bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic accuracy of point-of-care ultrasound of the posterior fatpad in elbow fractures
Authors: Haak Svenja L , van der Veen Thea , Stolmeijer Renate , Boendermaker Annemieke E , van der Kolk Brigitta (Britt) YM , ter Maaten Jan C , Ter Avest Ewoud , Lameijer Heleen
Published: January 2025

Background

Point-of-care ultrasound (POCUS) can potentially be used in the triage of patients with elbow injuries. However, the diagnostic accuracy of POCUS performed by non-radiologists for the exclusion of elbow fractures is yet unknown. This study aimed to investigate the diagnostic potential of POCUS of the posterior fatpad performed by non-radiologists in the workup of adult patients presenting with elbow injuries.

Methods

A multicentre, prospective cohort study was conducted between January 2021 and August 2022 in four EDs to determine the diagnostic accuracy of an elevated posterior fatpad on POCUS to demonstrate or exclude an elbow fracture in patients presenting with elbow injuries to the ED. The study population consisted of a convenience sample. In patients ≥16 years of age with an elbow injury for which an X-ray was ordered, POCUS was performed by emergency physicians trained in ultrasound. POCUS (index test) results were compared with X-ray outcomes (reference standard) to determine the diagnostic accuracy of POCUS.

Results

A total of 215 patients were included, 143 (67%) of whom had a fracture confirmed on X-ray. POCUS was positive based on a visualised elevated posterior fatpad in 127 (59%) patients. An elevated posterior fatpad on POCUS had a sensitivity of 91% (95% CIs 85% to 95%), a specificity of 93% (95% CI 85% to 98%), a negative likelihood ratio of 0.10 (95% CI 0.06 to 0.16) and a positive likelihood ratio of 13.09 (95% CI 5.61 to 30.54) for the presence of an elbow fracture. Post hoc review of the images by expert sonographers improved sensitivity to 96% (95% CI 91% to 99%).

Conclusion

POCUS of the posterior fatpad is a promising adjunct to physical examination to determine the need for further diagnostic studies in the triage of patients with elbow injuries. Sensitivity after a limited training is high, but not perfect, and can likely further be improved with additional training.
B7-H3 CAR-T cell therapy combined with irradiation is effective in targeting bulk and radiation-resistant chordoma cancer cells
Authors: Wang Kun , Osei-Hwedieh David O , Walhart Tara A , Hung Yin P , Wang Yufeng , Cattaneo Giulia , Ma Tao , Dotti Gianpietro , Wang Xinhui , Ferrone Soldano , Schwab Joseph H
Published: January 2025

Background

Chordoma is a slow-growing, primary malignant bone tumor that arises from notochordal tissue in the midline of the axial skeleton. Surgical excision with negative margins is the mainstay of treatment, but high local recurrence rates are reported even with negative margins. High-dose radiation therapy (RT), such as with proton or carbon ions, has been used as an alternative to surgery, but late local failure remains a problem. B7-H3 is an immune checkpoint, transmembrane protein that is dysregulated in many cancers, including chordoma. This study explores the efficacy of B7-H3 chimeric antigen receptor T (CAR-T) therapy in vitro and in vivo.

Methods

Chordoma cancer stem cells (CCSCs) were identified using flow cytometry, sphere formation, and western blot analysis. The expression of B7-H3 in paraffin-embedded chordoma tissue was determined by immunohistochemical staining, and the expression of B7-H3 in chordoma cells was measured by flow cytometry. Retroviral particles containing either B7-H3 or CD19 CAR-expressing virus were transduced into T cells derived from peripheral blood mononuclear cells isolated from healthy human donor blood to prepare CAR-T cells. Animal bioluminescent imaging was used to evaluate the killing effect of CAR-T cells on chordoma cells in vivo. An irradiator was used for all irradiation (IR) experiments.

Results

The combination of B7-H3 CAR-T cell therapy and IR has a greater killing effect on killing radiation-resistant CCSCs and bulk chordoma cells compared with CAR-T cell or IR monotherapy. Additionally, increased expression of B7-H3 antigens on CCSCs and bulk tumor cells is associated with enhanced CAR-T cell killing in vitro and in vivo xenograft mouse models. Upregulation of B7-H3 expression by IR increases CCSCs sensitivity to B7-H3 CAR-T cell-mediated killing.

Conclusions

Our preliminary data show that IR and B7-H3 CAR-T cell therapy is synergistically more effective than either IR or CAR-T cell monotherapy in killing chordoma cells in vitro and in a xenograft mouse model. These results provide preclinical evidence for further developing this combinatorial RT and B7-H3 CAR-T cell therapy model in chordoma
First-in-human, multicenter, open-label, phase I study of ATOR-1017 (evunzekibart), a 4-1BB antibody, in patients with advanced solid malignancies
Authors: Carneiro Ana , Hahn Amanda , Ellmark Peter , Enell Smith Karin , Schultz Lena , Ambarkhane Sumeet , Yachnin Jeffrey , Ullenhag Gustav J.
Published: January 2025

Background

ATOR-1017 (evunzekibart) is a human agonistic immunoglobulin G4 antibody targeting the costimulatory receptor 4-1BB (CD137). ATOR-1017 activates T cells and natural killer cells in the tumor environment, leading to immune-mediated tumor cell death.

Methods

In this first-in-human, multicenter, phase I study, ATOR-1017 was administered intravenously every 21 days as a monotherapy to patients with advanced, unresectable solid tumors having received multiple standard-of-care treatments. The study used single patient cohorts for rapid dose escalation up to 40 mg; thereafter a modified 3+3 design up to 900 mg. Escalating doses were given until disease progression, unacceptable toxicity, or withdrawal of consent. The primary objective of the study included determination of the maximum tolerated dose (MTD) via assessment of adverse events and dose-limiting toxicities (DLTs). Secondary objectives included determination of the pharmacokinetics, immunogenicity and clinical efficacy assessed with CT scans using immune Response Evaluation Criteria in Solid Tumors. Exploratory objectives included pharmacodynamic (PD) assessment of immune system biomarkers.

Results

Of the 27 patients screened, 25 received treatment with ATOR-1017. The median time on study was 13.1 weeks (range 4.3–92.3). The MTD of ATOR-1017 was not reached. Treatment-related adverse events (TRAEs) were reported in 13 (52%) of 25 patients; most common (≥10%) were fatigue (n=4 (16.0%) patients) and neutropenia (n=3 (12.0%) patients). Five patients experienced a severe (≥ grade 3) TRAE; neutropenia (n=2), febrile neutropenia (n=1), chest pain (n=1), increased liver enzymes (n=1), and leukopenia and thrombocytopenia (n=1). No patients discontinued due to TRAEs and no DLTs were observed. Pharmacokinetic data demonstrated approximate dose-proportional kinetics. Dose-dependent increases in PD biomarkers, including soluble 4-1BB, are indicative of target-mediated biological activity. Best response was stable disease in 13 out of 25 patients (52%), maintained for 6 months or longer in six patients (24%).

Conclusions

Treatment with ATOR-1017 was safe and well tolerated at all dose levels and demonstrated biological activity. Furthermore, almost one-third of patients experienced long-lasting stable disease in this heavily pretreated population. The encouraging safety and preliminary efficacy data warrant further clinical development of ATOR-1017, possibly in combination with other anticancer agents.
Leveraging mRNA technology for antigen based immuno-oncology therapies
Authors: Floudas Charalampos S , Sarkizova Siranush , Ceccarelli Michele , Zheng Wei
Published: January 2025

The application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement in cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system to the tumor and boost the efficacy of immune therapies. Selecting suitable tumor antigens is the key step to devising effective vaccinations and amplifying the immune response. Tumor neoantigens are de novo epitopes derived from somatic mutations, avoiding T-cell central tolerance of self-epitopes and inducing immune responses to tumors. The identification and prioritization of patient-specific tumor neoantigens are based on advanced computational algorithms taking advantage of the profiling with next-generation sequencing considering factors involved in human leukocyte antigen (HLA)-peptide-T-cell receptor (TCR) complex formation, including peptide presentation, HLA-peptide affinity, and TCR recognition. This review discusses the development and clinical application of mRNA vaccines in oncology, with a particular focus on recent clinical trials and the computational workflows and methodologies for identifying both shared and individual antigens. While this review centers on therapeutic mRNA vaccines targeting existing tumors, it does not cover preventative vaccines. Preclinical experimental validations are crucial in cancer vaccine development, but we emphasize the computational approaches that facilitate neoantigen selection and design, highlighting their role in advancing mRNA vaccine development. The versatility and rapid development potential of mRNA make it an ideal platform for personalized neoantigen immunotherapy. We explore various strategies for antigen target identification, including tumor-associated and tumor-specific antigens and the computational tools used to predict epitopes capable of eliciting strong immune responses. We address key design considerations for enhancing the immunogenicity and stability of mRNA vaccines, as well as emerging trends and challenges in the field. This comprehensive overview highlights the therapeutic potential of mRNA-based cancer vaccines and underscores ongoing research efforts aimed at optimizing these therapies for improved clinical outcomes.
Working years lost in people with epilepsy: a population-based cohort study
Authors: Dreier Julie Werenberg , Trabjerg Betina B , Lolk Kasper , Plana-Ripoll Oleguer , Christensen Jakob
Published: January 2025

Background

We quantify the loss of working years for people with epilepsy compared with the general population and consider variation by aetiology, psychiatric comorbidity, sex and age.

Methods

This population-based cohort study included all individuals aged 18–65 years living in Denmark from 1995 to 2018. Using nationwide registers since 1977, we identified people with epilepsy and obtained information on the main source of income or employment for each year during follow-up from 1995 to 2020. The main outcome was number of working years lost in people with epilepsy compared with the general population of same sex and age, capturing both working life lost due to permanent (death, disability pension, early retirement) and temporary (unemployment, sick leave) factors.

Results

The study comprised 5 466 140 individuals, including 74 980 (1.4%) with epilepsy. In people with epilepsy, the number of working years was on average reduced by 6.6 (95% CI: 6.5 to 6.7) years compared with the general population, largely due to disability pension (4.8 years, 95% CI: 4.7 to 4.9) and premature death (1.6 years, 95% CI: 1.6 to 1.7). Loss of working life was more pronounced in those with a presumed underlying aetiology (9.0 years (95% CI: 8.9 to 9.2) vs 5.4 years (95% CI: 5.2 to 5.5) in those with unknown aetiology), those with psychiatric comorbidity (14.5 years (95% CI: 14.2 to 14.7) vs 5.6 years (95% CI: 5.5 to 5.7) in those without), men (7.2 years (95% CI: 7.1 to 7.3) vs 5.9 (95% CI: 5.8 to 6.0) years in women) and people with early onset of epilepsy (eg, 11.5 years (95% CI: 11.3 to 11.7) among those with onset <20 years).

Conclusions

Epilepsy was associated with significant loss of working life resulting from both disability and premature death.
Roadmap for the transition to robotic radial cystectomy for patients with bladder cancer in a tertiary urology unit: planning for change
Authors: Keenan Robert Anthony
Published: January 2025

Background

Radical cystectomy has the potential to be a curative strategy for patients with aggressive bladder cancer. Emerging evidence over the last 20 years has shown that minimally invasive surgical approaches using robotics in performing this highly complex and morbid operation can achieve the same oncological outcomes while reducing complications for the patient.

Objective

This paper aims to present a managerial and leadership roadmap for change to robotic cystectomy for patients with advanced bladder cancer to achieve improved patient outcomes while embracing technological developments in the delivery of cancer care.

Methods

Using the Irish Health Service Executive guide for change, we propose and detail a three-stage plan (define, design and deliver) to guide the organisation from the concept of the transition to performing the first operative case.

Results

A walkthrough from identifying a vision for change for robotic cystectomy to designing a step-by-step process is discussed. By providing a template for success, this approach can be applied to any health jurisdiction worldwide and can be adapted as needed.

Conclusion

Although challenging, major change within the healthcare setting through a structured approach provides a valuable opportunity for a department to grow, develop and become a champion of patient care.
Asymptotic analysis to Van der Pol equation and regularized long-wave equation
Authors: Li Guangjin
Published: January 2025

In this paper, we introduce a renormalization (TR) method based on Taylor expansion, which is used to solve nonlinear vibration problems and soliton equations. It provides a new mathematical tool for obtaining the asymptotic analytic solutions of these equations. By the TR method, we solve the Van der Pol equation and the regularized long-wave equation, which obtain the corresponding asymptotic solutions, respectively. For the first equation, compared to some existing perturbation methods, the TR method can obtain its solution without relying on physical intuition and prior assumptions. For the second equation, due to the lack of small parameter, other perturbation methods are difficult to solve for it, and the process of solving its exact solutions is relatively complicated. However, the TR method can easily and quickly obtain its asymptotic solution. The numerical comparison between the asymptotic solution obtained and the solution obtained by other methods verified the effectiveness and accuracy of the proposed method. The results show that the TR method is a simple and powerful mathematical tool for solving nonlinear vibration problems and soliton equations, which has important application value.
Ideology and the Expression of Brands: Fashion Brands and Attitudes in the Domain of Enterprise Development and Consumer Strategies
Authors: Svendsen Jens Martin , Preiholt Håkan
Published: January 2025

Ideology plays a vital role in politics, but not only so. Also in consumer life, ideologically based attitudes and stances are immanent. Building on four different business models within the fashion industry, a model with two axes is presented. The two axes are conceptual recursion and consumption as social ideology. Fashion easily contains a progressive attitude; the social environment creates a milieu where consumers and businesses operate, and in this ambiance of ideas they will be able to (inside-out or outside-in) foot themselves in ideology. Hence, fashion can be said to uphold ideological attitudes, whether explicit or not. The model captures these ideological mindsets. It makes clear how the business models in themselves are ridden by ideology and the expression of brands, as well as bringing an overall understanding of the role ideology plays in entrepreneurship and enterprise development in the fashion industry.
Stedin’s Collaborative Path to Employee-Driven Innovation
Authors: Pahos Nikolaos , Verburg Robert , Sand Martin , Uitermarkt Stefan , Haas Joery de
Published: January 2025

Employee-driven innovation (EDI) burgeons as an important mechanism to drive the exploration activities by making the general employees responsible for innovation. However, little is known about the conditions under which EDI is most effective. To get a better understanding of EDI, we examine how Stedin, an established global player within the energy distribution industry based in the Netherlands, involves its general employees in innovation activities. Stedin actively supports EDI through strategic programmes designed to stimulate employee innovation. Our findings highlight that collaboration is a main driver of EDI at Stedin. In the early implementation phases, dynamic, heterogeneous, informal and distant collaborations are essential, while the later phases benefit from more stability and intimacy. The insights from our detailed case study provide actionable guidelines for organising EDI initiatives in practice.
Eulerian, Lagrangian and broad continuous solutions to a balance law with non convex flux II
Authors: Alberti Giovanni , Bianchini Stefano , Caravenna Laura
Published: January 2025

We consider a continuous solution [Formula: see text] of the balance law [Formula: see text] in one space dimension, where the flux function [Formula: see text] is of class [Formula: see text] and the source term [Formula: see text] is bounded. This equation admits an Eulerian interpretation (namely the distributional one) and a Lagrangian interpretation (which can be further specified). Since [Formula: see text] is only continuous, these interpretations do not necessarily agree; moreover each interpretation naturally entails a different equivalence class for the source term [Formula: see text]. In this paper we complete the comparison between these notions of solutions started in the companion paper [G. Alberti, S. Bianchini and L. Caravenna, Eulerian, lagrangian and broad continuous solutions to a balance law with non convex flux I, J. Differ. Equ. 261 (2016) 4298–4337], and analize in detail the relations between the corresponding notions of source term.
Large amplitude traveling waves for the non-resistive MHD system
Authors: Ciampa Gennaro , Montalto Riccardo , Terracina Shulamit
Published: January 2025

We prove the existence of large amplitude bi-periodic traveling waves (stationary in a moving frame) of the two-dimensional non-resistive Magnetohydrodynamics (MHD) system with a traveling wave external force with large velocity speed [Formula: see text] and of amplitude of order [Formula: see text] where [Formula: see text] is a large parameter. For most values of [Formula: see text] and for [Formula: see text] large enough, we construct bi-periodic traveling wave solutions of arbitrarily large amplitude as [Formula: see text]. More precisely, we show that the velocity field is of order [Formula: see text], whereas the magnetic field is close to a constant vector as [Formula: see text]. Due to the presence of small divisors, the proof is based on a nonlinear Nash–Moser scheme adapted to construct nonlinear waves of large amplitude. The main difficulty is that the linearized equation at any approximate solution is an unbounded perturbation of large size of a diagonal operator and hence the problem is not perturbative. The invertibility of the linearized operator is then performed by using tools from micro-local analysis and normal forms together with a sharp analysis of high- and low-frequency regimes with respect to the large parameter [Formula: see text]. To the best of our knowledge, this is the first result in which global in time, large amplitude solutions are constructed for the 2D non-resistive MHD system with periodic boundary conditions and also the first existence result of large amplitude quasi-periodic solutions for a nonlinear PDE in higher space dimension.
Anisotropic regularity of weakly stable solutions to Majda’s hyperbolic mixed problem
Authors: Secchi Paolo
Published: January 2025

In this paper, we study Majda’s example for stability of mixed problems introduced in [A. Majda, Compressible Fluid Flow and Systems of Conservation Laws in Several Space Variables, Applied Mathematical Sciences, Vol. 53 (Springer Verlag, 1984)]. After some transformation we analyze the stability of the problem by computing the roots of the Kreiss–Lopatinskiĭ determinant and recover the different cases as in Majda [Compressible Fluid Flow and Systems of Conservation Laws in Several Space Variables, Applied Mathematical Sciences, Vol. 53 (Springer Verlag, 1984)]. Then, we focus on the weakly stable case and prove the a priori estimate of the solution. The proof follows by adapting the approach of Coulombel and Secchi [The stability of compressible vortex sheets in two space dimensions, Indiana Univ. Math. J. 53 (2004) 941–1012] for the linear stability of 2D compressible vortex sheets with the simplification introduced by Chen et al. [Linear stability of compressible vortex sheets in two-dimensional elastodynamics, Adv. Math. 311 (2017) 18–60]. Compared to [J.-F. Coulombel and P. Secchi, The stability of compressible vortex sheets in two space dimensions, Indiana Univ. Math. J. 53 (2004) 941–1012], we improve the a priori energy estimate in that the solution is estimated in suitable weighted Sobolev spaces, anisotropic in the frequency space, whose definition reflects the properties of the associated Lopatinskiĭ determinant. Moreover, we show that this a priori energy estimate is optimal. This very simple example appears useful for the comprehension of the method of proof of the a priori estimate, beyond the technicalities of [R. M. Chen, J. Hu and D. Wang, Linear stability of compressible vortex sheets in two-dimensional elastodynamics, Adv. Math. 311 (2017) 18–60; J.-F. Coulombel and P. Secchi, The stability of compressible vortex sheets in two space dimensions, Indiana Univ. Math. J. 53 (2004) 941–1012].
The Impact of Policy Uncertainty and Economic Freedom on Bank Stability: Global Evidence
Authors: Dang Buu Kiem , Anh Hien Nguyen , Pham Thi Van Trinh
Published: January 2025

The objective of this study is to evaluate the impacts of policy uncertainty and economic freedom on the stability of national banking systems worldwide. The research sample includes 165 countries and covers the period from 1997 to 2021. The study employs panel data estimation methods including the fixed effects model, random effects model, Driscoll-Kraay standard errors approach, and system GMM. The findings consistently show that policy uncertainties, including world policy uncertainty, trade policy uncertainty, and global economic policy uncertainty, negatively affect bank stability. Additionally, economic freedom policies can help mitigate the negative impact of policy uncertainty.
Combining Multi-Objective Bayesian Optimization with Reinforcement Learning for TinyML
Authors: Deutel Mark , Kontes Georgios , Mutschler Christopher , Teich Jürgen
Published: January 2025

Deploying deep neural networks (DNNs) on microcontrollers (TinyML) is a common trend to process the increasing amount of sensor data generated at the edge, but in practice, resource and latency constraints make it difficult to find optimal DNN candidates. Neural architecture search (NAS) is an excellent approach to automate this search and can easily be combined with DNN compression techniques commonly used in TinyML. However, many NAS techniques are not only computationally expensive, especially hyperparameter optimization (HPO), but also often focus on optimizing only a single objective, e.g., maximizing accuracy, without considering additional objectives such as memory requirements or computational complexity of a DNN, which are key to making deployment at the edge feasible. In this paper, we propose a novel NAS strategy for TinyML based on multi-objective Bayesian optimization (MOBOpt) and an ensemble of competing parametric policies trained using Augmented Random Search (ARS) reinforcement learning (RL) agents. Our methodology aims at efficiently finding tradeoffs between a DNN’s predictive accuracy, memory requirements on a given target system, and computational complexity. Our experiments show that we consistently outperform existing MOBOpt approaches on different datasets and architectures such as ResNet-18 and MobileNetV3.
Insights from a Career at the Border of Developmental Psychology and Cognitive Neuroscience
Authors: Diamond Adele
Published: January 2025

Much has changed since I started my PhD research in 1980. Neither the field of developmental cognitive neuroscience nor the term “executive functions” existed then. In some ways this piece is backward-looking, such as discussing how our research introduced the importance of the executive function of inhibitory control for cognitive development and that infants and young children are much smarter than we thought. The way our field has queried infants and young children often prevented us from seeing their competencies. That is still too true in studying children from different backgrounds. In other ways, this piece is forward-looking, such as when discussing evidence that the conceptualization of working memory as an executive function and as the key function of dorsolateral prefrontal cortex has been too narrow. It is not just separation in time that must be bridged (traditionally the province of working memory) but also separations in space, and the latter are just as important for cognitive development and just as dependent on the executive function brain network, including dorsolateral prefrontal cortex. It is also forward-looking in discussing the critical importance of motor, social, and emotional development for cognitive development and executive functions, as well as bidirectional relations among these different facets of development. Study of the different aspects of human development are still far too siloed, as are the different fields of science. Examples are provided of how the fields of neuroscience (including neurochemistry and molecular genetics) and child development inform and complement one another. Implications for educators, parents, and researchers are interwoven throughout.
Collagen Extraction From Bigeye Tuna (Thunnus obesus) Bone Byproduct: Process Modeling and Technoeconomic Assessment Using SuperPro Designer
Authors: Shiddiiq Abyan , Yulianti Elly Septia , Gozan Misri , Rahman Siti Fauziyah
Published: January 2025

This study evaluates the potential of utilizing tuna bone byproducts for acid‐soluble collagen (ASC) extraction in Indonesia, targeting the biomedical industry’s growing collagen demand. Through the SuperPro Designer Simulator, the research assesses the economic feasibility of four varying input capacities (50, 100, 500, and 1000 kg). The simulation reveals that the most economical production process occurs with 1000 kg of raw materials, yielding a net present value (NPV) of $3,848,000, an internal rate of return (IRR) of 35.55%, and a payback period (PBP) of 2.16 years. The 1000‐kg scenario emerged as the most economical input capacity due to its ability to adequately cover the substantial initial investment required. This outcome highlights the importance of scale efficiencies and operational optimizations in enhancing profitability, suggesting that large‐scale operations are essential for justifying the significant capital expenditures involved. This project faces significant challenges in the limited availability of raw materials and the current extraction method’s efficiency, which could hinder the feasibility of scaling up production. This study identifies strategic solutions to these challenges by reducing investment through contract and shared manufacturing systems to lower upfront costs and improve the extraction process for higher efficiency and yield. These measures aim to address material scarcity and enhance production method efficacy, making the project more sustainable and economically viable. This study advocates further research and development to optimize the tuna bone byproduct extraction process as a solution to establish a competitive approach for collagen production within Indonesia’s biodiversity‐rich maritime sector.
The Effect of Oral Magnesium Supplement on Postoperative Pain Following Mandibular Third Molar Surgery: A Split‐Mouth Randomized Placebo‐Controlled Trial
Authors: Nimkulrat Sutthipat , Phinyo Phichayut , Powcharoen Warit
Published: January 2025

Objective: This study aimed to evaluate the analgesic efficacy of oral magnesium supplements, administered as an analgesic adjuvant to ibuprofen, on acute postoperative pain within 72 h following mandibular third molar (MTM) surgery.

Materials and Methods: This triple‐blind, placebo‐controlled, split‐mouth randomized study was conducted among 25 patients (50 MTMs), who intended to remove both MTMs. All patients underwent two surgeries separated by an interval of at least 4 weeks. For each surgery period, patients were randomly assigned with either receiving NSAIDs plus oral magnesium supplement (25 MTMs) or NSAIDs plus placebo (25 MTMs) for three days after surgery. The postoperative pain intensity at rest and movement were primarily evaluated at 24 h, postoperatively. Participants were also asked to record pain intensity at 6, 48, and 72 h, postoperatively, rescue analgesic consumption, time to first rescue analgesic, and magnesium‐related adverse events.

Results: The combination of ibuprofen plus oral magnesium supplement significantly decreased pain intensity at rest 24 h, postoperatively, compared to placebo (estimated mean difference −15.08; 95%CI −29.01 to −1.14). However, the pain intensity at rest and movement were similar between groups at other time points. There was no significant difference among groups in terms of rescue analgesic consumption and time to first rescue analgesic. No magnesium‐related adverse event was observed.

Conclusion: The addition of oral magnesium supplement as an analgesic adjuvant to NSAIDs significantly decreased pain intensity at rest 24 h following MTM surgery. Nevertheless, this result might not provide clinically relevant benefits for pain control following MTM surgery.

Trial Registration: ClinicalTrials.gov identifier: TCTR20221003004
Supplementary Figures S1-S8 from Phosphocreatine Promotes Epigenetic Reprogramming to Facilitate Glioblastoma Growth Through Stabilizing BRD2
Authors: Chen Lishu , Qi Qinghui , Jiang Xiaoqing , Wu Jin , Li Yuanyuan , Liu Zhaodan , Cai Yan , Ran Haowen , Zhang Songyang , Zhang Cheng , Wu Huiran , Cao Shuailiang , Mi Lanjuan , Xiao Dake , Huang Haohao , Jiang Shuai , Wu Jiaqi , Li Bohan , Xie Jiong , Qi Ji , Li Fangye , Liang Panpan , Han Qiuying , Wu Min , Zhou Wenchao , Wang Chenhui , Zhang Weina , Jiang Xin , Zhang Kun , Li Huiyan , Zhang Xuemin , Li Ailing , Zhou Tao , Man Jianghong
Published: January 2025

Supplementary Figures S1 shows that GSCs produce high levels of phosphocreatine through upregulating CKB. Supplementary Figures S2 shows that ZEB1 promotes CKB transcription in GSCs. Supplementary Figures S3 shows that knockdown of CKB impedes GBM growth. Supplementary Figures S4 shows that disruption of phosphocreatine production impedes GBM growth. Supplementary Figures S5 shows that cCr treatment shows no side effect on mice. Supplementary Figures S6 shows that phosphocreatine binds to BRD2 and inhibits its ubiquitin mediated proteasomal degradation. Supplementary Figures S7 shows that phosphocreatine promotes chromosome segregation and GSC proliferation through BRD2 mediated transcription. Supplementary Figures S8 shows that disruption of phosphocreatine biosynthesis by cCr improves JQ1 therapeutic efficacy in GBM.
Table 1 from Clinical Proteomics Reveals Vulnerabilities in Noninvasive Breast Ductal Carcinoma and Drives Personalized Treatment Strategies
Authors: Mitsa Georgia , Florianova Livia , Lafleur Josiane , Aguilar-Mahecha Adriana , Zahedi Rene P. , del Rincon Sonia V. , Basik Mark , Borchers Christoph H. , Batist Gerald
Published: January 2025

Overlapping molecules from independent gene expression studies and this proteomic profiling
ХРОМАТОГРАФІЧНЕ ДОСЛІДЖЕННЯ КОМПОНЕНТНОГО СКЛАДУ І ВМІСТУ ФЕНОЛЬНИХ СПОЛУК ПЕРЕСТРІЧУ ГАЙОВОГО (MELAMPYRUM NEMOROSUM L.)
Authors: Reznik V. V. , Grytsyk A. R.
Published: January 2025

Мета роботи. Визначити компонентний склад флавоноїдів, фенолкарбонових кислот і катехінів у траві  перестрічу гайового (Melampyrum nemorosum L.) вітчизняної заготівлі.
Матеріали і методи. Траву M. nemorosum заготовляли у 2022 р. у фазі цвітіння в околицях с. Микитинці Косівського району Івано-Франківської області. Компонентний склад фенолкарбонових кислот, флавоноїдів і катехінів визначали методом високоефективної рідинної хроматографії (ВЕРХ) на рiдинному хроматографi “Agilent Technologies 1200”, який укомплектований проточним вакуумним дегазатором, чотириканальним насосом градієнта низького тиску, автосамплером, термостатом колонок, діодноматричним детектором, з використанням колонок Zorbax SB-С18 та Zorbax SB-Aq.
Результати й обговорення. Методом ВЕРХ у траві M. nemorosum ідентифіковано та встановлено їх кількісний вміст 9 флавоноїдів (рутин, кверцетин-3-β-глюкозид, нарингін, неогесперидин, кверцетин, нарінгенін, апігенін, рамнетин, кемпферол), серед яких 5 флавонолів, 3 флавонони і 1 флавон. Крім того, було виявлено 3 катехінові сполуки (катехін, епікатехін, та галокатехін), а також 9 фенолкарбонових кислот (гідроксифенілоцтова, хлорогенова, кофейна, сирінгова, бензойна, n-кумарова, транс-ферулова, синапова, транс-корична) .
Висновки. 1. За допомогою ВЕРХ-аналізу визначено компонентний склад флавоноїдів, фенолкарбонових кислот і катехінів трави M. nemorosum, яку заготовлено в Україні. 2. Серед сполук флавоноїдної природи переважали рутин (3388,58 мкг/г), кверцетин (716,44 мкг/г), нарингін (679,21 мкг/г), рамнетин (662,69 мкг/г) та неогесперидин (588,90 мкг/г). Серед фенолкарбонових кислот домінувала бензойна кислота (948,54 мкг/г), а серед катехінів – епікатехін (415,71 мкг/г). 3. Перспективним напрямком подальших досліджень є вивчення компонентного складу фенольних сполук трави M. nemorosum, які заготовлено у різних регіонах України.
ДОКІНГ ТА КВАНТОВО-ХІМІЧНІ ДОСЛІДЖЕННЯ ПРОТИПУХЛИННИХ МЕХАНІЗМІВ ПОХІДНИХ МОНОХЛОРООЦТОВОЇ ТА ДИХЛОРООЦТОВОЇ КИСЛОТ
Authors: Havryshchuk L. M. , Melnyk D. O. , Khylyuk D. V. , Horishny V. Ya. , Lesyk R. B.
Published: January 2025

Мета. Це дослідження спрямоване на проведення порівняльного квантово-хімічного аналізу похідних монохлорооцтової (МХК) та дихлорооцтової (ДХК) кислот, їх реакційної здатності при взаємодії з білковими мішенями та визначення молекулярних механізмів, що лежать в основі їх біологічної активності.
Матеріали та методи. Під час дослідження використовувалися квантово-хімічні розрахунки та молекулярний докінг для дослідження електронних властивостей і біологічних взаємодій синтезованих сполук. Усі структури були оптимізовані за допомогою DFT (B3LYP/6-311++G(d,p)) у Gaussian 09. Результати квантово-хімічних розрахунків були візуалізовані за допомогою GaussView 5.0.8. Молекулярний докінг передбачав моделювання кон’югатів глутатіон-хлороацетамід при фізіологічному pH, мінімізацію структур у програмному забезпеченні Avogadro та аналіз взаємодії з GST (PDB ID: 11GS) за допомогою алгоритму FlexX у LeadIT. Взаємодії прив’язування візуалізувалися за допомогою BIOVIA Discovery Studio з параметрами стикування, перевіреними за допомогою порівняння RMSD з експериментальними даними.
Результати і обговорення. Аналіз граничних молекулярних орбіталей та дескрипторів пов’язаних з їх енергією показав збільшення активності МХК зі збільшенням їх електрофільності. Хоча на окремих лініях результати, що випадали з даної залежності можуть бути пов’язані з особливостями їх структури. Аналіз молекулярного електростатичного потенціалу показав наявність стеричних перешкод зумовлених великими розмірами атомів хлору, які зменшують можливості для атаки МХК. Зміна енергії Гіббса реакції заміщення теж вказує на легший перебіг заміщення в МХК. Результати молекулярного докінгу показали можливість ефективного ковалентного зв’язування з глутатіон S-трансферазою як МХК так і ДХК. Проте ще однією причиною зменшення активності є можливість гідролізу ДХК-аддукту з глутатіоном, оскільки досліджені сполуки не перешкоджають доступу води при зв’язуванні в активному центрі.
Висновки. Зменшення реакційної здатності ДХА в порівнянні з аналогами МХА пов’язані зі стеричними утрудненнями, та впливом атома хлору в перехідному стані. Загалом нижча біологічної активність ДХА пов’язана як зі зменшенням їх реакційної здатності так і з можливістю до гідролізу їх продуктів приєднання до залишків цистеїну. Отримані результати можуть стати основою для створення нових таргетних препаратів з підвищеною ефективністю та селективністю.
СИНТЕЗ ПОХІДНИХ 6-АРИЛ/ГЕТЕРИЛТРИАЗОЛО[3,4-b][1,3,4]ТІАДІАЗОЛІВ ТА ДОСЛІДЖЕННЯ ЇХ ПРОТИМІКРОБНОЇ АКТИВНОСТІ
Authors: Myrko I. I.
Published: January 2025

Мета роботи. Синтез нових 6-арил/гетерилтриазоло[3,4-b][1,3,4]тіадіазолів та дослідження їх антибактеріальної та протигрибкової активності.
Матеріали і методи. Органічний синтез, елементний аналіз, 1Н ЯМР спектроскопія, фармакологічний скринінг, докінг.
Результати й обговорення. Здійснено синтез похідних 6-феніл/піридил-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазолу. Досліджено їх протимікробну активність. Встановлено, що 3-(4-хлоробензил)-6-феніл-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазол 2 володіє високою антибактеріальною активністю по відношенню до S. aureus ATCC 43300, а 3-(4-хлор/метоксибензил)-6-піридин-3-іл-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазоли 3, 4a, b ефективно інгібують ріст штаму грибків C. Neoformans ATCC 208821. Використовуючи докінгові дослідження сполук, що проявили протигрибкову активність, визначено величину енергії зв’язування, конформаційне розташування лігандів в активному центрі ланостерол 14α-деметилази, а також природу амінокислотних залишків і тип взаємодії, який реалізується.
Висновки. Розроблено метод синтезу похідних 6-феніл/піридил-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазолу. Ідентифіковано сполуки, що володіють високою протимікробною активністю по відношенню до штамів S. aureus ATCC 43300 та C. Neoformans ATCC 208821.
Lateral Atrial Expression Patterns Provide Insights into Local Transcription Disequilibrium Contributing to Disease Susceptibility
Authors: Isaacs Aaron , Zeemering Stef , Winters Joris , Batlle Montserrat , Bidar Elham , Boukens Bas , Casadei Barbara , Chua Winnie , Crijns Harry J.G.M. , Fabritz Larissa , Guasch Eduard , Hatem Stephane N. , Hermans Ben , Kääb Stefan , Kawczynski Michal , Maesen Bart , Maessen Jos , Mont Lluis , Sinner Moritz F. , Wakili Reza , Verheule Sander , Kirchhof Paulus , Schotten Ulrich , Stoll Monika
Published: January 2025

BACKGROUND:

Transcriptional dysregulation, possibly affected by genetic variation, contributes to disease etiology. Due to dissimilarities in development, function, and remodeling during disease progression, transcriptional differences between the left atrium (LA) and right atrium (RA) may provide insight into diseases such as atrial fibrillation.

METHODS:

Lateral differences in atrial transcription were evaluated in CATCH ME (Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly) using a 2-stage discovery and replication design. The design took advantage of the availability of 32 paired samples, for which both LA and RA tissue were obtained, as a discovery cohort, and 98 LA and 69 RA unpaired samples utilized as a replication cohort.

RESULTS:

A total of 714 transcripts were identified and replicated as differentially expressed (DE) between LA and RA, as well as 98 exons in 55 genes. Approximately 50% of DE transcripts were colocated with another frequently correlated DE transcript (
P
FDR
≤0.05 for 579 regions). These “transcription disequilibrium” blocks contained examples including side-specific differential exon usage, such as the
PITX2
locus, where
ENPEP
showed evidence of differential exon usage. Analysis of this region in conjunction with
BMP10
identified rs9790621 as associated with
ENPEP
transcription in LA, while rs7687878 was associated with
BMP10
expression in RA. In RA,
BMP10
and
ENPEP
were strongly correlated in noncarriers, which was attenuated in risk-allele carriers, where
BMP10
and
PITX2
expression were strongly correlated.

CONCLUSIONS:

These results significantly expand knowledge of the intricate, tissue-specific transcriptional landscape in human atria, including DE transcripts and side-specific isoform expression. Furthermore, they suggest the existence of blocks of transcription disequilibrium influenced by genetics.
Structural and Functional Characterization of the Aorta in Hypertrophic Obstructive Cardiomyopathy
Authors: Ibrahim Ayman M. , Roshdy Mohamed , Latif Najma , Elsawy Amr , Sarathchandra Padmini , Hosny Mohammed , Hekal Soha , Attia Ahmed , Elmozy Wesam , Elaithy Amany , Elguindy Ahmed , Afifi Ahmed , Aguib Yasmine , Yacoub Magdi
Published: January 2025

BACKGROUND:

Changes in the phenotype and genotype in hypertrophic cardiomyopathy (HCM) are thought to involve the myocardium as well as extracardiac tissues. Here, we describe the structural and functional changes in the ascending aorta of obstructive patients with HCM.

METHODS:

Changes in the aortic wall were studied in a cohort of 101 consecutive patients with HCM undergoing myectomy and 9 normal controls. Biopsies were examined histologically, immunohistochemically, and by electron microscopy. Changes in protein expression were quantified using morphometry and Western blotting. Pulse wave velocity was measured using cardiac magnetic resonance in 85 patients with HCM and compared with 117 age-matched normal controls.

RESULTS:

In HCM, the number of medial lamellar units was significantly decreased, associated with an increase in interlamellar distance and aortic wall thickness, as compared with controls. Electron microscopy showed an altered lamellar structure with disorientation of elastin fibers from the circumferential direction. There was a significant decrease in collagen content, α-smooth muscle actin, smooth muscle myosin, smooth muscle 22 and integrin β1, as well as a significant increase in calponin and caspase-3. Fibulins 1, 2, and 5 showed reduced expression in HCM-aortic biopsies. Functionally, pulse wave velocity was significantly higher in patients with HCM compared with healthy controls, with an association between higher pulse wave velocity and more severe molecular and clinical parameters.

CONCLUSIONS:

The increased wall stiffness observed in the aortas of obstructive patients with HCM is associated with structural alterations in the medial lamellar unit, including changes in smooth muscle cells and the extracellular matrix, indicating potential arterial dysfunction.
New additions and further records of non-native Coleoptera in Romania
Authors: DRĂGHICI ANDREEA-CĂTĂLINA , PINTILIOAIE ALEXANDRU-MIHAI , MURARIU DUMITRU , MANCI COSMIN-OVIDIU , RUZZIER ENRICO
Published: January 2025

This report details the discovery of five new non-native Coleoptera species for the Romanian fauna: Cis chinensis Lawrence, 1991 (Ciidae), Latheticus oryzae C.O. Waterhouse, 1880, Palorus subdepressus (Wollaston, 1864), Tribolium destructor Uyttenboogaart, 1933 (Tenebrionidae), and Litargus balteatus LeConte, 1856 (Mycetophagidae). Furthermore, additional occurrences for 19 species whose data were deficient were provided. The identification of unrecorded alien species in a natural setting indicates that they are well established and warrant further monitoring to determine their current distribution at the national level and potential impact on the environment and human activities. This indicates the current extent of our understanding of the diversity of non-native coleopterans in Romania and emphasizes the necessity of further investigation into this group, with a particular focus on those species with the potential to become invasive.
A revision of the taxonomic status of Xestotrogus Reitter, 1902 and related taxa, with the description of a new species from Iraqi Kurdistan (Coleoptera: Scarabaeidae: Melolonthinae)
Authors: ULIANA MARCO , KHUDHUR FARHAD A.
Published: January 2025

An undescribed species of Rhizotrogini recently collected in Iraqi Kurdistan evidenced the unclear diagnosis of the genus-level taxa to which it could be attributed, prompting their revision. As a result, the currently monotypic subgenus Xestotrogus Reitter, 1902 is removed from subgeneric rank under the genus Xanthotrogus Reitter, 1902, treated as a valid genus and re-diagnosed. Cyprotrogus Nikolajev, 2004, also monotypic, is recognized as its junior subjective synonym. The new species, the third known of the genus, is then described as Xestotrogus sagrmaticus Uliana & Khudhur, new species. External morphology, aedeagus and endophallus of each species are illustrated.
Ocean-Land Teleconnections and Chaotic Atmospheric Variability
Authors: Koster Randal D. , Schubert Siegfried D. , DeAngelis Anthony M. , Chang Yehui , Scaife Adam A.
Published: January 2025

A large ensemble of multidecadal atmospheric general circulation model (AGCM) simulations is examined to determine a quantity central to the model’s potential predictability – the fraction of the simulated monthly air temperature (T2M) variability that is tied to the imposed sea surface temperature (SST) boundary conditions as opposed to the background atmospheric noise. Combining this information with ensemble simulation data from other AGCMs in turn allows an inter-model comparison of two separate quantities: model potential T2M predictability and the underlying (in the absence of noise) teleconnections between SSTs and continental T2M. To a large extent, the models tend to agree with each other regarding both – they all show, for example, the expected highest predictability in the Tropics as well as low potential predictability in Central Asia, and, particularly for DJF and MAM, they show very similar ocean-land teleconnections throughout the Americas. However, the models do show some differences in teleconnections, indicating room for model improvement that could, in principle, lead to benefits for long-term prediction. Importantly, by combining the model results with observational temperature data, we provide a new estimation of real-world predictability, a property of Nature that is not directly observable. The latter results suggest, with caveats, that for monthly T2M in the Tropics, AGCMs tend to overestimate the ratio of predictable variance to noise-derived variance.
Student Voices About Educational Inequalities and Justice: Problematizing a Neoliberal Education System
Authors: Chan Yau Yu , Tang Hei-hang Hayes
Published: January 2025

Rising educational inequality is considered as one pressing social problem in many national education systems. There is limited existing literature that examines how youth from different social backgrounds perceive and consider social inequalities and “justice.” This study addresses this research gap by probing the perspectives of different young peoplewho have experienced the competitive Hong Kong education system through qualitative interviews. The findings revealed that youth, despite facing challenges, adopted a relatively “positive” mindset by focusing on what they could change rather than being fatalistic about social reproduction. Both middle-class and working-class young people in the sample did not view differences in family capital as inequalities but believed in education’s role in promoting social mobility within a meritocratic system. The study also suggests redefining “life successes” from traditional measures of status and wealth to the perspectives of students that value job and life satisfaction. Critical analyses that highlight the embedded neoliberalism were conducted on these problematic findings, and the implications for educational policies were discussed.