bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying neural network structures explained by personality traits: combining unsupervised and supervised machine learning techniques in translational validity assessment
Authors: Stoyanova Kristina , Stoyanov Drozdstoy , Khorev Vladimir , Kurkin Semen
Published: December 2024

There have been studies previously the neurobiological underpinnings of personality traits in various paradigms such as psychobiological theory and Eysenck’s model as well as five-factor model. However, there are limited results in terms of co-clustering of the functional connectivity as measured by functional MRI, and personality profiles. In the present study, we have analyzed resting-state connectivity networks and character type with the Lowen bioenergetic test in 66 healthy subjects. There have been identified direct correspondences between network metrics such as eigenvector centrality (EC), clustering coefficient (CC), node strength (NS) and specific personality characteristics. Specifically, N Acc L and OFCmed were associated with oral and masochistic traits in terms of EC and CC, while Insula R is associated with oral traits in terms of NS and EC. It is noteworthy that we observed significant correlations between individual items and node measures in specific regions, suggesting a more targeted relationship. However, the more relevant finding is the correlation between metrics (NS, CC, and EC) and overall traits. A hierarchical clustering algorithm (agglomerative clustering, an unsupervised machine learning technique) and principal component analysis were applied, where we identified three prominent principal components that cumulatively explain 76% of the psychometric data. Furthermore, we managed to cluster the network metrics (by unsupervised clustering) to explore whether neural connectivity patterns could be grouped based on combined average network metrics and psychometric data (global and local efficiencies, node strength, eigenvector centrality, and node strength). We identified three principal components, where the cumulative amount of explained data reaches 99%. The correspondence between network measures (CC and NS) and predictors (responses to Lowen’s items) is 62% predicted with a precision of 90%.
Neural network-based thermal analysis of stratified nanostructured materials with couple-stress nanofluid flow and gyrotactic microorganisms under exponential heating/cooling conditions
Authors: Jubair Sidra , Ali Bilal , Siddiqui Md Irfanul Haque
Published: December 2024

The heterogeneous fluid model is expressed for the nanofluid flow to study the significance of the Fourier’s and Fick’s laws. The magnetohydrodynamics couple-stress bioconvective nanofluid flow is considered across an extending surface with the effect of exponential heat source/sink and stratified boundary conditions. The solid nanoparticulates and concentrations of motile microorganisms are added to the nonlinear system of differential equations conveying the non-Newtonian nanoliquid flow model. Moreover, the combined effect of the heat flux and thermal radiation is also evaluated. The similarity transformations are employed to transfigure the system of partial differential equations into the lowest order of ordinary differential equations. The Artificial Neural Network Levenberg Marquardt Back-propagation optimization algorithm is employed to solve these equations. To authenticate the outcomes, the dataset is formed using the MATLAB package “bvp4c”. The dataset is created for diverse circumstances of flow factors, as well as validation and testing of the Artificial Neural Network. The accuracy of the model is estimated through numerous statistical tools (histogram, curve fitting, regression measures, and performance plots). The outcomes are presented through the table and figures. It has been noticed that the couple-stress nanofluid flow declines with the influence of magnetic field and mixed convection. The couple-stress nanofluid temperature augments with the enhancement of the thermophoresis effect, buoyancy ratio factor, Rayleigh number, and thermal radiation. Moreover, the concentration curve lessens under the impact of the Lewis number while enriched with the outcome of the concentration stratification parameter. The absolute error of reference and targeted date is attained within 10[Formula: see text]–10[Formula: see text] that proves the exceptional precision of the results.
Framework for the Generation of Tourist Experiences
Authors: Rueda Caicedo Lyda Jovanna , Bermón Angarita Leonardo , López Trujillo Marcelo
Published: December 2024

The tourism sector requires tools that allow for the creation of tourist experiences, based on the knowledge gleaned from service encounters between frontline employees and tourists. The objective of this study is to propose a framework, based on knowledge management, for the generation of tourist experiences. The study was carried out in three stages: first, a literature review related to tourist experiences, knowledge management, service encounters, and frontline employees was conducted. Next, a BPMN-based framework was designed. Finally, the proposed framework was validated through surveys with tourism experts from a cluster of tourism companies. The framework provides conceptual guidelines with useful worksheets for entrepreneurs that form part of tourism clusters, with which to generate tourist experiences.
Prioritizing Speech Test Cases
Authors: Yang Zhou , Shi Jieke , Asyrofi Muhammad Hilmi , Xu Bowen , Zhou Xin , Han DongGyun , Lo David
Published: December 2024

As automated speech recognition (ASR) systems gain widespread acceptance, there is a pressing need to rigorously test and enhance their performance. Nonetheless, the process of collecting and executing speech test cases is typically both costly and time-consuming. This presents a compelling case for the strategic prioritization of speech test cases, which consist of a piece of
audio
and the corresponding
reference text
. The central question we address is:
In what sequence should speech test cases be collected and executed to identify the maximum number of errors at the earliest stage?
In this study, we introduce
Prophet
(
PR
i
O
ritising s
P
eec
H
t
E
s
T
cases), a tool designed to predict the likelihood that speech test cases will identify errors. Consequently,
Prophet
can assess and prioritize these test cases without having to run the ASR system, facilitating large-scale analysis. Our evaluation encompasses

\(6\)

distinct prioritization techniques across

\(3\)

ASR systems and

\(12\)

datasets. When constrained by the same test budget, our approach identified

\(15.44\%\)

more misrecognized words than the leading the state-of-the-art method. We select top-ranked speech test cases from the prioritized list to fine-tune ASR systems and analyze how our approach can improve the ASR system performance. Statistical evaluations show that our method delivers a considerably higher performance boost for ASR systems compared to established baseline techniques. Moreover, our correlation analysis confirms that fine-tuning an ASR system with a dataset where the model initially underperforms tends to yield greater performance improvements.
Browsing Linked Open Data in Cultural Heritage: A Shareable Visual Configuration Approach
Authors: Candela Gustavo
Published: December 2024

Over the last decade Cultural Heritage (CH) organisations have been exploring new ways to make their content available and browsable using the Semantic Web and Linked Open Data (LOD). The objective of the present study was to introduce a framework to browse LOD in CH institutions using a shareable visual configuration approach. The framework was then applied to a selection of LOD repositories. Common features and best practices were identified. A detailed analysis, that can be useful for organisations interested in publishing and explore their datasets, is provided. Open issues requiring further work are outlined.
On Collaboration and Automation in the Context of Threat Detection and Response with Privacy-Preserving Features
Authors: Nitz Lasse , Akbari Gurabi Mehdi , Cermak Milan , Zadnik Martin , Karpuk David , Drichel Arthur , Schäfer Sebastian , Holmes Benedikt , Mandal Avikarsha
Published: December 2024

Organizations and their security operation centers often struggle to detect and respond effectively to an extensive quantity of ever-evolving cyberattacks. While collaboration, such as threat intelligence sharing between security teams, and response automation are often discussed in the cybersecurity community, issues like data sensitivity and confidence in detection may hinder their adoption. This work investigates the potentials and challenges of collaboration and automation to enhance incident response processes. We propose a reference architecture for data sharing in threat detection and response, aiming to boost collaborative and automated efforts across organizations while also considering privacy-preserving features. To address these challenges and potentials, we discuss how such a framework could enhance current response processes within and between organizations, validated with results in local attack detection, incident response, and data sharing.
In Situ Growth of Ag-ZnO Nanorods on Graphitic Carbon Nitride for SERS Detection of Rhodamine 6G
Authors: Jagannathan Mohanraj , Cho Sungbo
Published: December 2024

Sensing azo dyes has received significant attention due to their environmental impact and harm to human health. A cellulose-paper-based surface-enhanced Raman scattering (SERS) substrate with a hierarchical Ag-ZnO@GCN nanorod composite was successfully prepared by hydrothermal method. The intended hierarchical nanocomposite was prepared using a facile and economically feasible method. The optical, functional group, structural profile, phase formation, and surface morphology of the prepared AZCN-80, AZCN-120, and AZCN-160 were characterized using UV–vis, Fourier transform infrared spectroscopy, Raman, X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray analysis. The physicochemical characterization results demonstrated that this ubiquitous nanorod composite considerably enhanced the SERS sensing performance for detecting harmful organic molecules, specifically rhodamine 6 G (R6G). In addition, the fabricated paper-based AZCN-160 substrate exhibited good linearity with a range of 10–5 to 10–15 M, with an R2 value of 0.96 compared to that of AZCN-80 and AZCN-120. Therefore, the paper-based SERS substrate developed in this study is a “proof-of-concept” strategy for designing and constructing efficient and effective molecular sensors for real-time sensing and monitoring.
Advancements and Challenges in Electrode and Electrolyte Materials for Proton Exchange Membrane Fuel Cells: A Comprehensive Review
Authors: Punyawudho Konlayutt , Pugalenthi Mariyappan Raja , Shu Xiong , Kaneco Satoshi , Wongwuttanasatian Tanakorn , Suksri Amnart , Payattikul Laksamee
Published: December 2024

Proton exchange membrane fuel cell (PEMFC) technology is vital for a cleaner and more sustainable future, offering high efficiency, quiet operation, fuel flexibility, and zero‐emission energy production with versatile applications. The drawbacks of PEMFC include its high cost, susceptibility to degradation, and challenges in scaling up production for commercial use. The gas diffusion layer (GDL), the catalyst layer (CL), and the polymer electrolyte are all very important parts of fuel cell technology. Through the optimization of these components, researchers may strive to develop fuel cells that are more efficient, cost‐effective, durable, and high‐performing, therefore enabling the provision of clean and sustainable energy. In this article, we have reviewed the various components of GDL, CL, and polymer electrolyte materials and their impact on the performance of PEMFC. The various characteristics of the GDL such as porosity, hydrophobic/hydrophilic, polytetrafluoroethylene (PTFE), and carbon materials, are fully discussed in this review article. These topics also cover the CL’s properties, including the catalyst, carbon support, ionomer, and solvent. Explore the different polymer electrolytes that are based on aliphatic Nafion and aromatic hydrocarbons‐based membrane. Finally, this review paper gives suggestions for the way forward in regard to creating electrodes and electrolytes for PEMFCs that are cost‐effective, efficient, and durable.
The Intricate Mechanisms of Functional Foods Oyster Mushroom and Fenugreek on Type 2 Diabetic Animal Model
Authors: Razon Arafat Hassan , Alauddin Md. , Farzana Nisat , Mazumdar Sanaullah , Amin Md. Ruhul , Tusher Md. Mahedi Hassan , Asrafuzzaman Md. , Hasan Nahid , Rahman Mahfuzur , Saiedullah Muhammad , Rokeya Begum , Faruque Md. Omar
Published: December 2024

Mushrooms and fenugreek are widely used to reduce hyperglycemia, and fenugreek is also used as a culinary ingredient to enhance flavor and aroma. This study is aimed at investigating the underlying mechanisms of the hypoglycemic effects of mushrooms and fenugreek in a Type 2 diabetic rat model. Adenosine monophosphate (AMP)–activated protein kinase (AMPK) functions to reduce hyperglycemia through insulin‐independent pathways and protects beta‐cells. Diabetic model rats were administered standard diets supplemented with 5% oyster mushroom powder (mushroom‐treated (MT) group) and 5% fenugreek seed powder (fenugreek‐treated (FT) group) for 8 weeks. The results showed improvements in both glycemic and lipid profiles, with both oyster mushroom and fenugreek enhancing the phosphorylation of AMPK in muscle tissue. However, no effect on insulin secretion was observed. These findings suggest that both substances reduce hyperglycemia through an insulin‐independent pathway. In silico analysis of both mushroom and fenugreek seed extracts revealed bioactive compounds having a strong binding affinity to α‐glucosidase, which suggests mushroom and fenugreek supplements might control postprandial blood glucose levels.
HBV Remodels PP2A Complexes to Rewire Kinase Signaling in Hepatocellular Carcinoma
Authors: Turnham Rigney E. , Pitea Adriana , Jang Gwendolyn M. , Xu Zhong , Lim Huat Chye , Choi Alex L. , Von Dollen John , Levin Rebecca S. , Webber James T. , McCarthy Elizabeth , Hu Junjie , Li Xiaolei , Che Li , Singh Ananya , Yoon Alex , Chan Gary K.L. , Kelley Robin K. , Swaney Danielle L. , Zhang Wei , Bandyopadhyay Sourav , Theis Fabian J. , Eckhardt Manon , Chen Xin , Shokat Kevan M. , Ideker Trey , Krogan Nevan J. , Gordan John D.
Published: December 2024

Hepatitis B virus (HBV) infections promote liver cancer initiation by inducing inflammation and cellular stress. Despite a primarily indirect effect on oncogenesis, HBV is associated with a recurrent genomic phenotype in hepatocellular carcinoma (HCC), suggesting that it impacts the biology of established HCC. Characterization of the interaction of HBV with host proteins and the mechanistic contributions of HBV to HCC initiation and maintenance could provide insights into HCC biology and uncover therapeutic vulnerabilities. In this study, we used affinity purification mass spectrometry to comprehensively map a network of 145 physical interactions between HBV and human proteins in HCC. A subset of the host factors targeted by HBV proteins were preferentially mutated in non–HBV-associated HCC, suggesting that their interaction with HBV influences HCC biology. HBV interacted with proteins involved in mRNA splicing, mitogenic signaling, and DNA repair, with the latter set interacting with the HBV oncoprotein X (HBx). HBx remodeled the PP2A phosphatase complex by excluding striatin regulatory subunits from the PP2A holoenzyme, and the HBx effects on PP2A caused Hippo kinase activation. In parallel, HBx activated mTOR complex 2, which can prevent YAP degradation. mTOR complex 2–mediated upregulation of YAP was observed in human HCC specimens and mouse HCC models and could be targeted with mTOR kinase inhibitors. Thus, HBV interaction with host proteins rewires HCC signaling rather than directly activating mitogenic pathways, providing an alternative paradigm for the cellular effects of a tumor-promoting virus.

Significance: Integrative proteomic and genomic analysis of HBV/host interactions illuminated modifiers of hepatocellular carcinoma behavior and key signaling mechanisms in advanced disease, which suggested that HBV may have therapeutically actionable effects.
Adenosine Uptake through the Nucleoside Transporter ENT1 Suppresses Antitumor Immunity and T-cell Pyrimidine Synthesis
Authors: Allard David , Cormery Jeanne , Bricha Salma , Fuselier Camille , Abbas Aghababazadeh Farnoosh , Giraud Lucie , Skora Emma , Haibe-Kains Benjamin , Stagg John
Published: December 2024

Immunosuppression by adenosine is an important cancer immune checkpoint. Extracellular adenosine signals through specific receptors and can be transported across the cell membrane through nucleoside transporters. Although adenosine receptors are well-known to regulate tumor immunity, the impact of adenosine transporters remains unexplored. In this study, we investigated the effect on tumor immunity of equilibrative nucleoside transporter-1 (ENT1), the major regulator of extracellular adenosine concentrations. Blocking or deleting host ENT1 significantly enhanced CD8+ T-cell–dependent antitumor responses. Tumors inoculated into ENT1-deficient mice showed increased infiltration of effector CD8+ T cells with an enhanced cytotoxic transcriptomic profile and significant upregulation of granzyme B, IFNγ, IL2, TNFα, and CXCL10. ENT1 deficiency was further associated with decreased tumor-infiltrating T regulatory cells and CD206high macrophages and suppressed CCL17 production. ENT1 deficiency notably potentiated the therapeutic activity of PD-1 blockade. T cells upregulated ENT1 upon activation, and blocking ENT1 enhanced their function when cocultured with cognate antigen/HLA-matched melanoma cells. Mechanistically, ENT1-mediated adenosine uptake inhibited the activity of phosphoribosyl pyrophosphate synthetase in activated T cells, thereby suppressing production of uridine 5′-monophosphate and its derivatives required for DNA and RNA synthesis. In summary, this study identified ENT1-mediated adenosine uptake as an important mechanism of adenosine-mediated immunosuppression and pyrimidine starvation that can be targeted to enhance antitumor T-cell responses.

Significance: ENT1 is a potential therapeutic target to overcome immunosuppression induced by extracellular adenosine and to increase the activity of PD-1 blockade.
Imlunestrant Is an Oral, Brain-Penetrant Selective Estrogen Receptor Degrader with Potent Antitumor Activity in ESR1 Wild-Type and Mutant Breast Cancer
Authors: Bhagwat Shripad V. , Mur Cecilia , Vandekopple Matthew , Zhao Baohui , Shen Weihua , Marugán Carlos , Capen Andrew , Kindler Lisa , Stephens Jennifer R. , Huber Lysiane , Castanares Mark A. , Garcia-Tapia David , Cohen Jeff D. , Bastian Jolie , Mattioni Brian , Yuen Eunice , Baker Thomas K. , Rodriguez Cruz Vivian , Fei Dongling , Manro Jason R. , Pulliam Nicholas , Dowless Michele S. , Ortiz Ruiz Maria Jesus , Yu Chunping , Puca Loredana , Klippel Anke , Bacchion Francesca , Ismail-Khan Roohi , Rodrik-Outmezguine Vanessa , Peng Sheng-Bin , Lallena María Jose , Gong Xueqian , de Dios Alfonso
Published: December 2024

Targeting of the estrogen receptor (ER) by antiestrogens is the standard of care for patients with ER+ HER2− advanced/metastatic breast cancer. Although antiestrogens that degrade ERα (fulvestrant) or block estrogen production (aromatase inhibitors) have improved patient outcomes, clinically important challenges remain related to drug administration, limited bioavailability, lack of brain exposure, and acquired resistance due to ESR1 mutations. These limitations indicate a need for more robust ER-targeted therapies. Here, we discovered and characterized imlunestrant, a next-generation potent, brain-penetrant oral selective ER degrader. Imlunestrant degraded ERα and decreased ERα-mediated gene expression both in vitro and in vivo. Cell proliferation and tumor growth in ESR1 wild-type (WT) and mutant models were significantly inhibited by imlunestrant. Combining imlunestrant with abemaciclib (CDK4/6 inhibitor), alpelisib (PI3K inhibitor), or everolimus (mTOR inhibitor) further enhanced tumor growth inhibition, regardless of ESR1 mutational status. In an ER+ breast cancer intracranial tumor model, imlunestrant prolonged survival compared with vehicle or alternative selective ER degrader therapies. Together, these findings support the potential of imlunestrant to degrade ERα and suppress the growth of ESR1-WT and mutant breast cancer, including brain metastatic tumors.

Significance: Imlunestrant, a next-generation, brain-penetrant oral ERα degrader, displays potent activity in ESR1 wild-type and mutant breast cancer, enhances combination activity with standard-of-care agents, and inhibits growth of ER+ intracranial tumors.
Abstract A008: Evaluation of natural and synthetic compounds on epithelial to mesenchymal transition in triple negative breast cancer
Authors: Faruk Asef , Patel Saloni , Hallak Ramez , Flaherty Patrick , Cavanaugh Jane
Published: December 2024

Epithelial to mesenchymal transition (EMT) is a biological process through which epithelial cells undergo cytoskeletal changes and transform into a mesenchymal phenotype. This phenotypical transformation leads to enhanced migratory capabilities and increased resistance to apoptosis and drug therapies. The EMT characterized in part by an increase in vimentin, a mesenchymal marker, and a decrease in E-cadherin, an epithelial marker, plays a significant role in cancer metastasis and progression. The MEK5/ERK5 pathway is essential in regulating cell survival, proliferation, and migration. Inhibition of the MEK5/ERK5 pathway by small molecule inhibitors decreases cellular proliferation and impedes migration of cancer cells, including triple negative breast cancer (TNBCs) cells. A type III allosteric inhibitor of MEK5 designed by our collaborators reverses the EMT and induces a mesenchymal to epithelial transition (MET). Using a TNBC cell line, MDA-MB-231, genetically engineered with RFP tagged vimentin, we established a cellular assay to evaluate analogues of our lead type III inhibitor to further investigate the role of the MEK5-ERK pathway in the EMT, design optimal compounds that induce an MET, and explore structure-activity relationships for kinase inhibition. This research will help identify targets for EMT and optimize compound modification to improve potency and efficiency.

Citation Format: Asef Faruk, Saloni Patel, Ramez Hallak, Patrick Flaherty, Jane Cavanaugh. Evaluation of natural and synthetic compounds on epithelial to mesenchymal transition in triple negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A008.
Abstract A013: Prioritization of Eleven-Nineteen-Leukemia (ENL) inhibitors as orally available drug candidates for acute myeloid leukemia
Authors: Liu Wenshe R. , Guo Xuejiao , Alta Sandeep , Xu Shiqing
Published: December 2024

Acute myeloid leukemia (AML) is the second most prevalent and fatal form of leukemia. The growth of AML cells harboring oncogenic MLL rearrangements relies on The YEATS domain-containing protein ENL. Many small molecule inhibitors targeting ENL have been developed. To prioritize these inhibitors for in vivo studies, a NanoBRET system was introduced to evaluate their cellular permeability and potency. This screening identified Inhibitor 13 as a promising candidate. This inhibitor has remarkable metabolic stability and potent anti-proliferative effects on MLL-fusion leukemia cell lines. In AML-xenografted mice, Inhibitor 13 significantly improved survival. Subsequent optimization efforts led to the development of SR-C-107 (R), which exhibited strong activity against AML both at the cellular level (CC50 (MOLM-13): 1.25 ± 0.18 μM; CC50 (MV4-11): 0.81 ± 0.15 μM) and in vivo. These findings establish SR-C-107 (R) as a compelling candidate for AML treatment and lay the groundwork for the development of next-generation AML inhibitors.

Citation Format: Wenshe R. Liu, Xuejiao Guo, Sandeep Alta, Shiqing Xu. Prioritization of Eleven-Nineteen-Leukemia (ENL) inhibitors as orally available drug candidates for acute myeloid leukemia. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A013
Abstract IA006: Progress, pitfalls and promise: the journey to effective and well tolerated DNA damage response inhibitor combinations in the clinic
Authors: Yap Timothy A.
Published: December 2024

A mounting body of evidence now indicates that poly(ADP-ribose) polymerase (PARP) inhibitors have the potential to be used as a foundation for both monotherapy and combination strategies across a wide spectrum of molecular backgrounds and tumor types. There are multiple promising combination therapeutic strategies, such as those with other DNA damage response (DDR) inhibitors such as ATR inhibitors, immune checkpoint inhibitors, and non-DDR-targeted agents that induce "chemical BRCAness". Despite promising efficacy data, several of the combinations have been hampered by supra-additive toxicities, restricting the combination of full monotherapy doses and schedules of component drugs. I will discuss the progress, pitfalls and promise of different classes of DNA damage response (DDR) inhibitor combinations in the clinic, and discuss potential clinical strategies to develop effective and well tolerated combinations to target PARP inhibitor resistance and to widen the application of DDR agents beyond approved indications

Citation Format: Timothy A. Progress, pitfalls and promise: the journey to effective and well tolerated DNA damage response inhibitor combinations in the clinic. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA006
Abstract IA009: An integrative approach to nanomedicine: Leveraging new tools to advance drug delivery
Authors: Boehnke Natalie
Published: December 2024

In the era of personalized cancer medicine, therapeutics are becoming increasingly complex, requiring advanced delivery systems, such as nanoparticles, to ensure their safety and efficacy. While current formulation strategies focus predominantly on drug loading, stability, and enhanced circulation, the role that nanoparticle composition plays in driving interactions with the biological environment to improve cell targeting and tumor accumulation remains an underexplored concept. Successful translation of drug delivery systems is additionally hampered by an incomplete understanding of how these parameters influence delivery outcomes in the context of biological heterogeneity. We have leveraged barcoded and pooled screening approaches to comprehensively gain new and fundamental insights into the material properties and biological features, and combinations thereof, that mediate successful delivery outcomes. The development of chemical barcoding strategies and pooled pan-cancer screens will be discussed along with how findings from these screens can be utilized to design simple yet effective targeted delivery systems for next-generation therapeutics.

Citation Format: Natalie Boehnke. An integrative approach to nanomedicine: Leveraging new tools to advance drug delivery [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA009.
Effects of roxadustat on thyroid profiles in patients and animals with chronic kidney disease
Authors: Li Wangyang , Cao Tao , Huang Guangluan , Guo Jianying , Zhu Tangkun , Hu Haofei , Huang Huiwei , Liu Xueting , Wu Liling , Chen Jia , Qi Dongli , Chen Tie , Wan Qijun , Cheng Yuan
Published: December 2024

Background
Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor used in renal anemia treatment, has been associated with thyroid hormone suppression. This study investigated the patterns of thyroid profile changes following roxadustat administration and their clinical implications.
Methods
In this retrospective study (2019-2023) at Shenzhen Second People's Hospital, patients were categorized based on TSH reduction during follow-up (≥50% decrease vs<50% decrease). Thyroid profiles, clinical symptoms, and laboratory indicators were analyzed. Quality of life was assessed using EQ-5D-3L and ThyPRO questionnaires. Complementary animal experiments were conducted to verify the effects of roxadustat on thyroid function.
Results
A total of 118 patients were finally enrolled in our study. Among patients with initially normal thyroid function, 31 developed euthyroid sick syndrome post-roxadustat treatment. Treatment significantly decreased T3, FT3, FT4, and TSH levels, with TSH showing marked reduction within the first 10 weeks. Contrastingly, animal models exhibited decreased T3 but increased TSH levels, regardless of renal status. Blood lipid levels decreased in all patients, particularly in those with substantial TSH reduction. Despite thyroid alterations, quality of life scores remained unchanged between roxadustat-treated and untreated patients, with no overt clinical symptoms in either humans or animals.
Conclusions
While roxadustat induces significant thyroid hormone suppression in patients, these alterations rarely manifest as clinical symptoms. Euthyroid sick syndrome is the predominant thyroid dysfunction pattern observed. Regular thyroid function monitoring is recommended during roxadustat therapy, particularly during the initial treatment phase when TSH changes are most pronounced.
Unveiling the Past: A Journey Through Philippine History
Authors: Nuevo – Toring Kimberly Cui , Toring Eugene Escalona , Legaspi Nonita P
Published: December 2024

"Unveiling the Past is a captivating exploration of the Philippines' rich and complex history. This book delves deep into the nation's past, from its ancient origins to the modern era, offering readers a comprehensive understanding of the forces that have shaped the Filipino people and their culture.
The authors skillfully weave together historical narratives, primary sources, and personal anecdotes to create a vivid and engaging account of the Philippines' journey. Key events, such as the Spanish colonization, the Philippine Revolution, and the American colonial period, are examined in detail, highlighting the significant impact they had on the country's development. One of the strengths of this book lies in its ability to present historical events from multiple perspectives. By considering the viewpoints of both colonizers and colonized, the author offers a nuanced and balanced portrayal of the past. This approach allows readers to develop a critical understanding of historical processes and to appreciate the complexities of the human experience. Furthermore, Unveiling the Past emphasizes the importance of historical memory and its role in shaping national identity. The book explores how historical narratives have been constructed, challenged, and reinterpreted over time, revealing the power of history to both unite and divide."
Multicenter Analysis of the Relationship Between Operative Team Familiarity and Safety and Efficiency Outcomes in Cardiac Surgery
Authors: Bauer Tyler M. , Janda Allison M. , Wu Xiaoting , Ling Carol , Shook Douglas C. , Querejeta-Roca Gabriela , Shann Kenneth G. , Smith Trevor , Mathis Michael R. , Kaneko Tsuyoshi , Sundt Thoralf M. , Schonberger Robert B. , Harrington Steven D. , Dias Roger D. , Pagani Francis D. , Likosky Donald S. , Yule Steven , Caldwell Matthew D. , Corso Jason J. , Louis Nathan , Krein Sarah L. , Manojlovich Milisa , Stakich-Alpirez Korana , Sturmer David , Yalamuri Suraj , Lawton Jennifer , Abernathy Jake , Cleveland Joseph , Clendenen Nathan , Justison George , Fried Michael , Nemeh Hassan , Fitzsimons Michael G. , Dickinson Timothy , Stulak John , de la Cruz Kim I.
Published: December 2024

BACKGROUND:

Safety in cardiac surgical procedures is predicated on effective team dynamics. This study associated operative team familiarity (ie, the extent of clinical collaboration among surgical team members) with procedural efficiency and Society of Thoracic Surgeons (STS) adjudicated patient outcomes.

METHODS:

Institutional STS adult cardiac surgery registry and electronic health record data from 2014 to 2021 were evaluated across 3 quaternary hospitals. Team familiarity was defined as the mean number of cardiac operations performed by surgeon-anesthesiologist, surgeon-perfusionist, and anesthesiologist-perfusionist dyads within 1 year of the operation. The primary outcomes were (1) safety, measured by the STS’ composite major morbidity and operative mortality measure, and (2) procedural efficiency, assessed by cardiopulmonary bypass duration. Team familiarity was stratified by terciles (low, moderate, and high) for crude analyses and analyzed continuously for adjusted analyses. Multivariable logistic and linear regression models were used to assess the association between team familiarity and outcomes.

RESULTS:

Team familiarity was calculated for 13 581 operations. The median (interquartile range) patient age was 64 (55–72) years, and 31.9% (4328/13 581) were women. Terciles of team familiarity were defined as low (<6.00 average shared operations), moderate (6.00–9.67), and high (>9.67). Teams in lower terciles had higher observed STS morbidity and mortality rates (low, 17.9%; moderate, 18.0%; high, 16.0%;
P
=0.02) and longer median cardiopulmonary bypass duration (low, 137 minutes; moderate, 131 minutes; high, 118 minutes;
P
<0.001). After risk adjustment, team familiarity was not significantly associated with STS morbidity and mortality (estimate, −0.001 [95% CI, −0.998 to 0.997]) but was inversely associated with cardiopulmonary bypass duration (estimate, −2.02 minutes per 1 unit increase in team familiarity [95% CI, −2.30 to −1.75]).

CONCLUSIONS:

Increased team familiarity was not associated with STS morbidity and mortality but was inversely correlated with cardiopulmonary bypass duration, demonstrating potential benefit. Interventions aimed at improving team familiarity among operative teams may increase procedural efficiency.
Association of Duration of Recognized Hypertension and Stroke Risk: The REGARDS Study
Authors: Howard George , Muntner Paul , Lackland Daniel T. , Plante Timothy B. , Cushman Mary , Stamm Brian , Judd Suzanne E. , Howard Virginia J.
Published: December 2024

BACKGROUND:

The focus for reducing hypertension-related cardiovascular disease is the management of blood pressure. Limited data are available on the potential benefit of delaying the onset of hypertension.

METHODS:

Stroke-free Black and White participants from the REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke; recruited 2003–2007) were followed through 2022 for incident stroke events. Participants were stratified by duration of recognized hypertension: normotensive (0 years), ≤5 years, 6 to 20 years, or 21+ years. The baseline systolic blood pressure (SBP), the number of classes of antihypertensive medications, and the risk of incident stroke were assessed by duration strata adjusting for demographics, cerebrovascular risk factors, SBP, and use of antihypertensive medications (where appropriate).

RESULTS:

Of 30 239 study participants, we included 27 310 participants (mean age, 65 years; 45% male), followed a median of 12.4 years, during which 1763 incident stroke events occurred. On average, participants with hypertension duration ≤5 years, 6 to 20 years, and 21+ years were taking 1.68 (95% CI, 1.65–1.71), 2.04 (95% CI, 2.01–2.07), and 2.28 (95% CI, 2.25–2.31) classes of antihypertensive medications, respectively. The adjusted mean SBP level was higher with each increasing duration of recognized hypertension (0, ≤5, 6–20, and 21+ years): 123.9 mm Hg (95% CI, 123.3–124.6), 129.7 mm Hg (95% CI, 129.1–130.2), 131.7 mm Hg (95% CI, 130.6–131.5), and 132.6 mm Hg (95% CI, 132.0–133.1). Compared with normotensive individuals, the hazard for incident stroke increased from 1.31 (95% CI, 1.05–1.63) for ≤5 years duration, 1.50 (95% CI, 1.21–1.87) for 6 to 20 years duration, and 1.67 (95% CI, 1.32–2.10) for 21+ years duration.

CONCLUSIONS:

Longer duration of recognized hypertension was associated with more classes of antihypertensive medications, higher mean SBP, and higher stroke risk even after adjustment for age and SBP. Collectively, this suggests that delaying the onset of hypertension could reduce the burden of stroke.
Do Amyloid Cerebral Deposits Influence the Long-Term Poststroke Cognitive Outcome?: The IDEA3 Study
Authors: Godefroy Olivier , Trinchard Niels , Marchal Etienne , Lamy Chantal , Canaple Sandrine , Meyer Marc-Etienne , Roussel Martine , Wollenweber Frank A. , Barbay M. , Courselle-Arnoux Audrey , Leclercq Claire , Despretz-Wannepain Sandrine , Berrissoul Hassan , Picard Carl , Diouf Momar , Loas Gwénolé , Deramond Hervé , Constans Jean-Marc , Shields Trevor
Published: December 2024

BACKGROUND:

Although the presence of amyloid deposits is associated with a more severe cognitive status in patients with stroke at baseline, its influence on the subsequent cognitive outcome has not been extensively assessed. The primary objective of the present study of the IDEA3 (Imagerie des dépôts amyloïdes cérébraux par florbetapir AV-45 et diagnostic des déficits cognitifs et démence post Accident Vasculaire Cérébral) cohort was to determine the influence of amyloid positron emission tomography (PET) status on the 5-year cognitive outcome.

METHODS:

This longitudinal study performed in Amiens University Hospital (inclusions: October 2014 to October 2019; last visits: October 2018 to February 2023) has included 91 patients with stroke (ischemic stroke, 89%; hemorrhagic stroke, 11%) with florbetapir PET data at baseline (positive, n=14). Patients underwent annually comprehensive clinical and cognitive assessments for 5 years after the PET scan. The primary outcome was incident dementia; secondary outcomes were incident cognitive impairment, total prevalence of cognitive impairment, and modified Rankin Scale score.

RESULTS:

A survival analysis (mean poststroke follow-up, 80.4±27 months) showed that the incidence of incident dementia was higher in the PET-positive patients (odds ratio, 9.6 [95% CI, 2.5–36.9];
P
=0.001), as was the incidence of incident cognitive impairment (odds ratio, 10 [95% CI, 1.9–52.3];
P
=0.003). A Cox regression analysis showed that the association between amyloid status and the incidences of dementia (
P
=0.001) and cognitive impairment (
P
=0.007) was still significant after adjustment for age, education, prestroke modified Rankin Scale score and cognitive impairment, stroke type, and the PET status×stroke type interaction. Considering the overall prevalence at the last follow-up in the whole study population (n=91 patients), PET positivity was associated with an elevated risk of dementia (odds ratio, 6 [95% CI, 1.76–20.5];
P
=0.002) and poststroke cognitive impairment (odds ratio, 6.25 [95% CI, 1.77–22];
P
=0.002). The final modified Rankin Scale score did not differ (
P
=0.3) according to PET status.

CONCLUSIONS:

Our results demonstrate the major impact of amyloid deposition on the stroke outcome and emphasized the need for comprehensive etiologic workup in patients with poststroke cognitive impairment.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02813434.
Effect of the Variable Kuroshio Intrusion Pathway on Deep Flow in the Northern South China Sea
Authors: Quan Qi , Zhang Han , Liu Xiaohui , Yu Yi , Yang Yang , He Qingyou , Wang Ya Ping
Published: December 2024

The effect of the variable Kuroshio intrusion pathway on deep flow in the northern South China Sea (NSCS) is investigated using observational and theoretical analyses. With significant seasonality in path variation, the leaking path is found to be most frequent, whereas the looping (leaping) path is transient and prefers to occur in winter (summer). Such multipath variability contributes greatly to the highest surface eddy kinetic energy in the NSCS, with the energy peaking for the looping path in winter, followed by the leaking and leaping paths. The information flow–based causality analysis suggests that the energetic surface perturbations in the Kuroshio intrusion region are causal to the intraseasonal variability in deep flow east of the Dongsha Islands, wherein the linkage is strongest within the Kuroshio Loop Current eddy shedding event related to the looping path. Therefore, the underlying dynamics for the vertical coupling is illustrated by this event, in which the eddy is highly compressed to the surface because of sloping topography and its energy is partially transferred downward through vertical pressure work to force the abyssal topographic Rossby waves. Moreover, the energetics and instability analyses reveal that barotropic instability dominates the energy transfer from background flow to eddies in the Kuroshio intrusion region, which energizes the surface perturbations most intensively for the looping path, followed by the leaking and leaping paths. The characteristic scales of the most unstable mode estimated by the reduced-gravity model are analogous to the observations and account for the rapid growth of surface perturbations in the Kuroshio intrusion region.
Development and Validation of a Global Thin Ice Thickness Algorithm for SMMR
Authors: Kashiwase Haruhiko , Ohshima Kay I. , Tamura Takeshi
Published: December 2024

Thin ice thickness algorithms using satellite passive microwave radiometers are frequently used to quantify sea ice production in coastal polynyas. The objective of this paper is to develop and validate a thin ice thickness algorithm using only low-frequency (LF) data (19- and 37-GHz channels), applicable back to 1978 when the Scanning Multichannel Microwave Radiometer (SMMR) observations started. We compared several recent satellite observations for 22 cases of typical polynya events in the Southern Ocean and developed a new method to discriminate three types of thin ice (active frazil, thin solid ice, and a mixture of the two) using only LF data. Combined with ice-type discrimination, the obtained LF ice thickness (20 cm or less) has a bias of less than 1 cm and an RMSD of about 5 cm, as shown by validation data from 24 cases of typical polynya events that occurred prior to 1992 in the Southern Ocean and the Bering Sea. Although the error in ice-type discrimination with LF data is relatively large in comparison with previous studies, these results still suggest that the LF ice thickness could be a continuous global data since 1978. We also developed a false thin ice detection algorithm using only LF data and created daily false thin ice masks from 1978 to the present, which are also essential for estimating global sea ice production. The use of our new LF algorithm will allow quantification of the global sea ice production over nearly half a century since 1978.

Significance Statement

Sea ice production is a key element for dense water formation and thus deep/intermediate overturning circulation. Global estimation of sea ice production will be achieved through a heat budget analysis incorporating a thin ice thickness algorithm of satellite passive microwave radiometers. The previous algorithms use high-frequency channel data that only became available after 1992. In this study, we have developed an algorithm of ice type and thin ice thickness using only low-frequency channels (19 and 37 GHz) data, which allows us to obtain the thin ice thickness distribution on a global scale from 1978 to the present. This will further lead to a unified global estimate of sea ice production over a time scale of nearly half a century.
Formulation of nasal analgesic sprays with diclofenac sodium, ibuprofen, paracetamol, and evaluation of in vitro toxicity
Authors: Yenigun Vildan Betul , Yenigun Alper , Sagiroglu Ali Asram , Kocyigit Abdurrahim , Ozturan Orhan
Published: December 2024

Objective

Intranasal analgesic sprays represent a safe, efficacious method for pain relief, with a shorter working time compared to oral painkillers. This study aimed to develop nasal sprays using commonly available over-the-counter analgesics, providing an alternative treatment option that is more convenient and potentially more effective in managing pain, particularly in pediatric patients.

Methods

Three different nasal spray formulations with the contents of diclofenac sodium, ibuprofen, and paracetamol were created, and characterization studies were completed. The possible cytotoxic, genotoxic, and apoptotic effects of nasal sprays were studied on human normal skin fibroblastic cells (CCD-1079Sk) using WST cell viability test, alkaline single-cell gel electrophoresis analysis, and acridine orange/ethidium bromide staining, respectively.

Results

The formulations’ physical appearance and drug content were assessed, yielding nonsignificant results ( p > 0.05). All formulations were determined at pH 5.5–6.2 so that the pH values of the prepared formulations were compatible with the pH value of the nasal mucosa. Selected nasal spray formulations were stable for 90 days, and the safe doses were chosen as 0.0625, 0.375, and 1.25 mg/mL for diclofenac, ibuprofen, and paracetamol, respectively, by not showing toxicity even at 24 h.

Conclusion

This study demonstrated that nasal sprays containing paracetamol, ibuprofen, and diclofenac sodium can be successfully formulated. These new formulations may provide alternative treatment and easier application for patients unable to swallow or refuse to take oral analgesics.
A Systematic Literature Review of Research on Teacher Empowerment
Authors: Celik Osman Tayyar , Sari Tamer , Karagozoglu Ahmet Alper
Published: December 2024

This bibliometric analysis examines the crucial role of teacher empowerment in enhancing educational environments by providing educators with autonomy, resources, and support. Using data from Web of Science and Scopus databases, 330 documents were analyzed to identify recent developments and trends in the field, particularly within urban education and culture. Findings indicate a growing interest in teacher empowerment, highlighting key themes such as teacher engagement, collaboration, and empowering leadership. The study underscores the influence of cultural structures on teacher empowerment policies and concludes with recommendations for policymakers, governments, and Ministries of Education to further support teacher empowerment.
Indigenous students’ experiences with racial microaggressions in Taiwan / Experiencias de estudiantes indígenas con microagresiones raciales en Taiwán
Authors: Chen Wei-Lin
Published: December 2024

Prior research has demonstrated that Black, Indigenous and People of Colour (BIPOC) experience racial microaggressions in educational settings. This study investigates how racial microaggressions against Indigenous students in K–16 educational settings in Taiwan occur and how they compare to what students experience in the United States and Canada. The research team interviewed 21 college-aged Indigenous students in 2021; participants described their interactions with peers and teachers or faculty, experiences utilizing school resources and perception of learning environments in school (K–12) and on campus. The analysis revealed that Indigenous students experience racial microaggressions at three levels: (1) interpersonal context, i.e., facing jealous accusations in class, hearing racist comments and encountering stereotypes and negative beliefs; (2) anti-Indigenous pedagogical practices, i.e., teachers or faculty misunderstand Indigenous cultures or treat Indigenous students as cultural symbols or spokespersons; and (3) systemic exclusion, i.e., the absence of Indigenous cultures in curricula and academic affairs.