bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breaking barriers: Smart vaccine platforms for cancer immunomodulation
Authors: Gomari Mohammad Mahmoudi , Ghantabpour Taha , Pourgholam Nima , Rostami Neda , Hatfield Stephen M. , Namazifar Farzaneh , Abkhiz Shadi , Eslami Seyed Sadegh , Ramezanpour Mahsa , Darestanifarahani Mahsa , Astsaturov Igor , Bencherif Sidi A. 
Published: February 2025

AbstractDespite significant advancements in cancer treatment, current therapies often fail to completely eradicate malignant cells. This shortfall underscores the urgent need to explore alternative approaches such as cancer vaccines. Leveraging the immune system's natural ability to target and kill cancer cells holds great therapeutic potential. However, the development of cancer vaccines is hindered by several challenges, including low stability, inadequate immune response activation, and the immunosuppressive tumor microenvironment, which limit their efficacy. Recent progress in various fields, such as click chemistry, nanotechnology, exosome engineering, and neoantigen design, offer innovative solutions to these challenges. These achievements have led to the emergence of smart vaccine platforms (SVPs), which integrate protective carriers for messenger ribonucleic acid (mRNA) with functionalization strategies to optimize targeted delivery. Click chemistry further enhances SVP performance by improving the encapsulation of mRNA antigens and facilitating their precise delivery to target cells. This review highlights the latest developments in SVP technologies for cancer therapy, exploring both their opportunities and challenges in advancing these transformative approaches.
Genetic Characterization of the Immortalized Human Nasopharyngeal Carcinoma Cell Line NPC/HK1
Authors: Makowska Anna , Kontny Udo , van Helden Josef , Hildebrandt Barbara , Schüler Herdit M. , Weiskirchen Ralf 
Published: February 2025

ABSTRACTBackgroundHuman nasopharyngeal carcinoma (NPC) cell lines are in vitro model systems that are widely available, easy to handle, and provide an unlimited supply of material. They also bypass ethical concerns associated with the use of primary human cells or tissue. However, many of these cell lines including 5‐8F, 6‐10B, CNE‐1, CNE‐2, HNE‐1, HONE‐1, SUNE1, SUNE2, and NPC‐TW01 have been shown to be misidentified or cross‐contaminated. While simple molecular genotyping techniques such as short tandem repeat profiling of human cell lines are available to confirm cell line identity, scientists often do not implement strategies to avoid misidentification. This has resulted in a large volume of publications containing incorrect information.MethodsIn this paper, we have established a cell line karyogram that contains several marker chromosomes and a set of typical aberrations characteristic of NPC/HK1.Results and ConclusionsCombined with the typical multiloci short tandem repeat signature of NPC/HK1, the cytogenetic analysis provides an effective means to avoid unreliable experimental outcomes and scientific misinterpretation.
Lanthanides Gd and Tm Can Inhibit Carnitine/Acylcarnitine Transporter: Insights from All‐Atoms Simulations
Authors: Prejanò Mario , Tonazzi Annamaria , Giangregorio Nicola , Indiveri Cesare , Marino Tiziana 
Published: February 2025

AbstractRecent experimental evidence highlighted the inhibition of carnitine/acylcarnitine carrier (CAC), an important mitochondrial transmembrane protein for living organisms, by the early lanthanide Pr3+. A possible explanation of such a behaviour was found in the preference of the cation for amino acids like aspartate and glutamate containing a carboxylate in the side chain, laying in the inter‐membrane space. Interaction of the cation with these residues can cause halt the transfer of the protein‘s substrates between the matrix and cytoplasm thus opening to new scenarios concerning the CAC‐metal interactions and its relative inhibition. In the present work, the panel of metals binding the CAC protein is predictively expanded including Gd3+ and Tm3+, selected as representative species of middle and late lanthanides, respectively. A more realistic membrane‐containing model of the protein was built and the comparative analysis of the molecular dynamics (MD) simulations of CAC apo‐form with its complexed systems, named CAC−Pr, CAC−Gd and CAC−Tm, was performed. The analysis of the trajectories revealed that the inhibition is caused by the coordination of D132 and E179 to the cations and that such interactions generate a reorganization of important salt‐bridges inside the framework of CAC. In detail, MD simulations highlighted that a spontaneous conformational change from cytoplasmatic‐state (c‐state) to matrix‐state (m‐state) induced by cations and that, in this condition, the protein channel is occluded, thus explaining the inhibition.
Visible‐Light Photoredox Catalytic Direct N‐(Het)Arylation of Lactams
Authors: Boselli Monica Fiorenza , Ghosh Indrajit , Intini Niccolò , Fattalini Marco , Puglisi Alessandra , König Burkhard , Benaglia Maurizio 
Published: February 2025

AbstractLactam rings are essential structural motifs in organic chemistry, widely present in natural products and clinically important drugs, such as antibiotics and antiepileptics. Existing methods for synthesizing N‐functionalized lactams often require harsh conditions, toxic reagents, or complex catalytic systems. Here, we report a mild and efficient photochemical approach for generating N‐centered radicals, enabling straightforward N‐heteroarylation of lactams. This versatile method enables the synthesis of a range of N‐(het)arylated lactams and is effective even in aqueous media, facilitating the functionalization of biomolecules. Furthermore, the photochemical reaction is easily scalable under continuous flow conditions, making it highly suitable for large‐scale applications.
Regulating the Cytotoxicity of Anticancer Drugs by Pillar[6]arene‐based Host‐Guest Complex
Authors: Jia Xinyu , Wei Haoyu , Huang Yan , Duan Wengui , Liu Luzhi 
Published: February 2025

AbstractCreating molecular‐level host‐guest complexes with properties responsive to endogenous substance stimuli‐responsive as drug delivery systems, is critical for improving drug stability, reducing side effects, and amplifying therapeutic efficacy. Herein, a delivery system for the chemotherapeutic drug chlorambucil (CLB) was developed using the host‐guest interaction with amino‐pillar[6]arene (NP6). NP6 exhibits a high affinity for CLB (Ka=3.5×103 M−1), resulting in a 1 : 1 host‐guest complex NP6@CLB. This complex not only effectively prevents premature drug leakage and improves drug stability but also significantly reduces the cytotoxicity of CLB on L‐02 cells. Notably, NP6 also demonstrated superior complexation (Ka=3.6×103 M−1) with ATP, an endogenous substance in cells. During NP6@CLB delivery, ATP can compete with CLB to form a host‐guest complex with NP6. This process blocks drug efflux while releasing CLB, thereby synergistically enhancing the antitumor effects on HeLa cells. This “one stone, two birds” design strategy—where host‐guest complexes facilitate both direct drug delivery and synergistic enhancement of antitumor properties via ATP binding, opens a new perspective for constructing multifunctional supramolecular chemotherapeutic platforms based on pillar[n]arene.
Continuous Flow Synthesis of β‐Aminoketones as Masked Vinyl Ketone Equivalents
Authors: Bannon Ruairi , Smyth Megan , Moody Thomas S. , Wharry Scott , Roth Philippe M. C. , Gauron Guillaume , Baumann Marcus 
Published: February 2025

AbstractHerein we report the efficient synthesis of β‐aminoketones via addition of a vinyl Grignard reagent into amides followed by trapping of the vinyl ketone intermediate with the magnesium‐amide by‐product. The reaction was successfully translated from a batch process into continuous flow mode to increase its efficiency, safety and scalability. Different set‐ups were evaluated to minimize/overcome clogging issues arising from magnesium salt precipitates. Ultimately, the resulting β‐aminoketones were obtained in high yields and productivities with residence times of less than 90 seconds at elevated temperatures of 50 °C. Importantly, the β‐aminoketone products are valuable building blocks that can be unmasked to reactive vinyl ketones via a Cope elimination process.
Protonation of Nitrogen‐Containing Covalent Organic Frameworks for Enhanced Catalysis
Authors: Gu Yu‐Hao , Xu Xinyu , Yuan Shuai 
Published: February 2025

AbstractCovalent organic frameworks (COFs) are a class of porous crystalline materials with ordered structures and tunable properties, which have been widely explored in catalysis, sensing, gas storage, and separation. Among various post‐synthetic modifications, protonation emerges as a simple yet effective strategy to fine‐tune the properties of nitrogen‐containing COFs, thereby enhancing their catalytic performance. This concept article highlights the contribution of protonation on the mass transfer kinetics, charge distribution, photo‐response, charge transfer, and other properties related to photocatalysis and electrocatalysis. The applications of protonated COFs are explored in catalytic processes including hydrogen evolution, CO2 reduction, H2O2 synthesis, and singlet oxygen generation. We also emphasize the necessity of considering the protonation process when nitrogen‐containing COFs are applied in acidic environments to accurately reveal the structure‐activity relationship. By analyzing recent advancements in protonated COFs, this article underscores the potential and challenges of protonation as a powerful tool for advancing COF‐based catalytic systems.
The Diverse Reactivity of an Al(I) Carbenoid Towards Phosphorus‐Based Ylides. The Crucial Role of Co‐Crystallised Lithium Halide
Authors: Dmitrienko Anton , Pilkington Melanie , Nikonov Georgii I. 
Published: February 2025

AbstractAttempts to generate NacNacAl‐based (NacNac=[ArNC(Me)CHC(Me)NAr]−; Ar=2,6‐iPr2C6H3) alkylidenes via reactions with trimethyl(methylidene), triphenyl(methylidene) and triethyl(ethylidene) phosphiranes led to new and unexpected reactivity patterns. Reaction with Me3P=CH2 resulted in the intermolecular deprotonation of the NacNac −CCH3 backbone. Reaction with Ph3P=CH2*LiI afforded an equimolar mixture of NacNacAlH2 and the ortho‐metalated adduct, NacNac'Al(η(C,C)2−CH2=PPh2(o‐C6H4)) (NacNac’=[ArNC(Me)CHC(=CH2)NAr]2−). Finally, the use of Et3P=CHMe*LiBr resulted in the fragmentation of the NacNac moiety.
An overview of the potential utilization of solid acid catalysts for enhanced biodiesel production through hydrodynamic cavitation assistance: A mini‐review
Authors: Sai Bharadwaj Aryasomayajula Venkata Satya Lakshmi , Gupta Navneet Kumar 
Published: February 2025

AbstractUtilizing a catalytic approach for producing biodiesel from non‐edible oils holds promise as a solution for the next generation of fuels. Therefore, the emerging research on replacing conventional catalysts and developing new waste‐derived heterogeneous catalysts with acid–base properties in the intensified biodiesel production process aims to achieve significant scientific outcomes including developing a low‐cost biorefinery and mitigating the increasing energy demand. Hence, a prospective replacement of green renewable solid acid catalysts over conventional or regularly used catalysts in the production of biodiesel using hydrodynamic cavitation‐assisted reactors has been discussed in this review. The synthesis and importance of different solid acid catalysts zeolite‐based and heteropolyacids is also discussed in this review. It is concluded that, to date, these catalysts are well used in biomass pyrolysis and very minimal in the pretreatment of lignocellulosic biomass, but there is no proper report on their application in the biodiesel synthesis from various non‐commercial feedstocks. In this study, it is also reported that the hydrodynamic cavitation‐assisted synthesis of biodiesel represents a novel approach with the potential to significantly boost yield and serve as a breakthrough method for industrial applications. The economic survey, circular economy, and life‐cycle assessment studies concerning the proposed study are also presented in this study, from which it is concluded that the complete replacement of these green catalysts in the production of biodiesel will aid in the development of a clean and green sustainable environment.
Prognosis of Out‐of‐Hospital Cardiac Arrest in Underserved Rural Area
Authors: Ezon Dor , Shwartz Hagay , Gleitman Sagi , Israeli Zeev , Miller Asaf , Birati Edo Y. 
Published: February 2025

ABSTRACTBackgroundEpidemiological data are lacking on patients in the rural areas who are being admitted after out‐of‐hospital cardiac arrest (OHCA). We report here the first descriptive analysis study of patients who were hospitalized and treated after OHCA at an academic medical center in the Lower Galilee which located in the north part of Israel.MethodsThis is a descriptive, retrospective analysis of all patients admitted after OHCA to Tzafon Medical Center between the years 2017 and 2023. The analysis consists of the epidemiological, social, and clinical data based on the electronic medical records.ResultsA total of 62 patients were included in this analysis, 82% were men with a median age of 61.5 years old. Thirty‐four percent had history of ischemic heart disease (IHD) and 60% history of hypertension. Twenty‐seven (44%) patients died during their admission. In 49 (79%) patients the first rhythm on emergency medical service (EMS) arrival was a shockable rhythm and 30 (48%) patients had a ST‐elevation myocardial infarction (STEMI) on electrocardiogram (ECG). Patients who were admitted to the hospital after OHCA were more likely to be discharged alive if they had no history of IHD (n = 27; p = 0.037), hypertension, or hyperlipidemia. Moreover, the presence of first shockable rhythm on the first ECG that performed by EMS was associated with higher rates of survival (n = 33; p < 0.001).ConclusionsWe present the first single‐center epidemiological analysis of patients admitted after OHCA at a rural area in Israel, with an in‐hospital survival rate of 56%. Patients without history of IHD, hypertension, hyperlipidemia, and acute kidney injury and those with first shockable rhythm were more likely to discharged alive.
Phenomapping the Response of Patients With Ischemic Cardiomyopathy With Reduced Ejection Fraction to Surgical Revascularization
Authors: Satish Tejus , Hendren Nicholas S. , Peltz Matthias , Heid Christopher A. , Farr Maryjane , Bavry Anthony , Girotra Saket , Kumbhani Dharam J. , Drazner Mark H. , Tang W. H. Wilson , Grodin Justin L. 
Published: February 2025

ABSTRACTBackgroundCoronary artery bypass grafting (CABG) has demonstrated long‐term mortality benefits in patients with HFREF and obstructive coronary artery disease (CAD), but whether phenotypic heterogeneity influences the benefits of CABG is unknown. We applied clustering analysis to STICHES (Surgical Treatment for Ischemic Heart Failure Extension Study) to identify phenogroups with different long‐term risk profiles and investigate differences in CABG benefits between phenogroups.Methods and ResultsSTICHES was a randomized controlled trial evaluating the effect of CABG in addition to medical therapy versus medical therapy alone. We split the STICHES participants into derivation (n = 753) and validation (n = 459) cohorts. We phenomapped the derivation cohort using penalized model‐based clustering. We fit multivariable Cox models to investigate long‐term differences in all‐cause mortality, cardiovascular (CV) mortality, and a composite of all‐cause mortality/CV hospitalization between phenogroups and whether phenogroup assignment modified the effects of CABG on these outcomes. Findings were internally validated on the validation cohort. Four phenogroups were identified in the derivation cohort. The highest‐risk group was at a twofold greater risk of death (HR: 2.0, 95% CI: 1.4–2.9, p < 0.001) and CV death (HR: 2.0, 95% CI: 1.3–3.1, p = 0.002), and a 1.5‐fold greater risk for death/CV hospitalization (HR: 1.5, 95% CI: 1.1–2.1, p = 0.016). Phenogroup assignment did not modify the effects of CABG on the outcomes (p > 0.05 for all). Similar results were obtained in the validation cohort.ConclusionsThe beneficial effects of CABG on all‐cause mortality, CV mortality, and a composite of all‐cause mortality and CV hospitalization persist despite phenotypic heterogeneity in HFREF and CAD.
Design and Synthesis of 68Ga‐Labeled Peptide‐Based Heterodimers for Dual Targeting of NTS1 and GRPR
Authors: Bodin Sacha , Previti Santo , Jestin Emmanuelle , Rémond Emmanuelle , Vimont Delphine , Lamare Frédéric , Ait‐Arsa Imade , Hindié Elif , Cavelier Florine , Morgat Clément 
Published: February 2025

AbstractTumor heterogeneity remains one of the main obstacles for cancer diagnosis and treatment. The simultaneous targeting of several cancer biomarkers is an appealing approach for improved diagnostic procedures. Neurotensin receptor 1 (NTS1) and Gastrin‐Releasing Peptide Receptor (GRPR) are both G‐protein coupled receptors with complementary profile of expression in several cancer types. This work proposes the design, the synthesis and the in vitro radiopharmaceutical characterization of three heterodimers, based on GRP/NT modified peptides, radiolabeled with gallium‐68. Two NTS1/GRPR targeting pharmacophores containing linear hybrids that differ in the C‐terminus were synthesized (i. e., JMV 7110 and JMV 7253). The branched analogue of the silicon‐containing heterodimer JMV 7110, namely JMV 7266, was also synthesized. After radiolabeling with 68Ga, saturation binding studies performed on HT29 (NTS1+/GRPR−) and PC3 (NTS1+/GRPR+) cells demonstrated a significant loss in NTS1 and GRPR affinity compared to the reference monomers with the exception of the NTS1 affinity of [68Ga]Ga‐JMV 7266 which was preserved. Considering cellular processing, NTS1‐internalization at 1 h was the highest with [68Ga]Ga‐JMV 7266 and was similar to the reference compound. Interestingly [68Ga]Ga‐JMV 7266 demonstrated lower efflux than the other linear heterodimers but also than its NT reference compound. The branched structure of [68Ga]Ga‐JMV 7266 seems beneficial for dual NTS1/GRPR targeting.
Computation of Viscoelastic Shear Shock Waves Using Finite Volume Schemes With Artificial Compressibility
Authors: Berjamin Harold 
Published: February 2025

ABSTRACTThe formation of shear shock waves in the brain has been proposed as one of the plausible explanations for deep intracranial injuries. In fact, such singular solutions emerge naturally in soft viscoelastic tissues under dynamic loading conditions. To improve our understanding of the mechanical processes at hand, the development of dedicated computational models is needed. The present study concerns three‐dimensional numerical models of incompressible viscoelastic solids whose motion is analysed by means of shock‐capturing finite volume methods. More specifically, we focus on the use of the artificial compressibility method, a technique that has been frequently employed in computational fluid dynamics. The material behaviour is deduced from the Fung–Simo quasi‐linear viscoelasiticity (QLV) theory where the elastic response is of Yeoh type. We analyse the accuracy of the method and demonstrate its applicability for the study of nonlinear wave propagation in soft solids. The numerical results cover accuracy tests, shock formation and wave focusing.
Coupled Finite Element Model of the Middle and Inner Ear as Virtual Test Environment for Stapes Surgery
Authors: Burovikhin D. , Lauxmann M. 
Published: February 2025

ABSTRACTIn order to evaluate the performance of different types of middle‐ear prostheses, a model of human ear was developed. The model was created using finite element (FE) method with the ossicles modeled as rigid bodies. First, the middle‐ear FE model was developed and validated using the middle‐ear transfer function measurements available in literature including pathological cases. Then, the inner‐ear FE model was developed and validated using tonotopy, impedance, and relative BM motion level curves from literature. Both models are based on preexisting research with some improvements and were combined into one coupled FE model. The stapes in the coupled FE ear model was replaced with a model of a stapes prosthesis to create a reconstructed ear model that can be used to estimate how different types of stapes protheses perform relative to each other as well as to the natural ear. The influence of the diameter of the prosthesis as well as the influence of the sealing and opening of the gap in the footplate were investigated along with different measures such as maximum basilar membrane displacement, intracochlear pressure, pressure in scala vestibuli, oval and round window volume displacements, and prosthesis displacement. This will help in designing new innovative types of stapes prostheses or any other type of middle‐ear prostheses, as well as to improve the ones that are already available on the market.
Bone Health Deterioration in Transfemoral Prosthetic Users: An Analytical Biomechanical Explanation
Authors: Zavaleta‐Ruiz Jose L. , Major Matthew J. , Pankaj Pankaj 
Published: February 2025

ABSTRACTThere is a five‐decade recorded history indicating that persons with transfemoral amputation experience bone loss in their amputated femur at levels seen in bedridden and post‐menopausal individuals, irrespective of age or mobility levels. We used computer simulation to recreate the mechanical environment created by the mechanical design of a prosthetic device in the surviving femur of individuals with transfemoral amputations. Finite element models of gait instances were developed from the hip joint computerized tomography scan of a subject along with a coupled ischial containment prosthetic socket fitted as per standard clinical guidelines. Accompanying mirror models, assembled similarly but without the prosthetic socket were used for stimulus comparison. Simulation showed that more than 90% of the trabecular bone volume in the amputated femur with an ischial containment socket registered compressive strain magnitudes below 300με. These strain magnitudes are below the threshold for bone maintenance as per mechanotransduction theory (i.e., they lie within the disuse window). Only 50% of the bone was in the disuse window for the mirror model for the gait instances considered. These results are consistent with reported in vivo evidence which shows that transfemoral prosthesis users may lose bone mass irrespective of age or mobility levels when using traditional socket designs. Clinically, this study shows that prosthetic sockets that support load through the ischium alter the kinetic chain and preclude application of mechanical stimulus that sustains healthy levels of bone mass in the proximal femur. The study also shows that femur length, prosthetic alignment and tissue tone influence this stimulus.