bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning-based prediction of pharmacokinetic parameters for individualized drug dosage optimization
Authors: Mtshali Sinenhlanhla , Jacobs Byron A.
Published: December 2024

This study presents a data-driven approach to predict pharmacokinetic parameters and generate concentration–time curves for a two-compartment model. The method employs inverse modelling using optimization algorithms to estimate patient-specific parameters from observed data. Machine learning techniques are then applied to solve the forward problem, enabling the prediction of concentration–time profiles for various dose levels. The study incorporates patient background characteristics to improve predictive performance, aiming to enable individualized drug dosing. Results demonstrate accurate parameter prediction and close matching of generated curves to observed data across six dose levels. This approach offers a novel framework for personalizing pharmacokinetic profiles and improving drug dosing strategies and therapeutic outcomes in clinical practice.
Automated cybersecurity compliance and threat response using AI, blockchain and smart contracts
Authors: Alevizos Lampis
Published: December 2024

To address the challenges of internal security policy compliance and dynamic threat response in organizations, we present a novel framework that integrates artificial intelligence (AI), blockchain, and smart contracts. We propose a system that automates the enforcement of security policies, reducing manual effort and potential human error. Utilizing AI, we can analyse cyber threat intelligence rapidly, identify non-compliances and automatically adjust cyber defence mechanisms. Blockchain technology provides an immutable ledger for transparent logging of compliance actions, while smart contracts ensure uniform application of security measures. The framework’s effectiveness is demonstrated through simulations, showing improvements in compliance enforcement rates and response times compared to traditional methods. Ultimately, our approach provides for a scalable solution for managing complex security policies, reducing costs and enhancing the efficiency while achieving compliance. Finally, we discuss practical implications and propose future research directions to further refine the system and address implementation challenges.
Embodiment, Dependence, and God
Authors: Timpe Kevin
Published: December 2024

The significance of our physical bodies is an important topic in contemporary philosophy and theology. Reflection on the body often assumes, even if only implicitly, idealizations that obscure important facts about what it means for humans to be 'enfleshed.' This Element explores a number of ways that reflection on bodies in their concrete particularities is important. It begins with a consideration of why certain forms of idealization are philosophically problematic. It then explores how a number of features of bodies can reveal important truths about human nature, embodiment, and dependence. Careful reflection on the body raises important questions related to community and interdependence. The Element concludes by exploring the ethical demands we face given human embodiment. Among other results, this Element exposes the reader to a wide diversity of human embodiment and the nature of human dependence, encouraging meaningful theological reflection on aspects of the human condition.
Heteronuclear PtII–PdII dimers formation through ligands subtle tailoring
Authors: Fan Peng , Yuan Lequn , Zhang Yuzhen
Published: December 2024

Bright Pt–Pd emitters have been synthesized for the first time, heralding a new era in phosphorescent emitters through a meticulous design and tailoring of ligands, thus introducing a novel approach to the preparation of luminescent materials.
Representation alignment contrastive regularisation for multi‐object tracking
Authors: Chen Shujie , Liu Zhonglin , Dong Jianfeng , Wang Xun , Zhou Di
Published: December 2024

Achieving high‐performance in multi‐object tracking algorithms heavily relies on modelling spatial‐temporal relationships during the data association stage. Mainstream approaches encompass rule‐based and deep learning‐based methods for spatial‐temporal relationship modelling. While the former relies on physical motion laws, offering wider applicability but yielding suboptimal results for complex object movements, the latter, though achieving high‐performance, lacks interpretability and involves complex module designs. This work aims to simplify deep learning‐based spatial‐temporal relationship models and introduce interpretability into features for data association. Specifically, a lightweight single‐layer transformer encoder is utilised to model spatial‐temporal relationships. To make features more interpretative, two contrastive regularisation losses based on representation alignment are proposed, derived from spatial‐temporal consistency rules. By applying weighted summation to affinity matrices, the aligned features can seamlessly integrate into the data association stage of the original tracking workflow. Experimental results showcase that our model enhances the majority of existing tracking networks' performance without excessive complexity, with minimal increase in training overhead and nearly negligible computational and storage costs.
A V2G power response model based on the prediction, evaluation, and correction of charging stations real‐time frequency regulation capability
Authors: Ding Leyan , Yang Jun , Ke Song , Shi Xingye , Fan Peixiao , Wang Hongli
Published: December 2024

With the charging stations (CSs) construction and the vehicle‐to‐grid (V2G) development, electric vehicles (EVs) have become an important load‐side controllable resource. Therefore, a V2G power response model based on the prediction, evaluation, and correction of CSs real‐time frequency regulation (FR) capability is proposed in this paper. Firstly, a hierarchical control framework for large‐scale EVs aggregated to participate in power grid dispatching/FR service is proposed. Secondly, an extreme gradient boosting (XGBoost)‐convolutional neural network (CNN)‐bidirectional long‐term and short‐term memory (BiLSTM)‐attention prediction model for CSs FR capability is proposed, which combines the advantages of CNN and BiLSTM to strengthen the mining of multi‐dimensional features. Meanwhile, a rolling evaluation‐correction model for CSs FR capability based on the EV CC–CV charging process is proposed, which improves the evaluation fineness and aggregation fitness. Furthermore, a V2G power response model considering the EV battery loss is established. Finally, the simulation results show that compared with LSTM, XGBoost‐CNN‐BiLSTM, support vector machine, and other prediction models, the proposed XGBoost‐CNN‐BiLSTM‐attention CSs FR capability prediction model with improvement has a better prediction accuracy. In addition, the V2G power response model can achieve the coordination between the EV users’ charging demands and FR tasks.
Stereoselective Construction of Glycosides Enabled by Glycosyl/ Glycal Metal Species
Authors: Qian Deyun , Wu Xiaomei , Yan Xin
Published: December 2024

Glycosyl/glycal metal functionalization has emerged as an efficient protocol for the construction of glycosides. Benefitting from the rapid development of organometallic chemistry and transition-metal-catalyzed cross-coupling reactions, glycosyl-metal-mediated glycosylation has significantly expanded the space for glycoside synthesis recently. In this short review, we underscore the representative progress in this area, categorizing the advancements by the type of glycosyl/glycal metal species. The reaction mechanism, stereochemical control, synthetic utility, and unmet challenges are also discussed.

1 Introduction

2 Glycosyl/Glycal Lithium-Based Glycosylations

2.1 Preparation of Glycosyl/Glycal Lithium Reagents

2.2 Glycosylation with Glycosyl/Glycal Lithiums

3 Glycosyl/Glycal Stannane-Based Glycosylations

3.1 Preparation of Glycosyl/Glycal Stannane Reagents

3.2 Glycosylation with Glycosyl/Glycal Stannanes

4 Glycosyl/Glycal Boron-Based Glycosylations

4.1 Preparation of Glycosyl/Glycal Boron Compounds

4.2 Glycosylation with Glycosyl/Glycal Boron Compounds

5 Glycosylations Enabled by in situ Formed Glycosyl-Metal Intermediates

5.1 Hydrofunctionalization of Glycals

5.2 Functionalization/Glycosylation of Glycals

6 Conclusion and Outlook
Medication incidents at supported disability accommodation (group homes) in Victoria, Australia: a retrospective audit of calls to a poisons information centre
Authors: Hormiz Rita , Stanley Beata , Elliott Rohan A.
Published: December 2024

Background Many residents of shared supported disability homes (sometimes referred to as group homes) require assistance from staff to manage their medicines. Disability support workers in Australia often call a 24-h emergency poisons information service for advice following a medication incident. Objective To describe the number, type and timing of medication incident calls to the Victorian Poisons Information Centre from supported disability homes in Victoria, Australia. Methods This was a retrospective audit of poisons centre calls from supported disability homes over a 3-month period (October to December 2021). Incidents not related to therapeutic medication use, including deliberate self-poisoning, were excluded. Calls were categorised by incident-type, time-of-call and risk of an adverse event (low/moderate/high) based on the type of medicine involved. Results A total of 391 medication incident calls were included (mean 4.3 per day). The most common incidents were missed doses (n = 145/391, 37%) and accidental overdoses (e.g. double-dose) (n = 80/391, 20%). Most calls to the poisons centre (n = 284/391, 73%) were received outside business hours (before 9 am or after 5 pm). For incidents where the medicine(s) were known (n = 326), a moderate-risk medicine (most commonly an anticonvulsant or antipsychotic) or high-risk medicine (most commonly an anticoagulant or opioid) was involved in two-thirds of cases (n = 217, 66.6%). Conclusions Calls to an emergency poisons information service about medication incidents were common, and were mostly outside business hours. Nearly half of the calls were about incidents unrelated to poisoning or toxicology, including missed doses. The study highlights a gap in medication management support for residents and disability support workers, especially after-hours, that needs to be addressed.
What is creative imagining?
Authors: Langkau Julia
Published: December 2024

The aim of this paper is to give an account of the use of imagination at the core of artistic creative processes involving experiential imagination, and to show that this use of the imagination does not always lead to a creative output. Creative imagining is a value-guided process, where the values are essentially subjective in that they are given in the phenomenal aspects of experience or imagined experience. But creative imagining is neither sufficient nor necessary for artistic creative processes. It is not sufficient because creativity in other domains may involve value-guided experiential imagining, and it is not necessary because some art may be produced without the use of imagination, or in a manner that employs mostly other forms of imagination.
Runaway pretence
Authors: D’Cruz Jason
Published: December 2024

Deceptive displays of emotion can be used to manipulate another person’s beliefs, desires and emotions. This is an important but often neglected function of imaginative pretence. Pretending to be angry or aggrieved is a powerful strategy to gain emotional leverage. But subjects who deploy such tactics expose themselves to the peculiar hazard of losing track of the fact they are pretending. Such manipulators risk losing grip on their all-things-considered emotional take in a way that undermines their own goals and harms relationships.
Exploring silica accumulation in bamboo leaves: a study on phytolith morphology and epidermal patterning in the tropical giant bamboo Dendrocalamus copelandii
Authors: Rotmuenwai Naritsa , Aryuyo Ketsara , Kruethaworn Nuttida , Wattananit Witoon , Yookongkaew Nimnara
Published: December 2024

Background and Aims

Bamboo is a grass in the Poaceae family with various applications. Bamboo leaves can accumulate high silica. However, silica deposition in bamboo has received limited study. Therefore, this research investigated silica accumulation in Dendrocalamus copelandii leaves. The study includes the localization of silica through phytolith morphology, examination of the distribution patterns of phytoliths in epidermal tissues, analysis of silica accumulation within specialized silica cells (short cells) and analysis of silicon concentration across various leaf developmental stages.

Methods

We used imaging techniques, including differential interference contrast and a scanning electron microscope incorporating an energy-dispersive X-ray spectrometer, to investigate silica accumulation in bamboo leaves. We also analysed the silicon concentration using inductively coupled plasma–optical emission spectroscopy.

Key Results

Leaves of D. copelandii exhibited 11 phytolith morphotypes, namely Bilobate, Polylobate, Saddle, Acute, Acute bulbosus, Microhair, Stomata, Bulliform flabellate, Elongate sinuate, Elongate entire and Tracheary. Most of these phytoliths were found in short cells (Bilobate, Polylobate and Saddle) of epidermal tissues. The short cells were arranged transversely along the leaf length. Bilobate phytoliths were found in both the abaxial and adaxial epidermis, whereas the Saddle morphotype was found only in the abaxial epidermis. Silica accumulation in the short cells of unexpanded leaves begins at the leaf apex, spreads to the middle and base positions, and accumulates initially in the abaxial epidermis, then the adaxial epidermis. Moreover, bamboo leaves accumulate a higher silicon concentration as they age.

Conclusions

Phytolith morphotypes and silica accumulation in epidermal short cells are key factors in understanding silica deposition. Leaf age and climate significantly impact the silicon concentration in bamboo leaves. Our findings are informative for archaeological studies and for plant taxonomical classification. The results are also applicable for biotechnological applications.
Does phylogenetic relatedness imply similar manipulative ability in parasites?
Authors: Gopko Mikhail , Sotnikov Danila , Savina Kseniia , Molchanov Andrei , Mironova Ekaterina
Published: December 2024

Many parasites can alter the behaviour of their hosts in a manner beneficial to the parasite (parasitic manipulations). Obviously, examples of non-manipulative parasites also exist; however, their number might be underestimated because of publication bias. Trematodes from the Diplostomidae family that infect fish eyes are often considered manipulators. However, only one eye-dwelling species (Diplostomum pseudospathaceum) of this family has been shown to do so in controlled laboratory conditions. We studied experimentally whether another common diplostomid species (Tylodelphys clavata) manipulated host defensive behaviour using salmonids (Salvelinus malma) reared and infected in the laboratory. We tested fish activity, depth preference, and dip net avoidance (common fish defensive traits) in different lighting conditions. Although the experimental design was identical to those used earlier for D. pseudospathaceum, no manipulative abilities were detected in T. clavata. Infected fish did not differ from control ones in terms of the expression of the defensive behavioural traits tested. Interestingly, fish activity was confounded by fish size in control but not infected fish; however, this pattern does not appear to be a manipulation. Our results show that even closely related parasites occupying similar habitat niches can differ dramatically in their ability to manipulate host behaviour.
Novel NUP160 mutations related to simultaneous congenital nephropathy and ovarian insufficiency
Authors: Liu Yuhao , Huang Xiaoying , Xu Lubin , Cao Yaqing , Nie Min , Li Mingxi
Published: December 2024

Nucleoporins, as major components of nuclear pore complex, have been recently discovered to participate in organ development. Here, we report a young female patient with nephrotic proteinuria resistant to immune suppressant treatment and congenital ovarian insufficiency. Renal pathology confirmed focal segmental glomerulosclerosis and whole-exome sequencing revealed compound heterozygous mutations in Nucleoporin 160 (NUP160), NM_015231.2 c.4154C>T (p.Pro1385Leu) and c.1102–9T>G. Notably, NUP160 mutations have been associated with congenital nephropathy in four families. We also ruled out competing genetic variants implicated in focal segmental glomerulosclerosis and ovarian dysgenesis. Our identification of two novel NUP160 mutations associated with congenital nephropathy and ovarian insufficiency simultaneously contributes to a deeper understanding of nuclear pore complex function in the urogenital system.
eGFR slope modelling predicts long-term clinical benefit with nefecon in a real-world IgAN population
Authors: Barratt Jonathan , Stone Andrew M , Reich Heather N , Lafayette Richard A
Published: December 2024

Background

Nefecon is an oral, targeted-release formulation of budesonide approved to reduce kidney function loss in patients with immunoglobulin A nephropathy (IgAN). In the phase 3 NefIgArd trial, 9 months of nefecon treatment preserved estimated glomerular filtration rate (eGFR) and reduced urine protein–creatinine ratio versus placebo, for 15 months post-treatment. A modelling analysis was conducted to predict nefecon's long-term benefits on clinical outcomes.

Methods

A published linear regression model was used to extrapolate nefecon's effect on the eGFR slope in NefIgArd to predict its effect on the clinical outcome of kidney failure, eGFR <15 ml/min/1.73 m2, or sustained doubling of serum creatinine. This model was applied to registry data from patients with IgAN at Leicester General Hospital (LGH), whose records were matched to individual NefIgArd patients on the basis of their urine protein–creatinine ratio and eGFR values.

Results

A total of 1684 LGH-NeflgArd ‘matched pairs’ were obtained. Nefecon was predicted to delay the time to clinical outcome by 12.8 years (95% confidence interval 4.8–27.9), with median time to outcome of 9.6 years for patients receiving supportive care only versus 22.4 years for nefecon-treated patients. The NeflgArd 2-year eGFR slope yielded a log hazard ratio for the clinical outcome of 0.38 (95% confidence interval 0.21–0.63), a 62% risk reduction versus placebo. Of patients receiving only supportive care, 52% were modelled to have a clinical outcome within 10 years versus 24% of nefecon-treated patients.

Conclusion

This modelling analysis indicates that the eGFR benefit seen with nefecon predicts a substantial delay in progression to kidney failure.
TTC7A missense variants in intestinal disease can be classified by molecular and cellular phenotypes
Authors: Shojaei Jeshvaghani Zahra , Mijnders Marjolein , Muffels Irena , van Beekhuizen Sander , Kotlarz Daniel , Lindemans Caroline A , Koletzko Sibylle , Klein Christoph , Mokry Michal , Nieuwenhuis Edward , Kuijk Ewart
Published: December 2024

Biallelic mutations in tetratricopeptide repeat domain 7A (TTC7A) give rise to intestinal and immune disorders. However, our understanding of the genotype–phenotype relationship is limited, because TTC7A variants are mostly compound heterozygous and the disease phenotypes are highly diverse. This study aims to clarify how different TTC7A variants impact the severity of intestinal epithelial disorders. We individually characterized the molecular and cellular consequences of 11 different TTC7A missense mutations in TTC7A knockout Caco-2 cells. We examined variant-specific RNA expression profiles, TTC7A protein abundance, and endoplasmic reticulum (ER) stress by using RNA sequencing and imaging flow cytometry. For six variants we detected no significant alterations on these assays, suggesting that protein function may not be severely compromised. However, for five variants we observed molecular phenotypes, with overlapping gene expression signatures between specific variants. Remarkably, the TTC7AE71K variant displayed a unique expression profile, along with reduced TTC7A RNA and protein expression, which set it apart from all other variants. The findings from this study offer a better understanding of the role of specific TTC7A variants in disease and provide a framework for the classification of the variants based on the severity of impact. We propose a classification system for TTC7A variants that could help diagnosis, guide future treatment decisions and may aid in developing effective molecular therapies for patients that carry specific TTC7A variants.
Research on improving visual adaptive route planning of distribution network UAV by using deep learning technology
Authors: Cai Chao , Dai Jin , Cai Yong , Ling Zaixun , Yi Chen
Published: December 2024

The efficiency and safety of distribution network inspections are crucial to maintaining the reliability of electricity supply in various sectors. Traditional manual inspection methods are not only inefficient but also pose risks due to human limitations and environmental factors. This paper proposes a novel approach to enhancing the route planning of Unmanned Aerial Vehicles (UAVs) through Deep Reinforcement Learning, integrated with advanced image processing and control strategies. We employ ResNet-50 for target detection and DeepLabV3+ for semantic segmentation to improve environmental feature recognition. Furthermore, a Deep Q Network combined with a hybrid action space and sophisticated Model Predictive Control strategies is utilized to optimize the UAV’s path planning, enhancing both safety and mission efficiency. The proposed method is validated through experimental simulations that demonstrate its superiority over existing techniques, offering improvements in adaptive route planning for UAVs in distribution network environments.
Combination therapy strategies against multidrug resistant bacteria in vitro and in vivo
Authors: Wang Daliang , Yang Jie , Yang Lilan , Du Yanglin , Zhu Qunchao , Ma Chendong , Zhou Dongdong
Published: December 2024

Exploring effective combination antibacterial therapies has become a research focus. This study selected seven common antibiotics to perform a series of tests on different Gram-negative bacteria isolated from clinical samples of chronic obstructive pulmonary disease patients. More than 70% of the strains exhibited multidrug resistance but remained sensitive to polymyxin B. The checkerboard assay revealed a significant synergistic effect between polymyxin B and tetracycline against different resistant strains, with fractional inhibitory concentration index values consistently below 0.5. Further time-kill curve analysis demonstrated that the use of minimal inhibit concentration of polymyxin B or tetracycline alone had limited bactericidal effects, while their combination significantly reduced bacterial counts by 2–3 log colony-forming units within 12 h. Additionally, the survival rate of larvae treated with the polymyxin B and tetracycline combination was significantly higher than that of the mono-therapy and untreated groups. In brief, this study demonstrates that the combination of polymyxin B and tetracycline exhibits potent antibacterial activity against multidrug resistant Gram-negative bacteria both in vitro and in vivo.
Utility of external fixation for traumatic periprosthetic fracture after total ankle arthroplasty in patients with rheumatoid arthritis: A report of two cases
Authors: Okamura Gensuke , Noguchi Takaaki , Etani Yuki , Ebina Kosuke , Okada Seiji , Hashimoto Jun , Hirao Makoto
Published: December 2024

This report describes two cases of implant-stable traumatic periprosthetic fractures after total ankle arthroplasty in patients with rheumatoid arthritis. One case with a low body mass index (14 kg/m2) achieved complete bone union with the use of an external fixator, while the other case with a high body mass index (32.83 kg/m2) failed to achieve bone union with the external fixator; however, complete union was achieved utilising secondary internal plate fixation. Although open reduction and internal fixation using a plate is the standard procedure in implant-stable periprosthetic fracture cases, fixation using an external fixator might be suitable for patients with rheumatoid arthritis with low body weight and low body mass index, from the perspective of preventing surgical site complications.
Identifying the best treatment choice for relapsing/refractory glioblastoma: a systematic review with multiple Bayesian network meta-analyses
Authors: Schettini Francesco , Pineda Estela , Rocca Andrea , Buché Victoria , Donofrio Carmine Antonio , Mazariegos Manuel , Ferrari Benvenuto , Tancredi Richard , Panni Stefano , Cominetti Marika , Di Somma Alberto , González Josep , Fioravanti Antonio , Venturini Sergio , Generali Daniele
Published: December 2024

Background

Glioblastoma is a highly aggressive primary central nervous system tumor characterized by poor outcomes. In case of relapse or progression to adjuvant chemotherapy, there is no univocal preferred regimen for relapsing glioblastoma.

Methods

We conducted a systematic review and Bayesian trial-level network meta-analyses (NMA) to identify the regimens associated with the best outcomes. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and overall response rates (ORR). We estimated separate treatment rankings based on the surface under the cumulative ranking curve values. Only phase II/III prospective comparative trials were included.

Results

Twenty-four studies (3733 patients and 27 different therapies) were ultimately included. Twenty-three different regimens were compared for OS, 21 for PFS, and 26 for ORR. When taking lomustine as a common comparator, only regorafenib was likely to be significantly superior in terms of OS (hazard ratio: 0.50, 95% credible interval: 0.33-0.75). Regorafenib was significantly superior to other 16 (69.6%) regimens, including NovoTTF-100A, bevacizumab monotherapy, and several bevacizumab-based combinations. Regarding PFS and ORR, no treatment was clearly superior to the others.

Conclusions

This NMA supports regorafenib as one of the best available options for relapsing/refractory glioblastoma. Lomustine, NovoTTF-100A, and bevacizumab emerge as other viable alternative regimens. However, evidence on regorafenib is controversial at best. Moreover, most studies were underpowered, with varying inclusion criteria and primary endpoints, and no longer adapted to the most recent glioblastoma classification. A paradigmatic change in clinical trials’ design for relapsing/refractory glioblastoma and more effective treatments are urgently required.
Liveborn children with trisomy 18: A retrospective review
Authors: Armour Evelyn , MacPherson Melissa J , Mack Cheryl , Yaskina Maryna , van Manen Michael
Published: December 2024

Background

Historically, children born alive with trisomy 18 were considered to have a lethal genetic condition such that no medical interventions were provided. While survival is now recognized to be possible, these children’s lives include aspects of technological dependency, medical complexity, and neurodevelopmental disabilities.

Objectives

The primary aim of this study was to describe the outcomes of a contemporary Canadian population-based cohort of children born alive with trisomy 18.

Methods

A retrospective study was conducted to review the records of children born alive with trisomy 18 from January 2012 to December 2023 in Central/Northern Alberta. Demographic and clinical information were abstracted, including features reported in the literature associated with morbidity and mortality. Outcomes were described, including technological dependency, time spent in the hospital, and survival.

Results

In total, 37 liveborn infants with complete trisomy 18 were identified. While most died in hospital following medical-surgical interventions and/or comfort-care palliation, nine were discharged home. All of these children had been born at term with a birthweight ≥1750 g. While they relied on medical technologies such as home oxygen and feeding tubes at the time of discharge, most were able to spend a considerable amount of time at home rather than being re-hospitalized. At the time of this review, four remain alive varying in age from 6 to 9 years.

Conclusions

Trisomy 18 is not a homogeneous clinical condition. Some children may have their lives extended to spend their lives at home with their families.
When theory meets practice in transformative innovation policy evaluation: experiences from Sweden
Authors: Haddad Carolina R , Wise Emily , Arnold Erik
Published: December 2024

Government policies increasingly focus on transformative innovation policy (TIP), as programmes are being reoriented towards addressing societal challenges and contributing to sustainability transitions. Evaluation practices need modification to keep up with this change. While a small number of frameworks for TIP evaluation have been proposed, building upon different sustainability transition approaches, little is known regarding the extent to which TIP thinking has been integrated into policy evaluation practice. Hence, there is a need, first, to understand the implications of TIP for evaluation, based on the TIP literature and, second, to investigate the extent to which TIP thinking is used in innovation policy evaluation practice, and the main challenges policymakers face in making evaluation more transformation oriented. To do this, we adapt Edler et al.’s (2012, The Practice of Evaluation in Innovation Policy in Europe’, Research Evaluation, 21: 167–82) innovation policy evaluation dimensions to create a framework within which to develop an archetypal TIP programme evaluation, based on the literature. We then investigate the take-up of TIP principles in evaluation in the specific case of Sweden. We use a cross-case comparison of three Swedish innovation programmes, namely the Vinnväxt programme for sustainable regional growth, Challenge Driven Innovation, and the Strategic Innovation Programmes, to analyse the extent to which innovation policy evaluation practice aligns with this archetypal framework. Finally, we identify three challenges policymakers face when trying to reorient evaluations towards being more aligned with this archetypal framework.
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

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

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>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<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>5/hr, n=1329, 90%) there was a weak correlation between aortic diameter and AHI (r=0.23, p<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

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<0.001 for both). The number of REM epochs was greater in the narcolepsy group compared to their controls (p<0.001), the IH group (p<0.05) and subjectively sleepy group (p<0.05), while the average duration of REM epochs was shorter in the narcolepsy group compared to both the IH (p<0.05) and subjectively sleepy groups (p<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

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

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

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

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

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 < 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

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.