bluuebunny/crossref_metadata_2025_split huggingface dataset:
The World's consumption of free web‐based Otolaryngology‐Head and Neck Surgery educational resources: A global assessment of video usage trends
Authors: Lawrence Amelia S. , Fei‐Zhang David J. , Hassett Leslie C. , Carlson Matthew L. , Wiedermann Joshua P. 
Published: April 2024

AbstractObjectivesOnline educational platforms with open access have seen a growing adoption in the field of medical education. However, the extent of their global usage is still unclear. To fill this knowledge gap, our objective is to examine the usage patterns of two renowned open‐access resources in Otolaryngology. This includes identifying the most sought‐after topics and understanding the demographics of their users.MethodsRetrospective study of web analytics data between 2016 and 2021 extracted from the Headmirror.com and Mayo Clinic Otolaryngology YouTube channel platforms analyzing demographic and education topic trends via descriptive, geospatial, time‐series, t‐tests, and ANOVA analyses.ResultsViewership spanned 124 countries in 7 different geographic regions, with 72 countries comprising low‐ to middle‐income countries, mostly represented ages of 25–34 years old, came from high‐income countries rather than low‐income (p < .001), and used mobile phones followed by computers for device access. Video‐educational material comprised of subspecialty topics on Rhinology and Sinus Surgery (25%) at the highest end and Facial Trauma (1%) at the lowest. Controlling for the age of the video content, the most‐accessed videos comprised of subspecialty topics on Head and Neck Surgery at the highest end and Laryngology at the lowest with significant differentiation across topics of interest (p < .044).ConclusionsThis assessment of web‐analytics platforms from two widely used otolaryngology free, online‐access materials showed increasing global usage trends with significant differentiating factors along viewership demographics, as well as sought‐after subspecialty topics of interest. In turn, our results not only lay the groundwork for characterizing the global otolaryngology audience but also for future development of targeted educational materials and accessibility initiatives aimed at ameliorating global educational disparities in the field.
Manipulation of Coupled X‐Ray‐Excited Persistent Luminescence and Upconversion in Er3+ Doped Fluoride Nanoparticles for Multifaceted Applications
Authors: Xu Weixin , Zheng Ye , Liu Xiaofeng , Zhou Min , Deng Renren , Yang Yanmin , Qiu Jianrong 
Published: April 2024

AbstractLanthanide doped nanoparticles (NPs) exhibit tunable X‐ray‐excited optical luminescence and X‐ray‐excited persistent luminescence (XEPL), holding broad prospects for applications in display/anti‐counterfeiting and X‐ray imaging. The development of effective strategies for multi‐dimensional applications based on lanthanide‐doped fluoride NPs are a constant challenge. Here, core–shell structured fluoride NPs, in which the heavy metal fluoride shell effectively suppresses the non‐radiative relaxation and simultaneously improve the X‐ray absorption of the shell are designed and fabricated. Under X‐ray irradiation, the developed NPs exhibit an increased number of secondary electrons which migrate to Er3+ centers at the interface and greatly improve the XEPL intensity. Additionally, the introduction of Mn2+ further enhances the XEPL intensity and offers an effective route to control the red‐green ratio of the upconversion spectrum. The NPs co‐doped with Mn2+ exhibit a bright green XEPL under X‐ray irradiation and a red emission under 1532 nm laser excitation. It is further validated that these NPs can be utilized for advanced anti‐counterfeiting and high‐resolution delayed imaging based on a film containing NPs as a scintillation screen. These findings suggest a new strategy of designing Er3+ doped NPs for multi‐dimensional applications.
A promising future of metal‐N‐heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents
Authors: Zhao Qian , Han Bo , Peng Cheng , Zhang Nan , Huang Wei , He Gu , Li Jun‐Long 
Published: April 2024

AbstractMetal complexes based on N‐heterocyclic carbene (NHC) ligands have emerged as promising broad‐spectrum antitumor agents in bioorganometallic medicinal chemistry. In recent decades, studies on cytotoxic metal–NHC complexes have yielded numerous compounds exhibiting superior cytotoxicity compared to cisplatin. Although the molecular mechanisms of these anticancer complexes are not fully understood, some potential targets and modes of action have been identified. However, a comprehensive review of their biological mechanisms is currently absent. In general, apoptosis caused by metal–NHCs is common in tumor cells. They can cause a series of changes after entering cells, such as mitochondrial membrane potential (MMP) variation, reactive oxygen species (ROS) generation, cytochrome c (cyt c) release, endoplasmic reticulum (ER) stress, lysosome damage, and caspase activation, ultimately leading to apoptosis. Therefore, a detailed understanding of the influence of metal–NHCs on cancer cell apoptosis is crucial. In this review, we provide a comprehensive summary of recent advances in metal–NHC complexes that trigger apoptotic cell death via different apoptosis‐related targets or signaling pathways, including B‐cell lymphoma 2 (Bcl‐2 family), p53, cyt c, ER stress, lysosome damage, thioredoxin reductase (TrxR) inhibition, and so forth. We also discuss the challenges, limitations, and future directions of metal–NHC complexes to elucidate their emerging application in medicinal chemistry.
Debamestrocel multimodal effects on biomarker pathways in amyotrophic lateral sclerosis are linked to clinical outcomes
Authors: Lindborg Stacy R. , Goyal Namita A. , Katz Jonathan , Burford Matthew , Li Jenny , Kaspi Haggai , Abramov Natalie , Boulanger Bruno , Berry James D. , Nicholson Katharine , Mozaffar Tahseen , Miller Robert , Jenkins Liberty , Baloh Robert H. , Lewis Richard , Staff Nathan P. , Owegi Margaret Ayo , Dagher Bob , Blondheim‐Shraga Netta R. , Gothelf Yael , Levy Yossef S. , Kern Ralph , Aricha Revital , Windebank Anthony J. , Bowser Robert , Brown Robert H. , Cudkowicz Merit E. 
Published: April 2024

AbstractIntroduction/AimsBiomarkers have shown promise in amyotrophic lateral sclerosis (ALS) research, but the quest for reliable biomarkers remains active. This study evaluates the effect of debamestrocel on cerebrospinal fluid (CSF) biomarkers, an exploratory endpoint.MethodsA total of 196 participants randomly received debamestrocel or placebo. Seven CSF samples were to be collected from all participants. Forty‐five biomarkers were analyzed in the overall study and by two subgroups characterized by the ALS Functional Rating Scale‐Revised (ALSFRS‐R). A prespecified model was employed to predict clinical outcomes leveraging biomarkers and disease characteristics. Causal inference was used to analyze relationships between neurofilament light chain (NfL) and ALSFRS‐R.ResultsWe observed significant changes with debamestrocel in 64% of the biomarkers studied, spanning pathways implicated in ALS pathology (63% neuroinflammation, 50% neurodegeneration, and 89% neuroprotection). Biomarker changes with debamestrocel show biological activity in trial participants, including those with advanced ALS. CSF biomarkers were predictive of clinical outcomes in debamestrocel‐treated participants (baseline NfL, baseline latency‐associated peptide/transforming growth factor beta1 [LAP/TGFβ1], change galectin‐1, all p < .01), with baseline NfL and LAP/TGFβ1 remaining (p < .05) when disease characteristics (p < .005) were incorporated. Change from baseline to the last measurement showed debamestrocel‐driven reductions in NfL were associated with less decline in ALSFRS‐R. Debamestrocel significantly reduced NfL from baseline compared with placebo (11% vs. 1.6%, p = .037).DiscussionFollowing debamestrocel treatment, many biomarkers showed increases (anti‐inflammatory/neuroprotective) or decreases (inflammatory/neurodegenerative) suggesting a possible treatment effect. Neuroinflammatory and neuroprotective biomarkers were predictive of clinical response, suggesting a potential multimodal mechanism of action. These results offer preliminary insights that need to be confirmed.
Extension of the a posteriori finite element method (APFEM) to geometrical alterations and application to stochastic homogenisation
Authors: Ammouche Yanis , Jérusalem Antoine 
Published: April 2024

AbstractWe recently proposed an efficient method facilitating the parametric study of a finite element mechanical simulation as a postprocessing step, that is, without the need to run multiple simulations: the a posteriori finite element method (APFEM). APFEM only requires the knowledge of the vertices of the parameter space and is able to predict accurately how the degrees of freedom of a simulation, i.e., nodal displacements, and other outputs of interests, for example, element stress tensors, evolve when simulation parameters vary within their predefined ranges. In our previous work, these parameters were restricted to material properties and loading conditions. Here, we extend the APFEM to additionally account for changes in the original geometry. This is achieved by defining an intermediary reference frame whose mapping is defined stochastically in the weak form. Subsequent deformation is then reached by correcting for this stochastic variation in the reference frame through multiplicative decomposition of the deformation gradient tensor. The resulting framework is shown here to provide accurate mechanical predictions for relevant applications of increasing complexity: (i) quantifying the stress concentration factor of a plate under uniaxial loading with one and two elliptical holes of varying eccentricities, and (ii) performing the stochastic homogenisation of a composite plate with uncertain mechanical properties and geometry inclusion. This extension of APFEM completes our original approach to account parametrically for geometrical alterations, in addition to boundary conditions and material properties. The advantages of this approach in our original work in terms of stochastic prediction, uncertainty quantification, structural and material optimisation and Bayesian inferences are all naturally conserved.
Forecasting wind power using Optimized Recurrent Neural Network strategy with time‐series data
Authors: Kumar Krishan , Prabhakar Priti , Verma Avnesh 
Published: April 2024

AbstractFuel prices are rising, bringing attention to the utilization of alternative energy sources (RES). Even though load forecasting is more accurate at making predictions than wind power forecasting is. To address the operational challenges with the supply of electricity, wind energy forecasts remain essential. A certain kind of technology has recently been applied to forecast wind energy. On wind farms, a variety of wind power forecasting methods have been developed and used. The main idea underlying recurrent networks is parameter sharing across the multiple layers and neurons, which results in cycles in the network's graph sequence. Recurrent networks are designed to process sequential input. A novel hybrid optimization‐based RNN model for wind power forecasting is proposed in this research. Using the SpCro algorithm, a proposed optimization method, the RNN's weights are adjusted. The Crow Search Optimization (CSA) algorithm and the Sparrow search algorithm are combined to form the SpCro Algorithm (SSA). The suggested Algorithm was developed using the crow's memory traits and the sparrow's detecting traits. The proposed system is simulated in MATLAB, and the usefulness of the suggested approach is verified by comparison with other widely used approaches, such as CNN and DNN, in terms of error metrics. Accordingly, the MAE of the proposed method is 45%, 10.02%, 10.04%, 33.58%, 94.81%, and 10.01% higher than RNN, SOA+RNN, CSO+RNN, SSA+DELM, CFU‐COA, and GWO+RNN method.
Preference Phenotypes in Thyroid Nodule Management: A Patient Segmentation Approach
Authors: Naunheim Matthew R. , Wasserman Isaac , von Sneidern Manuela R. , Huston Molly N. , Randolph Gregory W. , Shrime Mark G. 
Published: April 2024

AbstractObjectivePatient preferences regarding thyroid nodules are poorly understood. Our objective is to (1) employ a discrete choice experiment (DCE) to explore risk tradeoffs in thyroid nodule management, and (2) segment respondents into preference phenotypes.Study DesignDCE.SettingThyroid surgery clinic, online survey.MethodsA DCE including 5 attributes (cancer risk, voice concerns, incision/scar, medication requirement, follow‐up frequency) was refined with qualitative patient and physician input. A final DCE including 8 choice tasks, demographics, history, and risk tolerance was administered to participants with and without thyroid disease. Analysis was performed with multinomial logit modeling and latent class analysis (LCA) for preference phenotyping.ResultsA total of 1026 respondents were included; 480 had thyroid disease. Risk aversion was associated with increasing age (P < .001), female gender (P < .001), and limited education (P = .038), but not previous thyroid disease. Cancer risk most significantly impacted decision‐making. Of the total possible utility change from thyroid nodule decision‐making, 47.8% was attributable to variations in cancer risk; 20.0% from medication management; 14.9% from voice changes; 12.7% from incision/scar; and 4.6% from follow‐up concerns. LCA demonstrated 3 classes with distinct preference phenotypes: the largest group (64.2%) made decisions primarily based on cancer risk; another group (18.2%) chose based on aversion to medication; the smallest group (17.7%) factored in medication and cancer risk evenly.ConclusionCancer risk and the need to take medication after thyroid surgery factor into patient decision‐making most heavily when treating thyroid nodules. Distinct preference phenotypes were demonstrated, reinforcing the need for individual preference assessment before the treatment of thyroid disorders.
A multiscale scheme for homogenization to characterize the flexural performances of injection molded short glass fiber reinforced polyether ether ketone composites
Authors: Zhan Zhangjie , Wu Wanxia , Zhao Jian , Guo Yuting , Su Dongxiao , Ge Yuzhou 
Published: April 2024

AbstractThe characterization of the flexural performances of short glass fiber reinforced polyether‐ether‐ketone (SGFR‐PEEK) composites fabricated by injection molding is a crucial and challenging task due to the process‐induced fiber orientation at different locations, resulting layered shell‐core‐shell microstructures and exhibiting large variations in mechanical performances. This article proposes a method for predicting the bending performance of SGFR‐PEEK and indicates the influence of fiber orientation on its bending behavior. This article reports a new scheme that combines multiscale homogenization with periodic microstructures and presents an experimental investigation of the flexural properties of SGFR‐PEEK composites. The distributions of fiber orientation through the thickness extracted from the micro‐computed tomography (μCT) were analyzed and reproduced with a layered skin‐shell‐core structure along the thickness at meso‐scale finite element model within representative volume elements (RVEs) of the macroscopic composites. Then, the effective properties of the RVEs were predicted using the homogenization method with the periodic boundary condition. The elastic modulus of skin‐shell‐core layers in the direction of flow are 4260.51, 4541.27, 4628.52, and 4630.84 MPa, respectively. The classical laminate theory (CLT) and the second homogenization implementation were then utilized in conjunction with the obtained mechanical properties of RVEs to predict the effective macrostructural behavior. The flexural modulus of the composite material was determined to be 5448.7 MPa through a three‐point bending test. The results obtained through lamination plate reinforcement theory and finite element simulation were 5887.4 and 5785.9 MPa, respectively, showing good agreement with the experimental findings. It is shown that the proposed multiscale scheme yields satisfactory agreement with experimental measurements. In addition, the effect of layered skin‐shell‐core microstructures on the flexural behavior was discussed.Highlights
RVEs of layered shell‐core‐shell microstructures were generated with specified fiber orientations.
The homogenization scheme with the periodic boundary condition was adopted to accurately predict each layer mechanical properties.
The proposed multiscale scheme was compared with experimental results and yielded satisfactory predictions.
The effect of layered skin‐shell‐core microstructures on the flexural behavior was thoroughly studied by the multiscale analytical approach.
Proteasome‐dependent degradation of histone H1 subtypes is mediated by its C‐terminal domain
Authors: García‐Gomis D. , López J. , Calderón A. , Andrés M. , Ponte I. , Roque A. 
Published: April 2024

AbstractHistone H1 is involved in chromatin compaction and dynamics. In human cells, the H1 complement is formed by different amounts of somatic H1 subtypes, H1.0‐H1.5 and H1X. The amount of each variant depends on the cell type, the cell cycle phase, and the time of development and can be altered in disease. However, the mechanisms regulating H1 protein levels have not been described. We have analyzed the contribution of the proteasome to the degradation of H1 subtypes in human cells using two different inhibitors: MG132 and bortezomib. H1 subtypes accumulate upon treatment with both drugs, indicating that the proteasome is involved in the regulation of H1 protein levels. Proteasome inhibition caused a global increase in cytoplasmatic H1, with slight changes in the composition of H1 bound to chromatin and chromatin accessibility and no alterations in the nucleosome repeat length. The analysis of the proteasome degradation pathway showed that H1 degradation is ubiquitin‐independent. The whole protein and its C‐terminal domain can be degraded directly by the 20S proteasome in vitro. Partial depletion of PA28γ revealed that this regulatory subunit contributes to H1 degradation within the cell. Our study shows that histone H1 protein levels are under tight regulation to prevent its accumulation in the nucleus. We revealed a new regulatory mechanism for histone H1 degradation, where the C‐terminal disordered domain is responsible for its targeting and degradation by the 20S proteasome, a process enhanced by the regulatory subunit PA28γ.
Diverse crystalline protein scaffolds through metal‐dependent polymorphism
Authors: Liutkus Mantas , Sasselli Ivan R. , Rojas Adriana L. , Cortajarena Aitziber L. 
Published: April 2024

AbstractAs protein crystals are increasingly finding diverse applications as scaffolds, controlled crystal polymorphism presents a facile strategy to form crystalline assemblies with controllable porosity with minimal to no protein engineering. Polymorphs of consensus tetratricopeptide repeat proteins with varying porosity were obtained through co‐crystallization with metal salts, exploiting the innate metal ion geometric requirements. A single structurally exposed negative amino acid cluster was responsible for metal coordination, despite the abundance of negatively charged residues. Density functional theory calculations showed that while most of the crystals were the most thermodynamically stable assemblies, some were kinetically trapped states. Thus, crystalline porosity diversity is achieved and controlled with metal coordination, opening a new scope in the application of proteins as biocompatible protein‐metal‐organic frameworks (POFs). In addition, metal‐dependent polymorphic crystals allow direct comparison of metal coordination preferences.
Computational and experimental identification of keystone interactions in Ebola virus matrix protein VP40 dimer formation
Authors: Narkhede Yogesh , Saxena Roopashi , Sharma Tej , Conarty Jacob P. , Ramirez Valentina Toro , Motsa Balindile B. , Amiar Souad , Li Sheng , Chapagain Prem P. , Wiest Olaf , Stahelin Robert V. 
Published: April 2024

AbstractThe Ebola virus (EBOV) is a lipid‐enveloped virus with a negative sense RNA genome that can cause severe and often fatal viral hemorrhagic fever. The assembly and budding of EBOV is regulated by the matrix protein, VP40, which is a peripheral protein that associates with anionic lipids at the inner leaflet of the plasma membrane. VP40 is sufficient to form virus‐like particles (VLPs) from cells, which are nearly indistinguishable from authentic virions. Due to the restrictions of studying EBOV in BSL‐4 facilities, VP40 has served as a surrogate in cellular studies to examine the EBOV assembly and budding process from the host cell plasma membrane. VP40 is a dimer where inhibition of dimer formation halts budding and formation of new VLPs as well as VP40 localization to the plasma membrane inner leaflet. To better understand VP40 dimer stability and critical amino acids to VP40 dimer formation, we integrated computational approaches with experimental validation. Site saturation/alanine scanning calculation, combined with molecular mechanics‐based generalized Born with Poisson‐Boltzmann surface area (MM‐GB/PBSA) method and molecular dynamics simulations were used to predict the energetic contribution of amino acids to VP40 dimer stability and the hydrogen bonding network across the dimer interface. These studies revealed several previously unknown interactions and critical residues predicted to impact VP40 dimer formation. In vitro and cellular studies were then pursued for a subset of VP40 mutations demonstrating reduction in dimer formation (in vitro) or plasma membrane localization (in cells). Together, the computational and experimental approaches revealed critical residues for VP40 dimer stability in an alpha‐helical interface (between residues 106–117) as well as in a loop region (between residues 52–61) below this alpha‐helical region. This study sheds light on the structural origins of VP40 dimer formation and may inform the design of a small molecule that can disrupt VP40 dimer stability.
Optimal maintenance policy considering imperfect switching for a multi‐state warm standby system
Authors: Qi Fa‐Qun , Wang Yun‐Ke , Huang Hong‐Zhong 
Published: April 2024

AbstractA novel maintenance policy for a two‐component warm standby system with multiple standby states is presented in this paper. Two standby states, that is, cold and warm standby, for components in the system are considered. Components can realize the transition from the cold standby to the warm standby state by periodic switching, intended to shorten recovery time and save system operating costs. Preventive maintenance (PM) and preventive switching (PS) of components are considered. In the PS strategy, the standby component can switch before the operating component fails. In addition, additional standby failure modes based on idle time are studied. Derive the long‐term average cost of the system through the semi‐regenerative process. A numerical example eventually verifies the feasibility of this paper's proposed maintenance and switching strategy.