bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential application of oxidized cellulose/alginate loaded hydroxyapatite/graphene oxide beads in bone tissue engineering
Authors: Dacrory Sawsan , Ali Lamiaa M. A. , Ouahrani-Bettache Safia , Daurat Morgane , El-Sakhawy Mohamed , Hesemann Peter , Bettache Nadir , Kamel Samir 
Published: February 2025

Abstract
Bone regeneration is one of the most effective methods for treating bone defects. In this work, tricarboxylic cellulose/sodium alginate loaded with hydroxyapatite (HA) and/or graphene oxide (GO) was coagulated by calcium ions to create beads as scaffolds. In the first, cellulose was oxidized to water-soluble tricarboxylic cellulose (TCC) by 2,2,6,6‐tetramethylpiperidine-1-oxyl (TEMPO), periodate, and chlorite oxidation. HA was extracted from eggshells via microwave treatment, and GO was synthesized using the Hummer method. The structural behavior of the formed beads was meticulously investigated through various characterization techniques such as Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The SEM images confirmed the formation of particles of micrometric size without any specific morphology. Incorporating GO or HA does not affect the morphologies of the materials on the micrometric scale. The cytocompatibility of different bead preparations was studied on murine mesenchymal stem cells. Moreover, the swellability in water and biodegradability by cellulase enzyme of prepared beads were studied. The results show that the prepared beads may be promising for bone tissue engineering.
DrugDiff: small molecule diffusion model with flexible guidance towards molecular properties
Authors: Oestreich Marie , Merdivan Erinc , Lee Michael , Schultze Joachim L. , Piraud Marie , Becker Matthias 
Published: February 2025

Abstract
With the cost/yield-ratio of drug development becoming increasingly unfavourable, recent work has explored machine learning to accelerate early stages of the development process. Given the current success of deep generative models across domains, we here investigated their application to the property-based proposal of new small molecules for drug development. Specifically, we trained a latent diffusion model—DrugDiff—paired with predictor guidance to generate novel compounds with a variety of desired molecular properties. The architecture was designed to be highly flexible and easily adaptable to future scenarios. Our experiments showed successful generation of unique, diverse and novel small molecules with targeted properties. The code is available at https://github.com/MarieOestreich/DrugDiff.

Scientific Contribution
This work expands the use of generative modelling in the field of drug development from previously introduced models for proteins and RNA to the here presented application to small molecules. With small molecules making up the majority of drugs, but simultaneously being difficult to model due to their elaborate chemical rules, this work tackles a new level of difficulty in comparison to sequence-based molecule generation as is the case for proteins and RNA. Additionally, the demonstrated framework is highly flexible, allowing easy addition or removal of considered molecular properties without the need to retrain the model, making it highly adaptable to diverse research settings and it shows compelling performance for a wide variety of targeted molecular properties.
kMoL: an open-source machine and federated learning library for drug discovery
Authors: Cozac Romeo , Hasic Haris , Choong Jun Jin , Richard Vincent , Beheshti Loic , Froehlich Cyrille , Koyama Takuto , Matsumoto Shigeyuki , Kojima Ryosuke , Iwata Hiroaki , Hasegawa Aki , Otsuka Takao , Okuno Yasushi 
Published: February 2025

Abstract
Machine learning is quickly becoming integral to drug discovery pipelines, particularly quantitative structure-activity relationship (QSAR) and absorption, distribution, metabolism, and excretion (ADME) tasks. Graph Convolutional Network (GCN) models have proven especially promising due to their inherent ability to model molecular structures using graph-based representations. However, maximizing the potential of such models in practice is challenging, as companies prioritize data privacy and security over collaboration initiatives to improve model performance and robustness. kMoL is an open-source machine learning library with integrated federated learning capabilities developed to address such challenges. Its key features include state-of-the-art model architectures, Bayesian optimization, explainability, and federated learning mechanisms. It demonstrates extensive customization possibilities, advanced security features, straightforward implementation of user-specific models, and high adaptability to custom datasets without additional programming requirements. kMoL is evaluated through locally trained benchmark settings and distributed federated learning experiments using various datasets to assess the features and flexibility of the library, as well as the ability to facilitate fast and practical experimentation. Additionally, results of these experiments provide further insights into the performance trade-offs associated with federated learning strategies, presenting valuable guidance for deploying machine learning models in a privacy-preserving manner within drug discovery pipelines. kMoL is available on GitHub at https://github.com/elix-tech/kmol.

Scientific contribution The primary scientific contribution of this research project is the introduction and evaluation of kMoL, an open-source machine learning library with integrated federated learning capabilities. By demonstrating advanced customization and security capabilities without additional programming requirements, kMoL represents an accessible yet secure open-source platform for collaborative drug discovery projects. Additionally, the experiment results provide further insights into the performance trade-offs associated with federated learning strategies, presenting valuable guidance for deploying machine learning models in a privacy-preserving manner within drug discovery pipelines.
Comparative analysis of pulsatile nanofluid flow under slip conditions through stenosed arteries
Authors: Dawood A. S. , Kroush Faisal A. , Abumandour Ramzy M. , Eldesoky Islam M. 
Published: February 2025

Abstract
This paper focuses on the crucial aim of testing solution accuracy in scientific research. It compares an analytical solution of blood flow and experimental data, offering a statistical analysis to assess the efficacy of the proposed model. The variable pressure gradient through a two-dimensional stenosis cylindrical artery addresses a gap in previous works. Using a perturbation approach, analytical solutions for critical parameters such as the velocity, wall shear stress, pressure gradient, flow rate, temperature and the Nusselt number are obtained across various physical parameters. The statistical analysis of our model shows excellent agreement with existing experimental data, underscoring the reliability of our proposed approach. This study revealed increased wall shear stress with stenosis height and contrasting behaviour for the slip parameter. The temperature increases with increasing nanoparticle volume fraction and Prandtl number but decreases with increasing radiation. Furthermore, the Nusselt number increases with the Eckert number and decreases with the radiation parameter. This research contributes valuable insights into blood flow dynamics and the effects of various physical parameters, enhancing understanding and informing future studies in the field.
Regulatory efforts to address the access gap for foreign new drugs in China: the priority review program and related policies
Authors: Zhu Xingyue , Zhang Jinsui 
Published: February 2025

Abstract

Background
China has implemented the priority review (PR) program and flexible registration requirements for new drugs with significant clinical value since 2016 to accelerate drug access. We aim to explore the impact of the reform efforts on the drug access gap between China and the US.

Methods
We collected data on the imported new drug approvals that were licensed in China between 2007 and 2023, and measured their launch delays as compared to the US. Difference-in-difference models were used to compare the launch delays of PR approvals and non-PR approvals before and after the implementation of the PR. Propensity score matching was used to construct the imputed PR and non-PR approvals in the pre-PR period.

Results
A total of 410 imported approvals were licensed in China in 2007-2023. Most approvals (316[77.1%]) were licensed after the PR was implemented, of which 189[59.8%] received the PR designation. The difference-in-difference models found that the PR program reduced drug launch delay by 1157.0 days (robust standard error, 571.0; P<0.05) and reduced drug submission delay by 1037.3 days (robust standard error, 520.8; P<0.05). The PR identified drugs with high clinical value and informed flexible registration requirements for them, which accelerated drug submission and market entry.

Conclusions
Our findings proved the importance of value-based prioritization of new drugs and flexibility in the statutory evidentiary standard in the drug approval process. Further efforts from the drug agency are needed to leverage the regulatory flexibility to provide fast market entry of new drugs without compromising their quality.
Deep learning-based Intraoperative MRI reconstruction
Authors: Ottesen Jon André , Storas Tryggve , Vatnehol Svein Are Sirirud , Løvland Grethe , Vik-Mo Einar Osland , Schellhorn Till , Skogen Karoline , Larsson Christopher , Bjørnerud Atle , Groote-Eindbaas Inge Rasmus , Caan Matthan W. A. 
Published: February 2025

Abstract

Background
We retrospectively evaluated the quality of deep learning (DL) reconstructions of on-scanner accelerated intraoperative MRI (iMRI) during respective brain tumor surgery.

Methods
Accelerated iMRI was performed using dual surface coils positioned around the area of resection. A DL model was trained on the fastMRI neuro dataset to mimic the data from the iMRI protocol. The evaluation was performed on imaging material from 40 patients imaged from Nov 1, 2021, to June 1, 2023, who underwent iMRI during tumor resection surgery. A comparative analysis was conducted between the conventional compressed sense (CS) method and the trained DL reconstruction method. Blinded evaluation of multiple image quality metrics was performed by two neuroradiologists and one neurosurgeon using a 1-to-5 Likert scale (1, nondiagnostic; 2, poor; 3, acceptable; 4, good; and 5, excellent), and the favored reconstruction variant.

Results
The DL reconstruction was strongly favored or favored over the CS reconstruction for 33/40, 39/40, and 8/40 of cases for readers 1, 2, and 3, respectively. For the evaluation metrics, the DL reconstructions had a higher score than their respective CS counterparts for 72%, 72%, and 14% of the cases for readers 1, 2, and 3, respectively. Still, the DL reconstructions exhibited shortcomings such as a striping artifact and reduced signal.

Conclusion
DL shows promise in allowing for high-quality reconstructions of iMRI. The neuroradiologists noted an improvement in the perceived spatial resolution, signal-to-noise ratio, diagnostic confidence, diagnostic conspicuity, and spatial resolution compared to CS, while the neurosurgeon preferred the CS reconstructions across all metrics.

Relevance statement
DL shows promise to allow for high-quality reconstructions of iMRI, however, due to the challenging setting of iMRI, further optimization is needed.

Key Points

iMRI is a surgical tool with a challenging image setting.

DL allowed for high-quality reconstructions of iMRI.

Additional optimization is needed due to the challenging intraoperative setting.

Graphical Abstract
Trending Modalities in Type 2 Diabetes Prevention
Authors: Lundgrin Erika L , Hatipoglu Betul 
Published: February 2025

Abstract

Context
Prediabetes now affects a substantial proportion of the population, marking a growing group of individuals at increased risk for the development of type 2 diabetes (T2D). Given the profound effect of T2D on an individual's morbidity and mortality, T2D prevention is of critical importance.

Evidence Acquisition
We searched PubMed and Ovid MEDLINE databases for recent systematic reviews, meta-analyses, and original research articles pertaining to prediabetes and the prevention of T2D.

Evidence Synthesis
T2D prevention strategies have focused on intensive lifestyle modification as well as numerous medications that ultimately improve insulin resistance. Recently, a better understanding of the gut microbiome's role in diabetes progression has suggested a possible preventive role for fecal transplant. Finally, multiple incretin pharmaceutical agents have been developed that show promise in the prevention and treatment of T2D.

Conclusion
The number of novel ways to prevent T2D is rapidly growing. A thorough understanding of the indications, outcomes, and limitations of these new therapies is critical for all who care for individuals with diabetes.
Z pamiętnika książkowej krawcowej
Authors: Juchnowicz Anna 
Published: February 2025

W artykule zawarto rozważania o roli przemijania w życiu książki, zwłaszcza książki artystycznej. Zaczynając od przykładów książek „zwykłych”, autorka analizuje przemiany, jakie zachodzą w tych przedmiotach pod wpływem ich użytkowania. Następnie porównuje je z technikami szycia składek, które rozwija w ramach zainteresowań introligatorskich, a w książkach artystycznych traktuje jako inspirację. Jednym z ważniejszych aspektów książki jest to, że stanowi ona obiekt ruchomy, ale i zmieniający się w czasie. Te cechy są wspólne zarówno dla książek artystycznych, jak i książek „zwykłych”, o ile ich istnienie nie jest wirtualne.
Dança envolvente e ficção visionária:
Authors: Migliano Milene 
Published: February 2025

Proponho um texto para colocar em contato dois filmes que têm como protagonistas corpos vibrantes - que enfrentam e confrontam violências e opressões. Corpos de mulheres cis, trans, negras, indígenas, não-bináries que em suas trajetórias reinventam os usos de/e seus corpos periféricos. Afeita a uma submetodologia indisciplinada (MOMBAÇA, 2016; BRANDÃO; LIRA, 2020), parto de cenas dos filmes em direção à uma cartografia dos afetos em trânsito entre os corpos audiovisuais em dança e o meu corpo encarnado de pesquisadora implicada, interessada na dimensão do fazer sentir, mais do que fazer sentido. A ética amorosa (hooks, 2020) em busca de reparação e encontro com outras epistemes fazem emergir corpos “delincuirs” em enfrentamento contíguo.
Occurrence of cellular senescence in chronic human shoulder tendinopathies and its attenuation ex vivo by inhibition of Enhancer of Zeste 2
Authors: Bühler Dominik , Hilpert Morgane , Barbero Andrea , Müller Andreas M. , Müller Sebastian A. , Martin Ivan , Pelttari Karoliina 
Published: February 2025

AimsOur aim was to investigate occurrence of senescent cells directly in tendon tissue biopsies from patients with chronic shoulder tendinopathies, and to correlate senescence with Enhancer of zeste 2 (EZH2) expression, the functional subunit of the epigenetic master regulator polycomb repressive complex.MethodsHuman proximal long head of biceps tendons from patients with different chronic shoulder pathologies (n = 22), and controls from patients with humerus fracture (n = 6) and pathology (n = 4), were histologically scored for degeneration and analyzed for gene and protein expression of tendon specific factors, senescence markers, and EZH2. Tissues were further exposed to senotherapeutic compounds and the USA Food and Drugs Administration-approved selective EZH2 inhibitor EPZ-6438 and their senescence-associated secretory phenotype (SASP) assessed.ResultsExpression of senescence markers (CDKN2A/p16, CDKN2D/p19) and EZH2 was significantly higher in tendinopathies compared to fracture or healthy tissue controls and positively correlated with the degree of tissue degeneration. Immunofluorescent stainings demonstrated colocalization of p16 and p19 with EZH2 in tenocytes. Treatment of tendon biopsies with EPZ-6438 reduced secretion of a panel of SASP factors, including interleukin-6 (IL6), IL8, matrix metalloproteinase-3 (MMP3) or GRO1, similarly to the senotherapeutic compound AG490.ConclusionWe demonstrate that senescence traits accumulate in pathological tendon tissues and positively correlate with tissue degeneration. Increased expression of CDKN2A/p16 and CDKN2D/p19 coincides with EZH2 expression, while its inhibition decreased the secretion of SASP factors, indicating a possible regulatory role of EZH2 in tenocyte senescence in tendinopathies. Reduction of cellular senescence, e.g. with EPZ-6438, opens ways to new potential therapeutic approaches for enhancing regeneration in chronic tendinopathies.Cite this article: Bone Joint Res 2025;14(2):143–154.
Reflexiones y recomendaciones sobre simulaciones de licenciatura o grado con escenarios éticos como pilar de la formación en profesionales de salud
Authors: Forero Villalobos Jenny , Soublette Sánchez Alix , Húmeres Flores Paulina , Castillo Valderrama Katerina , Ruiz Vidal Eugenia Ruiz Vidal , Navarro Torres Rossana , Palma Vidal Natalia , Krebs Brahm Rossemarie , Armijo Rivera Soledad 
Published: February 2025

Objetivo: Proponer recomendaciones para la enseñanza de la bioética en estudiantes de pregrado de carreras del área de la salud, basadas en la experiencia docente y analizar su implementación mediante la educación basada en simulación. Desarrollo: En la formación de pregrado de profesionales de la salud surgen preocupaciones significativas respecto a la enseñanza de la ética, destacando la necesidad de preparar a los estudiantes para enfrentar dilemas éticos complejos en su práctica clínica. Los escenarios simulados con temáticas éticas se presentan como una herramienta eficaz para abordar estas preocupaciones, permitiendo a los estudiantes experimentar y reflexionar sobre situaciones morales en un entorno controlado. Identificar y explorar tanto dilemas éticos tradicionales como actuales en diversas carreras de salud es crucial para desarrollar experiencias de aprendizaje significativas. Además, la aplicabilidad de las recomendaciones de la Sociedad Internacional de Simulación proporciona una guía estructurada para diseñar simulaciones de interés ético, asegurando que estas experiencias sean relevantes y efectivas en la formación ética de los futuros profesionales de la salud. Conclusión: Las simulaciones de pregrado con escenarios éticos son un pilar fundamental en la formación de profesionales de la salud, preparándolos para enfrentar los retos éticos de su futura práctica clínica promoviendo competencias éticas y la reflexión crítica entre los estudiantes.
Gender Differences in Self-Reported Social Participation in Adults With Autism
Authors: Song Wei , Salzer Mark S. , Steinberg Hillary R. , Shea Lindsay L. 
Published: February 2025

Abstract
There is a lack of research on gender differences in adults’ with autism participation in social activities (i.e., activities that provide interactions with others in the community). Using a large statewide sample (N = 775, 217 females and 558 males), we examined gender differences in the social participation of adults with autism while considering the presence of an intellectual disability (ID). No gender differences were found in total participation days. However, women with autism without ID reported participating in lower percentages of social activities that were important to them and perceiving sufficient participation in lower percentages of these important social activities than their male counterparts. They also reported lower satisfaction with participation level (i.e., perceived sufficiency in participation in important social activities) in social activities that were important to them than women with autism with ID. Implications of findings for understanding gender differences in autism across the life course are discussed.
Local DEA app: Saving lives with accessible and well-located automated external defibrillators
Authors: Eiri Giovanna Natsumi , Júnior Hudson Rogerio Proença , Massago Miyoko , Giacomin Vinicius Lopes , Moriya Karoline Harummy Romero , de Amorim Aboboreira Mateus , Ueda Felipe Hideaki , Machado Aline Cardoso , Gabella Júlia Loverde , Bitencour Marcos Rogério , Tavares Gurgel Sanderland José , Vissoci João Ricardo Nickenig , Paris Teixeira Heloise Manica , de Andrade Luciano 
Published: February 2025

Purpose
Developing technological solutions to reduce care delay and mortality in out-of-hospital cardiac arrest (OHCA) cases is a challenge both in Brazil and worldwide. The aim of this study was to develop and validate a geolocation application for locating automated external defibrillators (AEDs) in the urban area of a medium-sized city in southern Brazil.

Methods
A mobile application was developed to locate AEDs in public places, indicating the best route to the nearest AED with an intuitive design for emergency use. The app provides information on cardiopulmonary resuscitation (CPR), initial care, and AED use. The research steps included a literature review on the double diamond design process, prototyping, expert validation, and simulation tests.

Results
The Local DEA app, developed for Android and iOS, offers features such as route calculation to the nearest AED and emergency services. In an evaluation conducted by 30 experts, the app was well accepted for its ease of use and efficiency (Cronbach’s alpha = 0.92). Simulation tests demonstrated that the strategic installation of accessible and well-located AEDs improves coverage and significantly reduces travel time to emergency care as compared with ambulance travel times (p < 0.001).

Conclusion
The Local DEA app is a promising tool for reducing mortality in OHCA, enabling AED geolocation, use instructions, and CPR guidelines. When combined with the strategic placement of public-access AEDs, the application can increase the likelihood of survival in OHCA cases.
Comparative analysis of acute and chronic painful temporomandibular disorders: Insights into pain, behavioral, and psychosocial features
Authors: Yap Adrian Ujin , Jo Jung Hwan , Kim Sunghae , Lee Byeong-min , Park Ji Woon 
Published: February 2025

Objective
The scarcity of literature necessitates further research to differentiate between acute and chronic painful temporomandibular disorders (TMDs). This study compared pain characteristics, oral behaviors, jaw function, and psychosocial distress between TMD patients with acute and chronic pain, examined correlations among variables, and identified factors associated with chronic pain-related TMDs (PT).

Methods
Anonymized data were gathered from consecutive patients seeking TMD treatment at a university-based oral medicine clinic. Axis I diagnoses were made using the Diagnostic Criteria for TMDs, and patients with PT were categorized into acute (AP) and chronic pain (CP) groups. Axis II assessments were performed, evaluating pain characteristics, oral behaviors, jaw functional limitation, somatic symptoms, depression, and anxiety. Statistical analysis utilized chi-square/non-parametric tests and logistic regression (α =  0.05).

Results
Among the 488 PT patients, 34.6% experienced AP and 65.4% had CP. Significant differences were observed in pain intensity, interference, disability, jaw overuse behavior, functional limitation, somatic symptom burden, depression, and anxiety. (CP>  AP). Moderate-to-strong correlations were found in both the AP (rs =  0.43–0.83) and CP (rs =  0.46–0.87) groups, although the specific relationships between pain, behavioral, and psychosocial factors differed somewhat. The multivariate regression model revealed that only pain intensity (OR =  1.01) and oral behaviors (OR =  1.06) significantly increased the odds of chronic PT.

Conclusion
Chronic pain was more prevalent in PT patients and associated with greater severity in pain, behavioral, and psychosocial variables. Pain intensity and oral behaviors were linked to an increased likelihood of chronic pain.