker 4-hydroxynonenal (4-HNE) depicted high colocalization with NETs and was correlated with the neutrophil infiltration of the lung tissues, suggesting that it could serve as a suitable marker for the identification of NETs and the severity of the disease. Moreover, local inhalation therapy to reduce the excess lipid oxidation and NETs in the lungs of severely infected patients might be useful to ameliorate their clinical conditions.
Genomic and Epigenomic Mechanisms of the Interaction between Parasitic and Host Plants
Authors: Ashapkin Vasily V. , Kutueva Lyudmila I. , Aleksandrushkina Nadezhda I. , Vanyushin Boris F. , Teofanova Denitsa R. , Zagorchev Lyuben I.
Published: January 2023

Parasitic plants extract nutrients from the other plants to finish their life cycle and reproduce. The control of parasitic weeds is notoriously difficult due to their tight physical association and their close biological relationship to their hosts. Parasitic plants differ in their susceptible host ranges, and the host species differ in their susceptibility to parasitic plants. Current data show that adaptations of parasitic plants to various hosts are largely genetically determined. However, multiple cases of rapid adaptation in genetically homogenous parasitic weed populations to new hosts strongly suggest the involvement of epigenetic mechanisms. Recent progress in genome-wide analyses of gene expression and epigenetic features revealed many new molecular details of the parasitic plants’ interactions with their host plants. The experimental data obtained in the last several years show that multiple common features have independently evolved in different lines of the parasitic plants. In this review we discuss the most interesting new details in the interaction between parasitic and host plants.
Discovery of Small Molecule COX-1 and Akt Inhibitors as Anti-NSCLC Agents Endowed with Anti-Inflammatory Action
Authors: Altıntop Mehlika Dilek , Akalın Çiftçi Gülşen , Yılmaz Savaş Nalan , Ertorun İpek , Can Betül , Sever Belgin , Temel Halide Edip , Alataş Özkan , Özdemir Ahmet
Published: January 2023

Targeted therapies have come into prominence in the ongoing battle against non-small cell lung cancer (NSCLC) because of the shortcomings of traditional chemotherapy. In this context, indole-based small molecules, which were synthesized efficiently, were subjected to an in vitro colorimetric assay to evaluate their cyclooxygenase (COX) inhibitory profiles. Compounds 3b and 4a were found to be the most selective COX-1 inhibitors in this series with IC50 values of 8.90 µM and 10.00 µM, respectively. In vitro and in vivo assays were performed to evaluate their anti-NSCLC and anti-inflammatory action, respectively. 2-(1H-Indol-3-yl)-N′-(4-morpholinobenzylidene)acetohydrazide (3b) showed selective cytotoxic activity against A549 human lung adenocarcinoma cells through apoptosis induction and Akt inhibition. The in vivo experimental data revealed that compound 3b decreased the serum myeloperoxidase and nitric oxide levels, pointing out its anti-inflammatory action. Moreover, compound 3b diminished the serum aminotransferase (particularly aspartate aminotransferase) levels. Based on the in vitro and in vivo experimental data, compound 3b stands out as a lead anti-NSCLC agent endowed with in vivo anti-inflammatory action, acting as a dual COX-1 and Akt inhibitor.
Influence of Butyrate on Impaired Gene Expression in Colon from Patients with High Blood Pressure
Authors: Li Jing , Richards Elaine M. , Handberg Eileen M. , Pepine Carl J. , Alakrad Eyad , Forsmark Chris E. , Raizada Mohan K.
Published: January 2023

Hypertension (HTN) is associated with gut dysbiosis and the depletion of butyrate-producing bacteria in animal models and people. Furthermore, fecal material transfer from donor hypertensive patients increases blood pressure in normotensive recipient animals and ameliorates HTN-associated pathophysiology. These observations have implications in the impaired interactions between the gut and gut microbiota in HTN. Although this concept is supported in animal models, little is known about human HTN. Therefore, our objective for this study was to compare gene expression with transcriptomics and its potential to influence microbiota in subjects with normal and high blood pressure (HBP). Colon samples from reference subjects with normal blood pressure (REF) and HBP were used for RNA-seq to analyze their transcriptomes. We observed the significant downregulation of gene sets governing immune responses (e.g., SGK1 and OASL), gut epithelial function (e.g., KRT20 and SLC9A3R1), gut microbiota (e.g., PPARG and CIDEC) and genes associated with cardiovascular and gut diseases (e.g., PLAUR and NLN) in HBP subjects; the expression of genes within these pathways correlated with blood pressure. Potential drug targets in the gut epithelium were identified using the Drug Gene International Database for possible use in HTN. They include peroxisome proliferator-activated receptor gamma (PPRG), active serum/glucocorticoid regulated kinase 1 (SGK1) and 3 beta-hydroxysteroid isomerase type II inhibitor (HSD3B). Finally, butyrate, a microbiota-derived short-chain fatty acid, restored the disrupted expression of certain functional genes in colonic organoids from HBP subjects. Patients with HBP exhibit a unique transcriptome that could underlie impaired gut–microbiota interactions. Targeting these interactions could provide a promising new therapeutic intervention for hypertension management.
The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism
Authors: Tian Ling-Yu , Smit Daniel J. , Jücker Manfred
Published: January 2023

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Metabolic reprogramming is considered a new hallmark of cancer, but it remains unclearly described in HCC. The dysregulation of the PI3K/AKT/mTOR signaling pathway is common in HCC and is, therefore, a topic of further research and the concern of developing a novel target for liver cancer therapy. In this review, we illustrate mechanisms by which this signaling network is accountable for regulating HCC cellular metabolism, including glucose metabolism, lipid metabolism, amino acid metabolism, pyrimidine metabolism, and oxidative metabolism, and summarize the ongoing clinical trials based on the inhibition of the PI3K/AKT/mTOR pathway in HCC.
The Effect of the Histone Chaperones HSPA8 and DEK on Tumor Immunity in Hepatocellular Carcinoma
Authors: Yang Chuanxin , Shao Yaodi , Wang Xiangjun , Wang Jie , Wang Puxiongzhi , Huang Chao , Wang Wei , Wang Jian
Published: January 2023

Complex immune contexture leads to resistance to immunotherapy in hepatocellular carcinoma (HCC), and the need for new potential biomarkers of immunotherapy in HCC is urgent. Histone chaperones are vital determinants of gene expression and genome stability that regulate tumor development. This study aimed to investigate the effect of histone chaperones on tumor immunity in HCC. Bioinformatics analyses were initially performed using The Cancer Genome Atlas (TCGA) database, and were validated using the Gene Expression Omnibus (GEO) database and the International Cancer Genome Consortium (ICGC) database. Immune-related histone chaperones were screened with the Spearman rank coefficient. Consensus clustering was utilized to divide the HCC samples into two clusters. ESTIMATE, CIBERSORT and ssGSEA analyses were performed to assess immune infiltration. The expression of immunomodulatory genes, chemokines and chemokine receptors was analyzed to evaluate sensitivity to immunotherapy. The differentially expressed genes (DEGs) were included in weighted gene coexpression network analysis (WGCNA) to identify the hub genes. Enrichment analyses were used to investigate the functions of the hub genes. The Kaplan-Meier method and log-rank test were conducted to draw survival curves. A Cox regression analysis was utilized to identify independent risk factors affecting prognosis. HSPA8 and DEK were screened out from 36 known histone chaperones based on their strongest correlation with the ESTIMATE score. Cluster 2, with high HSPA8 expression and low DEK expression, tended to have stronger immune infiltration and better sensitivity to immunotherapy than Cluster 1, with low HSPA8 expression and high DEK expression. Furthermore, WGCNA identified 12 hub genes closely correlated with immune infiltration from the DEGs of the two clusters, of which FBLN2 was proven to be an independent protective factor of HCC patients. HSPA8 and DEK are expected to be biomarkers for precisely predicting the effect of immunotherapy, and FBLN2 is expected to be a therapeutic target of HCC.
Near Infrared Photoimmunotherapy: A Review of Recent Progress and Their Target Molecules for Cancer Therapy
Authors: Mohiuddin T. M. , Zhang Chaoyu , Sheng Wenjie , Al-Rawe Marwah , Zeppernick Felix , Meinhold-Heerlein Ivo , Hussain Ahmad Fawzi
Published: January 2023

Near infrared photoimmunotherapy (NIR-PIT) is a newly developed molecular targeted cancer treatment, which selectively kills cancer cells or immune-regulatory cells and induces therapeutic host immune responses by administrating a cancer targeting moiety conjugated with IRdye700. The local exposure to near-infrared (NIR) light causes a photo-induced ligand release reaction, which causes damage to the target cell, resulting in immunogenic cell death (ICD) with little or no side effect to the surrounding normal cells. Moreover, NIR-PIT can generate an immune response in distant metastases and inhibit further cancer attack by combing cancer cells targeting NIR-PIT and immune regulatory cells targeting NIR-PIT or other cancer treatment modalities. Several recent improvements in NIR-PIT have been explored such as catheter-driven NIR light delivery, real-time monitoring of cancer, and the development of new target molecule, leading to NIR-PIT being considered as a promising cancer therapy. In this review, we discuss the progress of NIR-PIT, their mechanism and design strategies for cancer treatment. Furthermore, the overall possible targeting molecules for NIR-PIT with their application for cancer treatment are briefly summarised.
Anti-Hypoxia Nanoplatforms for Enhanced Photosensitizer Uptake and Photodynamic Therapy Effects in Cancer Cells
Authors: Nkune Nkune Williams , Abrahamse Heidi
Published: January 2023

Photodynamic therapy (PDT) holds great promise in cancer eradication due to its target selectivity, non-invasiveness, and low systemic toxicity. However, due to the hypoxic nature of many native tumors, PDT is frequently limited in its therapeutic effect. Additionally, oxygen consumption during PDT may exacerbate the tumor’s hypoxic condition, which stimulates tumor proliferation, metastasis, and invasion, resulting in poor treatment outcomes. Therefore, various strategies have been developed to combat hypoxia in PDT, such as oxygen carriers, reactive oxygen supplements, and the modulation of tumor microenvironments. However, most PDT-related studies are still conducted on two-dimensional (2D) cell cultures, which fail to accurately reflect tissue complexity. Thus, three-dimensional (3D) cell cultures are ideal models for drug screening, disease simulation and targeted cancer therapy, since they accurately replicate the tumor tissue architecture and microenvironment. This review summarizes recent advances in the development of strategies to overcome tumor hypoxia for enhanced PDT efficiency, with a particular focus on nanoparticle-based photosensitizer (PS) delivery systems, as well as the advantages of 3D cell cultures.
Phytochemicals as Immunomodulatory Agents in Melanoma
Authors: Tabolacci Claudio , De Vita Daniela , Facchiano Antonio , Bozzuto Giuseppina , Beninati Simone , Failla Cristina Maria , Di Martile Marta , Lintas Carla , Mischiati Carlo , Stringaro Annarita , Del Bufalo Donatella , Facchiano Francesco
Published: January 2023

Cutaneous melanoma is an immunogenic highly heterogenic tumor characterized by poor outcomes when it is diagnosed late. Therefore, immunotherapy in combination with other anti-proliferative approaches is among the most effective weapons to control its growth and metastatic dissemination. Recently, a large amount of published reports indicate the interest of researchers and clinicians about plant secondary metabolites as potentially useful therapeutic tools due to their lower presence of side effects coupled with their high potency and efficacy. Published evidence was reported in most cases through in vitro studies but also, with a growing body of evidence, through in vivo investigations. Our aim was, therefore, to review the published studies focused on the most interesting phytochemicals whose immunomodulatory activities and/or mechanisms of actions were demonstrated and applied to melanoma models.
A Comprehensive Review on Silk Fibroin as a Persuasive Biomaterial for Bone Tissue Engineering
Authors: Li Minghui , You Jiaqian , Qin Qiuyue , Liu Manxuan , Yang Yixin , Jia Kewen , Zhang Yidi , Zhou Yanmin
Published: January 2023

Bone tissue engineering (BTE) utilizes a special mix of scaffolds, cells, and bioactive factors to regulate the microenvironment of bone regeneration and form a three-dimensional bone simulation structure to regenerate bone tissue. Silk fibroin (SF) is perhaps the most encouraging material for BTE given its tunable mechanical properties, controllable biodegradability, and excellent biocompatibility. Numerous studies have confirmed the significance of SF for stimulating bone formation. In this review, we start by introducing the structure and characteristics of SF. After that, the immunological mechanism of SF for osteogenesis is summarized, and various forms of SF biomaterials and the latest development prospects of SF in BTE are emphatically introduced. Biomaterials based on SF have great potential in bone tissue engineering, and this review will serve as a resource for future design and research.
Leptin, Adiponectin, and Melatonin Modulate Colostrum Lymphocytes in Mothers with Obesity
Authors: Pereira Gabrielle do Amaral Virginio , Morais Tassiane Cristina , França Eduardo Luzia , Daboin Blanca Elena Guerrero , Bezerra Italla Maria Pinheiro , Pessoa Rafael Souza , de Quental Ocilma Barros , Honório-França Adenilda Cristina , Abreu Luiz Carlos de
Published: January 2023

Pregnancy complicated by obesity is associated with adverse triggered gestational and neonatal outcomes, with reductions in the subtypes of CD4+ T-lymphocytes representing the modulators of inflammation. It needs to be better established how maternal nutritional statuses impact the neuroendocrine–immune system’s action and affect the immunological mechanisms of the maternal–infant relationship via breastfeeding. This study examined the effects of maternal obesity on human colostrum lymphocytes and the intracellular mechanisms of lymphocyte modulation in the presence of leptin, adiponectin, and melatonin via cell proliferation; the release of intracellular calcium; and apoptosis induction. This cross-sectional study analyzed colostrum samples from 52 puerperal splits and divided them into overweight and eutrophic groups. Colostrum lymphocytes underwent immunophenotyping and cell proliferation by flow cytometry and intracellular calcium release and apoptosis assays by immunofluorescence in the presence or absence of hormones. Significant differences were considered when p < 0.05 by the chi-square or t-test. Maternal obesity reduced the population of T-lymphocytes and TCD4+ in human colostrum and proliferative activities (p < 0.05). These hormones restore lymphocyte proliferation to a level similar to the eutrophic group (p < 0.05). Leptin, adiponectin, melatonin hormones, and biological actions consolidated in the scientific literature also represent maternal and infant protection mechanisms via colostrum and the modulation of human colostrum lymphocytes.
Prospect of Bioactive Curcumin Nanoemulsion as Effective Agency to Improve Milk Based Soft Cheese by Using Ultrasound Encapsulation Approach
Authors: Bagale Uday , Kadi Ammar , Abotaleb Mostafa , Potoroko Irina , Sonawane Shirish Hari
Published: January 2023

The aim of this paper was to determine the effect of stabilized curcumin nanoemulsions (CUNE) as a food additive capable of directionally acting to inhibit molecules involved in dairy products’ quality and digestibility, especially cheese. The objects were cheeses made from the milk of higher grades with addition of a CUNE and a control sample. The cheeses were studied using a scanning electron microscope (SEM) in terms of organoleptic properties, such as appearance, taste, and aroma. The results show that the addition of CUNEs improved the organoleptic properties compared to the control cheese by 150% and improved its shelf life. The SEM study shows that formulation with CUNE promotes the uniform distribution of porosity. The CUNE-based cheese shows a better sensory evaluation compared to the emulsion without curcumin. CUNE-processed cheese provided better antioxidant and antimicrobial analysis than the control sample and offers added value to the dairy sector.
Looking at Biomolecular Interactions through the Lens of Correlated Fluorescence Microscopy and Optical Tweezers
Authors: Haghizadeh Anahita , Iftikhar Mariam , Dandpat Shiba S. , Simpson Trey
Published: January 2023

Understanding complex biological events at the molecular level paves the path to determine mechanistic processes across the timescale necessary for breakthrough discoveries. While various conventional biophysical methods provide some information for understanding biological systems, they often lack a complete picture of the molecular-level details of such dynamic processes. Studies at the single-molecule level have emerged to provide crucial missing links to understanding complex and dynamic pathways in biological systems, which are often superseded by bulk biophysical and biochemical studies. Latest developments in techniques combining single-molecule manipulation tools such as optical tweezers and visualization tools such as fluorescence or label-free microscopy have enabled the investigation of complex and dynamic biomolecular interactions at the single-molecule level. In this review, we present recent advances using correlated single-molecule manipulation and visualization-based approaches to obtain a more advanced understanding of the pathways for fundamental biological processes, and how this combination technique is facilitating research in the dynamic single-molecule (DSM), cell biology, and nanomaterials fields.
Oxidation State in Peritoneal Dialysis in Patients with Type 2 Diabetes Mellitus
Authors: Pazarín-Villaseñor Leonardo , García-Salas Yessica , Yanowsky-Escatell Francisco Gerardo , Pacheco-Moisés Fermín Paul , Andrade-Sierra Jorge , Campos-Bayardo Tannia Isabel , Román-Rojas Daniel , García-Sánchez Andrés , Miranda-Díaz Alejandra Guillermina
Published: January 2023

End-stage renal disease (ESRD) progression is closely related to oxidative stress (OS). The study objective was to determine the oxidant and antioxidant status in peritoneal dialysis (PD) patients with type 2 diabetes mellitus (DM). An analytical cross-sectional study from the PD program was carried out with 62 patients, 22 with and 40 without DM. Lipoperoxides (LPO) levels in patients with DM, 3.74 ± 1.09 mM/L, and without DM, 3.87 ± 0.84 mM/L were found to increase compared to healthy controls (HC) 3.05 ± 0.58 mM/L (p = 0.006). The levels of the oxidative DNA damage marker (8-OH-dG) were found to be significantly increased in patients with DM, 1.71 ng/mL (0.19–71.92) and without DM, 1.05 ng/mL (0.16–68.80) front to 0.15 ng/mL (0.15–0.1624) of HC (p = 0.001). The antioxidant enzyme superoxide dismutase (SOD) activity was found to be significantly increased in patients with DM, 0.37 ± 0.15 U/mL, and without DM, 0.37 ± 0.17 compared to HC, 0.23 ± 0.05 U/mL (p = 0.038). The activity of the enzyme glutathione peroxidase (GPx) showed a significant increase (p < 0.001) in patients with DM, 3.56 ± 2.18 nmol/min/mL, and without DM, 3.28 ± 1.46 nmol/min/mL, contrary to the activity obtained in HC, 1.55 ± 0.34 nmol/min/mL. In conclusion, we found an imbalance of oxidative status in patients undergoing PD with and without DM through the significant increase in LPO oxidants and the marker of oxidative damage in DNA. The activity of the antioxidant enzymes SOD and GPx were significantly increased in patients with and without DM undergoing PD, possibly in an attempt to compensate for the deregulation of oxidants. Antioxidant enzymes could be promising therapeutic strategies as a complement to the management of chronic kidney diseases.
Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms—A Systematic Review
Authors: Lucidi Daniela , Cantaffa Carla , Miglio Matteo , Spina Federica , Alicandri Ciufelli Matteo , Marchioni Alessandro , Marchioni Daniele
Published: January 2023

Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between September and November 2022. The authors considered the three main histological patterns of sinonasal tumors, namely Squamous Cell Carcinoma, Intestinal-Type Adenocarcinoma, and Olfactory Neuroblastoma. In total, 246 articles were eventually included in the analysis. The genetic and epigenetic changes underlying the oncogenic process were discussed, through a qualitative synthesis of the included studies. The identification of a comprehensive model of carcinogenesis for each sinonasal cancer subtype is needed, in order to pave the way toward tailored treatment approaches and improve survival for this rare and challenging group of cancers.
DNA Damage Response Gene Signature as Potential Treatment Markers for Oral Squamous Cell Carcinoma
Authors: Pomella Silvia , Cassandri Matteo , Melaiu Ombretta , Marampon Francesco , Gargari Marco , Campanella Vincenzo , Rota Rossella , Barillari Giovanni
Published: January 2023

Oral squamous cell carcinoma (OSCC) is a rapidly progressive cancer that often develops resistance against DNA damage inducers, such as radiotherapy and chemotherapy, which are still the standard of care regimens for this tumor. Thus, the identification of biomarkers capable of monitoring the clinical progression of OSCC and its responsiveness to therapy is strongly required. To meet this need, here we have employed Whole Genome Sequencing and RNA-seq data from a cohort of 316 patients retrieved from the TCGA Pan-Cancer Atlas to analyze the genomic and transcriptomic status of the DNA damage response (DDR) genes in OSCC. Then, we correlated the transcriptomic data with the clinical parameters of each patient. Finally, we relied on transcriptomic and drug sensitivity data from the CTRP v2 portal, performing Pearson’s correlation analysis to identify putative vulnerabilities of OSCC cell lines correlated with DDR gene expression. Our results indicate that several DDR genes show a high frequency of genomic and transcriptomic alterations and that the expression of some of them correlates with OSCC grading and infection by the human papilloma virus. In addition, we have identified a signature of eight DDR genes (namely CCNB1, CCNB2, CDK2, CDK4, CHECK1, E2F1, FANCD2, and PRKDC) that could be predictive for OSCC response to the novel antitumor compounds sorafenib and tipifarnib-P1. Altogether, our data demonstrate that alterations in DDR genes could have an impact on the biology of OSCC. Moreover, here we propose a DDR gene signature whose expression could be predictive of OSCC responsiveness to therapy.
Myofilament Alterations Associated with Human R14del-Phospholamban Cardiomyopathy
Authors: Kumar Mohit , Haghighi Kobra , Koch Sheryl , Rubinstein Jack , Stillitano Francesca , Hajjar Roger J. , Kranias Evangelia G. , Sadayappan Sakthivel
Published: January 2023

Phospholamban (PLN) is a major regulator of cardiac contractility, and human mutations in this gene give rise to inherited cardiomyopathies. The deletion of Arginine 14 is the most-prevalent cardiomyopathy-related mutation, and it has been linked to arrhythmogenesis and early death. Studies in PLN-humanized mutant mice indicated an increased propensity to arrhythmias, but the underlying cellular mechanisms associated with R14del-PLN cardiac dysfunction in the absence of any apparent structural remodeling remain unclear. The present study addressed the specific role of myofilaments in the setting of R14del-PLN and the long-term effects of R14del-PLN in the heart. Maximal force was depressed in skinned cardiomyocytes from both left and right ventricles, but this effect was more pronounced in the right ventricle of R14del-PLN mice. In addition, the Ca2+ sensitivity of myofilaments was increased in both ventricles of mutant mice. However, the depressive effects of R14del-PLN on contractile parameters could be reversed with the positive inotropic drug omecamtiv mecarbil, a myosin activator. At 12 months of age, corresponding to the mean symptomatic age of R14del-PLN patients, contractile parameters and Ca2+ transients were significantly depressed in the right ventricular R14del-PLN cardiomyocytes. Echocardiography did not reveal any alterations in cardiac function or remodeling, although histological and electron microscopy analyses indicated subtle alterations in mutant hearts. These findings suggest that both aberrant myocyte calcium cycling and aberrant contractility remain specific to the right ventricle in the long term. In addition, altered myofilament activity is an early characteristic of R14del-PLN mutant hearts and the positive inotropic drug omecamtiv mecarbil may be beneficial in treating R14del-PLN cardiomyopathy.
Leading Edge: Intratumor Delivery of Monoclonal Antibodies for the Treatment of Solid Tumors
Authors: Blanco Ester , Chocarro Luisa , Fernández-Rubio Leticia , Bocanegra Ana , Arasanz Hugo , Echaide Miriam , Garnica Maider , Piñeiro-Hermida Sergio , Kochan Grazyna , Escors David
Published: January 2023

Immunotherapies based on immune checkpoint blockade have shown remarkable clinical outcomes and durable responses in patients with many tumor types. Nevertheless, these therapies lack efficacy in most cancer patients, even causing severe adverse events in a small subset of patients, such as inflammatory disorders and hyper-progressive disease. To diminish the risk of developing serious toxicities, intratumor delivery of monoclonal antibodies could be a solution. Encouraging results have been shown in both preclinical and clinical studies. Thus, intratumor immunotherapy as a new strategy may retain efficacy while increasing safety. This approach is still an exploratory frontier in cancer research and opens up new possibilities for next-generation personalized medicine. Local intratumor delivery can be achieved through many means, but an attractive approach is the use of gene therapy vectors expressing mAbs inside the tumor mass. Here, we summarize basic, translational, and clinical results of intratumor mAb delivery, together with descriptions of non-viral and viral strategies for mAb delivery in preclinical and clinical development. Currently, this is an expanding research subject that will surely play a key role in the future of oncology.
Development of an Engineered Slurry-Infiltrated Fibrous Concrete: Experimental and Modelling Approaches
Authors: Yas Mohammed H. , Kadhum Mohammed M. , Al-Dhufairi Watheq G. B.
Published: January 2023

Concrete is the central pile for the infrastructure that maintains civilisation and human life. The concrete industry faces many challenges, including improving mechanical properties, eco-friendliness, and durability. In this context, the present study focuses on evaluating and modelling themechanical properties of engineered concrete, namely slurry-infiltrated fibrous concrete (SIFCON). The main experiments will be devoted to measuring and modelling the failures of slabs made from SIFCON under two loading systems, namely static and impact loading systems. The model was developed using a non-linear finite element analysis. The experiments considered the influence of the geometry of the reinforcement steel fibres (hook-end fibres, microfibres, and combined hook-end and microfibres), sizes of fibres, and slab dimensions. The outcomes of this investigation showed that increasing the slab’s thickness enhances the load-bearing capacity of the SIFCON slab, and the microfibres and combined hook-end and microfibres improved the load-bearing capacity of the slab compared to the hook-end fibre. Generally, it was noticed that the outcomes of the experiments agreed with the modelling outcomes. Nevertheless, it was noticed that experimentally measured axial deformation was more significant than the predicted axial deformation. In summary, the difference between experimental and modelling outcomes was 1.1–10.2%, with a standard deviation of 0.0264. Based on the excellent ability of SIFCON to resist impacts and dynamic loads, it is recommended to be used in pavements, military structures, nuclear reactor walls, and in areas subjected to high bending moments, such as corner connections subjected to opening bending moments.
Treatment of Rapamycin and Evaluation of an Autophagic Response in the Gut of Bactericera cockerelli (Sulč)
Authors: Oh Junepyo , Tamborindeguy Cecilia
Published: January 2023

Autophagy is a catabolic process that results in the autophagosomic–lysosomal degradation of bulk cytoplasmic content, abnormal protein aggregates, and excess of/or damaged organelles to promote cell survival. Autophagy is also a component of innate immunity in insects and is involved in the clearance of pathogens, including bacteria. The potato psyllid, Bactericera cockerelli, transmits the plant bacterial pathogen ‘Candidatus Liberibacter solanacearum’ (Lso) in the Americas and causes serious damage to solanaceous crops. Our previous studies showed that autophagy could be involved in the psyllid response to Lso and could affect pathogen acquisition. However, the tools to evaluate this response have not been validated in psyllids. To this end, the effect of rapamycin, a commonly used autophagy inducer, on potato psyllid survival and the expression of autophagy-related genes was evaluated. Further, the autophagic activity was assessed via microscopy and by measuring the autophagic flux. Artificial diet-feeding assays using rapamycin resulted in significant psyllid mortality, an increase in the autophagic flux, as well as an increase in the amount of autolysosomes. This study represents a stepping stone in determining the role of autophagy in psyllid immunity.
Effect of Left Atrial Pulmonary Vein Angiography on Safety and Efficacy for High-Power, Short-Duration Pulmonary Vein Isolation in Patients with Atrial Fibrillation
Authors: Weyand Sebastian , Adam Viola , Beuter Matthias , Hanger Simon , Heinzmann David , Schrezenmeier Willibald , Seizer Peter
Published: January 2023

Imaging of pulmonary vein (PV) anatomy by angiography before pulmonary vein isolation (PVI) for atrial fibrillation (AF) has long been standard practice in many centers. Nowadays, very accurate anatomical maps can be generated by the use of high-resolution mapping catheters, and very effective ablation lesions can be generated by the use of the high-power, short-duration (HPSD) technique. In our center, PV angiography was routinely performed before PVI. However, since there is no clear evidence for this, we refrained from performing PV angiography. This study aimed to investigate whether PV angiography is still necessary when using high-resolution mapping catheters after ablation in the high-power, short-duration (HPSD) technique. A total of 139 consecutive patients with atrial fibrillation (66.25 ± 11.68 years old, 62.39% male) undergoing radiofrequency PVI were included in the study. Ablation was performed with the HPSD technique using a fixed protocol for energy delivery of 50 watts (contact force 3–20 g). We observed no significant effect on the efficacy, efficiency and complications of the ablation procedure if pulmonary vein angiography was omitted before HPSD PVI. Thus, using our protocol, it may be useful that PV angiography is avoided, especially in young patients and those with chronic renal disease.
The Impact of Lung Cancer in Patients with Combined Pulmonary Fibrosis and Emphysema (CPFE)
Authors: Feng Xiaoyi , Duan Yishan , Lv Xiafei , Li Qinxue , Liang Binmiao , Ou Xuemei
Published: January 2023

Given the high risk of lung cancer (LC) in patients with combined pulmonary fibrosis and emphysema (CPFE), and the difficulty of early diagnosis, it is important to understand the impact of LC in these patients. The effect of LC on the development of acute exacerbation (AE) as a natural course of CPFE is still unknown. We retrospectively reviewed medical records of patients at the West China Hospital and enrolled 59 patients with CPFE combined with LC and 68 CPFE patients without LC for initial diagnosis matched in the same period. We compared the clinical characteristics and imaging features of CPFE patients with LC and without LC, and analyzed the associated factors for the prevalence of LC using binary logistic regression. Cox proportional hazards regression analysis was performed to explore risk factors of AE as a natural course of CPFE. Patients with CPFE combined with LC were more common among elderly male smokers. The most common pathological type of tumor was adenocarcinoma (24/59, 40.7%) and squamous cell carcinoma (18/59, 30.5%). Compared with those in the without LC group, the proportions of men, and ex- or current smokers, and the levels of smoking pack-years, serum CRP, IL-6, fibrinogen, complement C3 and C4 in patients with LC were significantly higher (p < 0.05). There was no significant difference in the proportion of natural-course-related AE (10.2% vs. 16.2%, p > 0.05) between the two groups. Logistic regression analysis demonstrated that pack-years ≥ 20 (OR: 3.672, 95% CI: 1.165–11.579), family history of cancer (OR: 8.353, 95% CI: 2.368–10.417), the level of fibrinogen > 4.81 g/L (OR: 3.628, 95% CI: 1.403–9.385) and serum C3 > 1.00 g/L (OR: 5.299, 95% CI: 1.727–16.263) were independently associated with LC in patients with CPFE. Compared to those without AE, CPFE patients with AE had significantly higher levels of PLR and serum CRP, with obviously lower DLCO and VC. The obviously increased PLR (HR: 3.731, 95% CI: 1.288–10.813), and decreased DLCO%pred (HR: 0.919, 95% CI: 0.863–0.979) and VC%pred (HR: 0.577, 95% CI: 0.137–0.918) rather than the presence of LC independently contributed to the development of natural-course-related AE in patients with CPFE. Pack-years, family history of cancer, the levels of fibrinogen and serum C3 were independently associated with LC in patients with CPFE. The presence of LC did not significantly increase the risk of AE as a natural course of CPFE. Clinicians should give high priority to CPFE patients, especially those with more severe fibrosis and systemic inflammation, in order to be alert for the occurrence of AE.
Contributions of Adaptive Laboratory Evolution towards the Enhancement of the Biotechnological Potential of Non-Conventional Yeast Species
Authors: Fernandes Ticiana , Osório Carolina , Sousa Maria João , Franco-Duarte Ricardo
Published: January 2023

Changes in biological properties over several generations, induced by controlling short-term evolutionary processes in the laboratory through selective pressure, and whole-genome re-sequencing, help determine the genetic basis of microorganism’s adaptive laboratory evolution (ALE). Due to the versatility of this technique and the imminent urgency for alternatives to petroleum-based strategies, ALE has been actively conducted for several yeasts, primarily using the conventional species Saccharomyces cerevisiae, but also non-conventional yeasts. As a hot topic at the moment since genetically modified organisms are a debatable subject and a global consensus on their employment has not yet been attained, a panoply of new studies employing ALE approaches have emerged and many different applications have been exploited in this context. In the present review, we gathered, for the first time, relevant studies showing the ALE of non-conventional yeast species towards their biotechnological improvement, cataloging them according to the aim of the study, and comparing them considering the species used, the outcome of the experiment, and the employed methodology. This review sheds light on the applicability of ALE as a powerful tool to enhance species features and improve their performance in biotechnology, with emphasis on the non-conventional yeast species, as an alternative or in combination with genome editing approaches.