bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tele-Mindfulness Program for Mental Health in Previously Hospitalized COVID-19 Patients: A quasi-experimental study
Authors: Milani Giada , Zerbinati Luigi , Grassi Luigi , Fregna Giulia , Schincaglia Nicola , Baroni Andrea , Lamberti Nicola , Manfredini Fabio , Straudi Sofia 
Published: December 2024

Background: Nearly half of subjects after COVID-19 still experience symptoms after 12 weeks, as described in the Post-Covid Syndrome (PCS). Other than the physical alterations perceived, mental health disorders have been frequently reported. Mindfulness-Based Interventions (MBIs) showed beneficial effects on psychological well-being in patients with respiratory dysfunctions, but they have been rarely tested in severe COVID-19 survivors. Objective: In a quasi-experimental study, test the clinical and psychological effects of a 12-week Tele–MBI in previously hospitalized COVID-19 patients and analyze the feasibility of the intervention. Methods: Subjects earlier hospitalized due to COVID-19 were enrolled 12 weeks after the infection onset, they were assigned to the intervention group (TG) or to the control one (n-TG). Subjects enrolled in the TG attended a 12-week home-based T-MBI and patients of both groups received multimodal rehabilitation interventions according to their own therapeutic needs. Mental health (anxiety, depression, post-traumatic stress disorder (PTSD) symptoms, sleep quality, self-efficacy, and resilience) and quality of life were detected before and after treatment. The feasibility of the T-MBI applied was also investigated. Results: A total of 88 subjects were included (44 in the TG and 44 in the n-TG; 63.6% males, mean age 64.4 ± 10.6). Most characteristics were similar between groups at the baseline; TG patients showed greater improvements in different psychological metrics (anxiety, depression, PTSD, resilience, and self-efficacy) compared to n-TG while no differences were found for perceived quality of life. T-MBI was well-accepted by patients. Conclusion: Tele-Mindfulness program seems effective in reducing anxiety, depression, and post-traumatic stress disorder symptoms and increasing resilience and self-efficacy in subjects who required hospitalization due to COVID-19.
Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease
Authors: Kambara Yui , Fujiwara Hideaki , Yamamoto Akira , Gotoh Kazuyoshi , Tsuji Shuma , Kunihiro Mari , Oyama Tadashi , Terao Toshiki , Sato Ayame , Tanaka Takehiro , Peltier Daniel , Seike Keisuke , Nishimori Hisakazu , Asada Noboru , Ennishi Daisuke , Fujii Keiko , Fujii Nobuharu , Matsuoka Ken-ichi , Soga Yoshihiko , Reddy Pavan , Maeda Yoshinobu 
Published: December 2024

Abstract
The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD.
Maternal high-fat diet orchestrates offspring hepatic cholesterol metabolism via MEF2A hypermethylation-mediated CYP7A1 suppression
Authors: Zhang Ling , Zou Wenyu , Zhang Shixuan , Wu Honghua , Gao Ying , Zhang Junqing , Zheng Jia 
Published: December 2024

Abstract
Background
Maternal overnutrition, prevalent among women of childbearing age, significantly impacts offspring health throughout their lifetime. While DNA methylation of metabolic-related genes mediates the transmission of detrimental effects from maternal high-fat diet (HFD), its role in programming hepatic cholesterol metabolism in offspring, particularly during weaning, remains elusive.

Methods
Female C57BL/6 J mice were administered a HFD or control diet, before and during, gestation and lactation. Hepatic cholesterol metabolism genes in the liver of offspring were evaluated in terms of their expression. The potential regulator of cholesterol metabolism in the offspring’s liver was identified, and the function of the targeted transcription factor was evaluated through in vitro experiments. The methylation level of the target transcription factor was assessed using the MassARRAY EpiTYPER platform. To determine whether transcription factor expression is influenced by DNA methylation, in vitro experiments were performed using 5-azacitidine and Lucia luciferase activity assays.

Results
Here, we demonstrate that maternal HFD results in higher body weight and hypercholesterolemia in the offspring as early as weaning age. Maternal HFD feeding exacerbates hepatic cholesterol accumulation in offspring primarily by inhibiting cholesterol elimination to bile acids, with a significant decrease of hepatic cholesterol 7α-hydroxylase (CYP7A1). RNA-seq analysis identified myocyte enhancer factor 2A (MEF2A) as a key transcription factor in the offspring liver, which was significantly downregulated in offspring of HFD-fed dams. MEF2A knockdown led to CYP7A1 downregulation and lipid accumulation in HepG2 cells, while MEF2A overexpression reversed this effect. Dual luciferase reporter assays confirmed direct modulation of CYP7A1 transcription by MEF2A. Furthermore, the reduced MEF2A expression was attributed to DNA hypermethylation in the Mef2a promoter region. This epigenetic modification manifested as early as the fetal stage.

Conclusions
This study provides novel insights into how maternal HFD orchestrates hepatic cholesterol metabolism via MEF2A hypermethylation-mediated CYP7A1 suppression in offspring at weaning.
Opportunities for nanomaterials in more sustainable aviation
Authors: Pendashteh Afshin , Mikhalchan Anastasiia , Blanco Varela Tamara , Vilatela Juan J. 
Published: December 2024

AbstractNew materials for electrical conductors, energy storage, thermal management, and structural elements are required for increased electrification and non-fossil fuel use in transport. Appropriately assembled as macrostructures, nanomaterials can fill these gaps. Here, we critically review the materials science challenges to bridge the scale between the nanomaterials and the large-area components required for applications. We introduce a helpful classification based on three main macroscopic formats (fillers in a matrix, random sheets or aligned fibres) of high-aspect ratio nanoparticles, and the corresponding range of bulk properties from the commodity polymer to the high-performance fibre range. We review progress over two decades on macroscopic solids of nanomaterials (CNTs, graphene, nanowires, etc.), providing a framework to rationalise the transfer of their molecular-scale properties to the scale of engineering components and discussing strategies that overcome the envelope of current aerospace materials. Macroscopic materials in the form of organised networks of high aspect ratio nanomaterials have higher energy density than regular electrodes, superior mechanical properties to the best carbon fibres, and electrical and thermal conductivity above metals. Discussion on extended electrical properties focuses on nanocarbon-based materials (e.g., doped or metal-hybridised) as power or protective conductors and on conductive nanoinks for integrated conductors. Nanocomposite electrodes are enablers of hybrid/electric propulsion by eliminating electrical transport limitations, stabilising emerging high energy density battery electrodes, through high-power pseudocapacitive nanostructured networks, or downsizing Pt-free catalysts in flying fuel cells. Thermal management required in electrified aircraft calls for nanofluids and loop heat pipes of nanoporous conductors. Semi-industrial interlaminar reinforcement using nanomaterials addresses present structural components. Estimated improvements for mid-range aircraft include > 1 tonne weight reduction, eliminating hundreds of CO2 tonnes released per year and supporting hybrid/electric propulsion by 2035.
Non-extractable residues (NER) in persistence assessment: effect on the degradation half-life of chemicals
Authors: Jespersen Cindy , Trapp Stefan , Kästner Matthias 
Published: December 2024

AbstractThe ECHA guidance on persistence (P) assessment has been updated with respect to non-extractable residues (NER). Unless further characterized, total NER shall be considered as non-degraded parent compound. We investigated how different NER fractions affect degradation half-lives (DegT50) of chemicals and the P assessment. Total NER consist of the fractions sorbed/sequestered (NER I), covalently bound (NER II), and bioNER (incorporated into the biomass, NER III). NER I pose a risk due to potential release, NER II have much lower release potential, and bioNER do not have any. NER I and NER II are considered as xenoNER. Data from 46 degradation tests with 24 substances were analyzed to find DegT50 for four scenarios: (i) extractable parent compound, (ii) parent plus total NER, (iii) parent plus xenoNER, and (iv) parent plus NER I. The microbial turnover to biomass (MTB) model was applied to calculate bioNER, and then xenoNER were calculated as total NER minus bioNER. The half-lives were determined by the fit program CAKE, using single first-order kinetics (SFO) for all fits. We found increasing degradation half-lives for the scenarios: extractable parent only < parent + NER I < parent + xenoNER < parent + total NER. A third of all chemicals show half-lives above the persistence criterion (120 days in OECD 307 and 308, and 40 days in OECD 309) for scenario i, and two thirds with scenario ii and, therefore, would be classified as ‘persistent’. For two compounds, the subtraction of bioNER led to a change to ‘not persistent’. The inclusion of NER in the P assessment (ECHA 2017, 2023) will thus have significant effects on the DegT50 of compounds and the persistence assessment. Experimental quantification of NER I (scenario iv) significantly reduces half-lives, in comparison to total NER (scenario ii). The results are closer to half-lives for parent only (scenario i) and give the lowest acceptable DegT50 below the vP criteria under the latest guidance. In addition, refining the DegT50 based on modelled bioNER can provide a more realistic option for persistence assessment, without laborious and costly analyses for NER I determination, when considered in the regulatory assessment of persistence. Moreover, bioNER can also be calculated for existing test data.
Wide-field fluorescein angiography findings in active anterior scleritis
Authors: Romo-Aguas Juan C. , Zavaleta-Mercado Miguel , Cheja-Kalb Rashel , Hubbe-Tena Claudia , Concha-del-Río Luz Elena 
Published: December 2024

Abstract
Objective
Describe the proportion of patients with wide-field fluorescein angiographic (WFFA) findings in patients with active anterior scleritis.

Methods
An observational, descriptive, cross-sectional study of the WFFA findings of patients with active anterior scleritis including nodular, diffuse, or necrotizing involvement was performed. Studies were performed with the Heidelberg Spectralis module (102º). Images were saved and assessed by two masked co-authors.

Results
Seventy-nine eyes from 39 patients, 31 (79%) females with a mean age of 50.5 years ± 13.98. Mean best-corrected visual acuity (BCVA) of 0.1343 ± 0.2475 logMar or 20/27. WFFA findings were observed in 39.58% of eyes with active scleritis and in 16.66% of eyes without scleritis. Systemic association was present at 50%, with ANCA-associated vasculitis being the most prevalent. WFFA findings were more frequent in cases of anterior diffuse scleritis and correlated with scleritis severity when central and peripheral leakage (p < 0.022) and cystoid macular edema (p < 0.013) were present.

Conclusions
Almost 40% of eyes with anterior scleritis have WFFA findings of vascular leakage and 16% of eyes without scleritis. Retinal vascular leakage needs to be explored as a sign of local and/or systemic activity in patients with anterior scleritis and may have implications for disease severity and management.
Primary ciliary dyskinesia as a rare cause of male infertility: case report and literature overview
Authors: Novák Jan , Horáková Lenka , Puchmajerová Alena , Vik Viktor , Krátká Zuzana , Thon Vojtěch 
Published: December 2024

Abstract
Background
Primary ciliary dyskinesia (PCD) is a heterogenous disease caused by mutations of miscellaneous genes which physiologically play an important role in proper structure and/or function of various cellular cilia including sperm flagella. Besides male infertility, the typical phenotypes, based on decreased mucociliary clearance, are lifelong respiratory issues, i.e., chronic bronchitis leading to bronchiectasis, chronic rhinosinusitis, and chronic otitis media. Moreover, since motile cilia are important during embryological development in the sense of direction of gut rotation, 50% of affected individuals develop situs inversus – so-called Kartagener’s syndrome.

Case presentation
We present two cases of PCD as a rare cause of male infertility.

Conclusions
Primary ciliary dyskinesia should be suspected in infertile males having (sub)normal sperm concentration values with persistent zero motility together with patient’s and/or family history of respiratory symptoms like bronchiectasis, chronic cough, rhinitis, recurrent sinusitis, and otitis media. Due to more than 50 identified mutations until now, the causal mechanism of male infertility is miscellaneous and not in all cases known in detail. Besides impaired sperm motility, other mechanisms significantly decreasing efficacy of assisted reproduction techniques play a pivotal role. Thus, proper diagnostic work-up including, among others, sperm DNA fragmentation, is mandatory to avoid ineffective treatment burden.
Robustness assessment of regressions using cluster analysis typologies: a bootstrap procedure with application in state sequence analysis
Authors: Roth Leonard , Studer Matthias , Zuercher Emilie , Peytremann-Bridevaux Isabelle 
Published: December 2024

Abstract
Background
In standard Sequence Analysis, similar trajectories are clustered together to create a typology of trajectories, which is then often used to evaluate the association between sequence patterns and covariates inside regression models. The sampling uncertainty, which affects both the derivation of the typology and the associated regressions, is typically ignored in this analysis, an oversight that may lead to wrong statistical conclusions. We propose utilising sampling variation to derive new estimates that further inform on the association of interest.

Methods
We introduce a novel procedure to assess the robustness of regression results obtained from the standard analysis. Bootstrap samples are drawn from the data, and for each bootstrap, a new typology replicating the original one is constructed, followed by the estimation of the corresponding regression models. The bootstrap estimates are then combined using a multilevel modelling framework that mimics a meta-analysis. The fitted values from this multilevel model allow to account for the sampling uncertainty in the inferential analysis. We illustrate the methodology by applying it to the study of healthcare utilisation trajectories in a Swiss cohort of diabetic patients.

Results
The procedure provides robust estimates for an association of interest, along with 95% prediction intervals, representing the range of expected values if the clustering and associated regressions were performed on a new sample from the same underlying distribution. It also identifies central and borderline trajectories within each cluster. Regarding the illustrative application, while there was evidence of an association between regular lipid testing and subsequent healthcare utilisation patterns in the original analysis, this is not supported in the robustness assessment.

Conclusions
Investigating the relationship between trajectory patterns and covariates is of interest in many situations. However, it is a challenging task with potential pitfalls. Our Robustness Assessment of Regression using Cluster Analysis Typologies (RARCAT) may assist in ensuring the robustness of such association studies. The method is applicable wherever clustering is combined with regression analysis, so its relevance goes beyond State Sequence Analysis.
Replacing serum with dried blood microsampling for pharmacokinetics, viral neutralisation and immunogenicity bioanalysis supporting future paediatric development of RSM01, a candidate respiratory syncytial virus neutralising monoclonal antibody
Authors: White Joleen T. , Terstappen Jonne , Levi Micha , Radivojevic Andrijana , Noble Robert , Anderson Aparna B. , Wise-Blackman Gwendolyn , Dunne Michael W. 
Published: December 2024

Abstract
Background
Virus neutralising antibodies in serum are considered key correlates of protection for vaccines and monoclonal antibodies against respiratory syncytial virus (RSV). RSM01 is a novel, highly-potent, half-life-extended and fully-human monoclonal antibody candidate targeting the RSV prefusion F protein. Currently in Phase 1 development, RSM01 is primarily being developed to potentially provide an effective and affordable RSV prevention strategy in low- and middle-income countries. To evaluate the ability of dried blood collection to generate data sets and conclusions comparable to serum collection, we compared pharmacokinetics (PK) of RSM01, immunogenicity, and virus neutralisation for dried capillary blood samples with serum samples.

Methods
RSM01 PK, anti-drug antibodies (ADA), and RSV-neutralising antibodies from the Phase 1 trial were analyzed and compared between matched serum and dried blood samples. Deming regression analysis was performed using baseline-corrected values to evaluate correlation between measurements in liquid serum versus dried blood.

Results
The analysis showed good correlation (R2 > 0.95) between individual RSM01 concentrations measured in both serum and capillary blood. Analysis of RSM01 PK parameters in capillary blood yielded equivalent conclusions as from serum. A strong correlation (R2 > 0.95) was observed between RSV neutralising activity measured in both serum and capillary blood. In addition, RSV neutralising activity was correlated with RSM01 concentrations in both serum and capillary blood data sets. For ADA, individual sample results had 96% agreement (290/302) and overall participant ADA status had 93% agreement (52/56).

Conclusions
Both RSM01 concentrations and RSV neutralising activity showed a strong correlation between the serum and blood measurements. ADA measurements also had an agreement of > 90% for individual samples and overall participant status. Our results demonstrate that dried blood is a suitable specimen type for collection and evaluation in the RSM01 clinical development program and shows promise as a useful approach to reduce patient burden in clinical trials, particularly for infants in low- and middle-income countries.

Trial Registration
Clinicaltrials.gov NCT05118386 November 12, 2021.
DKI and 1H-MRS in angiogenesis evaluation of soft tissue sarcomas: a prospective clinical study based on MRI-pathology control method
Authors: Han Wubing , Xin Cheng , Wang Zeguo , Wang Fei , Cheng Yu , Yang Xingrong , Zhou Yangyun , Liu Juntong , Yu Wanjiang , Wang Shaowu 
Published: December 2024

Abstract
Background
The vascular endothelial growth factor (VEGF) and microvessel density (MVD) have been widely employed as angiogenesis indicators in the diagnosis and treatment of soft tissue sarcomas. While diffusion kurtosis imaging (DKI) and proton magnetic resonance spectroscopy (1H-MRS) imaging hold potential in assessing angiogenesis in other tumors, their reliability in correlating with angiogenesis in soft tissue sarcomas remains uncertain, contingent upon accurately acquiring the region of interest (ROI).

Methods
23 patients with soft tissue sarcomas (STSs) confirmed by pathology were selected, underwent DKI and 1H-MRS at 3.0T MRI. The DKI parameters mean diffusivity (MD), mean kurtosis (MK), kurtosis anisotropy (KA), and 1H-MRS parameters choline (Cho), lipid/lactate (LL) were measured by two radiologists. Two pathologists obtained pathological slices using a new sampling method called MRI-pathology control and evaluated VEGF and MVD in the selected regions. Correlations between MRI parameters and angiogenesis markers were assessed by Person or Spearman tests.

Results
The DKI parameters MD and KA, and the 1H-MRS parameters Cho and LL, have varying degrees of correlation with the expression levels of VEGF and MVD. Among them, Cho exhibits the strongest correlation (r = 0.875, P < 0.001; r = 0.807, P < 0.001).

Conclusion
Based on this preliminary clinical studies, DKI and 1H-MRS parameters are correlated with angiogenesis markers obtained through the “MRI-pathology control” method.
Accumulating evidence from meta-analyses of prognostic studies on oral cancer: towards biomarker-driven patient selection
Authors: Almangush Alhadi , Alabi Rasheed Omobolaji , Pirinen Matti , Mäkitie Antti , Leivo Ilmo 
Published: December 2024

Abstract
Background
Many histopathologic prognostic markers, identified by routine hematoxylin and eosin (HE) staining, have been proposed for predicting the survival of patients with oral squamous cell carcinoma (OSCC). Subsequently, several meta-analyses have been conducted on these prognostic markers. We sought to analyze the accumulated evidence from these meta-analyses.

Methods
An electronic database search of PubMed, Scopus, Ovid Medline, Web of Science, and Cochrane Library was conducted to retrieve all meta-analysis articles published on histopathologic prognostic markers of OSCC. The risk of bias of the included studies was analyzed using the Risk of Bias in Systematic Reviews (ROBIS) tool. The synthesis of the results was conducted following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Results
There were 16 meta-analysis articles published on the histological prognostic markers of OSSC. The accumulated evidence from these meta-analyses highlighted the powerful prognostic value of depth of invasion, tumor thickness, perineural invasion, lymphovascular invasion, worst pattern of invasion, tumor budding, and tumor-stroma ratio. The highest odds ratio (OR) of a relationship between a histopathologic prognostic marker and outcome was for the depth of invasion (OR 10.16, 95% CI 5.05–20.46) and tumor thickness (OR 7.32, 95% CI 5.3–10.1) in predicting lymph node metastasis.

Conclusion
The published meta-analyses present robust evidence on the significance of emerging histopathologic markers, namely, worst pattern of invasion, tumor budding, and tumor-stroma ratio. It is time to consider such markers in daily pathology reporting and risk stratification of OSCC.