bluuebunny/crossref_metadata_2025 huggingface dataset:
Iliacus Muscle Hematoma an Uncommon Complication in a Rehabilitation Unit: A Case Report Study
Authors: Battaglia Riccardo , Cerasa Antonio , Pugliese Maria Elena , Lucca Lucia Francesca , Tonin Paolo
Published: February 2022

Iliacus muscle hematoma is a very rare condition in rehabilitation wards. A 35-year-old pregnant woman at seven months with cerebellar hematoma with signs of compression underwent a cesarean procedure together with neurosurgical decompression of the posterior cranial fossa procedure. After a period in an intensive unit without any complications, she was admitted to our neurorehabilitation ward and treated with antihypertensive therapy, heparin, and anti-seizure drugs. During a rehabilitation session, after a bed–wheelchair transfer, she was feeling very unwell suffering from severe right leg pain radiating to the mid-face leg. Despite unremarkable physical evidence (skin appearance, temperature, and peripheral arterial pulse in both legs), imaging data (ultrasound, CT, and MRI) confirmed the presence of a right iliac muscle hematoma (IMH). Enoxaparin was immediately stopped, and bed rest was prescribed in an antalgic position with tramadole acetaminophen for pain control. After a few days, the patient felt well and was discharged without any additional symptoms. Our study demonstrates that, when a sudden severe leg pain develops, IMH should be considered in the differential diagnosis. This finding suggests further research and tailored protocols for rehabilitation in patients at high risk for iliacus muscle hematoma.
Comparison of Metabolites and Gut Microbes between Patients with Parkinson’s Disease and Healthy Individuals—A Pilot Clinical Observational Study (STROBE Compliant)
Authors: Kim Cheol-Hyun , Jung Jeeyoun , Lee Young-ung , Kim Kwang-ho , Kang Sunny , Kang Geon-hui , Chu Hongmin , Kim Se-Young , Lee Sangkwan
Published: February 2022

Introduction: Even if levodopa, dopamine agonists, and others are used for patients with Parkinson’s disease, the effect is not sustained, and side effects such as motor fluctuation and dyskinesia are more likely to appear as the dose increases. Thus, new approaches for managing Parkinson’s disease are needed. This study aimed to compare the metabolites and gut microbes between patients with Parkinson’s disease and healthy individuals. Methods: This was an observational study with a case-control design. Metabolite and gut microbial analyses were performed using blood and stool samples collected from the subjects. Results: Among the metabolites, the acetate, citrate, methionine, and trimethylamine levels were significantly different between the two groups. In the gut microbes, abundance of Bacteroidetes, Prevotella, Phascolarctobacterium, Pseudoflavonifractor, Eisenbergiella, and Gemella were also significantly different between the two groups. Discussion: Metabolites are the products of gut microbes. Therefore, when the gut microbes change, the metabolites change accordingly. Metabolites and gut microbes that were significantly different between the two groups were mostly those involved in lipid and glucose metabolism. Our data may be helpful for the development of new drugs targeting metabolites and gut microbes through large-scale studies in the future.
The Safety and Efficacy of Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibodies for the Preventive Treatment of Migraine: A Protocol for Multiple-Treatment Systematic Review and Meta-Analysis
Authors: Fernández-Bravo-Rodrigo Jaime , Pascual-Morena Carlos , Flor-García Amparo , Saz-Lara Alicia , Sequí-Dominguez Irene , Álvarez-Bueno Celia , Barreda-Hernández Dolores , Cavero-Redondo Iván
Published: February 2022

Background: Migraine is a common and disabling primary headache disorder, associated with many medical comorbidities, highly prevalent, with complex treatment and management. Currently, monoclonal antibodies targeting the trigeminal sensory neuropeptide, calcitonin gene-related peptide (CGRP), are available. The aim of this protocol is to provide a review comparing the effects and safety profile of different monoclonal antibodies in migraine patients. Methods: The literature search will be performed through the MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), Web of Science and Scopus databases, following the PICO strategy. Real World studies and randomized clinical trials assessing the effect of monoclonal antibodies against CGRP interventions (erenumab, eptinezumab, fremanezumab and galcanezumab) on monthly migraine days (MMD), monthly headache days (MHD), headache impact test (HIT-6) and triptan days of use (TriD) will be included. In Real World studies, the DerSimonian and Laird method will be used to calculate pooled estimates of the mean change difference and in randomized clinical trials, a network meta-analysis will be performed to estimate the comparative effects of different monoclonal antibodies against CGRP. Results: The findings of this study will be reported in a peer-reviewed journal. Conclusions: This study will provide evidence to health professionals on the efficacy and safety of different monoclonal antibodies against CGRP on the outcomes studied.
Spatial and Temporal Analysis of Impacts of Hurricane Florence on Criteria Air Pollutants and Air Toxics in Eastern North Carolina
Authors: Bhandari Sharmila , Casillas Gaston , Aly Noor A. , Zhu Rui , Newman Galen , Wright Fred A. , Miller Anthony , Adler Gabriela , Rusyn Ivan , Chiu Weihsueh A.
Published: February 2022

Natural and anthropogenic disasters are associated with air quality concerns due to the potential redistribution of pollutants in the environment. Our objective was to conduct a spatiotemporal analysis of air concentrations of benzene, toluene, ethylbenzne, and xylene (BTEX) and criteria air pollutants in North Carolina during and after Hurricane Florence. Three sampling campaigns were carried out immediately after the storm (September 2018) and at four-month intervals. BTEX were measured along major roads. Concurrent criteria air pollutant concentrations were predicted from modeling. Correlation between air pollutants and possible point sources was conducted using spatial regression. Exceedances of ambient air criteria were observed for benzene (in all sampling periods) and PM2.5 (mostly immediately after Florence). For both, there was an association between higher concentrations and fueling stations, particularly immediately after Florence. For other pollutants, concentrations were generally below levels of regulatory concern. Through characterization of air quality under both disaster and “normal” conditions, this study demonstrates spatial and temporal variation in air pollutants. We found that only benzene and PM2.5 were present at levels of potential concern, and there were localized increases immediately after the hurricane. These substances warrant particular attention in future disaster response research (DR2) investigations.
Physical Activity Is Associated with Improved Visuomotor Processing in Older Adults with Moderate and Advanced Glaucomatous Visual Field Defect: A Cross-Sectional Study
Authors: Zwierko Teresa , Jedziniak Wojciech , Florkiewicz Beata , Lesiakowski Piotr , Śliwiak Marta , Kirkiewicz Marta , Lubiński Wojciech
Published: February 2022

Glaucoma affects a wide spectrum of daily essential activities in older adults. This study examined whether older adults with moderate and advanced stages of glaucoma exhibit differences in visuomotor task performance compared with age- and gender-matched ophthalmologically healthy control subjects and estimated the effects of physical activity (PA) levels, age, and severity of visual impairment on patients’ visuomotor task performance. Sixty older adults with moderate glaucoma, advanced glaucoma, and normal sight participated in the study. Visuomotor processing was assessed using laboratory-based simple and complex visuomotor reaction tasks. Monocular Humphrey Visual Field and binocular Humphrey Esterman Visual Field tests were used to estimate visual field defect severity. The International Physical Activity Questionnaire was used to assess PA levels. Participants with glaucoma had poorer scores in visuomotor tasks compared to participants with normal sight. Glaucoma patients’ PA levels, age, and binocular visual field defect explained 54% of the variation in complex reaction time. Low PA levels were identified as a risk factor for visuomotor processing decline. Compensatory mechanisms to improve the efficiency of visual field scanning in patients with more severe visual field defects may exist.
Resilience during Crisis and the Role of Age: Involuntary Telework during the COVID-19 Pandemic
Authors: Scheibe Susanne , De Bloom Jessica , Modderman Ton
Published: February 2022

We investigated the relationship between age, resilience, job demands and resources, and self-regulation in 1715 university employees during the COVID-19 pandemic (February 2021) by means of an online survey with closed and open questions. Correlation, regression, and qualitative analyses showed that older employees reported higher resilience than younger employees. This finding was robust after controlling for background factors (i.e., gender, expat status, job type, living alone). Age and resilience were directly related to higher job resources (i.e., job security and equipment), work–life balance, and seeing positives, whereas the relationship to demands was ambiguous. Age was unrelated to workload, negatively related to childcare, and positively to eldercare. Resilience was negatively related to workload but unrelated to childcare or eldercare demands. When all variables were combined to jointly predict resilience, age, job resources, and self-regulation resources predicted resilience, whereas demands (i.e., workload, childcare, and eldercare demands) did not. Our findings suggest that age-related advantages in well-being have persisted during the COVID-19 pandemic. Older workers were more likely to reframe the crisis and see it as an opportunity for personal growth. They possess and utilize resources in unique and beneficial ways, which could also benefit younger workers.
Gaming Behaviors and the Association with Sleep Duration, Social Jetlag, and Difficulties Falling Asleep among Norwegian Adolescents
Authors: Hamre Regina , Smith Otto Robert Frans , Samdal Oddrun , Haug Ellen
Published: February 2022

The relationship between gaming and sleep is mostly informed by studies of addictive gaming behavior, thus limiting our understanding of sleep in the context of nonproblematic engaged gaming. The present study investigated whether addicted, problem, and engaged gaming behavior was associated with sleep duration, social jetlag, and difficulties falling asleep. The sample consisted of 13- and 16-year-old Norwegian adolescents (n = 3228) participating in the Health Behavior in School-Aged Children (HBSC) survey in 2018. Participants were categorized into addicted, problem, engaged, and normal/non-gaming behavior groups according to which GAS-7 criteria they fulfilled. Robust generalized linear mixed models with a random intercept for class ID were used to examine the association between the sleep variables and gaming behavior. Addicted gaming behavior was unfavorably associated with all sleep parameters. The findings for engaged gaming and problem gaming behavior were somewhat mixed. Engaged gamers slept less on weekends, less on weekdays for those aged 16, and experienced greater social jetlag compared to the normal/non-gaming group. Problem gamers experienced greater social jetlag and had higher odds of experiencing difficulties falling asleep. Overall, the results suggest that all types of gaming behaviors might harm sleep health, but to a greater extent for the addicted gamers.
Health and Non-Health Determinants of Consumer Behavior toward Private Label Products—A Systematic Literature Review
Authors: Czeczotko Maksymilian , Górska-Warsewicz Hanna , Zaremba Robert
Published: February 2022

This study aimed to analyze the international literature on consumer behavior toward private label (PL) products, guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) method. We searched for peer-reviewed studies published until January 2021 in the Scopus and Web of Science databases using two main search terms, namely, “consumer behavior” and “private label,” which have several synonymous terms, such as “store brand,” “private brand,” and “own label.” A total of 44 eligible studies were selected for the analysis. We formulated research questions regarding the most studied categories of PL products, the non-health factors determining consumer behavior toward PL products, and the frequency of including health aspects in the choice of PL products. The following were analyzed in the studies included in the systematic literature review (SLR): general data and study design (authorship, year of publication, location, characteristics of the sample, and research category), research specifications (factors/variables, hypotheses, and measured parameters), and general findings (findings and practical recommendations). We found that most of the studies had analyzed dairy products as PL products, and the main non-health selection factors used were lower price and price–quality ratios. Health aspects were considered in only four of the analyzed studies, which focused on the evolution of PL products from low-cost products to sustainable brands with significant added value in terms of quality and health aspects.
Ecological Risk Assessment Related to the Presence and Toxicity of Potentially Toxic Elements in Ashes from Household Furnaces
Authors: Kicińska Alicja , Caba Grzegorz , Serwatka Hubert
Published: February 2022

The study material was comprised of 23 samples of ashes generated after the combustion of conventional and alternative fuels combined with selected fractions of municipal waste. The analyses performed involved determining the total concentration of As, Al, Cr, Fe, Ni, and their bioaccessible, ion-exchange, and carbonate-bound fractions. It was found that all of the samples analysed may display an elevated level of susceptibility to the reduction processes, which undoubtedly increases the mobility of trace elements, including the toxic ones. The predominant elements were Al and Fe, whereas considerably lower concentrations were observed for Ni, Cr, and As. The percentage share of the ion-exchange and carbonate-bound fraction ranged from 49% of the total concentration for As to as much as 0.35% in the case of Fe. The calculated Risk Assessment Code index points to a high risk related to the presence of As, medium to low risk related to the presence of Ni and Cr, and low to no risk related to the presence of Fe and Al. The calculated values of the Ecological Risk Index, associated with the combustion of selected municipal waste fractions and low-quality hard coals, combusted individually or in combination with different types of wood, point to a very high ecological risk. This is mainly related to the high concentrations and toxicity of As.
Froth-Flotation Separation as an Alternative for the Treatment of Soil Enriched with Fluorine Derived from Mica
Authors: Cho Jeonghwan , Jung Moon Young , Lee Hwan , An Jinsung
Published: February 2022

Fluorine (F) enrichment originating from natural sources is difficult to remove using chemical washing methods due to the large chemical-resistant residual fraction. This study evaluates the feasibility of using a froth-flotation separation method to remediate soil with a high F concentration caused by mica weathering, and it investigates the optimal conditions for this process, including pH of the slurry, collector dosage, and sample mechanical preparation strategy. The established optimum conditions are pH 3.5, 300 mg/kg collector dosage (tallow amine acetate), which can effectively separate quartz and mica, and a sieving-and-milling strategy that involves discarding particles of size < 0.05 mm, milling those in the range of 0.5–2.0 mm (until < approx. 0.3 mm), and mixing particles with sizes in the range of 0.05–0.5 mm. The target contamination level of 400 mg/kg for the test soil was not met after the first flotation separation process. However, after milling the residue of the first process and subjecting it to a second flotation separation process, the required contamination level was achieved. Consequently, the proposed froth-flotation separation process can be used as a successful alternative technique to remediate F-enriched soils from natural origin that have highly chemical-resistant forms.
Genome-Wide Prediction of Transcription Start Sites in Conifers
Authors: Bondar Eugeniya I. , Troukhan Maxim E. , Krutovsky Konstantin V. , Tatarinova Tatiana V.
Published: February 2022

The identification of promoters is an essential step in the genome annotation process, providing a framework for gene regulatory networks and their role in transcription regulation. Despite considerable advances in the high-throughput determination of transcription start sites (TSSs) and transcription factor binding sites (TFBSs), experimental methods are still time-consuming and expensive. Instead, several computational approaches have been developed to provide fast and reliable means for predicting the location of TSSs and regulatory motifs on a genome-wide scale. Numerous studies have been carried out on the regulatory elements of mammalian genomes, but plant promoters, especially in gymnosperms, have been left out of the limelight and, therefore, have been poorly investigated. The aim of this study was to enhance and expand the existing genome annotations using computational approaches for genome-wide prediction of TSSs in the four conifer species: loblolly pine, white spruce, Norway spruce, and Siberian larch. Our pipeline will be useful for TSS predictions in other genomes, especially for draft assemblies, where reliable TSS predictions are not usually available. We also explored some of the features of the nucleotide composition of the predicted promoters and compared the GC properties of conifer genes with model monocot and dicot plants. Here, we demonstrate that even incomplete genome assemblies and partial annotations can be a reliable starting point for TSS annotation. The results of the TSS prediction in four conifer species have been deposited in the Persephone genome browser, which allows smooth visualization and is optimized for large data sets. This work provides the initial basis for future experimental validation and the study of the regulatory regions to understand gene regulation in gymnosperms.
Multiple Abiotic Stresses Applied Simultaneously Elicit Distinct Responses in Two Contrasting Rice Cultivars
Authors: Habibpourmehraban Fatemeh , Wu Yunqi , Wu Jemma X. , Hamzelou Sara , Masoomi-Aladizgeh Farhad , Kamath Karthik Shantharam , Amirkhani Ardeshir , Atwell Brian J. , Haynes Paul A.
Published: February 2022

Rice crops are often subject to multiple abiotic stresses simultaneously in both natural and cultivated environments, resulting in yield reductions beyond those expected from single stress. We report physiological changes after a 4 day exposure to combined drought, salt and extreme temperature treatments, following a 2 day salinity pre-treatment in two rice genotypes—Nipponbare (a paddy rice) and IAC1131 (an upland landrace). Stomata closed after two days of combined stresses, causing intercellular CO2 concentrations and assimilation rates to diminish rapidly. Abscisic acid (ABA) levels increased at least five-fold but did not differ significantly between the genotypes. Tandem Mass Tag isotopic labelling quantitative proteomics revealed 6215 reproducibly identified proteins in mature leaves across the two genotypes and three time points (0, 2 and 4 days of stress). Of these, 987 were differentially expressed due to stress (cf. control plants), including 41 proteins that changed significantly in abundance in all stressed plants. Heat shock proteins, late embryogenesis abundant proteins and photosynthesis-related proteins were consistently responsive to stress in both Nipponbare and IAC1131. Remarkably, even after 2 days of stress there were almost six times fewer proteins differentially expressed in IAC1131 than Nipponbare. This contrast in the translational response to multiple stresses is consistent with the known tolerance of IAC1131 to dryland conditions.
Histological Grade and Tumor Stage Are Correlated with Expression of Receptor Activator of Nuclear Factor Kappa b (Rank) in Epithelial Ovarian Cancers
Authors: Gomez Raul , Tejada Miguel Á. , Rodríguez-García Víctor , Burgués Octavio , Santos-Llamas Ana I. , Martínez-Massa Andrea , Marín-Montes Antonio , Tarín Juan J. , Cano Antonio
Published: February 2022

The receptor activator of nuclear factor kappa B (RANK) is becoming recognized as a master regulator of tumorigenesis, yet its role in gynecological cancers remains mostly unexplored. We investigated whether there is a gradation of RANK protein and mRNA expression in epithelial ovarian cancer (EOC) according to malignancy and tumor staging. Immunohistochemical expression of RANK was examined in a cohort of 135 (benign n = 29, borderline n= 23 and malignant n = 83) EOCs. Wild type and truncated RANK mRNA isoform quantification was performed in a cohort of 168 (benign n = 26, borderline n = 13 and malignant n = 129) EOCs. RANK protein and mRNA values were increased in malignant vs. benign or borderline conditions across serous, mucinous and endometrioid cancer subtypes. Additionally, a trend of increased RANK values with staging was observed for the mucinous and serous histotype. Thus, increased expression of RANK appears associated with the evolution of disease to the onset of malignancy in EOC. Moreover, in some EOC histotypes, RANK expression is additionally associated with clinicopathological markers of tumor aggressiveness, suggesting a role in further progression of tumor activity.
The Effects of αvβ3 Integrin Blockage in Breast Tumor and Endothelial Cells under Hypoxia In Vitro
Authors: Casali Bruna C. , Gozzer Larissa T. , Baptista Matheus P. , Altei Wanessa F. , Selistre-de-Araújo Heloisa S.
Published: February 2022

Breast cancer is characterized by a hypoxic microenvironment inside the tumor mass, contributing to cell metastatic behavior. Hypoxia induces the expression of hypoxia-inducible factor (HIF-1α), a transcription factor for genes involved in angiogenesis and metastatic behavior, including the vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and integrins. Integrin receptors play a key role in cell adhesion and migration, being considered targets for metastasis prevention. We investigated the migratory behavior of hypoxia-cultured triple-negative breast cancer cells (TNBC) and endothelial cells (HUVEC) upon αvβ3 integrin blocking with DisBa-01, an RGD disintegrin with high affinity to this integrin. Boyden chamber, HUVEC transmigration, and wound healing assays in the presence of DisBa-01 were performed in hypoxic conditions. DisBa-01 produced similar effects in the two oxygen conditions in the Boyden chamber and transmigration assays. In the wound healing assay, hypoxia abolished DisBa-01′s inhibitory effect on cell motility and decreased the MMP-9 activity of conditioned media. These results indicate that αvβ3 integrin function in cell motility depends on the assay and oxygen levels, and higher inhibitor concentrations may be necessary to achieve the same inhibitory effect as in normoxia. These versatile responses add more complexity to the role of the αvβ3 integrin during tumor progression.
On-Growth and In-Growth Osseointegration Enhancement in PM Porous Ti-Scaffolds by Two Different Bioactivation Strategies: Alkali Thermochemical Treatment and RGD Peptide Coating
Authors: Rappe Katrin Steffanie , Ortiz-Hernandez Monica , Punset Miquel , Molmeneu Meritxell , Barba Albert , Mas-Moruno Carles , Guillem-Marti Jordi , Caparrós Cristina , Rupérez Elisa , Calero José , Manzanares María-Cristina , Gil Javier , Franch Jordi
Published: February 2022

A lack of primary stability and osteointegration in metallic implants may result in implant loosening and failure. Adding porosity to metallic implants reduces the stress shielding effect and improves implant performance, allowing the surrounding bone tissue to grow into the scaffold. However, a bioactive surface is needed to stimulate implant osteointegration and improve mechanical stability. In this study, porous titanium implants were produced via powder sintering to create different porous diameters and open interconnectivity. Two strategies were used to generate a bioactive surface on the metallic foams: (1) an inorganic alkali thermochemical treatment, (2) grafting a cell adhesive tripeptide (RGD). RGD peptides exhibit an affinity for integrins expressed by osteoblasts, and have been reported to improve osteoblast adhesion, whereas the thermochemical treatment is known to improve titanium implant osseointegration upon implantation. Bioactivated scaffolds and control samples were implanted into the tibiae of rabbits to analyze the effect of these two strategies in vivo regarding bone tissue regeneration through interconnected porosity. Histomorphometric evaluation was performed at 4 and 12 weeks after implantation. Bone-to-implant contact (BIC) and bone in-growth and on-growth were evaluated in different regions of interest (ROIs) inside and outside the implant. The results of this study show that after a long-term postoperative period, the RGD-coated samples presented higher quantification values of quantified newly formed bone tissue in the implant’s outer area. However, the total analyzed bone in-growth was observed to be slightly greater in the scaffolds treated with alkali thermochemical treatment. These results suggest that both strategies contribute to enhancing porous metallic implant stability and osteointegration, and a combination of both strategies might be worth pursuing.
Nanocarrier-Based Delivery of SN22 as a Tocopheryl Oxamate Prodrug Achieves Rapid Tumor Regression and Extends Survival in High-Risk Neuroblastoma Models
Authors: Alferiev Ivan S. , Guerrero David T. , Soberman Danielle , Guan Peng , Nguyen Ferro , Kolla Venkatadri , Fishbein Ilia , Pressly Blake B. , Brodeur Garrett M. , Chorny Michael
Published: February 2022

Despite the use of intensive multimodality therapy, the majority of high-risk neuroblastoma (NB) patients do not survive. Without significant improvements in delivery strategies, anticancer agents used as a first-line treatment for high-risk tumors often fail to provide clinically meaningful results in the settings of disseminated, recurrent, or refractory disease. By enhancing pharmacological selectivity, favorably shifting biodistribution, strengthening tumor cell killing potency, and overcoming drug resistance, nanocarrier-mediated delivery of topoisomerase I inhibitors of the camptothecin family has the potential to dramatically improve treatment efficacy and minimize side effects. In this study, a structurally enhanced camptothecin analog, SN22, reversibly coupled with a redox-silent tocol derivative (tocopheryl oxamate) to allow its optimally stable encapsulation and controlled release from PEGylated sub-100 nm nanoparticles (NP), exhibited strong NB cell growth inhibitory activity, translating into rapid regression and durably suppressed regrowth of orthotopic, MYCN-amplified NB tumors. The robust antitumor effects and markedly extended survival achieved in preclinical models recapitulating different phases of high-risk disease (at diagnosis vs. at relapse with an acquired loss of p53 function after intensive multiagent chemotherapy) demonstrate remarkable potential of SN22 delivered in the form of a hydrolytically cleavable superhydrophobic prodrug encapsulated in biodegradable nanocarriers as an experimental strategy for treating refractory solid tumors in high-risk cancer patients.
Expression of a Truncated Form of ODAD1 Associated with an Unusually Mild Primary Ciliary Dyskinesia Phenotype
Authors: Ostrowski Lawrence E. , Yin Weining , Smith Amanda J. , Sears Patrick R. , Bustamante-Marin Ximena M. , Dang Hong , Hildebrandt Friedhelm , Daniels Leigh Anne , Capps Nicole A. , Sullivan Kelli M. , Leigh Margaret W. , Zariwala Maimoona A. , Knowles Michael R.
Published: February 2022

Primary ciliary dyskinesia (PCD) is a rare lung disease caused by mutations that impair the function of motile cilia, resulting in chronic upper and lower respiratory disease, reduced fertility, and a high prevalence of situs abnormalities. The disease is genetically and phenotypically heterogeneous, with causative mutations in > 50 genes identified, and clinical phenotypes ranging from mild to severe. Absence of ODAD1 (CCDC114), a component of the outer dynein arm docking complex, results in a failure to assemble outer dynein arms (ODAs), mostly immotile cilia, and a typical PCD phenotype. We identified a female (now 34 years old) with an unusually mild clinical phenotype who has a homozygous non-canonical splice mutation (c.1502+5G>A) in ODAD1. To investigate the mechanism for the unusual phenotype, we performed molecular and functional studies of cultured nasal epithelial cells. We demonstrate that this splice mutation results in the expression of a truncated protein that is attached to the axoneme, indicating that the mutant protein retains partial function. This allows for the assembly of some ODAs and a significant level of ciliary activity that may result in the atypically mild clinical phenotype. The results also suggest that partial restoration of ciliary function by therapeutic agents could lead to significant improvement of disease symptoms.
A Combination of Chemotherapy and Oncolytic Virotherapy Sensitizes Colorectal Adenocarcinoma to Immune Checkpoint Inhibitors in a cDC1-Dependent Manner
Authors: El-Sayes Nader , Vito Alyssa , Salem Omar , Workenhe Samuel Tekeste , Wan Yonghong , Mossman Karen
Published: February 2022

Immune checkpoint therapy has shown great promise in the treatment of cancers with a high mutational burden, such as mismatch repair-deficient colorectal carcinoma (dMMR CRC). However, many patients fail to respond to immune checkpoint therapy. Using a mouse model of dMMR CRC, we demonstrated that tumors can be further sensitized to immune checkpoint therapy by using a combination of low-dose chemotherapy and oncolytic HSV-1. This combination induced the infiltration of CD8+ and CD4+ T cells into the tumor and the upregulation of gene signatures associated with the chemoattraction of myeloid cell subsets. When combined with immune checkpoint therapy, the combination promoted the infiltration of activated type 1 conventional dendritic cells (cDC1s) into the tumor. Furthermore, we found this combination strategy to be dependent on cDC1s, and its therapeutic efficacy to be abrogated in cDC1-deficient Batf3−/− mice. Thus, we demonstrated that the adjuvanticity of dMMR CRCs can be improved by combining low-dose chemotherapy and oncolytic HSV-1 in a cDC1-dependent manner.
Extracellular Matrix Synthesis and Remodeling by Mesenchymal Stromal Cells Is Context-Sensitive
Authors: Burk Janina , Sassmann Anna , Kasper Cornelia , Nimptsch Ariane , Schubert Susanna
Published: February 2022

Matrix remodeling could be an important mode of action of multipotent mesenchymal stromal cells (MSC) in extracellular matrix (ECM) disease, but knowledge is limited in this respect. As MSC are well-known to adapt their behavior to their environment, we aimed to investigate if their mode of action would change in response to healthy versus pathologically altered ECM. Human MSC-derived ECM was produced under different culture conditions, including standard culture, culture on Matrigel-coated dishes, and stimulation with the pro-fibrotic transforming growth factor-β1 (TGFβ1). The MSC-ECM was decellularized, characterized by histochemistry, and used as MSC culture substrate reflecting different ECM conditions. MSC were cultured on the different ECM substrates or in control conditions for 2 days. Culture on ECM increased the presence of surface molecules with ECM receptor function in the MSC, demonstrating an interaction between MSC and ECM. In MSC cultured on Matrigel-ECM and TGFβ1-ECM, which displayed a fibrosis-like morphology, gene expression of collagens and decorin, as well as total matrix metalloproteinase (MMP) activity in the supernatant were decreased as compared with control conditions. These results demonstrated that MSC adapt to their ECM environment, which may include pathological adaptations that could compromise therapeutic efficacy.
Developing a Mathematical Model of Intracellular Calcium Dynamics for Evaluating Combined Anticancer Effects of Afatinib and RP4010 in Esophageal Cancer
Authors: Chang Yan , Funk Marah , Roy Souvik , Stephenson Elizabeth , Choi Sangyong , Kojouharov Hristo V. , Chen Benito , Pan Zui
Published: February 2022

Targeting dysregulated Ca2+ signaling in cancer cells is an emerging chemotherapy approach. We previously reported that store-operated Ca2+ entry (SOCE) blockers, such as RP4010, are promising antitumor drugs for esophageal cancer. As a tyrosine kinase inhibitor (TKI), afatinib received FDA approval to be used in targeted therapy for patients with EGFR mutation-positive cancers. While preclinical studies and clinical trials have shown that afatinib has benefits for esophageal cancer patients, it is not known whether a combination of afatinib and RP4010 could achieve better anticancer effects. Since TKI can alter intracellular Ca2+ dynamics through EGFR/phospholipase C-γ pathway, in this study, we evaluated the inhibitory effect of afatinib and RP4010 on intracellular Ca2+ oscillations in KYSE-150, a human esophageal squamous cell carcinoma cell line, using both experimental and mathematical simulations. Our mathematical simulation of Ca2+ oscillations could fit well with experimental data responding to afatinib or RP4010, both separately or in combination. Guided by simulation, we were able to identify a proper ratio of afatinib and RP4010 for combined treatment, and such a combination presented synergistic anticancer-effect evidence by experimental measurement of intracellular Ca2+ and cell proliferation. This intracellular Ca2+ dynamic-based mathematical simulation approach could be useful for a rapid and cost-effective evaluation of combined targeting therapy drugs.
Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract
Authors: Cipollina Chiara , Bruno Andreina , Fasola Salvatore , Cristaldi Marta , Patella Bernardo , Inguanta Rosalinda , Vilasi Antonio , Aiello Giuseppe , La Grutta Stefania , Torino Claudia , Pace Elisabetta
Published: February 2022

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.
Mitochondrial Pathophysiology on Chronic Kidney Disease
Authors: Braga Patrícia C. , Alves Marco G. , Rodrigues Anabela S. , Oliveira Pedro F.
Published: February 2022

In healthy kidneys, interstitial fibroblasts are responsible for the maintenance of renal architecture. Progressive interstitial fibrosis is thought to be a common pathway for chronic kidney diseases (CKD). Diabetes is one of the boosters of CKD. There is no effective treatment to improve kidney function in CKD patients. The kidney is a highly demanding organ, rich in redox reactions occurring in mitochondria, making it particularly vulnerable to oxidative stress (OS). A dysregulation in OS leads to an impairment of the Electron transport chain (ETC). Gene deficiencies in the ETC are closely related to the development of kidney disease, providing evidence that mitochondria integrity is a key player in the early detection of CKD. The development of novel CKD therapies is needed since current methods of treatment are ineffective. Antioxidant targeted therapies and metabolic approaches revealed promising results to delay the progression of some markers associated with kidney disease. Herein, we discuss the role and possible origin of fibroblasts and the possible potentiators of CKD. We will focus on the important features of mitochondria in renal cell function and discuss their role in kidney disease progression. We also discuss the potential of antioxidants and pharmacologic agents to delay kidney disease progression.
Amniotic LPS-Induced Apoptosis in the Fetal Brain Is Suppressed by Vaginal LPS Preconditioning but Is Promoted by Continuous Ischemic Reperfusion
Authors: Dong Yupeng , Kimura Yoshitaka , Yaegashi Nobuo
Published: February 2022

Chorioamnionitis (CAM) is an increasingly common disease affecting pregnant women which derives from bacterial vaginosis. In different clinical cases, it has been shown that CAM can cause multiple risk factors for fetal brain damage, such as infection, and intra-uterine asphyxia. However, the molecular mechanism remains unknown. In this study, we established a novel CAM mouse model by exposing pregnant mice to a combination of three risk factors: vaginal lipopolysaccharides (LPS), amniotic LPS, and ischemic reperfusion. We found amniotic LPS caused Parkinson’s disease-like fetal brain damage, in a dose and time-dependent manner. Moreover, the mechanism of this fetal brain damage is apoptosis induced by amniotic LPS but it was inhibited by being pretreated with a vaginal LPS challenge before amniotic LPS injection. In contrast, amniotic LPS with continuous ischemic reperfusion caused a higher level of apoptotic cell death than amniotic LPS alone. In particular, a potential neuroprotective biomarker phosphorylation (p)-CREB (ser133) appeared in only vaginal LPS preconditioned before amniotic LPS, whereas ischemic reperfusion triggered IKK phosphorylation after amniotic LPS. Despite the need for many future investigations, this study also discussed a developed understanding of the molecular mechanism of how these phenotypes occurred.
Essential Oil Coating: Mediterranean Culinary Plants as Grain Protectants against Larvae and Adults of Tribolium castaneum and Trogoderma granarium
Authors: Papanikolaou Nikos E. , Kavallieratos Nickolas G. , Iliopoulos Vassilios , Evergetis Epameinondas , Skourti Anna , Nika Erifili P. , Haroutounian Serkos A.
Published: February 2022

Postharvest agricultural losses constitute a major food security risk. In contrast, postharvest protection is strongly linked with food safety. The present study aims to develop novel postharvest protection tools through a bioprospecting protocol utilizing edible essential oils (EOs) as grain coatings. For this purpose, six Mediterranean culinary plants were selected for evaluation. The EOs of juniper, Juniperus phoenicea L. (Pinales: Cupressaceae), marjoram, Origanum majorana L. (Lamiales: Lamiaceae), oregano, Origanum vulgare ssp. hirtum (Link) A.Terracc. (Lamiales: Lamiaceae), bay laurel, Laurus nobilis L. (Laurales: Lauraceae) and tarhan, Echinophora tenuifolia ssp. sibthorpiana (Guss.) Tutin (Apiales: Apiaceae) were retrieved through steam distillation, while lemon, Citrus limon (L.) Osbeck (Sapindales: Rutaceae) EO was retrieved through cold press extraction. All EOs were formulated to microemulsions (MEs) and applied uniformly as a coating on wheat against larvae and adults of Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) and Trogoderma granarium Everts (Coleoptera: Dermestidae). All EO-based MEs have been evaluated for the first time as grain coatings. They caused moderate to high mortality to T. castaneum larvae (67.8–93.3% 14 days post-exposure) and T. granarium adults (70.0–87.8% after 7 days of exposure). Citrus limon, O. majorana and E. tenuifolia ssp. sibthorpiana EO-based MEs were the most efficient against T. castaneum larvae, by exhibiting 93.3%, 91.1% and 90.0% mortality 14 days post-exposure, respectively. Origanum majorana, L. nobilis and J. phoenicea EO-based MEs were the most efficient against T. granarium adults, exhibiting 87.8%, 84.4% and 83.3% mortality after 7 days of exposure, respectively. These results indicate that EO-based ME coating is a potent tool against the tested postharvest pests.
The Resistance of Seven Host Plants to Tetranychus merganser Boudreaux (Acari: Tetranychidae)
Authors: Treviño-Barbosa Guadalupe , Ordaz-Silva Salvador , Gaona-García Griselda , Hernández-Juárez Agustín , Mora-Ravelo Sandra Grisell , Chacón Hernández Julio César
Published: February 2022

Red spider mites, Tetranychus merganser Boudreaux (Acari: Tetranychidae), is an agricultural pest that causes economic losses in papaya and nopal crops in Mexico. The aim of this research was to assess antibiosis and antixenosis as resistance mechanisms in seven host plants (Thevetia ahouai, Carica papaya, Phaseolus vulgaris, Moringa oleifera, Pittosporum tobira, Helietta parvifolia, Capsicum annuum var. glabriusculum) to red spider mites. Antixenosis was evaluated by non-preference for oviposition and feeding, antibiosis by infinitesimal rate of increase, finite rate of increase and doubling time, and the percentage of spider mites mortality. Oviposition and damage by feeding of T. merganser were significantly greater on C. papaya than on the other host plants. The growth rate of the spider mite was significantly lower in P. tobira and T. ahouai than in the other host plants. The percentage of hatched eggs of T. merganser was significantly higher in P. vulgaris than in the other plant species. Based on the demographic parameters, survival, food intake, and oviposition, these results indicated that compared with C. papaya, P. tobira and T. ahouai were more resistant. These results may be due to the fact that they were plants species of different families. The resistant plants can be studied as alternatives in the management of T. merganser.
Motor-Independent Cognitive Testing in Motor Degenerative Diseases
Authors: Schmitz-Peiffer Henning , Aust Elisa , Linse Katharina , Rueger Wolfgang , Joos Markus , Löhle Matthias , Storch Alexander , Hermann Andreas
Published: February 2022

Cognitive function is tested through speech- or writing-based neuropsychological instruments. The application and validity of those tests is impeded for patients with diseases that affect speech and hand motor skills. We therefore developed a “motor-free” gaze-controlled version of the Trail Making Test (TMT), including a calibration task to assess gaze accuracy, for completion by means of an eye-tracking computer system (ETCS). This electronic TMT version (eTMT) was evaluated for two paradigmatic “motor-neurodegenerative” diseases, Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). We screened 146 subjects, of whom 44 were excluded, e.g., because of vision deficits. Patients were dichotomized into subgroups with less (ALS−, PD−) or severe motor affection (ALS+, PD+). All 66 patients and all 36 healthy controls (HC) completed the eTMT. Patients with sufficient hand motor control (ALS−, PD−, PD+) and all HC additionally completed the original paper–pencil-based version of the TMT. Sufficient and comparable gaze fixation accuracy across all groups and the correlations of the eTMT results with the TMT results supported the reliability and validity of the eTMT. PD+ patients made significantly more errors than HC in the eTMT-B. We hereby proved the good applicability of a motor-free cognitive test. Error rates could be a particularly sensitive marker of executive dysfunction.
Assessment of the Effectiveness of Obstructive Sleep Apnea Treatment Using Optical Coherence Tomography to Evaluate Retinal Findings
Authors: Tejero-Garcés Gloria , Ascaso Francisco J. , Casas Paula , Adiego Maria I. , Baptista Peter , O’Connor-Reina Carlos , Vicente Eugenio , Plaza Guillermo
Published: February 2022

Retinal findings may change in patients with obstructive sleep apnea syndrome (OSAS). The present study aims to evaluate several retinal findings, such as macula layer thickness, the peripapillary retinal nerve fiber layer, and the optic nerve head in patients with OSAS, using optical coherence tomography (OCT); it also aims to monitor the result of several types of treatment of OSAS with OCT. A prospective comparative study was designed. Patients were recruited at a Sleep Unit of a University Hospital and underwent comprehensive ophthalmological examinations. Following exclusion criteria, fifty-two patients with OSAS were finally included. Patients were examined by OCT twice: once before treatment, and again after six months of treatment. In mild–moderate patients, where retinal swelling had been demonstrated, retinal thicknesses decreased [fovea (p = 0.026), as did inner ring macula (p = 0.007), outer ring macula (p = 0.015), and macular volume (p = 0.015)]. In severe patients, where retinal atrophy had been observed, retinal thickness increased [fovea (p < 0.001)]. No statistically significant differences in efficacy between treatments were demonstrated. In conclusion, OCT can evaluate the retina in patients with OSAS and help to monitor results after treatment. In severe OSAS, retinal thickness increased six months after treatment.
The Strategy against Iatrogenic Prematurity Due to True Umbilical Knot: From Prenatal Diagnosis Challenges to the Favorable Fetal Outcome
Authors: Bohiltea Roxana Elena , Varlas Valentin-Nicolae , Dima Vlad , Iordache Ana-Maria , Salmen Teodor , Mihai Bianca-Margareta , Bohiltea Alexia Teodora , Vladareanu Emilia Maria , Ducu Ioniță , Grigoriu Corina
Published: February 2022

True umbilical knot (TUK), although not a commonly encountered pathology, hasan important psychological burden on the mother and obstetrician. It has an extremely low prenatal ultrasound diagnosis rate, despite its adverse perinatal outcomes when unknown. We conducted a retrospective observational analytical study on a 7-year period (2015–2021), including all pregnancies overseen by a single fetal-maternal medicine specialist for monitoring and delivery. We analyzed the prenatal detection rate and correlations between prenatal diagnosis of TUK and pregnancy outcome in terms of associated maternal and fetal factors, time and mode of delivery, fetal weight at birth, maternal level of stress, and iatrogenic prematurity. We compared our results with an electronic search of the literature to study the relationship between TUK and prematurity. We prenatally diagnosed 16 TUKs, and there were two false positives and two undiagnosed knots. All of those women had birth at term. The main finding of the review was a small number of studies that included enough cases for analysis. The prematurity rate due to TUK is 14.2%, significantly increased compared to the general population. An umbilical artery flow velocimetry notch in twin pregnancies complicated by TUK was an important ultrasonographic finding. We consider intrauterine fetal death exceptional, and the main adverse neonatal outcome is due to iatrogenic prematurity caused by maternal anxiety of knowing the prenatal diagnosis and mode of delivery. The elective method for diagnosis should be the second-trimester ultrasound scan using three-dimensional (3D) reconstruction and cesarean delivery for a good neonatal outcome. Pregnant women should be counseled to understand the implications of iatrogenic prematurity, especially respiratory distress syndrome, to ensure these infants are delivered at term.