bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardioprotective effect of 19,20-epoxydocosapentaenoic acid (19,20-EDP) in ischaemic injury involves direct activation of mitochondrial sirtuin 3
Authors: Darwesh Ahmed M , Fang Liye , Altamimi Tariq R , Jamieson K Lockhart , Bassiouni Wesam , Valencia Robert , Huang Andy , Wang Faqi , Zhang Hao , Ahmed Marawan , Gopal Keshav , Zhang Yongneng , Michelakis Evangelos D , Ussher John R , Edin Matthew L , Zeldin Darryl C , Barakat Khaled , Oudit Gavin Y , Kassiri Zamaneh , Lopaschuk Gary D , Seubert John M 
Published: December 2024

Abstract

Aims
Although current clinical therapies following myocardial infarction (MI) have improved patient outcomes, morbidity, and mortality rates, secondary to ischaemic and ischaemia reperfusion (IR) injury remains high. Maintaining mitochondrial quality is essential to limit myocardial damage following cardiac ischaemia and IR injury. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in regulating mitochondrial function and cardiac energy metabolism. In the current study, we hypothesize that 19,20-epoxydocosapentaenoic acid (19,20-EDP) attenuates cardiac IR injury via stimulating mitochondrial SIRT3.

Methods and results
Ex vivo models of isolated heart perfusions were performed in C57BL/6 mice to assess the effect of 19,20-EDP on cardiac function and energy metabolism following IR injury. In vivo permanent occlusion of the left anterior descending coronary artery was performed to induce MI; mice were administered 19,20-EDP with or without the SIRT3 selective inhibitor 3-TYP. Mitochondrial SIRT3 targets and respiration were assessed in human left ventricular tissues obtained from individuals with ischaemic heart disease (IHD) and compared to non-failing controls (NFCs). Binding affinity of 19,20-EDP to human SIRT3 was assessed using molecular modelling and fluorescence thermal shift assay. Results demonstrated that hearts treated with 19,20-EDP had improved post-ischaemic cardiac function, better glucose oxidation rates, and enhanced cardiac efficiency. The cardioprotective effects were associated with enhanced mitochondrial SIRT3 activity. Interestingly, treatment with 19,20-EDP markedly improved mitochondrial respiration and SIRT3 activity in human left ventricle (LV) fibres with IHD compared to NFC. Moreover, 19,20-EDP was found to bind to the human SIRT3 protein enhancing the NAD+-complex stabilization leading to improved SIRT3 activity. Importantly, the beneficial effects of 19,20-EDP were abolished by SIRT3 inhibition or using the S149A mutant SIRT3.

Conclusion
These data demonstrate that 19,20-EDP-mediated cardioprotective mechanisms against ischaemia and IR injury involve mitochondrial SIRT3, resulting in improved cardiac efficiency.
The N6-methyladenosine demethylase ALKBH5 is a novel epigenetic regulator of aortic valve calcification
Authors: Wang Yueheng , He Shengping , Lan Lan , Yu Hongjiao , Zhao Huan , Xie Yuchen , Zhong Guoli , Yuan Liang , Li Kun , Hu Xiao , Macrae Vicky E , Fu Xiaodong , Chen Guojun , Zhu Dongxing 
Published: December 2024

Abstract

Aims
Calcific aortic valve disease (CAVD) is a common heart valve disease with significant clinical consequences. The mechanisms that drive the pathogenesis of CAVD remain to be fully elucidated. N6-methyladenosine (m6A), the most prevalent RNA epigenetic regulator, has recently been implicated in cardiovascular disease, but its role in CAVD has yet to be investigated. In this study, we investigated the potential function of m6A modification in CAVD.

Methods and results
Using clinical samples from CAVD patients in combination with human valve interstitial cell (hVIC) calcification model, we screened the expression of m6A modulators and discovered that alkB homolog 5, RNA demethylase (ALKBH5), a key m6A demethylase, was significantly down-regulated in calcified hVICs and human aortic valves. Consistently, increased m6A levels were seen in calcified hVICs, and treatment with 3-deazaadenosine (DAA), an inhibitor of m6A modification, significantly reduced hVIC osteogenic differentiation and calcification. In addition, we showed that silencing of ALKBH5 expression increased global m6A levels and accelerated hVIC osteogenic differentiation and calcification, whereas overexpression of ALKBH5 resulted in the opposite effect. We demonstrated that ALKBH5 directly modulate m6A levels of TGFBR2 and its mRNA stability, leading to altered TGFBR2 expression and SMAD2 signalling in hVICs. We further showed that inhibition of TGFBR2 or knockdown of SMAD2 attenuated ALKBH5 knockdown-induced hVIC osteogenic differentiation and calcification. The expression of the m6A reader protein YTH N6-methyladenosine RNA binding protein F1 (YTHDF1) was up-regulated during the process of hVIC calcification. Intriguingly, we revealed that the ALKBH5 silencing-induced increased hVIC osteogenic differentiation and calcification were abolished after knockdown of YTHDF1. These data suggest a potential role YTHDF1 in aortic valve calcification.

Conclusion
This study showed that ALKBH5 attenuated aortic valve calcification through the TGFBR2/SMAD2 signalling pathway via direct m6A modification of TGFBR2.
Comparing perch availability and perch use between African dwarf chameleon (Bradypodion) ecomorphs
Authors: Barends Jody M , Petford Melissa A , Tolley Krystal A 
Published: December 2024

Abstract
Adaptation to different environments can lead to local adaptations that facilitate morphological divergence between closely related taxa, potentially leading to speciation. Quantifying habitat variation can thus provide valuable insights into evolutionary processes. Arboreal dwarf chameleons of the genus Bradypodion exhibit 3 distinct ecomorphological forms: forest, shrub, and “little brown chameleons” (LBCs). It is assumed these ecomorphs are the result of convergence among species that are in similar habitats regardless of ancestry, or in some cases, morphological conservatism and retention of an ancestral form that is adapted to a shared habitat type. If so, then the habitat of different ecomorphs would differ in vegetation structure. Our results show that vegetation structure in fynbos/grassy habitats is characterized by significantly narrower perches than shrubby habitats, but both have a largely vertical perch orientation. In contrast, forests have significantly fewer vertical perches than fynbos/grassy habitats with significantly thicker diameter perches. Accordingly, LBC and shrub species used more vertically oriented perches than forest species, suggesting that perch use corresponds with the most widely available perch angles. Although LBC chameleons used the smallest diameter perches, when corrected for body size, there was no difference in perch diameter among ecomorphs. These results suggest that the body size of LBC chameleons is constrained by the prevalence of small-diameter perches in their habitat. Species in habitats with wider perches attain larger body size. These findings support the notion that variation in perch structure is critical for phenotypic convergence that has resulted in the 3 Bradypodion ecomorphs.
Type 2 myocardial infarction: challenges in diagnosis and treatment
Authors: Chapman Andrew R , Taggart Caelan , Boeddinghaus Jasper , Mills Nicholas L , Fox Keith A A 
Published: December 2024

Abstract
The Fourth Universal Definition of Myocardial Infarction recommends a classification based on aetiology, in recognition that the underlying pathophysiology of myocardial infarction influences the approach to investigation and treatment. Type 1 myocardial infarction occurs due to atherosclerotic plaque rupture with thrombosis, whereas type 2 myocardial infarction occurs due to an imbalance in myocardial oxygen supply or unmet need in myocardial oxygen demand, without atherothrombosis, usually in the context of another acute illness. In this state-of-the-art review, the diagnosis, investigation, and treatment of patients with type 2 myocardial infarction are considered, with general advice for clinical practice and a consideration of future research directions.
Dementia and risks of temperature-related mortality and hospitalizations in Germany
Authors: Conte Keivabu Risto , Zagheni Emilio , Fink Anne 
Published: December 2024

Abstract

Background
Extreme temperatures are associated with negative health outcomes, in particular for older adults with pre-existing conditions. While climate change is expected to increase exposure to temperature levels that are detrimental for health, little is known about how dementia shapes vulnerability to extreme temperatures.

Methods
We leveraged repeated quarterly individual-level health claims from 2004 to 2019 on 250,000 individuals in Germany aged 50 years and above with information on key neurodegenerative diseases such as dementia. We linked data on the location of residence of these individuals with high resolution gridded meteorological data. In our empirical analysis, we applied an individual-level Fixed Effects model to estimate how temperature affects the single patient’s probability of hospitalization and death, adjusted for seasonality and comorbidities.

Results
Our findings reveal that heat and cold exposure increase the risk of death. Conversely, the association between extreme temperatures and hospital admissions is more nuanced showing an increase only with cold exposure. Stratifying the analysis by individuals affected by dementia, we observe heat to increase mortality only for individuals with dementia and cold to determine an 8 times larger impact on them and a larger increase in hospitalization. Also, we observe individuals aged above 80 and with dementia do be the most at risk of death with exposure to cold and in particular heat.

Conclusion
Our study contributes to the growing body of evidence on the health impacts of climate change and emphasizes the need for targeted strategies to protect vulnerable groups, particularly patients with dementia, from adverse temperature effects.
Spatial targeting and integration across vaccination, vitamin A and deworming programs throughout India 2019–21
Authors: Rerolle Francois , Dey Arnab K , Benmarhnia Tarik , Arnold Benjamin F 
Published: December 2024

Abstract

Background
Currently, most large-scale public health programs, such as immunization or anti-parasitic deworming, work in relative isolation. Integrating efforts across programs could potentially improve their efficiency, but identifying populations that could benefit from multiple programs has been an operational challenge.

Methods
We analyzed a nationally representative survey conducted in India between 2019 and 2021 to assess and map coverage of seven vaccines [Bacillus Calmette–Guérin (BCG), hepatitis B, polio, diphtheria–tetanus–pertussis (DTP), haemophilus influenza type b (Hib), rotavirus and measles-containing vaccine (MCV)], plus Vitamin A supplementation and anti-parasitic deworming treatment among 86 761 children aged 1–3 years old.

Results
National coverage varied widely by program, from 42% (rotavirus) to 95% (BCG). There was high correlation between district-level coverage estimates (r ≥ 0.7) and extensive spatial overlap in low-coverage populations. In simulated implementation strategies, we show that an integrated strategy that targets full immunization coverage for four core vaccines (BCG, polio, DTP, MCV) would achieve similar coverage to an optimal (but unrealistic) implementation strategy and far better coverage than multiple efforts focused on individual vaccines. Targeting the most under-vaccinated districts within states based on spatial clustering or coverage thresholds led to further improvements in full coverage per child targeted. Integration of anti-parasitic deworming or rotavirus vaccination into a core vaccine delivery mission could nearly double their coverage (from ∼45% to ∼85%).

Conclusions
Integrated delivery and geographic targeting across core vaccines could accelerate India’s progress toward full immunization coverage. An integrated platform could greatly expand coverage of non-core vaccines and other child health interventions.
Longitudinal association between disability and suicide mortality in Republic of Korea
Authors: Lee Hwa-Young , Shin Dong Wook , Han Kyung-Do , Kawachi Ichiro 
Published: December 2024

Abstract

Background
The Republic of Korea has reported the highest suicide rate globally since 2018. Previous studies have highlighted disability as a significant risk factor for suicide. However, comprehensive examination on the association between suicide mortality and severities and types of disabilities, and on how these associations vary according to sociodemographic characteristics, health behaviours and comorbidity profiles has never been performed.

Methods
We performed a retrospective cohort study of a nationally representative sample of 3 591 398 individuals subject to the health check-up provided by the Korean National Health Insurance in 2009, including individuals with (n = 126 508) and without (n = 3 734 890) disabilities, and followed-up until December 2021

Results
Overall, the presence of disability was associated with an increased risk of suicide mortality [hazard ratio (HR), 1.38; 95% confidence interval (CI), 1.30–1.47] compared to the absence of disability. This risk was more pronounced in individuals with Grade 1–3 disabilities (HR, 1.68; 95% CI, 1.52–1.85) than those with Grade 4–6 disabilities (HR, 1.28; 95% CI, 1.20–1.47). Among various types of disabilities, individuals with a disability associated with a mental disorder had the highest HR (HR, 4.49; 95% CI, 3.38–5.97), followed by those with visual impairment (HR, 1.47; 95% CI, 1.26–1.73), brain damage (HR, 1.45; 95% CI, 1.18–1.79), hearing impairment (HR, 1.35; 95% CI, 1.15–1.58) and extremity disability (HR, 1.30; 95% CI, 1.21–1.40). Stratified analyses revealed that the suicide risk associated with disabilities was more pronounced in individuals with specific sociodemographic characteristics and health behaviours.

Conclusion
Our findings highlight the need to prioritize policy efforts to address suicide mortality among people with disabilities, considering the distinct risks associated with disability types and severity.
Two waves of photosymbiosis acquisition in extant planktonic foraminifera explained by ecological incumbency
Authors: Takagi Haruka , Nakamura Yasuhide , Schmidt Christiane , Kucera Michal , Saito Hiroaki , Moriya Kazuyoshi 
Published: December 2024

Abstract
Photosymbiosis, a mode of mixotrophy by algal endosymbiosis, provides key advantages to pelagic life in oligotrophic oceans. Despite its ecological importance, mechanisms underlying its emergence and association with the evolutionary success of photosymbiotic lineages remain unclear. We used planktonic foraminifera, a group of pelagic test-forming protists with an excellent fossil record, to reveal the history of symbiont acquisition among their three main extant clades. We used single-cell 18S rRNA gene amplicon sequencing to reveal symbiont identity and mapped the symbiosis on a phylogeny time-calibrated by fossil data. We show that the highly specific symbiotic interaction with dinoflagellates emerged in the wake of a major extinction of symbiont-bearing taxa at the end of the Eocene. In contrast, less specific and low-light-adapted symbioses with pelagophytes emerged 20 million years later, in multiple independent lineages in the Late Neogene, at a time when the vertical structure of pelagic ecosystems was transformed by global cooling. We infer that in foraminifera, photosymbiosis can evolve easily and that its establishment leads to diversification and ecological dominance to such an extent, that the proliferation of new symbioses is prevented by the incumbent lineages.
A rice rhizosphere plant growth-promoting Streptomyces corchorusii isolate antagonizes Magnaporthe oryzae and elicits defense responses in rice
Authors: Njoroge Hellen Wambui , Hu Jiangfei , Yu Yijie , Yuan Zhixiang , Lin Yuqing , Han Xixi , Liu Zhuang , Muia Anastasia Wairimu , Liu Hongxia 
Published: December 2024

Abstract

Aims
Rice blast, caused by Magnaporthe oryzae, is one of the most devastating diseases of rice (Oryza sativa L.). The aim of this study was to investigate the biocontrol potential of rice rhizosphere actinomycetes against M. oryzae Guy 11, and elucidate the antagonistic mechanisms.

Methods and results
An isolate characterized as a Streptomyces corchorusii strain (Sc75) using the 16S rRNA gene exhibited superior antifungal activity. Sc75 had an inhibitory effect of 69.25% ± 0.15% against M. oryzae and broad antifungal activity on other fungal plant pathogens in the dual culture assay. Its cell-free culture filtrate inhibited fungal growth and reduced mycelial mass. Also, the ethyl acetate crude extract completely inhibited conidia germination and appressoria formation on the hydrophobic coverslips and detached leaf at a concentration of 20 mg/ml. Its volatile organic compounds (VOCs) suppressed fungal growth by 98.42%. GC–MS analysis of the VOCs identified butanoic acid, 2-methyl-, methyl ester; di-tert-butyl peroxide; furan, 2-pentyl-; and undecanoic acid, 10-methyl-, methyl ester as the main components. In the greenhouse experiment, the disease severity was reduced and growth promotion was evident. Molecular investigation revealed that Sc75 upregulated defense-related genes involved in the synthesis of jasmonic acid, salicylic acid signaling pathway, and led to callose deposition and ROS production in the leaves. Finally, Sc75 produced hydrolytic enzymes, siderophore, indole acetic acid, gibberellic acid, phosphate solubilization, and 1-aminocyclopropane-1-carboxylate deaminase.

Conclusions
The rice rhizosphere soil harbors actinomycetes that can be explored as biocontrol agents against fungal pathogens such as M. oryzae. The isolate Sc75 had superior antifungal activity against M. oryzae and other selected plant pathogenic fungi. It showed remarkable antagonistic activity through direct antibiosis, production of VOCs, antifungal metabolites in the culture filtrates and crude extracts, and produced enzymes. In addition, the isolate promoted plant growth, reduced rice blast disease index in the greenhouse experiment, and elicited defense-related responses. Sc75 is a promising candidate for future exploration as a biofungicide and a biofertilizer.
Using large language models to detect outcomes in qualitative studies of adolescent depression
Authors: Xin Alison W , Nielson Dylan M , Krause Karolin Rose , Fiorini Guilherme , Midgley Nick , Pereira Francisco , Lossio-Ventura Juan Antonio 
Published: December 2024

Abstract

Objective
We aim to use large language models (LLMs) to detect mentions of nuanced psychotherapeutic outcomes and impacts than previously considered in transcripts of interviews with adolescent depression. Our clinical authors previously created a novel coding framework containing fine-grained therapy outcomes beyond the binary classification (eg, depression vs control) based on qualitative analysis embedded within a clinical study of depression. Moreover, we seek to demonstrate that embeddings from LLMs are informative enough to accurately label these experiences.

Materials and Methods
Data were drawn from interviews, where text segments were annotated with different outcome labels. Five different open-source LLMs were evaluated to classify outcomes from the coding framework. Classification experiments were carried out in the original interview transcripts. Furthermore, we repeated those experiments for versions of the data produced by breaking those segments into conversation turns, or keeping non-interviewer utterances (monologues).

Results
We used classification models to predict 31 outcomes and 8 derived labels, for 3 different text segmentations. Area under the ROC curve scores ranged between 0.6 and 0.9 for the original segmentation and 0.7 and 1.0 for the monologues and turns.

Discussion
LLM-based classification models could identify outcomes important to adolescents, such as friendships or academic and vocational functioning, in text transcripts of patient interviews. By using clinical data, we also aim to better generalize to clinical settings compared to studies based on public social media data.

Conclusion
Our results demonstrate that fine-grained therapy outcome coding in psychotherapeutic text is feasible, and can be used to support the quantification of important outcomes for downstream uses.
Investigation on the preferences for data quality assessment indicators of electronic health records: user-oriented perspective
Authors: Yang Liu , Ren Mudan , Sun Shuifa , Lu Ji , Wu Yirong 
Published: December 2024

Abstract

Objectives
This study aims to investigate whether different types of electronic health record (EHR) users have distinct preferences for data quality assessment indicators (DQAI) and explore how these preferences can guide the enhancement of EHR systems and the optimization of related policies.

Materials and Methods
High-frequency indicators were identified by a systematic literature review to construct a DQAI system, which was assessed by a user-oriented investigation involving doctors, nurses, hospital supervisors, and clinical researchers. The entropy weight method and fuzzy comprehensive evaluation model were employed for the system comprehensive evaluation. Exploratory factor analysis was used to construct dimensions, and visualization analysis was utilized to explore preferences at both the indicator and dimension levels.

Results
Sixteen indicators were identified to construct the DQAI system and grouped into 2 dimensions: structural and relational. The DQAI system achieved a comprehensive evaluation score of 90.445, corresponding to a “very important” membership level (62.5%). Doctors and nurses exhibited a higher score mean (4.43-4.66 out of 5) than supervisors (3.73-4.55 out of 5). Researchers emphasized credibility, with a score mean of 4.79 out of 5.

Discussion
The findings reveal that different types of EHR users exhibit distinct preferences for the DQAI at both indicator and dimension levels. Doctors and nurses thought that all indicators were important, clinical researchers emphasized credibility, and supervisors focused mainly on accuracy. Indicators in the relational dimension were generally more valued than structural ones. Doctors and nurses prioritized indicators of relational dimension, while researchers and supervisors leaned towards indicators of structural dimension. These insights suggest that tailored approaches in EHR system development and policy-making could enhance EHR data quality.

Conclusion
This study underscores the importance of user-centered approaches in optimizing EHR systems, highlighting diverse user preferences at both indicator and dimension levels.
Unraveling melorheostosis: insights into clinical features, diagnosis, and treatment
Authors: Bhattacharyya Timothy 
Published: December 2024

Abstract
Melorheostosis is a rare bone disease characterized by abundant bone formation with a characteristic radiographic appearance that resembles “dripping candle wax.” Recent data have shown that the majority of cases are due to somatic activating mutations in bone. Melorheostosis has several clinical and radiographic presentations, which are now known to be caused by different somatic mutations such as MAP2K1, SMAD3, KRAS, and LEMD3. This review provides a comprehensive look at the clinical features, diagnostic approaches, and current treatment options for melorheostosis, alongside future research directions aimed at improving patient outcomes.