bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Sociodemographic Predictors of Mental Health in a Representative Sample of Young Adults from Germany, Israel, Poland, and Slovenia: A Longitudinal Study during the COVID-19 Pandemic
Authors: Benatov Joy , Ochnik Dominika , Rogowska Aleksandra M. , Arzenšek Ana , Mars Bitenc Urša
Published: January 2022

The aim of this cross-national longitudinal study was to evaluate the prevalence and sociodemographic predictors of mental health indicators (coronavirus-related post-traumatic stress disorder (PTSD), perceived stress, anxiety, depression, and suicidal/self-harm ideation) during the coronavirus disease-2019 (COVID-19) pandemic in a three-month period among representative samples of young adults from Germany, Israel, Poland, and Slovenia. The participants were 1724 young adults between 20 and 40 years of age (M = 30.74, SD = 5.74). The first measurement (T1) was in February 2021 and the second (T2) was in May–June 2021. The samples were representative of young adults in each country: Germany (n = 418, 24%), Israel (n = 428, 25%), Poland (n = 446, 26%), and Slovenia (n = 431, 25%). Women constituted 54% (n = 935) of the total sample. The mental health indicators were coronavirus-related PTSD measured by PCL-S, perceived stress (PSS-10), anxiety (GAD-7), depression (PHQ-8), and suicidal ideation (PHQ-9). The participants completed an online questionnaire that also included a physical activity (PA) measurement and sociodemographic variables. The Pearson’s χ2 independence test was used for prevalence comparisons and McNemar’s χ2 was used for longitudinal changes, whereas generalized estimating equations (GEEs) were used for the predictors of change in mental health indices. Significant differences were found between countries in each mental health dimension in both T1 and T2, with moderate effect sizes for coronavirus-related PTSD and suicidal ideation. The highest rate of PTSD and depression risk was in Germany, the highest rates of stress and anxiety risk were in Poland, and there was insufficient PA in Slovenia. The anxiety, depression, and suicidal ideation rates were the lowest in Israel and Slovenia. Israeli participants reported the lowest rate of coronavirus-related PTSD among the other countries in T1 and T2. Significant decreases in coronavirus-related PTSD and stress were observed during T2 compared to T1 in the total sample. There was no change in the risk of anxiety, depression, or suicidal ideation. Being single was a predictor of changes in all mental health indices. Having children was a risk factor for coronavirus-related PTSD and high stress. Being a student was a predictor of depression and suicidal ideation. A younger age (20–29 years) predicted coronavirus-related PTSD risk, whereas female gender predicted high stress. The mental health indices improved over time or remained stable. The groups that are most prone to mental health problems were single individuals, students, and parents in young adulthood across all countries. Future intervention programs for young adults should consider these factors when prioritizing, planning, and implementing such programs.
Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment
Authors: Parker Jim , O’Brien Claire , Hawrelak Jason , Gersh Felice L.
Published: January 2022

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine-disrupting chemical exposure, and the influence of lifestyle factors such as poor-quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.
Burn Wound Healing: Clinical Complications, Medical Care, Treatment, and Dressing Types: The Current State of Knowledge for Clinical Practice
Authors: Markiewicz-Gospodarek Agnieszka , Kozioł Małgorzata , Tobiasz Maciej , Baj Jacek , Radzikowska-Büchner Elżbieta , Przekora Agata
Published: January 2022

According to the World Health Organization (WHO), it is estimated that each year approximately 11 million people suffer from burn wounds, 180,000 of whom die because of such injuries. Regardless of the factors causing burns, these are complicated wounds that are difficult to heal and are associated with high mortality rates. Medical care of a burn patient requires a lot of commitment, experience, and multidirectional management, including surgical activities and widely understood pharmacological approaches. This paper aims to comprehensively review the current literature concerning burn wounds, including classification of burns, complications, medical care, and pharmacological treatment. We also overviewed the dressings (with an emphasis on the newest innovations in this field) that are currently used in medical practice to heal wounds.
Cochlear Implant Results in Older Adults with Post-Lingual Deafness: The Role of “Top-Down” Neurocognitive Mechanisms
Authors: Zucca Milena , Albera Andrea , Albera Roberto , Montuschi Carla , Della Gatta Beatrice , Canale Andrea , Rainero Innocenzo
Published: January 2022

To date, no clear specific cognitive predictors of speech perception outcome in older adult cochlear implant (CI) users have yet emerged. The aim of this prospective study was to increase knowledge on cognitive and clinical predictors of the audiological outcome in adult cochlear implant users. A total of 21 patients with post-lingual deafness, who were candidates for cochlear implantation, were recruited at the Department of Ear, Nose and Throat, University of Torino (Italy) and subjected to a pre-operatory neuropsychological assessment (T0) and an audiological examination after 12 months of implantation (T12). Patients who, at T12, had a 60 dB verbal recognition above 80%, were younger (z = −2.131, p = 0.033) and performed better in the Verbal Semantic Fluency Test at T0 (z = −1.941, p = 0.052) than subjects who had a 60 dB verbal recognition at T12 below 80%. The most significant predictors of the CI audiological outcome at T12 were age (β = −0.492, p = 0.024) and patients’ TMT-A performance at baseline (β = −0.486, p = 0.035). We conclude that cognitive processing speed might be a good predictor of the level of speech understanding in older adult patients with CI after one year of implantation.
Lifestyle Variations during and after the COVID-19 Pandemic: A Cross-Sectional Study of Diet, Physical Activities, and Weight Gain among the Jordanian Adult Population
Authors: Hammouri Hanan , Almomani Fidaa , Abdel Muhsen Ruwa , Abughazzi Aysha , Daghmash Rawand , Abudayah Alaa , Hasan Inas , Alzein Eva
Published: January 2022

The way that COVID-19 has been handled since its inception in 2019 has had a significant impact on lifestyle-related behaviors, such as physical activities, diet, and sleep patterns. This study measures lifestyle-related behavior during the COVID-19 pandemic lockdown using a 22-item questionnaire. The responses were collected from March 2021 to September 2021. A total of four hundred and sixty-seven Jordanian participants were engaged in assessing the changes caused by the pandemic and their effect on BMI. The validity and reliability of the questionnaire were tested for 71 participants. Cronbach’s alpha values for the questionnaire exceeded 0.7, demonstrating good reliability and internal consistency. The effect of each question regarding physical activity and dietary habits over the BMI difference was studied using ANOVA. The study shows that more than half of the participants reported snacking more between meals and increased their sitting and screen time, while 74% felt more stressed and anxious. BMI difference among the individuals throughout the lockdown was significantly associated with these variables. In contrast, 62% of the participants showed more awareness about their health by increasing the intake of immunity-boosting foods, and 56% of the participants showed an increase in the consumption of nutrition supplements. Females and married individuals tended to be healthier. Therefore, their BMI showed stability compared to others based on their gender and marital status. Exercise, sleep, and avoiding ‘junk’ food, which contributes to weight gain and COVID-19 vulnerability, are strongly recommended.
Role of Infodemics on Social Media in the Development of People’s Readiness to Follow COVID-19 Preventive Measures
Authors: Dutta Bireswar , Peng Mei-Hui , Chen Chien-Chih , Sun Shu-Lung
Published: January 2022

Unparalleled levels of misinformation have contributed to widespread misunderstandings about the nature of the coronavirus, its cure and preventative measures. Misinformation crosses borders rapidly with the help of social media, and this phenomenon is constantly increasing. Thus, the current study proposes a research framework to explore how citizens’ trust in government and social media influences their readiness to follow COVID-19 preventive measures. Additionally, the role of a health infodemic was explored in perceptions and relationships among factors influencing an individual’s readiness to follow COVID-19 preventive measures with data collected from 396 participants in Taiwan. The findings indicate citizens’ trust in social media (TRSM), attitude (ATT), perceived benefit (PBT), personal innovativeness, and how peer referents positively influence their readiness. However, the relationship between citizens’ trust in the government (TRGT) and their readiness to follow COVID-19 preventive measures (INT) is not statistically significant. The current study also explores the negative moderating effect of health infodemics on the relationship between TRSM and INT, TRGT and INT, ATT and INT, PBT and INT. Thus, the Taiwanese government must consider the current study’s findings to develop attractively, informed, and evidence-based content, which helps its citizens improve their health literacy and counter the spread of misinformation.
Pesticide Residue Trends in Fruits and Vegetables from Farm to Fork in Kampala Metropolitan Area, Uganda—A Mixed Methods Study
Authors: Ssemugabo Charles , Guwatudde David , Ssempebwa John C. , Bradman Asa
Published: January 2022

This mixed methods study used laboratory measurements of pesticide residues in produce, semi-structured questionnaires, and in-depth interview data to describe trends in pesticide residue in produce and handling and processing practices for fruits (watermelon and passion fruit) and vegetables (tomato, cabbage, and eggplant) along the farm to fork chain. Of the 50 farmers visited, 34 (68.0%) sold their fruits and vegetables to transporters, 11 (22.0%) to market vendors, and 4 (8.0%) directly to homes and restaurants. The majority 42 (93.3%) of the consumers (home/restaurant) purchased their fruits and vegetables from market vendors and transporters. Washing with water or vinegar, wiping with a cloth, peeling the outer layer, and blending and cooking were the most common post-harvesting processing methods used by stakeholders along the supply chain. Some farmers and market vendors reported spraying fruits and vegetables with pesticides either prior- or post-harvest to increase shelf life. Statistically significant decreasing pesticide residue trends along the farm to fork chain were observed for dioxacarb, likely due to degradation or washing, peeling, cooking, blending, or wiping by consumers. Increasing trends were observed for methidathion and quinalphos possibly due to pesticide applications. There is a need in Uganda to promote practices that minimize pesticide use and exposure through diet, while maintaining food integrity.
Work-Related Intervention Needs of Medical Assistants and How to Potentially Address Them according to Supervising General Practitioners: A Qualitative Study
Authors: Scharf Jessica , Vu-Eickmann Patricia , Angerer Peter , Müller Andreas , in der Schmitten Jürgen , Loerbroks Adrian
Published: January 2022

Work stress is common among health care professionals and this observation also holds true for general practitioners (GPs) and their medical assistance staff in Germany. Therefore, prior studies have examined the work-related intervention needs of medical assistants (MAs). We sought to explore potential interventions that may help to address these needs according to GPs’ views. Between December 2018 and April 2019 GPs were recruited via physician networks and through personal visits in general practices. Information on the nature and prevalence of 20 work-related intervention needs of MAs was presented to GPs. GPs then participated in a qualitative interview to reflect on the MAs’ needs. Qualitative content analysis according to Mayring was carried out using MAXQDA. A total of 21 GPs participated and perceived many of the needs as justified. The least understanding was expressed for requests of MA related to occupational aspects that were already known prior to hiring. The responsibility to address needs was often assigned to the German health policy. GPs expressed though that they considered addressing the need for better leadership style as their own responsibility as supervisors. Furthermore, professional training was discussed as one opportunity to raise the recognition and remuneration of MAs. Measures to address the work-related intervention needs of MAs and to thereby improve the working conditions of MAs were discussed with GPs.
Spatial Distribution of Air Pollution, Hotspots and Sources in an Urban-Industrial Area in the Lisbon Metropolitan Area, Portugal—A Biomonitoring Approach
Authors: Abecasis Leonor , Gamelas Carla A. , Justino Ana Rita , Dionísio Isabel , Canha Nuno , Kertesz Zsofia , Almeida Susana Marta
Published: January 2022

This study aimed to understand the influence of industries (including steelworks, lime factories, and industry of metal waste management and treatment) on the air quality of the urban-industrial area of Seixal (Portugal), where the local population has often expressed concerns regarding the air quality. The adopted strategy was based on biomonitoring of air pollution using transplanted lichens distributed over a grid to cover the study area. Moreover, the study was conducted during the first period of national lockdown due to COVID-19, whereas local industries kept their normal working schedule. Using a set of different statistical analysis approaches (such as enrichment and contamination factors, Spearman correlations, and evaluation of spatial patterns) to the chemical content of the exposed transplanted lichens, it was possible to assess hotspots of air pollution and to identify five sources affecting the local air quality: (i) a soil source of natural origin (based on Al, Si, and Ti), (ii) a soil source of natural and anthropogenic origins (based on Fe and Mg), (iii) a source from the local industrial activity, namely steelworks (based on Co, Cr, Mn, Pb, and Zn); (iv) a source from the road traffic (based on Cr, Cu, and Zn), and (v) a source of biomass burning (based on Br and K). The impact of the industries located in the study area on the local air quality was identified (namely, the steelworks), confirming the concerns of the local population. This valuable information is essential to improve future planning and optimize the assessment of particulate matter levels by reference methods, which will allow a quantitative analysis of the issue, based on national and European legislation, and to define the quantitative contribution of pollution sources and to design target mitigation measures to improve local air quality.
Powering Research through Innovative Methods for Mixtures in Epidemiology (PRIME) Program: Novel and Expanded Statistical Methods
Authors: Joubert Bonnie R. , Kioumourtzoglou Marianthi-Anna , Chamberlain Toccara , Chen Hua Yun , Gennings Chris , Turyk Mary E. , Miranda Marie Lynn , Webster Thomas F. , Ensor Katherine B. , Dunson David B. , Coull Brent A.
Published: January 2022

Humans are exposed to a diverse mixture of chemical and non-chemical exposures across their lifetimes. Well-designed epidemiology studies as well as sophisticated exposure science and related technologies enable the investigation of the health impacts of mixtures. While existing statistical methods can address the most basic questions related to the association between environmental mixtures and health endpoints, there were gaps in our ability to learn from mixtures data in several common epidemiologic scenarios, including high correlation among health and exposure measures in space and/or time, the presence of missing observations, the violation of important modeling assumptions, and the presence of computational challenges incurred by current implementations. To address these and other challenges, NIEHS initiated the Powering Research through Innovative methods for Mixtures in Epidemiology (PRIME) program, to support work on the development and expansion of statistical methods for mixtures. Six independent projects supported by PRIME have been highly productive but their methods have not yet been described collectively in a way that would inform application. We review 37 new methods from PRIME projects and summarize the work across previously published research questions, to inform methods selection and increase awareness of these new methods. We highlight important statistical advancements considering data science strategies, exposure-response estimation, timing of exposures, epidemiological methods, the incorporation of toxicity/chemical information, spatiotemporal data, risk assessment, and model performance, efficiency, and interpretation. Importantly, we link to software to encourage application and testing on other datasets. This review can enable more informed analyses of environmental mixtures. We stress training for early career scientists as well as innovation in statistical methodology as an ongoing need. Ultimately, we direct efforts to the common goal of reducing harmful exposures to improve public health.
Gender and Social Inequalities in Awareness of Coronary Artery Disease in European Countries
Authors: Daponte-Codina Antonio , Knox Emily C. , Mateo-Rodriguez Inmaculada , Seims Amanda , Regitz-Zagrosek Vera , Maas Angela H. E. M. , White Alan , Barnhoorn Floris , Rosell-Ortiz Fernando
Published: January 2022

Coronary artery disease (CAD) is the single leading cause of death in Europe and the most common form of cardiovascular disease. Little is known about awareness in the European population. A cross-sectional telephone survey of 2609 individuals from six European countries was conducted to gather information on perceptions of CAD, risk factors, preventive measures, knowledge of heart attack symptoms and ability to seek emergency medical care. Level of awareness was compared according to gender, age, socioeconomic status (SES) and educational level. Women were approximately five times less likely than men to consider heart disease as a main health issue or leading cause of death (OR = 0.224, 95% CI: 0.178–0.280, OR = 0.196, 95% CI: 0.171–0.226). Additionally, women were significantly less likely to have ever had a cardiovascular screening test (OR = 0.515, 95% CI: 0.459–0.578). Only 16.3% of men and 15.3% of women were able to spontaneously identify the main symptoms of a heart attack. Almost half of the sample failed to state that they would call emergency services in case of a cardiac event. Significant differences according to age, SES and education were found for many indicators amongst both men and women. Development of a European strategy targeting improved awareness of CAD and reduced gender and social inequalities within the European population is warranted.
Comparative Assessment of Bacteriophage and Antibiotic Activity against Multidrug-Resistant Staphylococcus aureus Biofilms
Authors: Kaźmierczak Natalia , Grygorcewicz Bartłomiej , Roszak Marta , Bochentyn Beata , Piechowicz Lidia
Published: January 2022

Problems connected with biofilm-related infections and antibiotic resistance necessitate the investigation and development of novel treatment strategies. Given their unique characteristics, one of the most promising alternatives to conventional antibiotics are bacteriophages. In the in vitro and in vivo larva model study, we demonstrate that phages vB_SauM-A, vB_SauM-C, and vB_SauM-D are effective antibiofilm agents. The exposure of biofilm to phages vB_SauM-A and vB_SauM-D led to 2–3 log reductions in the colony-forming unit number in most of the multidrug-resistant S. aureus strains. It was found that phage application reduced the formed biofilms independently of the used titer. Moreover, the study demonstrated that bacteriophages are more efficient in biofilm biomass removal and reduction in staphylococci count when compared to the antibiotics used. The scanning electron microscopy analysis results are in line with colony forming unit (CFU) counting but not entirely consistent with crystal violet (CV) staining. Additionally, phages vB_SauM-A, vB_SauM-C, and vB_SauM-D can significantly increase the survival rate and extend the survival time of Galleria mellonella larvae.
Unravelling Mechanisms of Doxorubicin-Induced Toxicity in 3D Human Intestinal Organoids
Authors: Rodrigues Daniela , Coyle Luke , Füzi Barbara , Ferreira Sofia , Jo Heeseung , Herpers Bram , Chung Seung-Wook , Fisher Ciarán , Kleinjans Jos C. S. , Jennen Danyel , de Kok Theo M.
Published: January 2022

Doxorubicin is widely used in the treatment of different cancers, and its side effects can be severe in many tissues, including the intestines. Symptoms such as diarrhoea and abdominal pain caused by intestinal inflammation lead to the interruption of chemotherapy. Nevertheless, the molecular mechanisms associated with doxorubicin intestinal toxicity have been poorly explored. This study aims to investigate such mechanisms by exposing 3D small intestine and colon organoids to doxorubicin and to evaluate transcriptomic responses in relation to viability and apoptosis as physiological endpoints. The in vitro concentrations and dosing regimens of doxorubicin were selected based on physiologically based pharmacokinetic model simulations of treatment regimens recommended for cancer patients. Cytotoxicity and cell morphology were evaluated as well as gene expression and biological pathways affected by doxorubicin. In both types of organoids, cell cycle, the p53 signalling pathway, and oxidative stress were the most affected pathways. However, significant differences between colon and SI organoids were evident, particularly in essential metabolic pathways. Short time-series expression miner was used to further explore temporal changes in gene profiles, which identified distinct tissue responses. Finally, in silico proteomics revealed important proteins involved in doxorubicin metabolism and cellular processes that were in line with the transcriptomic responses, including cell cycle and senescence, transport of molecules, and mitochondria impairment. This study provides new insight into doxorubicin-induced effects on the gene expression levels in the intestines. Currently, we are exploring the potential use of these data in establishing quantitative systems toxicology models for the prediction of drug-induced gastrointestinal toxicity.
A Systematic Review of Circulatory microRNAs in Major Depressive Disorder: Potential Biomarkers for Disease Prognosis
Authors: Rasheed Madiha , Asghar Rabia , Firdoos Sundas , Ahmad Nadeem , Nazir Amina , Ullah Kakar Mohib , Li Noumin , Zhuang Fengyuan , Chen Zixuan , Deng Yulin
Published: January 2022

Major depressive disorder (MDD) is a neuropsychiatric disorder, which remains challenging to diagnose and manage due to its complex endophenotype. In this aspect, circulatory microRNAs (cimiRNAs) offer great potential as biomarkers and may provide new insights for MDD diagnosis. Therefore, we systemically reviewed the literature to explore various cimiRNAs contributing to MDD diagnosis and underlying molecular pathways. A comprehensive literature survey was conducted, employing four databases from 2012 to January 2021. Out of 1004 records, 157 reports were accessed for eligibility criteria, and 32 reports meeting our inclusion criteria were considered for in-silico analysis. This study identified 99 dysregulated cimiRNAs in MDD patients, out of which 20 cimiRNAs found in multiple reports were selected for in-silico analysis. KEGG pathway analysis indicated activation of ALS, MAPK, p53, and P13K-Akt signaling pathways, while gene ontology analysis demonstrated that most protein targets were associated with transcription. In addition, chromosomal location analysis showed clustering of dysregulated cimiRNAs at proximity 3p22-p21, 9q22.32, and 17q11.2, proposing their coregulation with specific transcription factors primarily involved in MDD physiology. Further analysis of transcription factor sites revealed the existence of HIF-1, REST, and TAL1 in most cimiRNAs. These transcription factors are proposed to target genes linked with MDD, hypothesizing that first-wave cimiRNA dysregulation may trigger the second wave of transcription-wide changes, altering the protein expressions of MDD-affected cells. Overall, this systematic review presented a list of dysregulated cimiRNAs in MDD, notably miR-24-3p, let 7a-5p, miR-26a-5p, miR135a, miR-425-3p, miR-132, miR-124 and miR-16-5p as the most prominent cimiRNAs. However, various constraints did not permit us to make firm conclusions on the clinical significance of these cimiRNAs, suggesting the need for more research on single blood compartment to identify the biomarker potential of consistently dysregulated cimiRNAs in MDD, as well as the therapeutic implications of these in-silico insights.
Whole-Exome Sequencing Identifies a Novel Germline Variant in PTK7 Gene in Familial Colorectal Cancer
Authors: Miao Beiping , Skopelitou Diamanto , Srivastava Aayushi , Giangiobbe Sara , Dymerska Dagmara , Paramasivam Nagarajan , Kumar Abhishek , Kuświk Magdalena , Kluźniak Wojciech , Paszkowska-Szczur Katarzyna , Schlesner Matthias , Lubinski Jan , Hemminki Kari , Försti Asta , Bandapalli Obul Reddy
Published: January 2022

Colorectal cancer (CRC) is the third most frequently diagnosed malignancy worldwide. Only 5% of all CRC cases are due to germline mutations in known predisposition genes, and the remaining genetic burden still has to be discovered. In this study, we performed whole-exome sequencing on six members of a Polish family diagnosed with CRC and identified a novel germline variant in the protein tyrosine kinase 7 (inactive) gene (PTK7, ENST00000230419, V354M). Targeted screening of the variant in 1705 familial CRC cases and 1674 healthy elderly individuals identified the variant in an additional familial CRC case. Introduction of this variant in HT-29 cells resulted in increased cell proliferation, migration, and invasion; it also caused down-regulation of CREB, p21 and p53 mRNA and protein levels, and increased AKT phosphorylation. These changes indicated inhibition of apoptosis pathways and activation of AKT signaling. Our study confirmed the oncogenic function of PTK7 and supported its role in genetic predisposition of familial CRC.
Intra-Articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Review of Their Current Molecular Mechanisms of Action and Their Degree of Efficacy
Authors: Rodríguez-Merchán Emérito Carlos
Published: January 2022

Knee osteoarthritis (OA) is estimated to affect more than 10% of the population, with a lifetime risk of 45%. Contemporary guidelines advise control of body weight, therapeutic physical exercise, drug treatment (oral non-steroidal anti-inflammatory drugs, paracetamol, opioids), and mechanical aids (walking aids, braces, orthoses). Nevertheless, these treatments typically have only short-term benefits. Intra-articular corticosteroids are typically advised, but only for short-term pain alleviation, given that their benefits last only a few weeks. The efficacy of hyaluronic acid is controversial. When the aforesaid options fail, total knee arthroplasty is generally recommended as an efficacious treatment. However, it is costly and can involve medical and postoperative complications. Therefore, determining alternate safe and effective treatments for knee OA is paramount. Platelet-rich plasma (PRP) has lately been investigated for the treatment of knee OA. This article reviews recent knowledge concerning PRP’s molecular mechanisms of action. The effectiveness of intra-articular PRP injections in the knee joint remains controversial, although most recent publications show pain alleviation in the short term. Orthopedic surgeons treating people with knee OA are becoming increasingly interested in PRP, despite indecisive clinical data and basic science information. Further studies comparing PRP with placebo are required.
Vitamin D-Binding Protein and the Free Hormone Hypothesis for Vitamin D in Bio-Naïve Patients with Psoriasis
Authors: Vandikas Maria Siekkeri , Landin-Wilhelmsen Kerstin , Gillstedt Martin , Osmancevic Amra
Published: January 2022

High levels of vitamin D-binding protein (DBP) have been reported in patients with psoriasis and the possibility of DBP as a marker of inflammation has been discussed. Furthermore, high DBP levels might negatively affect free 25(OH)D concentrations. According to the free hormone hypothesis, only the free fraction of a steroid hormone is capable of exerting biological action. Thus, free 25(OH)D level could be a better biomarker of vitamin D status than total 25(OH)D level. The objectives of this study were to identify the strongest determinants for DBP levels and to test the free hormone hypothesis for vitamin D in psoriasis. Additionally, we also aimed to investigate correlations between directly measured free 25(OH)D levels in serum and psoriasis disease severity compared to total 25(OH)D levels. This was a retrospective cross-sectional study including 40 bio-naïve patients with mild to severe plaque psoriasis. Psoriasis disease severity was evaluated using high sensitivity C-reactive protein (hsCRP), Psoriasis Area Severity Index (PASI) and visual analogue scale (VAS). Vitamin D metabolites including directly measured free 25(OH)D and serum DBP levels were measured. DBP levels were higher in patients with self-reported arthropathy than those without irrespective of confounding factors like sex, age and body weight. Total and free 25(OH)D levels correlated well (ρ = 0.77, p < 0.0001) and both were inversely correlated to intact parathyroid hormone (iPTH) (ρ = −0.33, p = 0.038 for total 25(OH)D and ρ = −0.40, p = 0.010 for free 25(OH)D). Only total 25(OH)D correlated to serum calcium levels (ρ = 0.32, p = 0.047). No correlations between any of the vitamin D metabolites and psoriasis disease severity were observed. In conclusion, DBP might be a new inflammatory biomarker in psoriasis, especially in psoriatic arthritis. Total 25(OH)D was a reliable measure for vitamin D status in this psoriasis cohort. However, evaluation of free 25(OH)D in patients with psoriatic disease and multiple co-morbidities and/or ongoing biologic treatment should be considered.
Recent Development in NKT-Based Immunotherapy of Glioblastoma: From Bench to Bedside
Authors: Li Yutao , Sharma Amit , Maciaczyk Jarek , Schmidt-Wolf Ingo G. H.
Published: January 2022

Glioblastoma multiforme (GBM) is an aggressive and dismal disease with a median overall survival of around 15 months and a 5-year survival rate of 7.2%. Owing to genetic mutations, drug resistance, disruption to the blood–brain barrier (BBB)/blood–brain tumor barrier (BBTB), and the complexity of the immunosuppressive environment, the therapeutic approaches to GBM represent still major challenges. Conventional therapies, including surgery, radiotherapy, and standard chemotherapy with temozolomide, have not resulted in satisfactory improvements in the overall survival of GBM patients. Among cancer immunotherapeutic approaches, we propose that adjuvant NKT immunotherapy with invariant NKT (iNKT) and cytokine-induced killer (CIK) cells may improve the clinical scenario of this devastating disease. Considering this, herein, we discuss the current strategies of NKT therapy for GBM based primarily on in vitro/in vivo experiments, clinical trials, and the combinatorial approaches with future therapeutic potential.
Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell-Derived Small Extracellular Vesicles and Modulates the Function of Endothelial Cells
Authors: Chung Jihwa , Kim Kyoung Hwa , Yu Namhee , An Shung Hyun , Lee Sanghyuk , Kwon Kihwan
Published: January 2022

Blood fluid shear stress (FSS) modulates endothelial function and vascular pathophysiology. The small extracellular vesicles (sEVs) such as exosomes are potent mediators of intercellular communication, and their contents reflect cellular stress. Here, we explored the miRNA profiles in endothelial cells (EC)-derived sEVs (EC-sEVs) under atheroprotective laminar shear stress (LSS) and atheroprone low-oscillatory shear stress (OSS) and conducted a network analysis to identify the main biological processes modulated by sEVs’ miRNAs. The EC-sEVs were collected from culture media of human umbilical vein endothelial cells exposed to atheroprotective LSS (20 dyne/cm2) and atheroprone OSS (±5 dyne/cm2). We explored the miRNA profiles in FSS-induced EC-sEVs (LSS-sEVs and OSS-sEVs) and conducted a network analysis to identify the main biological processes modulated by sEVs’ miRNAs. In vivo studies were performed in a mouse model of partial carotid ligation. The sEVs’ miRNAs-targeted genes were enriched for endothelial activation such as angiogenesis, cell migration, and vascular inflammation. OSS-sEVs promoted tube formation, cell migration, monocyte adhesion, and apoptosis, and upregulated the expression of proteins that stimulate these biological processes. FSS-induced EC-sEVs had the same effects on endothelial mechanotransduction signaling as direct stimulation by FSS. In vivo studies showed that LSS-sEVs reduced the expression of pro-inflammatory genes, whereas OSS-sEVs had the opposite effect. Understanding the landscape of EC-exosomal miRNAs regulated by differential FSS patterns, this research establishes their biological functions on a system level and provides a platform for modulating the overall phenotypic effects of sEVs.
The Mitochondrial PHB2/OMA1/DELE1 Pathway Cooperates with Endoplasmic Reticulum Stress to Facilitate the Response to Chemotherapeutics in Ovarian Cancer
Authors: Cheng Meiyu , Yu Huimei , Kong Qinghuan , Wang Bingrong , Shen Luyan , Dong Delu , Sun Liankun
Published: January 2022

Interactions between the mitochondrial inner and outer membranes and between mitochondria and other organelles closely correlates with the sensitivity of ovarian cancer to cisplatin and other chemotherapeutic drugs. However, the underlying mechanism remains unclear. Recently, the mitochondrial protease OMA1, which regulates internal and external signals in mitochondria by cleaving mitochondrial proteins, was shown to be related to tumor progression. Therefore, we evaluated the effect of OMA1 on the response to chemotherapeutics in ovarian cancer cells and the mouse subcutaneous tumor model. We found that OMA1 activation increased ovarian cancer sensitivity to cisplatin in vivo and in vitro. Mechanistically, in ovarian cancer, OMA1 cleaved optic atrophy 1 (OPA1), leading to mitochondrial inner membrane cristae remodeling. Simultaneously, OMA1 induced DELE1 cleavage and its cytoplasmic interaction with EIF2AK1. We also demonstrated that EIF2AK1 cooperated with the ER stress sensor EIF2AK3 to amplify the EIF2S1/ATF4 signal, resulting in the rupture of the mitochondrial outer membrane. Knockdown of OMA1 attenuated these activities and reversed apoptosis. Additionally, we found that OMA1 protease activity was regulated by the prohibitin 2 (PHB2)/stomatin-like protein 2 (STOML2) complex. Collectively, OMA1 coordinates the mitochondrial inner and outer membranes to induce ovarian cancer cell death. Thus, activating OMA1 may be a novel treatment strategy for ovarian cancer.
A Systematic Review of Expression and Immunogenicity of Human Endogenous Retroviral Proteins in Cancer and Discussion of Therapeutic Approaches
Authors: Müller Mikkel Dons , Holst Peter Johannes , Nielsen Karen Nørgaard
Published: January 2022

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that have become fixed in the human genome. While HERV genes are typically silenced in healthy somatic cells, there are numerous reports of HERV transcription and translation across a wide spectrum of cancers, while T and B cell responses against HERV proteins have been detected in cancer patients. This review systematically categorizes the published evidence on the expression of and adaptive immune response against specific HERVs in distinct cancer types. A systematic literature search was performed using Medical Search Headings (MeSH) in the PubMed/Medline database. Papers were included if they described the translational activity of HERVs. We present multiple tables that pair the protein expression of specific HERVs and cancer types with information on the quality of the evidence. We find that HERV-K is the most investigated HERV. HERV-W (syncytin-1) is the second-most investigated, while other HERVs have received less attention. From a therapeutic perspective, HERV-K and HERV-E are the only HERVs with experimental demonstration of effective targeted therapies, but unspecific approaches using antiviral and demethylating agents in combination with chemo- and immunotherapies have also been investigated.
Progesterone: A Unique Hormone with Immunomodulatory Roles in Pregnancy
Authors: Raghupathy Raj , Szekeres-Bartho Julia
Published: January 2022

Progesterone is well known for its numerous endocrinologic roles in pregnancy but is also endowed with fascinating immunomodulatory capabilities. It can downregulate the induction of inflammatory reactions, the activation of immune cells and the production of cytokines, which are critical mediators of immune responses. These features appear to be critical to the success of pregnancy, given the ability of maternal immune reactivity to interfere with pregnancy and to contribute to several pregnancy complications. This review summarizes the contribution of maternal immune effectors in general, and cytokines in particular, to pregnancy complications such as recurrent miscarriage, pre-eclampsia and preterm labor; it describes the promise offered by supplementation with progesterone and the oral progestogen dydrogesterone, as well as the progesterone-induced blocking factor in the prevention and/or treatment of these serious complications.
Expression of Doublecortin, Glial Fibrillar Acidic Protein, and Vimentin in the Intact Subpallium and after Traumatic Injury to the Pallium in Juvenile Salmon, Oncorhynchus masou
Authors: Pushchina Evgeniya V. , Zharikova Eva I. , Varaksin Anatoly A.
Published: January 2022

Fetalization associated with a delay in development and the preservation of the features of the embryonic structure of the brain dominates the ontogeny of salmonids. The aim of the present study was to comparatively analyze the distribution of the glial-type aNSC markers such as vimentin and glial fibrillar acidic protein (GFAP) and the migratory neuronal precursors such as doublecortin in the telencephalon subpallium of juvenile masu salmon, Oncorhynchus masou, in normal conditions and at 1 week after an injury to the dorsal pallium. Immunohistochemical labeling of vimentin, GFAP, and doublecortin in the pallium of intact juvenile masu salmon revealed single cells with similar morphologies corresponding to a persistent pool of neuronal and/or glial progenitors. The study of the posttraumatic process showed the presence of intensely GFAP-labeled cells of the neuroepithelial type that form reactive neurogenic zones in all areas of the subpallial zone of juvenile masu salmon. A comparative analysis of the distribution of radial glia in the dorsal, ventral, and lateral zones of the subpallium showed a maximum concentration of cells in the dorsal part of subpallium (VD) and a minimum concentration in the lateral part of subpallium VL. An essential feature of posttraumatic immunolabeling in the masu salmon subpallium is the GFAP distribution patterns that are granular intracellular in the apical periventricular zone (PVZ) and fibrillar extracellular in the subventricular (SVZ) and parenchymal zones (PZ). In contrast to those in intact animals, most of the GFAP+ granules and constitutive neurogenic niches in injured fish were localized in the basal part of the PVZ. With the traumatic injury to the subpallium, the number of Vim+ cells in the lateral and ventral regions significantly increased. At 1 week post-injury, the total immunolabeling of vimentin cells in the PVZ was replaced by the granular pattern of Vim immunodistribution spreading from the PVZ to the SVZ and deeper parenchymal layers of the brain in all areas of the subpallium. A significant increase in the number of DC+ cells was observed also in all areas of the subpallium. The number of cells increased both in the PVZ and in the SVZ, as well as in the deeper PZ. Thus, at 1 week after the injury to the dorsal pallium, the number of DC, Vim, and GFAP expressing cells of the neuroepithelial type in the subpallium of juvenile masu salmon increased, and additionally GFAP+ radial glia appeared in VD, which was absent from intact animals.
Transcriptional Signatures of Immune, Neural, and Endocrine Functions in the Brain and Kidney of Rainbow Trout (Oncorhynchus mykiss) in Response to Aeromonas salmonicida Infection
Authors: Liu Mengqun , Yang Xiaodong , Zeng Chu , Zhao Hongkui , Li Jifang , Hou Zhishuai , Wen Haishen
Published: January 2022

Rainbow trout (Oncorhynchus mykiss) serves as one of the most important commercial fish with an annual production of around 800,000 tonnes. However, infectious diseases, such as furunculosis caused by Aeromonas salmonicida infection, results in great economic loss in trout culture. The brain and kidney are two important organs associated with “sickness behaviors” and immunomodulation in response to disease. Therefore, we worked with 60 trout and investigated transcriptional responses and enrichment pathways between healthy and infected trout. We observed that furunculosis resulted in the activation of toll-like receptors with neuroinflammation and neural dysfunction in the brain, which might cause the “sickness behaviors” of infected trout including anorexia and lethargy. We also showed the salmonid-specific whole genome duplication contributed to duplicated colony stimulating factor 1 (csf-1) paralogs, which play an important role in modulating brain immunomodulation. Enrichment analyses of kidneys showed up-regulated immunomodulation and down-regulated neural functions, suggesting an immune-neural interaction between the brain and kidney. Moreover, the kidney endocrine network was activated in response to A. salmonicida infection, further convincing the communications between endocrine and immune systems in regulating internal homeostasis. Our study provided a foundation for pathophysiological responses of the brain and kidney in response to furunculosis and potentially offered a reference for generating disease-resistant trout strains.
An Overview of Epigenetics in Obesity: The Role of Lifestyle and Therapeutic Interventions
Authors: Mahmoud Abeer M.
Published: January 2022

Obesity has become a global epidemic that has a negative impact on population health and the economy of nations. Genetic predispositions have been demonstrated to have a substantial role in the unbalanced energy metabolism seen in obesity. However, these genetic variations cannot entirely explain the massive growth in obesity over the last few decades. Accumulating evidence suggests that modern lifestyle characteristics such as the intake of energy-dense foods, adopting sedentary behavior, or exposure to environmental factors such as industrial endocrine disruptors all contribute to the rising obesity epidemic. Recent advances in the study of DNA and its alterations have considerably increased our understanding of the function of epigenetics in regulating energy metabolism and expenditure in obesity and metabolic diseases. These epigenetic modifications influence how DNA is transcribed without altering its sequence. They are dynamic, reflecting the interplay between the body and its surroundings. Notably, these epigenetic changes are reversible, making them appealing targets for therapeutic and corrective interventions. In this review, I discuss how these epigenetic modifications contribute to the disordered energy metabolism in obesity and to what degree lifestyle and weight reduction strategies and pharmacological drugs can restore energy balance by restoring normal epigenetic profiles.
Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma
Authors: Barzegar Behrooz Amir , Talaie Zahra , Jusheghani Fatemeh , Łos Marek J. , Klonisch Thomas , Ghavami Saeid
Published: January 2022

Glioblastoma (GBM) is a devastating type of brain tumor, and current therapeutic treatments, including surgery, chemotherapy, and radiation, are palliative at best. The design of effective and targeted chemotherapeutic strategies for the treatment of GBM require a thorough analysis of specific signaling pathways to identify those serving as drivers of GBM progression and invasion. The Wnt/β-catenin and PI3K/Akt/mTOR (PAM) signaling pathways are key regulators of important biological functions that include cell proliferation, epithelial–mesenchymal transition (EMT), metabolism, and angiogenesis. Targeting specific regulatory components of the Wnt/β-catenin and PAM pathways has the potential to disrupt critical brain tumor cell functions to achieve critical advancements in alternative GBM treatment strategies to enhance the survival rate of GBM patients. In this review, we emphasize the importance of the Wnt/β-catenin and PAM pathways for GBM invasion into brain tissue and explore their potential as therapeutic targets.
Rapid, Label-Free Prediction of Antibiotic Resistance in Salmonella typhimurium by Surface-Enhanced Raman Spectroscopy
Authors: Zhang Ping , Wu Xi-Hao , Su Lan , Wang Hui-Qin , Lin Tai-Feng , Fang Ya-Ping , Zhao Hui-Min , Lu Wen-Jing , Liu Meng-Jia , Liu Wen-Bo , Zheng Da-Wei
Published: January 2022

The rapid identification of bacterial antibiotic susceptibility is pivotal to the rational administration of antibacterial drugs. In this study, cefotaxime (CTX)-derived resistance in Salmonella typhimurium (abbr. CTXr-S. typhimurium) during 3 months of exposure was rapidly recorded using a portable Raman spectrometer. The molecular changes that occurred in the drug-resistant strains were sensitively monitored in whole cells by label-free surface-enhanced Raman scattering (SERS). Various degrees of resistant strains could be accurately discriminated by applying multivariate statistical analyses to bacterial SERS profiles. Minimum inhibitory concentration (MIC) values showed a positive linear correlation with the relative Raman intensities of I990/I1348, and the R2 reached 0.9962. The SERS results were consistent with the data obtained by MIC assays, mutant prevention concentration (MPC) determinations, and Kirby-Bauer antibiotic susceptibility tests (K-B tests). This preliminary proof-of-concept study indicates the high potential of the SERS method to supplement the time-consuming conventional method and help alleviate the challenges of antibiotic resistance in clinical therapy.