bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annelid methylomes reveal ancestral developmental and aging-associated epigenetic erosion across Bilateria
Authors: Guynes Kero , Sarre Luke A. , Carrillo-Baltodano Allan M. , Davies Billie E. , Xu Lan , Liang Yan , Martín-Zamora Francisco M. , Hurd Paul J. , de Mendoza Alex , Martín-Durán José M. 
Published: August 2024

Abstract
Background
DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as “mosaic”. Yet, the role and developmental dynamics of 5mC and how these explain interspecies differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla.

Results
Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, alongside a gradual and global, age-dependent demethylation in adult stages. Additionally, reducing 5mC levels with cytidine analogs during early development impairs normal embryogenesis and reactivates TEs in the annelid Owenia fusiformis.

Conclusions
Our study indicates that global epigenetic erosion during development and aging is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely more important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.
Digital remote assessment of speech acoustics in cognitively unimpaired adults: feasibility, reliability and associations with amyloid pathology
Authors: van den Berg Rosanne L. , de Boer Casper , Zwan Marissa D. , Jutten Roos J. , van Liere Mariska , van de Glind Marie-Christine A.B.J. , Dubbelman Mark A. , Schlüter Lisa Marie , van Harten Argonde C. , Teunissen Charlotte E. , van de Giessen Elsmarieke , Barkhof Frederik , Collij Lyduine E. , Robin Jessica , Simpson William , Harrison John E , van der Flier Wiesje M. , Sikkes Sietske A.M. 
Published: August 2024

Abstract
Background
Digital speech assessment has potential relevance in the earliest, preclinical stages of Alzheimer’s disease (AD). We evaluated the feasibility, test-retest reliability, and association with AD-related amyloid-beta (Aβ) pathology of speech acoustics measured over multiple assessments in a remote setting.

Methods
Fifty cognitively unimpaired adults (Age 68 ± 6.2 years, 58% female, 46% Aβ-positive) completed remote, tablet-based speech assessments (i.e., picture description, journal-prompt storytelling, verbal fluency tasks) for five days. The testing paradigm was repeated after 2–3 weeks. Acoustic speech features were automatically extracted from the voice recordings, and mean scores were calculated over the 5-day period. We assessed feasibility by adherence rates and usability ratings on the System Usability Scale (SUS) questionnaire. Test-retest reliability was examined with intraclass correlation coefficients (ICCs). We investigated the associations between acoustic features and Aβ-pathology, using linear regression models, adjusted for age, sex and education.

Results
The speech assessment was feasible, indicated by 91.6% adherence and usability scores of 86.0 ± 9.9. High reliability (ICC ≥ 0.75) was found across averaged speech samples. Aβ-positive individuals displayed a higher pause-to-word ratio in picture description (B = -0.05, p = 0.040) and journal-prompt storytelling (B = -0.07, p = 0.032) than Aβ-negative individuals, although this effect lost significance after correction for multiple testing.

Conclusion
Our findings support the feasibility and reliability of multi-day remote assessment of speech acoustics in cognitively unimpaired individuals with and without Aβ-pathology, which lays the foundation for the use of speech biomarkers in the context of early AD.
Extraocular muscle Diffusion Weighted Imaging as a quantitative metric of posterior orbital involvement in thyroid associated orbitopathy
Authors: George Nicole M. , Feeney Claire , Lee Vickie , Avari Parizad , Ali Amina , Madani Gitta , Lingam Ravi Kumar , Bhatia Kunwar S. 
Published: August 2024

Abstract
Objectives
The clinical activity score (CAS) and European severity scale (ESS) are established clinical tools to assess thyroid eye disease (TED) but are limited in terms of subjectivity and their reliability in non-Caucasian individuals, and can underestimate significant disease in the posterior orbit. Preliminary data from pilot studies have shown that diffusion-weighted imaging (DWI) using extraocular muscle (EOM) apparent diffusion coefficient (ADC) measurements may provide complementary information in TED. This study expands on previous research to assess for correlations between clinical scores and EOM-ADCs in stratifying disease activity and severity in a large patient cohort from an ethnically diverse population.

Methods
A retrospective review of TED clinics between 2011 and 2021 identified 96 patients with a documented CAS and ESS and an orbital MRI that included DWI. From regions of interest manually placed on EOM bellies, the highest ADC was computed for each patient and analysed for correlations and associations with CAS and ESS using Spearman Rank correlation and Mann–Whitney U tests, and any potential discriminatory cut-offs using Receiver Operator Curve analyses. A p-value < 0.05 indicated statistical significance.

Results
EOM-ADCs showed a positive association with CAS (p ≤ 0.001). EOM-ADCs were higher in sight-threatening compared to mild disease (p ≤ 0.01). A cut-off of 995 mm2/s achieved AUC = 0.7744, equating to 77% sensitivity and 67% specificity for discrimination between mild-moderate and sight-threatening disease.

Conclusion
EOM-ADCs correlate with higher scores of disease severity and activity in TED. Besides providing quantitative data to support clinical tools, EOM-ADC cut-offs may identify patients at risk of developing sight-threatening diseases.

Critical relevance statement
This study critically evaluates the limitations of conventional clinical assessment tools for TED and demonstrates the utility of DWI scans with ADC measurements in identifying active disease, offering valuable insights to advance clinical radiology practice.

Key Points

Conventional tools for TED assessment have subjective limitations.

ADCs from non-echoplanar diffusion-weighted imaging correlate with clinical activity.

Non-echoplanar diffusion-weighted imaging offers quantitative assessment to aid clinical practice reliability.

Graphical Abstract
Preoperative prediction of microvascular invasion risk in hepatocellular carcinoma with MRI: peritumoral versus tumor region
Authors: Wei Guangya , Fang Guoxu , Guo Pengfei , Fang Peng , Wang Tongming , Lin Kecan , Liu Jingfeng 
Published: August 2024

Abstract
Objectives
To explore the predictive performance of tumor and multiple peritumoral regions on dynamic contrast-enhanced magnetic resonance imaging (MRI), to identify optimal regions of interest for developing a preoperative predictive model for the grade of microvascular invasion (MVI).

Methods
A total of 147 patients who were surgically diagnosed with hepatocellular carcinoma, and had a maximum tumor diameter ≤ 5 cm were recruited and subsequently divided into a training set (n = 117) and a testing set (n = 30) based on the date of surgery. We utilized a pre-trained AlexNet to extract deep learning features from seven different regions of the maximum transverse cross-section of tumors in various MRI sequence images. Subsequently, an extreme gradient boosting (XGBoost) classifier was employed to construct the MVI grade prediction model, with evaluation based on the area under the curve (AUC).

Results
The XGBoost classifier trained with data from the 20-mm peritumoral region showed superior AUC compared to the tumor region alone. AUC values consistently increased when utilizing data from 5-mm, 10-mm, and 20-mm peritumoral regions. Combining arterial and delayed-phase data yielded the highest predictive performance, with micro- and macro-average AUCs of 0.78 and 0.74, respectively. Integration of clinical data further improved AUCs values to 0.83 and 0.80.

Conclusion
Compared with those of the tumor region, the deep learning features of the peritumoral region provide more important information for predicting the grade of MVI. Combining the tumor region and the 20-mm peritumoral region resulted in a relatively ideal and accurate region within which the grade of MVI can be predicted.

Clinical relevance statement
The 20-mm peritumoral region holds more significance than the tumor region in predicting MVI grade. Deep learning features can indirectly predict MVI by extracting information from the tumor region and directly capturing MVI information from the peritumoral region.

Key Points

We investigated tumor and different peritumoral regions, as well as their fusion.

MVI predominantly occurs in the peritumoral region, a superior predictor compared to the tumor region.

The peritumoral 20 mm region is reasonable for accurately predicting the three-grade MVI.

Graphical Abstract
The policies on the use of large language models in radiological journals are lacking: a meta-research study
Authors: Zhong Jingyu , Xing Yue , Hu Yangfan , Lu Junjie , Yang Jiarui , Zhang Guangcheng , Mao Shiqi , Chen Haoda , Yin Qian , Cen Qingqing , Jiang Run , Chu Jingshen , Song Yang , Lu Minda , Ding Defang , Ge Xiang , Zhang Huan , Yao Weiwu 
Published: August 2024

Abstract
Objective
To evaluate whether and how the radiological journals present their policies on the use of large language models (LLMs), and identify the journal characteristic variables that are associated with the presence.

Methods
In this meta-research study, we screened Journals from the Radiology, Nuclear Medicine and Medical Imaging Category, 2022 Journal Citation Reports, excluding journals in non-English languages and relevant documents unavailable. We assessed their LLM use policies: (1) whether the policy is present; (2) whether the policy for the authors, the reviewers, and the editors is present; and (3) whether the policy asks the author to report the usage of LLMs, the name of LLMs, the section that used LLMs, the role of LLMs, the verification of LLMs, and the potential influence of LLMs. The association between the presence of policies and journal characteristic variables was evaluated.

Results
The LLM use policies were presented in 43.9% (83/189) of journals, and those for the authors, the reviewers, and the editor were presented in 43.4% (82/189), 29.6% (56/189) and 25.9% (49/189) of journals, respectively. Many journals mentioned the aspects of the usage (43.4%, 82/189), the name (34.9%, 66/189), the verification (33.3%, 63/189), and the role (31.7%, 60/189) of LLMs, while the potential influence of LLMs (4.2%, 8/189), and the section that used LLMs (1.6%, 3/189) were seldomly touched. The publisher is related to the presence of LLM use policies (p < 0.001).

Conclusion
The presence of LLM use policies is suboptimal in radiological journals. A reporting guideline is encouraged to facilitate reporting quality and transparency.

Critical relevance statement
It may facilitate the quality and transparency of the use of LLMs in scientific writing if a shared complete reporting guideline is developed by stakeholders and then endorsed by journals.

Key Points

The policies on LLM use in radiological journals are unexplored.

Some of the radiological journals presented policies on LLM use.

A shared complete reporting guideline for LLM use is desired.

Graphical Abstract
Cilostazol is a promising anti-pseudomonal virulence drug by disruption of quorum sensing
Authors: Al-Rabia Mohammed W. , Asfour Hani Z. , Alhakamy Nabil A. , Bazuhair Mohammed A. , Ibrahim Tarek S. , Abbas Hisham A. , Mansour Basem , Hegazy Wael A. H. , Seleem Noura M. 
Published: August 2024

AbstractResistance to antibiotics is a critical growing public health problem that desires urgent action to combat. To avoid the stress on bacterial growth that evokes the resistance development, anti-virulence agents can be an attractive strategy as they do not target bacterial growth. Quorum sensing (QS) systems play main roles in controlling the production of diverse virulence factors and biofilm formation in bacteria. Thus, interfering with QS systems could result in mitigation of the bacterial virulence. Cilostazol is an antiplatelet and a vasodilator FDA approved drug. This study aimed to evaluate the anti-virulence activities of cilostazol in the light of its possible interference with QS systems in Pseudomonas aeruginosa. Additionally, the study examines cilostazol’s impact on the bacterium’s ability to induce infection in vivo, using sub-inhibitory concentrations to minimize the risk of resistance development. In this context, the biofilm formation, the production of virulence factors and influence on the in vivo ability to induce infection were assessed in the presence of cilostazol at sub-inhibitory concentration. Furthermore, the outcome of combination with antibiotics was evaluated. Cilostazol interfered with biofilm formation in P. aeruginosa. Moreover, swarming motility, biofilm formation and production of virulence factors were significantly diminished. Histopathological investigation revealed that liver, spleen and kidney tissues damage was abolished in mice injected with cilostazol-treated bacteria. Cilostazol exhibited a synergistic outcome when used in combination with antibiotics. At the molecular level, cilostazol downregulated the QS genes and showed considerable affinity to QS receptors. In conclusion, Cilostazol could be used as adjunct therapy with antibiotics for treating Pseudomonal infections. This research highlights cilostazol’s potential to combat bacterial infections by targeting virulence mechanisms, reducing the risk of antibiotic resistance, and enhancing treatment efficacy against P. aeruginosa. These findings open avenues for repurposing existing drugs, offering new, safer, and more effective infection control strategies.
Balint groups: an effective tool for improving health professionals’ perceived well-being
Authors: Kannai Ruth , Krontal Shai , Freud Tamar , Biderman Aya 
Published: August 2024

Abstract
Background
Physician burnout is a common problem that negatively impacts their well-being and patient care. Balint groups (BGs) deal with doctor-patient relationships. Previous studies that have demonstrated the positive effects of BGs are descriptive and based on small sample sizes. This study aims to evaluate the perceptions of health professionals who participated in BGs, determine the impact of BGs on their personal and professional well-being, and identify the factors related to these positive outcomes.

Methods
On January and February 2023 the authors have distributed a questionnaire to 142 healthcare providers in a conference and internet networks. Most respondents were family physicians.

Results
Participation in BGs is seen to have a positive impact on healthcare professionals’ perceived well-being and professional development. Respondents who had participated in the BG reported a reduction in burnout, increased empathy, and enhanced professional identity and relationships with patients and colleagues. The study also highlighted the importance of duration of participation in BG, with attendance longer than 5 years linked to significantly more positive outcomes compared to less than 1 year. In a logistic regression analysis two factors were significantly associated with self-reported well-being: attending BGs for more than five years and perceiving BGs as a means of relieving burnout.

Conclusions
The findings suggest that medical organizations should encourage the regular availability of BGs to support physicians’ well-being.
Moment dynamics of oligomer formation in protein amyloid aggregation with secondary nucleation
Authors: Ding Yamin , Cai Liming , Kang Yanmei 
Published: August 2024

AbstractThe abnormal aggregation of proteins into amyloid fibrils, usually implemented by a series of biochemical reactions, is associated with various neurodegenerative disorders. Considering the intrinsic stochasticity in the involving biochemical reactions, a general chemical master equation model for describing the process from oligomer production to fibril formation is established, and then the lower-order statistical moments of different molecule species are captured by the derivative matching closed system, and the long-time accuracy is verified using the Gillespie algorithm. It is revealed that the aggregation of monomers into oligomers is highly dependent on the initial number of misfolded monomers; the formation of oligomers can be effectively inhibited by reducing the misfolding rate, the primary nucleation rate, elongation rate, and secondary nucleation rate; as the conversion rate decreases, the number of oligomers increases over a long time scale. In particular, sensitivity analysis shows that the quantities of oligomers are more sensitive to monomer production and protein misfolding; the secondary nucleation is more important than the primary nucleation in oligomer formation. These findings are helpful for understanding and predicting the dynamic mechanism of amyloid aggregation from the viewpoint of quantitative analysis.
Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside
Authors: Yin Yue , Feng Weibo , Chen Jie , Chen Xilang , Wang Guodong , Wang Shuai , Xu Xiao , Nie Yongzhan , Fan Daiming , Wu Kaichun , Xia Limin 
Published: August 2024

AbstractHepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment of advanced HCC, but problems such as drug resistance and immune-related adverse events still exist in clinical practice. The immunosuppressive tumor microenvironment (TME) of HCC restricts the efficacy of immunotherapy and is essential for HCC progression and metastasis. Therefore, it is necessary to elucidate the mechanisms behind immunosuppressive TME to develop and apply immunotherapy. This review systematically summarizes the pathogenesis of HCC, the formation of the highly heterogeneous TME, and the mechanisms by which the immunosuppressive TME accelerates HCC progression and metastasis. We also review the status of HCC immunotherapy and further discuss the existing challenges and potential therapeutic strategies targeting immunosuppressive TME. We hope to inspire optimizing and innovating immunotherapeutic strategies by comprehensively understanding the structure and function of immunosuppressive TME in HCC.
A valid and reliable explanatory model of learning processes in heritage education
Authors: Fontal Olaia , Arias Víctor B. , Arias Benito 
Published: August 2024

Abstract

Background
The main challenge in heritage education is to identify the verbs—and their hierarchical relations—that explain heritage learning as based on empirical evidence. The Heritage Learning Sequence (HLS) selects seven verbs (Knowing-Understanding-Respecting-Valuing-Caring-Enjoying-Transmitting) on the basis of (a) theoretical studies, (b) analyses of international standards, and (c) evaluation of heritage education programs. The study has the following objectives: (a) to clarify the heritage learning process; (b) to test a theoretical model that groups the verbs that make up the Heritage Learning Sequence (HLS), as well as the relationships between them; (c) to identify possible sub-models that explain the different heritage learning itineraries.

Methods
The Q-Herilearn scale (previously calibrated using SEM and IRT models) was administered to

$$N = 1454$$

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=
1454

individuals, focusing on seven factors (corresponding to each HLS verb) that measure heritage learning. Partial Least Squares Structural Equation Modeling (PLS-SEM) was used as a general analytical strategy.

Findings
The results obtained provided sufficient guarantees to validate the HLS and showed the adequate explanatory and predictive power and general fit of the proposed model (Heritage Learning Model); all twelve hypothesized direct influence relations between the main verbs that define heritage learning were confirmed. The statistical significance values suggested the existence of other internal subsequences that could be explored in further studies.

Contribution
Learning modeling provides a key structural framework for (a) the design of effective, efficient, and comprehensive tools to measure heritage learning and (b) their operationalization in heritage education designs.
Combined studies on glazed ceramic bodies from the Middle and Neo-Elamite periods (1500–539 BCE)
Authors: Aarab Ali , Cormier Laurent , Firoozmandi Bahman , Gérard Martine 
Published: August 2024

Abstract
The Elamites have assigned specialized names for different types of ceramics, signaling a specialized approach to ceramic production during the Middle and Neo-Elamite periods. They were pioneers in the use of glazed ceramics on the Iranian Plateau. This investigation focuses on the examination of 29 samples of glazed ceramic bodies originating from the Middle-Elamite (~ 1500–1100 BCE) and Neo-Elamite periods (~ 1100–539 BCE). The objective of this analysis, centered on the earliest instances of glazed ceramic bodies in Iran, is to obtain a comparative examination of the ceramic bodies. Such an approach can be useful for understanding the diverse production techniques used by Elamites in the Middle-Elamite and Neo-Elamite periods. To achieve this purpose, X-ray diffraction and petrography was used to determine the mineralogical characteristics of the ceramic bodies. Further insight into the chemical analysis of the samples was obtained through Electron Probe Micro-Analysis. The experimental data allowed the classification of the samples into four distinct groups. Particularly noteworthy in this categorization is the diversity observed in the Neo-Elamite samples. This diversity of Neo-Elamite ceramic bodies can be attributed to two primary factors. Firstly, the Neo-Elamite period witnessed a more varied array of techniques for producing glazed ceramic bodies compared to the Middle-Elamite period. Unlike the Middle-Elamite glazed ceramics, which were solely utilized for architectural decoration (glazed bricks) and were locally produced, the Neo-Elamite period marked the first instance of glazed ceramic vessels being used in the southwest of Iranian plateau, leading to a higher technological diversity. Secondly, the frequency of trade and importation of glazed ceramics from other regions to the southwest of Iran was notably higher during the Neo-Elamite period compared to the Middle-Elamite one. A notable distinction emerges in the Middle-Elam period, where exclusively quartz-based ceramic bodies were referenced, setting it apart from other sample types.