Search

Abstract Background The garden dormouse (Eliomys quercinus) has experienced a significant population decline across Europe in recent decades. While habitat loss and climate change are often cited as primary factors, pathogen exposure, either to novel or to previously known, may play a role in such a decline. This study aimed to investigate the presence of polyomaviruses in garden dormice, given that these viruses are highly prevalent and can cause disease, particularly in immunocompromised individuals. Methods The carcasses of garden dormice (n = 89) were collected throughout Germany. Kidney samples were tested for the presence of polyomavirus DNA using nested degenerate and specific diagnostic PCRs. Seroprevalence was assessed from chest cavity fluid samples through an enzyme-linked immunosorbent assay using polyomavirus VP1 virus-like particles produced in yeast. Results A new polyomavirus, related to chimpanzee (Pan troglodytes) polyomaviruses 4 and 5 and human Merkel cell polyomavirus, was identified in the garden dormouse. Two 5,380 bp-length complete viral genomes were sequenced from dormice kidney samples (sequences PQ246041 and PQ246042). Genes encoding the putative structural proteins VP1, VP2, and VP3, as well as the Large, Middle, and small T antigens, containing conserved functional domains were identified. Polyomavirus DNA was detected in 2 of 74 dormice (2.7%, 95% confidence interval: 0-6.4%) through PCR, while 12 of 69 animals (17.4%, 95% confidence interval: 8.4-26.3%) tested positive for polyomavirus-specific antibodies. Conclusions In conclusion, here we describe a novel polyomavirus in the garden dormouse with molecular and serological detection. Pairwise sequence comparison and phylogenetic analysis suggest that this novel virus may represent a novel species within the genus Alphapolyomavirus. Future work should examine if this virus is garden dormouse-specific and whether it is associated with disease in dormice.

BackgroundEvidence suggests that illness perceptions held by people living with multiple sclerosis (MS) impact affective distress and physical health outcomes. In a randomized controlled trial, we developed 2 MS Online Courses—the standard care course and the intervention course (IC). The IC was adapted from an evidence-based lifestyle program. Modifying lifestyle risk factors offers an opportunity to impact illness perceptions. Research on illness perceptions in people living with MS has focused predominately on quantitative methods. ObjectiveThis study aimed to explore the experiences and health outcomes of randomized controlled trial participants, including individuals’ perceived changes in attitudes toward MS and their health (ie, illness perceptions). MethodsQualitative responses provided by 38 participants (22 in the IC and 16 in the standard care course) were derived from semistructured interviews 1 month after completing the MS Online Course. The impact of course engagement and lifestyle modification on illness perceptions was explored using inductive thematic analysis. ResultsThemes of changes in illness perceptions were most prominent in the IC arm. Qualitative responses from 22 people living with MS informed the development of three themes: “self-efficacy for disease management,” “personal control,” and “illness coherence.” ConclusionsFindings provide novel insights into the formation and modification of illness perceptions. Lifestyle modification may serve as a valuable adjunct to clinician-administered therapies, improving the sense of personal control over MS, illness coherence, and self-efficacy for disease management. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12621001605886; https://tinyurl.com/2vyve9p9 International Registered Report Identifier (IRRID)RR2-10.1186/s12883-023-03298-0

Heart failure is one of the critical and most costly medical challenges of the 21st century. It is a chronic debilitating condition and adherence to medication, a precondition for successful treatment is often poor. There are various interventions for improving the adherence. Depending on the goal of the intervention, these are roughly patient centric, healthcare provider centric and system centric. We provide an overview of these interventions with a focus on effectiveness and appropriateness in different clinical situations. Their use can lead to improved patient outcomes and reduced economic burden of the disease.

Xray free-electron lasers (XFELs) enable experiments that would have been impractical or impossible at conventional X-ray laser facilities. Indeed, more XFEL facilities are being built and planned, with their aim to deliver larger pulse energies and higher peak brilliance. While seeking to increase the pulse power, it is quintessential to consider the maximum pulse fluence that a grazing-incidence FEL mirror can withstand. To address this issue, several studies were conducted on grazing-incidence damage by soft X-ray FEL pulses at the European XFEL facility. Boron carbide (B4C) coatings on polished silicon substrate were investigated using 1 keV photon energy, similar to the X-ray mirrors currently installed at the soft X-ray beamlines (SASE3). The purpose of this study is to compare the damage threshold of B4C and Si to determine the advantages, tolerance and limits of using B4C coatings.

Abstract Identifying components of modularized psychological interventions that contribute to symptom reduction is essential to improving depression treatment. In a secondary analysis of a randomized controlled trial (RCT), session-specific effects of Metacognitive Training-Silver, a group intervention for older adults with depression, were investigated. Thirty-eight older adults with major depressive disorder or dysthymia participated in up to eight sessions of MCT-Silver. A clinical assessment of depressive symptoms (Hamilton Depression Rating Scale) as well as additional interviews and questionnaires administered as part of the RCT were completed at pre- and post-intervention. Depressive symptoms, negative (meta)cognitive beliefs, emotion regulation strategies and attitudes toward aging were assessed pre- and post-session. The rate of change in each variable per module, elevation following the module in which the variable was addressed, and the rate of change post module were examined via linear mixed models. Clinician-rated depressive symptoms were significantly reduced from pre- to post-intervention (Cohens d = 1.31). Self-reported depression and negative mental filter measured within sessions improved significantly over treatment, whereas black-and-white thinking improved after module #3 (Should Statements, All or Nothing Thinking and Acceptance). Module-specific within-session effects were found for overgeneralization (module #1: Mental Filter) and rumination (module #6: Rumination and Social Withdrawal). Improvement in mental filter in module #1 was significantly associated with depression reduction. This study provides initial evidence that MCT-Silver partially meets its aims of reducing depression and specific cognitive variables within and across sessions. Improvement of the instrument used to measure change may improve detection of module-specific effects. Trial registration: NCT03691402.

Abstract This study employs machine learning to detect the severity of major depressive disorder (MDD) through binary and multiclass classifications. We compared models that used only biomarkers of oxidative stress with those that incorporate sociodemographic and health-related factors. Data collected from 830 participants, based on the Patient Health Questionnaire (PHQ-9) score, inform our analysis. In binary classification, the Random Forest (RF) classifier achieved the highest Area Under the Curve (AUC) of 0.84 when all features were included. In multiclass classification, the AUC improved from 0.84 with only oxidative stress biomarkers to 0.88 when all characteristics were included. To address data imbalance, weighted classifiers, and Synthetic Minority Over-sampling Technique (SMOTE) approaches were applied. Weighted random forest (WRF) improved multiclass classification, achieving an AUC of 0.91. Statistical tests, including the Friedman test and the Conover post-hoc test, confirmed significant differences between model performances, with WRF using all features outperforming others. Feature importance analysis shows that oxidative stress biomarkers, particularly GSH, are top ranked among all features. Clinicians can leverage the results of this study to improve their decision-making processes by incorporating oxidative stress biomarkers in addition to the standard criteria for depression diagnosis.

The intestinal microbiota is an important environmental factor implicated in CRC development. Intriguingly, modulation of DNA methylation by gut microbiota has been reported in preclinical models, although the relationship between tumor-infiltrating bacteria and CIMP status is currently unexplored. In this study, we investigated tumor-associated bacteria in 203 CRC tumor cases and validated the findings using The Cancer Genome Atlas datasets. We assessed the abundance of Bacteroides fragilis, Escherichia coli, Fusobacterium nucleatum, and Klebsiella pneumoniae through qPCR analysis and observed enrichment of all four bacterial species in CRC samples. Notably, except for E. coli, all exhibited significant enrichment in cases of CIMP. This enrichment was primarily driven by a subset of cases distinguished by high levels of these bacteria, which we labeled as “Superhigh”. The bacterial Superhigh status showed a significant association with CIMP (odds ratio 3.1, p-value = 0.013) and with MLH1 methylation (odds ratio 4.2, p-value = 0.0025). In TCGA CRC cases (393 tumor and 45 adj. normal), bacterial taxa information was extracted from non-human whole exome sequencing reads, and the bacterial Superhigh status was similarly associated with CIMP (odds ratio 2.9, p

AimAssessment of blood pressure during exercise is routine in athletes, but normal values remain equivocal. This study examines the response of systolic blood pressure (SBP) to exercise in a large cohort of athletes and establishes normative values by sex and age.MethodsCompetitive athletes free of cardiovascular disease underwent pre-participation exercise testing on a bicycle ergometer. Resting (SBPrest) and peak blood pressure (SBPpeak), heart rate (HRrest and HRpeak), and power output (WR) were recorded. Workload indexed values were calculated.ResultsThe cohort included 12,083 athletes (median age 15 years, 26.9% female). Median peak exercise SBP was similar between sexes, but WR-indexed measures including SBP/WR ratio and SBP/(WR/kg) slope were higher in females (0.9 vs. 0.7, p < 0.001; 10.94 vs. 9.52, p < 0.001). Univariate analyses revealed significant associations between SBPpeak and several predictors, including sex, age, weight, height, SBPrest, DBPrest, HRrest, HRpeak, and WR (all p < .001). Multivariate analysis showed that SBPrest (beta = 0.353, 95% CI [0.541, 0.609], p < 0.001), height (beta = 0.303, 95% CI [0.360, 0.447], p < 0.001), WR (beta = 0.171, 95% CI [0.029, 0.045], p < 0.001), and age (beta = 0.093, 95% CI [0.162, 0.241], p < 0.001) were the strongest predictors of SBPpeak.ConclusionThis study provides reference values for the interpretation of SBP responses to exercise in athletes. Multivariate analyses highlight the complex interplay of factors influencing peak SBP, including SBPrest, height, WR, age, DBPrest, sex, endurance sport category, and weight. In future studies, these findings may inform the development of personalised training strategies and risk stratification models in athletic populations.

BackgroundThe mammalian Natural Killer Complex (NKC) harbors genes and gene families encoding a variety of C-type lectin-like proteins expressed on various immune cells. The NKC is a complex genomic region well-characterized in mice, humans and domestic animals. The major limitations of automatic annotation of the NKC in non-model animals include short-read based sequencing, methods of assembling highly homologous and repetitive sequences, orthologues missing from reference databases and weak expression. In this situation, manual annotations of complex genomic regions are necessary.MethodsThis study presents a manual annotation of the genomic structure of the NKC region in a high-quality reference genome of the domestic cat and compares it with other felid species and with representatives of other carnivore families. Reference genomes of Carnivora, irrespective of sequencing and assembly methods, were screened by BLAST to retrieve information on their killer cell lectin-like receptor (KLR) gene content. Phylogenetic analysis of in silico translated proteins of expanded subfamilies was carried out.ResultsThe overall genomic structure of the NKC in Carnivora is rather conservative in terms of its C-type lectin receptor gene content. A novel KLRH-like gene subfamily (KLRL) was identified in all Carnivora and a novel KLRJ-like gene was annotated in the Mustelidae. In all six families studied, one subfamily (KLRC) expanded and experienced pseudogenization. The KLRH gene subfamily expanded in all carnivore families except the Canidae. The KLRL gene subfamily expanded in carnivore families except the Felidae and Canidae, and in the Canidae it eroded to fragments.ConclusionsKnowledge of the genomic structure and gene content of the NKC region is a prerequisite for accurate annotations of newly sequenced genomes, especially of endangered wildlife species. Identification of expressed genes, pseudogenes and gene fragments in the context of expanded gene families would allow the assessment of functionally important variability in particular species.

Abstract Type II diabetes mellitus (T2DM) is a rising global health burden due to its rapidly increasing prevalence worldwide, and can result in serious complications. Therefore, it is of utmost importance to identify individuals at risk as early as possible to avoid long-term T2DM complications. In this study, we developed an interpretable machine learning model leveraging baseline levels of biomarkers of oxidative stress (OS), inflammation, and mitochondrial dysfunction (MD) for identifying individuals at risk of developing T2DM. In particular, Isolation Forest (iForest) was applied as an anomaly detection algorithm to address class imbalance. iForest was trained on the control group data to detect cases of high risk for T2DM development as outliers. Two iForest models were trained and evaluated through ten-fold cross-validation, the first on traditional biomarkers (BMI, blood glucose levels (BGL) and triglycerides) alone and the second including the additional aforementioned biomarkers. The second model outperformed the first across all evaluation metrics, particularly for F1 score and recall, which were increased from 0.61 ± 0.05 to 0.81 ± 0.05 and 0.57 ± 0.06 to 0.81 ± 0.08, respectively. The feature importance scores identified a novel combination of biomarkers, including interleukin-10 (IL-10), 8-isoprostane, humanin (HN), and oxidized glutathione (GSSG), which were revealed to be more influential than the traditional biomarkers in the outcome prediction. These results reveal a promising method for simultaneously predicting and understanding the risk of T2DM development and suggest possible pharmacological intervention to address inflammation and OS early in disease progression.

BackgroundDigital health interventions increase access to multiple sclerosis (MS)–related knowledge for people living with MS; however, our understanding of factors associated with engagement in web-based learning is limited. ObjectiveThis study aims to examine associations between participant sociodemographic, health, and lifestyle-related characteristics and the commencement and completion of the Multiple Sclerosis Online Course (MSOC) in a randomized controlled trial (RCT). MethodsAn intervention course was developed based on the Overcoming MS Program—an evidence-based lifestyle modification program for MS, and a standard care course was developed based on international MS website information. An RCT was conducted to compare the effectiveness of the intervention course versus the standard care course in improving health outcomes in people living with MS. Participant data were collected from a baseline survey. Associations between baseline participant characteristics and MSOC commencement and completion, respectively, were assessed using multivariate log-binomial regression. ResultsOverall, 1893 participants enrolled in the RCT, and 45.27% (n=857) completed the baseline survey: 23.5% (n=444) in the intervention course and 21.8% (n=413) in the standard care course. Of these 857 participants, 631 (73.6%) commenced the standard care course or intervention course, and 49.1% (218/444) and 54.2% (224/413) completed the intervention course and standard care course, respectively. University education, partnered relationship status, and higher mental and physical quality of life were associated with 19%, 12%, 20%, and 22% higher rates of course commencement, respectively. Clinically significant fatigue was associated with a 10% reduction in the likelihood of commencement. Strongest associations with intervention course completion included middle and older adulthood, male sex, fatigue, and preexisting adherence to a diet program, with 96%, 27%, 24%, and 19% higher rates of completion observed, respectively, whereas higher self-efficacy was associated with up to 35% lower intervention course completion. Associations with standard care course completion included practicing meditation (20% higher completion), whereas employment was associated with 22% lower completion. ConclusionsSociodemographic and clinical factors, as well as lifestyle-related factors, were important factors in MSOC commencement and completion. These data may help guide the design and enhancement of digital health interventions tailored for people living with MS. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12621001605886; https://tinyurl.com/2vyve9p9 International Registered Report Identifier (IRRID)RR2-10.1186/s12883-023-03298-0

Introduction. Immunoablative therapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is one of the possible disease-modifying therapies (DMTs) for patients with multiple sclerosis (MS). In this case series, we would like to present six patients with MS, who underwent AHSCT as the first-line DMT. Case reports. Six MS patients with a rapid progression of disability with or without relapses underwent AHSCT as the first-line DMT at the University Hospital Ostrava between 2018 and 2021. The conditioning regimens for AHSCT used were a medium-intensity regime BEAM (Carmustine, Etoposid, Cytarabin, Melphalan) and low-intensity regime based on Cyclophosphamide. Four out of six patients showed some disability progression after AHSCT, so the rapid progression of MS was just slowed down by AHSCT. One patient developed activity on magnetic resonance imaging three months after AHSCT, and two experienced mild relapses during the follow-up period. None of our patients developed grade 4 non-hematological toxicity; all infections were mild. In one patient, an allergic reaction probably to dimethyl sulfoxide was observed. Conclusion. Our case series of 6 patients shows that AHSCT is a promising therapeutic approach to slow down the rapid progression of clinical disability in MS patients with a good safety profile.

Abstract Background Inhibition of cyclin-dependent kinase 9 (CDK9), a novel epigenetic target in cancer, can reactivate epigenetically silenced genes in cancer by dephosphorylating the SWI/SNF chromatin remodeler BRG1. Here, we characterized the anti-tumor efficacy of MC180295, a newly developed CDK9 inhibitor. Methods In this study, we explored the pharmacokinetics of MC180295 in mice and rats, and tested the anti-tumor efficacy of MC180295, and its enantiomers, in multiple cancer cell lines and mouse models. We also combined CDK9 inhibition with a DNA methyltransferase (DNMT) inhibitor, decitabine, in multiple mouse models, and tested MC180295 dependence on T cells. Drug toxicity was measured by checking body weights and complete blood counts. Results MC180295 had high specificity for CDK9 and high potency against multiple neoplastic cell lines (median IC50 of 171 nM in 46 cell lines representing 6 different malignancies), with the highest potency seen in AML cell lines derived from patients with MLL translocations. MC180295 is a racemic mixture of two enantiomers, MC180379 and MC180380, with MC180380 showing higher potency in a live-cell epigenetic assay. Both MC180295 and MC180380 showed efficacy in in vivo AML and colon cancer xenograft models, and significant synergy with decitabine in both cancer models. Lastly, we found that CDK9 inhibition-mediated anti-tumoral effects were partially dependent on CD8 + T cells in vivo, indicating a significant immune component to the response. Conclusions MC180380, an inhibitor of cyclin-dependent kinase 9 (CDK9), is an efficacious anti-cancer agent worth advancing further toward clinical use.

This conversation starts with the introduction of a large-scale research project conducted in 2022 in eight Central and South-Eastern European countries on how catalytic capital investment can enable the provision of affordable rental and cooperative housing in the region. The results of the project prove that while there is a large potential target group of such alternative housing models in these countries, the currently available housing finance tools are inadequate to help the emergence of the sector. In the second part of the conversation we introduce how MOBA Housing SCE intends to solve this problem through creating a bottom-up quasi revolving fund, which can financially help local projects in their early phase. Finally, we explain how MOBA approaches internationalism, co-housing principles, the need for shifting housing paradigms, and state socialist heritages of cooperativism.

Abstract Background DNA methylation analysis might identify prognostic CpG sites in CHOP‐treated dogs with multicentric high‐grade B‐cell lymphoma (MHGL) with heterogenous prognosis. Objective To identify prognostic CpG sites of MHGL through genome‐wide DNA methylation analysis with pyrosequencing validation. Animals Test group: 24 dogs. Validation group: 100 dogs. All client‐owned dogs were diagnosed with MHGL and treated with CHOP chemotherapy. Methods Cohort study. DNA was extracted from lymph node samples obtained via FNA. Genome‐wide DNA methylation analysis using Digital Restriction Enzyme Analysis of Methylation (DREAM) was performed on the test group to identify differentially methylated CpG sites (DMCs). Bisulfite pyrosequencing was used to measure methylation status of candidate DMCs in the validation group. Median survival times (MST) were analyzed using Kaplan‐Meier (log‐rank) product limit method. Results DREAM analyzed 101 576 CpG sites. Hierarchical clustering of 16 262 CpG sites in test group identified group with better prognosis (MST = 55‐477 days vs 10‐301 days, P = .007). Volcano plot identified 1371 differentially methylated CpG sites (DMCs). DMC near the genes of FAM213A (DMC‐F) and PHLPP1 (DMC‐P) were selected as candidates. Bisulfite‐pyrosequencing performed on validation group showed group with methylation level of DMC‐F

BackgroundDigital technologies have afforded people living with multiple sclerosis (MS) access to telehealth consultations, diagnostic tools, and monitoring. Although health care professionals remain the most trusted source of information, the internet has emerged as a valuable resource for providing MS-related information, particularly during the COVID-19 pandemic. Notably, people living with MS are increasingly seeking educational content for a range of topics related to the self-management of MS; however, web-based information seeking remains largely underevaluated. To address this gap and ensure that web-based health-related information is accessible and engaging, this study used qualitative methods to analyze the reflections from participants of web-based educational programs for people living with MS. ObjectiveThis study aimed to explore the motivations, behaviors, and expectations of web-based health information seeking for people living with MS. MethodsWe conducted semistructured interviews for 38 people living with MS 1 month after they completed the novel MS Online Course, which provided information on modifiable lifestyle-related risk factors for people living with MS. Of the 38 participants, 22 (58%) completed the intervention course and 16 (42%) completed the standard care course. Inductive thematic analysis was used within a qualitative paradigm, and 2 authors coded each interview separately and arrived at themes with consensus. ResultsWe identified 2 themes: motivation to learn and MS information on the web. The diagnosis of MS was described as a pivotal moment for precipitating web-based information seeking. People living with MS sought lifestyle-related information to facilitate self-management and increase control of their MS. Although social media sites and MS websites were considered useful for providing both support and information, discretion was needed to critically appraise information. Recognizable institutions were frequently accessed because of their trustworthiness. ConclusionsThis study provided novel insights into the motivations of people living with MS for seeking web-based health information. Furthermore, their preferences for the content and format of the web-based information accessed and their experiences and reactions to this information were explored. These findings may guide educators, researchers, and clinicians involved in MS care to optimize the engagement and processing of web-based health information seeking by people living with MS.

As multi-photon lithography technology matures, advanced integrated device design concepts become possible, positioned onto small surfaces, such as optical fibres. Only local adhesion anchors the printed object on the surface and ensure proper print-development without structure loss and long-term usability. Although surface treatments such as silanization are well known to considerably increase adhesion strength, quantification of adhesion is not straightforward and commonly assessed indirectly by surface characteristics and technological methods. The present work aims to quantify adhesion on a micrometer scale through SEM in situ tension experiments, that utilize a newly developed specimen geometry. Multiple specimens, with various footprints, were manufactured on both silanized and untreated fused silica substrates, allowing the comparable quantification of adhesion stresses between different surface conditions. Specimens on an untreated substrate failed with a high scatter in detaching force, whereas specimens on a silanized substrate tend to fail within the photoresist, either at the gauge section or just above the substrate, rather than at the interface itself. Thus, the adhesion stress was increased at least by a factor of 1.4 by the silanization treatment. Generally, a novel approach was developed, that can quantify local adhesions properties in realistic packaging or integrated circuits.

Background: Type 2 diabetes mellitus (T2DM) are 90% of diabetes cases, and its prevalence and incidence, including comorbidities, are rising worldwide. Clinically, diabetes and associated comorbidities are identified by biochemical and physical characteristics including glycemia, glycated hemoglobin (HbA1c), and tests for cardiovascular, eye and kidney disease. Objectives: Diabetes may have a common etiology based on inflammation and oxidative stress that may provide additional information about disease progression and treatment options. Thus, identifying high-risk individuals can delay or prevent diabetes and its complications. Design: In patients with or without hypertension and cardiovascular disease, as part of progression from no diabetes to T2DM, this research studied the changes in biomarkers between control and prediabetes, prediabetes to T2DM, and control to T2DM, and classified patients based on first-attendance data. Control patients and patients with hypertension, cardiovascular, and with both hypertension and cardiovascular diseases are 156, 148, 61, and 216, respectively. Methods: Linear discriminant analysis is used for classification method and feature importance, This study examined the relationship between Humanin and mitochondrial protein (MOTSc), mitochondrial peptides associated with oxidative stress, diabetes progression, and associated complications. Results: MOTSc, reduced glutathione and glutathione disulfide ratio (GSH/GSSG), interleukin-1β (IL-1β), and 8-isoprostane were significant ( P