bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the reporting of research impact assessments: a systematic review of biomedical funder research impact assessments
Authors: Abudu Rachel , Oliver Kathryn , Boaz Annette 
Published: December 2024

Abstract
The field of research impact assessment (RIA) has seen remarkable growth over the past three decades. Increasing numbers of RIA frameworks have been developed and applied by research funders and new technologies can capture some research impacts automatically. However, RIAs are too different to draw comparable conclusions about what type of methods, data or processes are best suited to assess research impacts of different kinds, or how funders should most efficiently implement RIAs. To usher in the next era of RIA and mature the field, future RIA methodologies should become more transparent, standardized and easily implementable. Key to these efforts is an improved understanding of how to practically implement and report on RIA at the funder-level. Our aim is to address this gap through two major contributions. First, we identify common items across existing best practice guidelines for RIA, creating a preliminary reporting checklist for standardized RIA reporting. Next, we systematically reviewed studies examining funders’ assessment of biomedical grant portfolios to examine how funders reported the results of their RIAs across the checklist, as well as the operational steps funders took to perform their RIA and the variation in how funders implemented the same RIA frameworks. We compare evidence on current RIA practices with the reporting checklist to identify good practice for RIA reporting, gaps in the evidence base for future research, and recommendations for future effective RIA.
P002 Relationship between OSA and Thoracic Aortic Dimensions
Authors: Cistulli D , Tong B , Currie P , Bin Y , Stewart G , Bannon P , Ugander M , Cistulli P 
Published: December 2024

Abstract

Introduction
Obstructive sleep apnoea (OSA) is highly prevalent and is associated with a range of cardiovascular diseases. An association between OSA and aortic aneurysms has been reported. This is thought to be a multifactorial association, but exaggerated intrathoracic pressure swings occurring during obstructed breathing events in OSA have been implicated. This study aimed to assess the association of the presence and severity of OSA and thoracic aortic dimensions.

Methods
This is a retrospective observational study utilising a clinical database. Patients were included if they had undergone transthoracic echocardiography in the six months prior to a diagnostic sleep study. They were divided into two groups: either no or mild OSA (apnoea-hypopnoea index (AHI) ≤15/hr), and moderate-to-severe OSA (AHI&gt;15/hr). Echocardiography measures included aortic root diameter in millimetres and indexed to body surface area (mm/m2).

Results
The study included 1470 patients (56% male, mean±SD age 63±14 years, body mass index 30±6kg/m2). Compared to patients with no or mild OSA (n=558, 38%), patients with moderate-to-severe OSA (n=1545, 62%) had larger absolute aortic root dimensions (35.0±4.1 versus 33.0±4.2mm, p&lt;0.0001), after correction for body surface area aortic root dimensions were similar between groups (1.7±0.2 versus 1.7±0.2mm, p=0.6122). Among patients with any OSA (AHI&gt;5/hr, n=1329, 90%) there was a weak correlation between aortic diameter and AHI (r=0.23, p&lt;0.0001).

Conclusions
More severe OSA is associated with increased absolute thoracic aorta dimensions. The clinical relevance of these findings remains to be determined.
P047 Using disruptions in sleep architecture to distinguish children with excessive daytime sleepiness
Authors: Lee J , Wong J , Shetty M , Plunkett G , Walter L , Davey M , Nixon G , Horne R 
Published: December 2024

Abstract

Background
Diagnosing narcolepsy and idiopathic hypersomnolence (IH) requires an overnight polysomnographic (PSG) followed by a daytime multiple sleep latency test (MSLT). We aimed to identify markers in sleep macro-architecture on PSG which could distinguish between children with these conditions and those with subjective sleepiness but a negative MSLT and controls.

Methods
All children referred for a MSLT between May 2010 to December 2023 were eligible. Each child was matched for age and sex to a control. Wake stability was defined as the maintenance of a continuous series of wake epochs before transitioning to sleep and sleep stability as the maintenance of a particular sleep stage before waking or transitioning to another sleep state. The number and duration of epochs of each sleep stage was recorded.

Results
28 children with narcolepsy, 11 with IH and 26 with subjective sleepiness were included. Children with narcolepsy exhibited higher levels of sleep stability as indicated by more sleep state changes and wake after sleep onset compared to their controls and to the subjectively sleepy group (p&lt;0.001 for both). The number of REM epochs was greater in the narcolepsy group compared to their controls (p&lt;0.001), the IH group (p&lt;0.05) and subjectively sleepy group (p&lt;0.05), while the average duration of REM epochs was shorter in the narcolepsy group compared to both the IH (p&lt;0.05) and subjectively sleepy groups (p&lt;0.05).

Conclusions
Our study suggests children with narcolepsy exhibit abnormalities in the stability of REM sleep which distinguishes them from those with IH and subjective sleepiness children.
Autophagy modulates tenogenic differentiation of cartilage-derived stem cells in response to mechanical tension via FGF signaling
Authors: Zuo Rui , Li Haoke , Cai Chenhui , Xia Wen , Liu Jiabin , Li Jie , Xu Yuan , Zhang Yi , Li Changqing , Wu Yuzhang , Zhang Chao 
Published: December 2024

Abstract

Background
In our previous study, we demonstrated that cartilage-derived stem cells (CDSCs) possess multi-differentiation potential, enabling direct bone-to-tendon structure regeneration after transplantation in a rat model. Therefore, the objective of this study is to investigate whether CDSCs are a suitable candidate for achieving biological regeneration of tendon injuries.

Methods
Tenogenic differentiation was evaluated through cell morphology observation, PCR, and Western blot (WB) analysis. Autophagic flux, transmission electron microscopy, and WB analysis were employed to elucidate the role of autophagy during CDSC tenogenic differentiation. Cell survival and tenogenesis of transplanted CDSCs were assessed using fluorescence detection of gross and frozen section images. Heterotopic ossification and quality of tendon healing were evaluated by immunofluorescence, hematoxylin-eosin (H&E), and Safrinin O/Fast Green stains.

Results
We found autophagy is activated in CDSCs when treated with cyclic tensile stress, which facilitates the preservation of their chondrogenic potential while impeding tenogenic differentiation. Inhibiting autophagy with chloroquine promoted tenogenic differentiation of CDSCs in response to cyclic tensile stress through activation of the Fgf2/Fgfr2 signaling pathway. This mechanism was further validated by 2 mouse transplantation models, revealed that autophagy inhibition could enhance the tendon regeneration efficacy of transplanted CDSCs at the patellar tendon resection site.

Conclusion
Our findings provide insights into CDSC transplantation for achieving biological regeneration of tendon injuries, and demonstrate how modulation of autophagy in CDSCs can promote tenogenic differentiation in response to tensile stress both in vivo and in vitro.
LncRNA NR_045147 modulates osteogenic differentiation and migration in PDLSCs via ITGB3BP degradation and mitochondrial dysfunction
Authors: Long Lujue , Zhang Chen , He Zhengquan , Liu Ousheng , Yang Haoqing , Fan Zhipeng 
Published: December 2024

Abstract
Periodontitis is an inflammation of the alveolar bone and soft tissue surrounding the teeth. Although mesenchymal stem cells (MSCs) have been implicated in periodontal regeneration, the mechanisms by which they promote osteogenesis remain unclear. We examined whether epigenetic modifications mediated by the long-noncoding RNA (lncRNA) NR_045147, which plays a crucial role in cancer, influence the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Alkaline phosphatase staining, alizarin red staining, and western blotting were used to detect the effects of NR_045147 on PDLSC osteogenic differentiation. Scratch migration and transwell chemotaxis assays were used to evaluate the effects of NR_045147 on PDLSC migration. Mitochondrial function was evaluated via Seahorse XF analysis to measure changes in cellular respiration upon manipulation of NR_045147 expression. Ubiquitination assays were performed to examine the protein stability and degradation pathways affected by the NR_045147–MDM2 interaction. An in vivo nude rat calvarial defect model was established and gene-edited PDLSCs were re-implanted to examine the osteogenic effects of NR_045147. NR_045147 significantly reduced PDLSC osteogenic differentiation and migration ability both in vitro and in vivo. Under inflammatory conditions, the loss of NR_045147 rescued osteogenesis. NR_045147 significantly blocked the expression of integrin beta3-binding protein (ITGB3BP). Mechanistically, NR_045147 promoted the ITGB3BP-MDM2 interaction, thus increasing ITGB3BP ubiquitination and degradation. NR_045147 regulated PDLSC mitochondrial respiration and ITGB3BP upregulation efficiently promoted their osteogenic differentiation and migration ability. Concluding, NR_045147 downregulation enhances PDLSC osteogenic differentiation and migration, connects changes in cellular metabolism to functional outcomes via mitochondrial respiration, and promotes ITGB3BP degradation by mediating its interaction with MDM2.
The impact of Benzophenone-3 on osteoarthritis pathogenesis: a network toxicology approach
Authors: Li Yongji , Wang Geqiang , Liu Peiran , Zhang Lin , Hu Hai , Yang Xiangjun , Liu Hongpeng 
Published: December 2024

Abstract

Background
Arthritis is a degenerative joint disease influenced by various environmental factors, including exposure to Benzophenone-3 (BP3), a common UV filter. This study aims to elucidate the toxicological impact of BP3 on arthritis pathogenesis using network toxicology approaches.

Method
We integrated data from the Comparative Toxicogenomics Database (CTD) and Gene Expression Omnibus (GEO) to identify differentially expressed BP3-related toxicological targets in osteoarthritis (OA). Enrichment analyses were conducted to determine the implicated biological processes, cellular components, and molecular functions. Further, the involvement of the PI3K-Akt signaling pathway was investigated, along with correlations with immune cell infiltration and immune-related pathways. Molecular docking analysis was performed to examine BP3 interactions with key PI3K-Akt pathway proteins.

Results
A total of 74 differentially expressed BP3-related targets were identified. Enrichment analysis revealed significant pathways, including PI3K-Akt, MAPK, and HIF-1 signaling. The PI3K-Akt pathway showed notable dysregulation in OA, with reduced activity and differential expression of key genes such as ANGPT1, ITGA4, and PIK3R1. Correlation analysis indicated significant associations between PI3K-Akt pathway activity and various immune cell types and immune pathways. Molecular docking highlighted strong interactions between BP3 and proteins like AREG, suggesting potential disruptions in signaling processes.

Conclusions
BP3 exposure significantly alters the expression of toxicological targets and disrupts the PI3KAkt signaling pathway, contributing to OA pathogenesis. These findings provide insights into the molecular mechanisms of BP3-induced OA and identify potential therapeutic targets for mitigating its effects.
Comparative study of cytotoxic Signaling pathways in H1299 cells exposed to alternative Bisphenols: BPA, BPF, and BPS
Authors: Kim Ji-Young , Shin Geun-Seup , An Mi-Jin , Lee Hyun-Min , Jo Ah-Ra , Park Yuna , Kim Jinho , Hwangbo Yujeong , Kim Chul-Hong , Kim Jung-Woong 
Published: December 2024

Abstract

Background
Bisphenols are prevalent in food, plastics, consumer goods, and industrial products. Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and bisphenol S (BPS), are known to act as estrogen mimics, leading to reproductive disorders, disruptions in fat metabolism, and abnormalities in brain development.

Objectives
Despite numerous studies exploring the adverse effects of bisphenols both in vitro and in vivo, the molecular mechanisms by which these compounds affect lung cells remain poorly understood. This study aims to compare the effects of BPA, BPF, and BPS on the physiological behavior of human nonsmall cell lung cancer (NSCLC) cells.

Materials and Methods
Human non-small cell lung cancer (NSCLC) H1299 cells were treated with various concentration of BPA, BPF and BPS during different exposure time. Cellular physiology for viability and cell cycle was assessed by the staining with apoptotic cell makers such as active Caspase-3 and cyclins antibodies. Toxicological effect was quantitatively counted by using flow-cytometry analysis.

Results
Our findings indicate that BPA induces apoptosis by increasing active Caspase-3 levels in H1299 cells, whereas BPF and BPS do not promote late apoptosis. Additionally, BPA was found to upregulate cyclin B1, causing cell cycle arrest at the G0/G1 phase and leading to apoptotic cell death through Caspase-3 activation. Conclusion: These results demonstrate that BPA, BPF, and BPS differentially impact cell viability, cell cycle progression, and cell death in human NSCLC cells.
Comparative carcinogenic and non-carcinogenic health risks, and cytogenotoxicity of wastewaters from natural and artificial fishponds indiscriminately disposed in Nigeria
Authors: Alabi Okunola Adenrele , Ashamo Olufemi M , Akinyanju Rhema Adedamola , Faleye Florence Yosola , Afolabi Tomiwa Amos , Ayeni Funmilayo Esther , Adeoluwa Yetunde Mercy 
Published: December 2024

Abstract
As the demand for fish increases, the amount of wastewater generated from fishponds is also increasing with potential environmental and public health effects from their indiscriminate disposal. This study aimed at comparative analyses of the physicochemical and heavy metal constituents and potential DNA damage by wastewaters from natural and artificial fishponds using Allium cepa assay. A. cepa were grown on 3.13, 6.25, 12.5, 25.0, and 50.0% (v/v; wastewater/tap water) concentrations of each wastewater. At 48 and 72 h, respectively, genotoxic and root growth inhibition analyses were carried out on the exposed onions. The onion root tips exposed to wastewaters showed a significant (P &lt; 0.05) inhibition of root growth and cell division in a concentration-dependent manner. Additionally, chromosomal abnormalities like spindle disturbances, sticky chromosomes, micronucleus, bridges, and binucleated cells were observed in the exposed onions and their induction was higher significantly relative to the negative control. Generally, wastewater from the natural fishpond caused higher chromosomal aberrations than the wastewater from artificial fishpond. It is our belief that the cytotoxicity and genotoxicity observed in the onions were primarily caused by heavy metals like Cr, Cd, Fe, Pb, Cu, and Zn found in the wastewaters. These metals also showed a significant carcinogenic and non-carcinogenic risks in children and adults with Cd as the highest contributor to these detrimental risks. Ingestion route was the major exposure route to the toxic metals in these wastewaters. Wastewater from the natural fishpond showed a higher health risk than the wastewater from the artificial fishpond. These findings suggest that the wastewaters from natural and artificial fishpond contain compounds that might induce cytogenotoxicity in exposed organisms.
Towards an integrative revision of Haplotaxidae (Annelida: Clitellata)
Authors: Martin Patrick , Fend Steven , Martinsson Svante , Klinth Mårten , Torii Takaaki , Erséus Christer 
Published: December 2024

Abstract
The classification and phylogenetic position of Haplotaxidae, an enigmatic family of clitellate worms, have long been discussed. We estimate the phylogeny for Clitellata as a whole, using a taxon sample adhering to current definitions of Haplotaxidae and including species attributable to Haplotaxis, plus a representation of other clitellates. Sequences of five markers, 4087 bp in total, were analysed by Bayesian Inference. A well-supported tree shows that Haplotaxidae is polyphyletic, consisting of at least five separate clades scattered among other clitellate lineages. We redefine Haplotaxidae s.s. to only include Haplotaxis, and erect four new families: Pelodrilidae Martin et al.fam. nov. for Pelodrilus, Hologynus, and Delaya; Haplotaxoididae Martin et al.fam. nov. for Haplotaxoides Fend gen. nov., with Haplotaxoides decipiens Fend sp. nov. and Haplotaxoides tehama Fend sp. nov.; Limpluvidae Martin et al.fam. nov. for Limpluvia setoensis Fend & Torii gen. et sp. nov.; and Ohtakianidae Martin et al.fam. nov. for Ohtakiana kakidaensis Fend & Torii gen. et sp. nov. To adhere to standard classification systems, we assign all five families to separate orders, Pelodrilida ord. nov., Haplotaxoidida ord. nov., Othakianida ord. nov., Limpluvida ord. nov., and Haplotaxida. Haplotaxidae s.s. and Pelodrilidae seem to belong to an incompletely resolved group also including lumbriculids, leeches, and earthworms. Moreover, a close relationship between Limpluvia, Ohtakiana, and the lumbriculid-hirudinean clade (i.e. taxon Lumbriculata) is strongly supported, whereas Haplotaxoididae are placed more basally in the clitellate phylogeny than the other haplotaxids s.l., their exact position remaining unresolved. The analysed Holarctic Haplotaxis populations (representing up to 10 species) appear separated more by geography than by obvious morphological characters.
Multiplex base editing ofBCL11Aregulatory elements to treat sickle cell disease
Authors: Fontana L. , Martinucci P. , Amistadi S. , Felix T. , Mombled M. , Tachtsidi A. , Corre G. , Chalumeau A. , Hardouin G. , Martin J. , Romano O. , Amendola M. , Antoniou P. , Miccio A 
Published: December 2024

AbstractSickle cell disease (SCD) is a genetic anemia caused by the production of an abnormal adult hemoglobin. The clinical severity is lessened by elevated fetal hemoglobin (HbF) production in adulthood. A promising therapy is the transplantation of autologous, hematopoietic stem/progenitor cells (HSPCs) treated with CRISPR/Cas9 to downregulate the HbF repressor BCL11A via generation of double strand breaks (DSBs) in the +58-kb erythroid-specific enhancer. Here, to further enhance HbF production without increasing the mutagenic load, we targeted both +58-kb and +55-kbBCL11Aerythroid-specific enhancers using base editors. We systematically dissected DNA motifs recognized by the key transcriptional activators within these regions and identified the critical nucleotides required for activator binding. Multiplex base editing of these residues was efficient and safe and generated no or little DSBs and genomic rearrangements. We observed substantial HbF reactivation, exceeding the levels achieved using the CRISPR/Cas9 nuclease-based strategy, thus efficiently rescuing the sickling phenotype. Multiplex base editing was efficient in long-term repopulating HSPCs and resulted in potent HbF reactivationin vivo. In summary, these results show that multiplex base editing ofBCL11Aerythroid-specific enhancers is a safe and potent strategy for treating sickle cell disease.
Dynamics of β-cardiac myosin between the super-relaxed and disordered-relaxed states
Authors: Cail Robert C. , Baez-Cruz Faviolla A. , Winkelmann Donald A. , Goldman Yale E. , Michael Ostap E. 
Published: December 2024

AbstractThe super-relaxed (SRX) state of myosin ATPase activity is critical for striated muscle function, and its dysregulation is linked to cardiomyopathies. It is unclear whether the SRX state exchanges readily with the disordered-relaxed (DRX) state, and whether the SRX state directly corresponds to the folded back interacting-head motif (IHM). Using recombinant β-cardiac heavy meromyosin (HMM) and subfragment 1 (S1), which cannot form the IHM, we show that the SRX and DRX populations are in rapid equilibrium, dependent on myosin head-tail interactions. Some mutations which cause hypertrophic (HCM) or dilated (DCM) cardiomyopathies alter the SRX-DRX equilibrium, but not all mutations. The cardiac myosin inhibitor mavacamten slows nucleotide release by an equal factor for both HMM and S1, thus only indirectly influencing the occupancy time of the SRX state. These findings suggest that purified myosins undergo rapid switching between SRX and DRX states, refining our understanding of cardiomyopathy mechanisms.
The role of specific phosphorylation patterns in the oligomerization of Tau-R4
Authors: Bressler Shachar Guy , Grunhaus Dana , Aviram Amit , Rüdiger Stefan G.D. , Hurevich Mattan , Friedler Assaf 
Published: December 2024

AbstractSpecific phosphorylation patterns control the activity of multiphosphorylated proteins. In case of the Tau protein, multiphosphorylation leads to the formation of different disease-related condensates and aggregates. Studying the role of these specific patterns at the protein level is crucial for understanding the molecular mechanisms of Tauopathies such as Alzheimer’s Disease. However, due to the extreme difficulty in obtaining recombinant proteins with specific phosphorylation patterns using kinase-based methods, it is practically impossible to study the connection between specific phosphorylation patterns and aggregation events at the protein level. Here we addressed this problem by reducing the system to the peptide level and studying the effect of specific phosphorylation patterns on the condensation and aggregation of a specific domain of Tau, R4 (residues 336-358). To achieve this aim, we have applied advanced methods to synthesize a library of multiphosphorylated peptides derived from R4. We showed that specific phosphorylation patterns stringently control the formation of Tau aggregates and condensates. Phosphorylation of Ser341 promoted aggregation of R4 while phosphorylation of Ser352 promoted its condensation. Interestingly, Ser356 phosphorylation inhibited both processes, which can be overridden by double-phosphorylation at Ser341/Ser352. Differences between the microenvironments of the phosphorylated residues lead to their different effects on R4 aggregation upon phosphorylation. Our results show that working at the domain level using advanced peptide synthesis methods is a highly useful and practical way to provide valuable information about the effects of post translational modifications on protein activity.