bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Flood Vulnerability from Rapid Urban Growth: A Case of Central Java — Indonesia
Authors: DEWI Retno Sari , HANDAYANI Wiwandari , PRATAMA Isnu Putra , De VRIES Walter T. , RUDIARTO Iwan , ARTININGSIH Artiningsih
Published: January 2024

Urban growth, in many Asian cities, may lead to increased exposure to flood and growing sensitivity mainly because of the presence of informal settlements. On the other hand, urban areas may offer better access to public facilities, improving adaptive capacity and enhancing the local government’s capabilities. This study aims to investigate to what extent urban growth exacerbates flood vulnerability in Central Java. Concurrently, floods are the most frequent disaster in the area. The approach used in the vulnerability assessment involves socioeconomic conditions (population density, the number of impoverished families, public facilities) associated with three main aspects (exposure, sensitivity, and adaptive capacity), resulting in the Exposure and Sensitivity Index and the Adaptive Capacity Index. Scoring and weighting analysis using secondary data in a sub-district unit from the Central Bureau of Statistics are applied. The result shows that urban growth contributes to the escalation of hazards and vulnerability. On the other hand, a high population also increases the number of public facilities and affects adaptive capacity in certain areas. Indeed, strategic urban development policies are critical to manage the three elements that form the flood vulnerability.
Marginal Probability-Based Integer Handling for CMA-ES Tackling Single- and Multi-Objective Mixed-Integer Black-Box Optimization
Authors: Hamano Ryoki , Saito Shota , Nomura Masahiro , Shirakawa Shinichi
Published: January 2024

This study targets the mixed-integer black-box optimization (MI-BBO) problem where continuous and integer variables should be optimized simultaneously. The covariance matrix adaptation evolution strategy (CMA-ES), our focus in this study, is a population-based stochastic search method that samples solution candidates from a multivariate Gaussian distribution (MGD), which shows excellent performance in continuous black-box optimization. The parameters of MGD, mean and (co)variance, are updated based on the evaluation value of candidate solutions in the CMA-ES. If the CMA-ES is applied to the MI-BBO with straightforward discretization, however, the variance corresponding to the integer variables becomes much smaller than the granularity of the discretization before reaching the optimal solution, which leads to the stagnation of the optimization. In particular, when binary variables are included in the problem, this stagnation more likely occurs because the granularity of the discretization becomes wider, and the existing integer handling for the CMA-ES does not address this stagnation. To overcome these limitations, we propose a simple integer handling for the CMA-ES based on lower-bounding the marginal probabilities associated with the generation of integer variables in the MGD. The numerical experiments on the MI-BBO benchmark problems demonstrate the efficiency and robustness of the proposed method. Furthermore, to demonstrate the generality of the idea of the proposed method, in addition to the single-objective optimization case, we incorporate it into multi-objective CMA-ES and verify its performance on bi-objective mixed-integer benchmark problems.
MF
2
ShrT: Multimodal Feature Fusion Using Shared Layered Transformer for Face Anti-spoofing
Authors: Antil Aashania , Dhiman Chhavi
Published: January 2024

In recent times, Face Anti-spoofing (FAS) has gained significant attention in both academic and industrial domains. Although various convolutional neural network (CNN)-based solutions have emerged, multimodal approaches incorporating RGB, depth, and information retrieval (IR) have exhibited better performance than unimodal classifiers. The increasing veracity of modern presentation attack instruments results in a persistent need to enhance the performance of such models. Recently, self-attention-based vision transformers (ViT) have become a popular choice in this field. Their fundamental aspects for multimodal FAS have not been thoroughly explored yet. Therefore, we propose a novel framework for FAS called MF
2
ShrT, which is based on a pretrained vision transformer. The proposed framework uses overlap patches and parameter sharing in the ViT network, allowing it to utilize multiple modalities in a computationally efficient manner. Furthermore, to effectively fuse intermediate features from different encoders of each ViT, we explore a T-encoder-based hybrid feature block enabling the system to identify correlations and dependencies across different modalities. MF
2
ShrT outperforms conventional vision transformers and achieves state-of-the-art performance on benchmarks CASIA-SURF and WMCA, demonstrating the efficiency of transformer-based models for presentation attack detection  PAD).
Intelligent Caching for Vehicular Dew Computing in Poor Network Connectivity Environments
Authors: Zhao Liang , Li Hongxuan , Zhang Enchao , Hawbani Ammar , Lin Mingwei , Wan Shaohua , Guizani Mohsen
Published: January 2024

In vehicular networks, some edge servers may not function properly due to the time-varying load condition and the uneven computing resource distribution, resulting in a low quality of caching services. To overcome this challenge, we develop a Vehicular dew computing (VDC) architecture for the first time by combining dew computing with vehicular networks, which can achieve wireless communication between vehicles in a resource-constrained environment. Consequently, it is crucial to develop an adaptive caching scheme that empowers vehicles to form efficient cooperation in VDC. In this paper, we propose an intelligent caching scheme based on VDC architecture, which includes two parts. First, to meet the dynamic nature of VDC, a spatiotemporal vehicle clustering algorithm is proposed to establish adaptive cooperation to assist content caching for vehicles. Second, the multi-armed bandit algorithm is employed to select suitable content for caching in vehicles based on real-time file popularity, and a model is established to dynamically update each vehicle’s request preferences. Extensive experiments are conducted to demonstrate that the proposed scheme has excellent performance in terms of cluster head stability and cache hit rate.
Models for Decarbonization in the Chemical Industry
Authors: Yao Yuan , Lan Kai , Graedel Thomas E. , Rao Narasimha D.
Published: January 2024

Various technologies and strategies have been proposed to decarbonize the chemical industry. Assessing the decarbonization, environmental, and economic implications of these technologies and strategies is critical to identifying pathways to a more sustainable industrial future. This study reviews recent advancements and integration of systems analysis models, including process analysis, material flow analysis, life cycle assessment, techno-economic analysis, and machine learning. These models are categorized based on analytical methods and application scales (i.e., micro-, meso-, and macroscale) for promising decarbonization technologies (e.g., carbon capture, storage, and utilization, biomass feedstock, and electrification) and circular economy strategies. Incorporating forward-looking, data-driven approaches into existing models allows for optimizing complex industrial systems and assessing future impacts. Although advances in industrial ecology–, economic-, and planetary boundary–based modeling support a more holistic systems-level assessment, more efforts are needed to consider impacts on ecosystems. Effective applications of these advanced, integrated models require cross-disciplinary collaborations across chemical engineering, industrial ecology, and economics.
The CD4 Versus CD8 T Cell Fate Decision: A Multiomics-Informed Perspective
Authors: Steier Zoë , Kim Esther Jeong Yoon , Aylard Dominik A. , Robey Ellen A.
Published: January 2024

The choice of developing thymocytes to become CD8+ cytotoxic or CD4+ helper T cells has been intensely studied, but many of the underlying mechanisms remain to be elucidated. Recent multiomics approaches have provided much higher resolution analysis of gene expression in developing thymocytes than was previously achievable, thereby offering a fresh perspective on this question. Focusing on our recent studies using CITE-seq (cellular indexing of transcriptomes and epitopes) analyses of mouse thymocytes, we present a detailed timeline of RNA and protein expression changes during CD8 versus CD4 T cell differentiation. We also revisit our current understanding of the links between T cell receptor signaling and expression of the lineage-defining transcription factors ThPOK and RUNX3. Finally, we propose a sequential selection model to explain the tight linkage between MHC-I versus MHC-II recognition and T cell lineage choice. This model incorporates key aspects of previously proposed kinetic signaling, instructive, and stochastic/selection models.
Determination of Nitrofuran in Aquaculture Water by Polycrystal Violet Sensor
Authors: Gou Wanglei , Li Xin , Qiu Jiao , Chen Wen , Jiang Jinlong , Ruan Jian
Published: January 2024

The aim of this study is to develop an electrochemical sensor that can detect nitrofuran antibiotic residues in aquaculture water with high sensitivity and selectivity. The polycrystal violet modified glassy carbon electrode (PCV/GCE) was prepared by electropolymerizing crystal violet monomer onto the surface of a glassy carbon electrode (GCE). The optimal preparation and analytical conditions for the sensor were investigated using furazolidone (FZD) as a research model for nitrofurans. The morphology and electrochemical behavior of the sensor were characterized by using scanning electron microscopy, cyclic voltammetry(CV), and electrochemical impedance spectroscopy (EIS). The results showed that the PCV/GCE sensor exhibited a good response to nitrofuran antibiotics. The linear ranges for FZD were 0.25 ∼ 28.0 μM and 28.0 ∼ 60 μM, respectively with detection limits of 0.18 μM. For nitrofurantoin and nitrofurazon, the linear ranges were 6.0 ∼ 40 μM and 3.5 ∼ 20 μM, respectively with detection limits of 0.20 μM and 0.14 μM. The spiked recoveries in real water samples tested ranged from 84% to 106.3%. This method has potential applications for the sensitive detection of nitrofuran antibiotics in aquaculture water due to its low analytical cost and simple sensor preparation.
Synthesis of Tin Doped Copper Oxide Nanocomposites for Electrochemical Sensor Application
Authors: Priya N. R. , Mahanthesha K. R. , Anagawadi Rohini B. , Sathosh B. M.
Published: January 2024

Poly (Tin doped copper oxide nanocomposites modified glassy carbon electrode) (Poly (Sn doped CuO nanocomposite)-MGCE) made sensor were confirmed by electrochemical finding norepinephrine (NE). The Sn doped CuO nanocomposites were made by precipitation technique. This nanocomposite was described through scanning electron microscope (SEM) and X-ray diffraction (XRD) methods. To find there doped properties of the Poly (Sn doped CuO nanocomposite)-MGCE were studied by cyclic voltammetry studies (CV). The above studies prove that the altered electrode have wide electroactive external area, the reduction and oxidation peak appeared at pH 7.4 supportive electrolyte concentration 0.2 M phosphate buffer solution (PBS). Poly(Sn doped CuO nanocomposite)-MGCE as limit of detection was low (LOD) value for NE was found to be 2.22 μM and the limit of quantification (LOQ) values for NE was appeared as 7.41 μM, wide linear range, high sensitivity (20 μΜ to 350 μM), functional to the injection mockup analysis and the attained outcomes are acceptable, excellent reproducibility displays excessive potential in practical applications.
Selective Detection of Creatinine Using Enzymatic Route for Diagnosis of Chronic Kidney Diseases
Authors: Kavita  , Verma R. K.
Published: January 2024

Chronic kidney diseases are becoming most common health issues due to growing age, hypertension and high cholesterol that causes poor kidney functioning and eventually death also. Creatinine is a serum present in blood and urine that measures the kidney functioning. We have designed a highly sensitive and precise sensor for the creatinine sensing. Eu—doping in tin oxide (SnO2) is used to enhance the sensitivity and limit of detection. A precise working range of this sensor is also found by the calibration curve between FWHM and figure of Merit with respect to the concentration of creatinine. A selectivity experiment with enzymatic route is followed to make this sensor selective for creatinine only. This sensor may find plentiful deliberation in the field of sensing and mainly in medical applications.
Using artificial intelligence platforms to support student learning in physiology
Authors: Favero Terence G.
Published: January 2024

Utilizing of artificial intelligence tools offers a promising new technology to support student learning. This article outlines several ways that students can employ these tools to support better learning along with a set of guidelines for all to be wary of when implementing these in an academic setting.
Performance Evaluation of an Existing Renewable Energy System at Gilutongan Island, Cebu, Philippines
Authors: Supapo Khrisydel Rhea M. , Lozano Lorafe , Querikiol Edward M.
Published: January 2024

Solar photovoltaics are considered the practical solution to energy access and climate change issues, especially in tropical countries that receive relatively more sunlight throughout the year. However, questions arise on the reliability of these systems in providing sufficient supply to meet the users’ electricity needs. This paper looks at the reliability of a solar project installed on two rooftops on an off‐grid island in Cebu, Philippines, that provides increased electricity access to 11 households. PVSyst and HOMER Pro software analyzed solar PV systems performance and techno‐economics. The simulations yielded the annual mean values of reference yield, array yield, final yield, array capture loss, system loss, performance ratio, and capacity factor are 5.66 kWh/m2/day, 3.51 kWh/kWp/day, 3.23 kWh/kWp/day, 2.15, 0.278, 57.10%, and 18.96%, respectively. The peak PV resource of 3.30 kWp/day can supply the 1.66 kWp/day of the consumer’s electrical demand. It was concluded that the current installation could supply the electrical load demand of the residents; however, consideration for the potential increase in demand must be in place. While renewable energy sources are relevant in achieving 100% electrification in rural communities, their ability to address the energy demands of the users must be carefully considered in planning and design.
Different Coping Constructs in Haematological Cancer Patients: The Influence of Dyadic on Individual Coping Interplay of DC and IC in Haematological Cancer
Authors: Sackmann Carlotta , Weißflog Gregor , Bodschwinna Daniela , Hönig Klaus , Ernst Jochen
Published: January 2024

Objective. The aim of the present study was to investigate the relationship between individual coping (IC) and dyadic coping (DC), more specifically the respective predictive impact of DC and sociodemographic, partnership-related, and medical variables on IC in haematological cancer patients. Methods. In this multicenter longitudinal study, we examined DCI (Dyadic Coping Inventory) and IC (Freiburg Questionnaire on Coping with Illness) in 214 haematological cancer patients after their treatment and six months later. Associations between the coping constructs were calculated using Pearson correlations. Multiple linear regression analyses were conducted to examine the predictive impact of patient-specific variables on IC strategies. Results. Pearson correlation revealed numerous significant associations between DC and IC at the baseline and follow-up, but none of them yielded r ≥ 0.4 (p<0.01). Regression analyses showed a predictive impact of supportive DC on compliance (p<0.05) and of common DC on active IC (p<0.01). Concerning patient-specific variables, age stood out as a positive predictor of trivialization (p<0.001) and compliance (p<0.01) and psychological distress as a predictor of depressive IC (

p

<

0.001

), distraction (p<0.05), and trivialization (p<0.05). Conclusion. Our results indicate that patients’ personal characteristics, such as age and psychological distress, outweigh the influence of DC on IC in haematological cancer patients.
A Framework for Valuation and Portfolio Optimization of Venture Capital Deals with Contractual Terms
Authors: Valaei Mohammadreza , Khodakarami Vahid
Published: January 2024

Venture capitalists invest not only in the business aspect of a deal but also in its contractual terms. Therefore, the selection of deals and the combination of contractual terms pose challenging decisions for them. This paper consists of two main sections. The first section introduces a novel framework for the valuation of venture capital (VC) deals, including startups and their contractual terms. By taking into account risk situations, this section presents the valuation of combined contractual terms, including call options, liquidity preference, and participant rights. In the second section, a new multiobjective mathematical model for VC deals and contractual terms portfolio selection is developed using right-tail probability, strategy alignment, and a utility function. To solve the proposed model, three metaheuristic algorithms—Non-Dominated Sorting Genetic Algorithm (NSGA-II), Multi-Objective Binary Harmony Search Algorithm, and Dynamic Tuning Parameter Binary Harmony Search Algorithm (DTPBHS)—are applied. Based on numerical examples, DTPBHS outperforms other algorithms in the “Mean Ideal Distance” index, but NSGA-II demonstrates the best performance in the “Rate of Achievement of two objectives simultaneously” index. Furthermore, we demonstrate that the proposed utility function is more robust than the right-tail probability function under default deals conditions.
Development of a Conceptual Framework for Adult Community Rehabilitation Policy, Planning, Care, and Research: A Multimethod Qualitative Approach
Authors: Sibley Kathryn M. , Barclay Ruth , Cooper Juliette , Edwards Jeanette , Guse Lorna W. , Leclair Leanne , Katz Alan , Korall Alexandra M. B. , Ripat Jacquie , Zawaly Kathleen
Published: January 2024

To address recognized gaps in community rehabilitation service coordination and advance delivery of rehabilitation services for adults living outside of institutions, we have developed a conceptual framework to inform the design of community rehabilitation policy, planning, care, and research. Employing a multimethod qualitative approach, we developed a draft framework based on a document review as well as interviews with community rehabilitation service and system providers, older people receiving community rehabilitation services, and family caregivers. We then consulted with community rehabilitation service and system providers, older adults, and family caregivers to revise the framework. We identified 194 relevant documents and 30 programs, and we analyzed interview data from 29 service and system providers as well as 6 dyads of older persons and family caregivers. We developed a definition of community rehabilitation and identified 11 components for the draft framework, which was presented to 16 participants for consultation. We used their feedback to revise the terms and definitions for the 11 components. We organized the final set of components into two categories: principles (culturally safe; equity‐focused; evidence‐informed; person and family‐centred; restorative) and organization (appropriate; coordinated; continuity; evaluated; stepped; team‐based). The contextualized, action‐oriented conceptual framework for adult community rehabilitation (CFACR) is supported by older people, family caregivers, and community rehabilitation health system providers. Continued work to refine and validate the components in more population groups and contexts will facilitate implementation and application of the CFACR.
Analysis of Soil Response during High‐Frequency Vibratory Steel Pipe Pile Driving in Soft Soil
Authors: Chen Fengjun , Li Xiaomi , Zhao Huiling , Hu Pei
Published: January 2024

High‐frequency vibratory pile driving exhibits remarkable efficiency in soft soil, with its impact on the surrounding soil to a limited range. Studying the evolution of stress and strain fields in the soil surrounding the pile during the pile driving process is of great significance for effective control of pile driving construction and accurate prediction of the pile foundation’s bearing capacity after installation. In this study, by means of numerical simulation with consideration of the large deformations of the soil and even discontinuities induced by the pile penetration into soil, the response of the soil during the high‐frequency vibratory steel pipe pile driving in silt soil was investigated. The research results show that with the increase of pile driving depth, the stress concentration zones in the soil near the pile tip continuously expanded, and the plastic strain zone mainly developed downward but little horizontally. When the vibration frequency was between 33 and 38 Hz, the pile driving efficiency was higher than that of 50 Hz. High‐frequency resonance free vibratory pile driving has smaller pile–soil stresses and plastic strains compared to traditional impacting pile and static pile, and it is less prone to the formation of soil plug. Therefore, high‐frequency vibratory pile driving technology exhibits good adaptability in the soft soil.
A Health Status Assessment Method of Fluid Loop System Based on Hierarchical Multi-Information Fusion
Authors: Li Rui , Zhang Junshen , Fang Hongzheng , Zhang Qing
Published: January 2024

As a kind of thermal control device, fluid loop systems must operate with the demands of high safety, high reliability, and long life. In order to accurately assess the health status of fluid loop systems, a hierarchical multi-information fusion (HMIF) method is proposed in this paper. Considering that fluid loop systems generally have distinct structural hierarchies, the health evaluation process in this method is divided into three levels, which are the indicator level, the component level, and the system level. In the evaluation process, the health indices are, respectively, constructed to quantify the health status at the three levels. At the indicator level, One-Class support vector machine algorithm is used to obtain the distribution space of each state monitoring indicator under a normal state. The indicator-level health indices are evaluated by calculating the ratio of the data located in the distribution space to the overall data. At the component level, a fuzzy theory is used to calculate the health indices of the component level. Health indices at the indicator level are first converted to membership degree by membership degree function. Then, the evaluation fusion strategy is used to deduce the membership degree of the component level. The health indices at the component level are obtained from the mapping relationship between the membership degree and the health index. At the system level, an adaptive weight adjustment strategy is proposed to fuze all component-level health indices. Taking a practical fluid loop system as an example, health indices at the three levels evaluated by the HMIF method are compared with the actual status. The results indicate that the proposed method can correctly judge the health state of the system and provide a reference for the maintenance and fault diagnosis of fluid loop systems.
Evaluation of Apatinib‐Related Hypertension and Identification of Clinical Risk Factors
Authors: Le Kaidi , Liu Min , Ma Yinglin , Yan Jiaqing , Li Ying , Li Guohui
Published: January 2024

Purpose. Hypertension (HTN) is one of the most common adverse drug reactions to tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF), but little is known about its clinical risk factors. The aim of this study was to elucidate the association between baseline clinical characteristics and the occurrence of HTN in advanced gastric cancer (GC) patients prescribed apatinib, a commonly used VEGF‐TKI in China, in a real‐world setting. Patients and Methods. Fifty‐five GC patients treated with apatinib from December 1st, 2016, to December 1st, 2020, were retrospectively included in electronic medical records. Adverse drug reactions were defined according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Univariate and multivariable logistic regression analyses were used to investigate potential clinical risk factors for apatinib‐related HTN. Results. The incidence of apatinib‐related HTN of all grades was 45.45%, and grade 3 HTN occurred in 16.36% of patients. The median maximal systolic blood pressure (SBP) during apatinib treatment was 153 mm·Hg, and the median time to event was 25 days. New‐onset HTN occurred in 10/33 (30.30%) patients. Preexisting HTN (odds ratio [OR]: 4.155; 95% confidence interval [CI]: 1.252, 13.787; p = 0.020) was the key independent risk factor associated with apatinib‐related HTN. Conclusion. The incidence of HTN was high in patients treated with apatinib, and preexisting HTN was an independent risk factor. It is important to provide thorough and close monitoring of patients during treatment with apatinib, especially for those with preexisting HTN. This trial is registered with ChiCTR1900024531.
Idiopathic Granulomatous Mastitis
Authors: Dilaveri Christina , Degnim Amy , Lee Christine , DeSimone Daniel , Moldoveanu Dan , Ghosh Karthik
Published: January 2024

Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory disorder of the breast that is often underrecognized. The exact etiology and pathophysiology are unknown, but milk stasis is felt to play a role. Classically, this condition is noninfectious, but many cases are noted to be associated with Corynebacterium species. Most patients affected are parous women with a mean age of 35, and many have breastfed within five years of diagnosis. Patients typically present with a painful mass and symptoms of inflammation, and these features can sometimes mimic breast cancer. Biopsy is needed to make a definitive diagnosis, and noncaseating granulomas are found on core biopsy. Many patients have a waxing and waning course over a period of six months to two years. Goal of treatment is to avoid surgery given poor wound healing, high risk of recurrence, and poor cosmetic outcomes. Medical treatment is preferred and includes observation, antibiotics, steroids, and immune modulators such as methotrexate. In more recent years, topical and intralesional steroids have become the treatment of choice, with similar outcomes to oral steroids.
Bibliometric Analysis on the Distributed Decision, Decentralized Decision, and Fuzzy Logic
Authors: Çağlayan Nihan , Abbasi Sina , Yilmaz İbrahim , Erdebilli Babek
Published: January 2024

This study aims to survey the bibliometric properties of distributed decisions, decentralized decisions, and fuzzy articles published between 1995 and 2023 in the Web of Science (WoS) database. During the analysis process, the keywords “distributed decision, decentralized decision, and fuzzy” were scanned in all languages, both in the titles and the content of all publication types. As a result of the analysis, 79 articles in all fields comprised the dataset. The most used keywords in the articles were related to the distributed decision, decentralized decision, and fuzzy logic, and the most frequently cited publications were examined using the social network analysis method, which uses VOSviewer (version 1.6.19) to visualize the relationships. The study’s goal on “active researchers, active journals, journal metrics, title document type, active countries, and active institutions” was to look at the words most frequently used in articles on distributed, decentralized, and fuzzy logic. The social network analysis represented the relationships between these keywords and the most frequently cited publications. The findings demonstrated a significant correlation between using these keywords in academic literature and their contribution to this field’s research. These results can assist researchers in finding potential partners and keeping up with current research trends. Overall, this study offers important new perspectives on the state of research on fuzzy logic, distributed decision making, and decentralized decision making.
Synthesis of a Calcium Silicate Cement Containing a Calcinated Strontium Silicate Phase
Authors: Zadsirjan Saeede , Dehkordi Negar Parvaneh , Heidari Soolmaz , Najafi Farhood , Zargar Nazanin , Feli Mojgan , Salimnezhad Sepideh
Published: January 2024

Objectives. The positive effects of strontium on dental and skeletal remineralization have been confirmed in the literature. This study aimed to assess the properties of a calcium silicate cement (CSC) containing a sintered strontium silicate phase. Materials and Methods. The calcium silicate and strontium silicate phases were synthesized by the sol–gel technique. Strontium silicate powder in 0 (CSC), 10 (CSC/10Sr), 20 (CSC/20Sr), and 30 (CSC/30Sr) weight percentages was mixed with calcium silicate powder. Calcium chloride was used in the liquid phase. X‐ray diffraction (XRD) of specimens was conducted before and after hydration. The setting time and compressive strength were assessed at 1 and 7 days after setting. The set discs of the aforementioned groups were immersed in the simulated body fluid (SBF) for 1 and 7 days. The ion release profile was evaluated by inductively coupled plasma‐optical emission spectrometry (ICP‐OES). Biomineralization on the specimen surface was evaluated by scanning electron microscopy/energy dispersive X‐ray spectroscopy (SEM/EDS). Data were analyzed by the Kolmogorov–Smirnov test, one‐way and mixed ANOVA, Levene’s test, and LSD post hoc test (P  < 0.05). Results. Except for an increasement in the peak intensity of hydrated specimens, XRD revealed no other difference in the crystalline phases of hydrated and nonhydrated specimens. The compressive strength was not significantly different at 1 and 7 days in any group (P  > 0.05). The setting time significantly decreased by an increase in percentage of strontium (P  < 0.05). Release of Ca and Si ions significantly decreased by an increase in percentage of strontium (P  < 0.05). SEM/EDS showed the formation of calcium phosphate deposits at 1 and 7 days. Conclusion. Incorporation of 10−30 wt% sintered strontium silicate phase as premixed in CSC can significantly decrease the setting time without compromising the compressive strength or biomineralization process of the cement.
Disparities in OncotypeDx Testing and Subsequent Chemotherapy Receipt by Geography and Socioeconomic Status
Authors: Van Alsten Sarah C. , Dunn Matthew R. , Hamilton Alina M. , Ivory Joannie M. , Gao Xiaohua , Kirk Erin L. , Nsonwu-Farley Joseph S. , Carey Lisa A. , Abdou Yara , Reeder-Hayes Katherine E. , Roberson Mya L. , Wheeler Stephanie B. , Emerson Marc A. , Hyslop Terry , Troester Melissa A.
Published: January 2024

Background:

OncotypeDx is a prognostic and predictive genomic assay used in early-stage hormone receptor–positive, HER2− (HR+/HER2−) breast cancer. It is used to inform adjuvant chemotherapy decisions, but not all eligible women receive testing. We aimed to assess variation in testing by demographics and geography, and to determine whether testing was associated with chemotherapy.

Methods:

For 1,615 women in the Carolina Breast Cancer Study with HR+/HER2−, Stage I–II tumors, we estimated prevalence differences (PD) and 95% confidence intervals (CI) for receipt of OncotypeDx genomic testing in association with and sociodemographic characteristics. We assessed associations between testing and chemotherapy receipt overall and by race. Finally, we calculated the proportion of eligible women receiving OncotypeDx by county-level rurality, census tract-level socioeconomic status, and Area Health Education Center regions.

Results:

38% (N = 609) of potentially eligible women were tested, with lower testing prevalences in Black (31%; PD, −11%; 95% CI, −16%–6%) and low-income women (24%; PD, −20%; 95% CI, −29% to −11%) relative to non-Black and higher income women. Urban participants were less likely to be tested than rural participants, though this association varied by region. Among women with low genomic risk tumors, tested participants were 29% less likely to receive chemotherapy than untested participants (95% CI, −40% to −17%). Racial differences in chemotherapy were restricted to untested women.

Conclusions:

Both individual and area-level socioeconomics predict likelihood of OncotypeDx testing.

Impact:

Variable adoption of OncotypeDx by socioeconomics and across geographic settings may contribute to excess chemotherapy among patients with HR+/HER2− cancers.

See related In the Spotlight, p. 635
Data from STAT3 and HIF1α Signaling Drives Oncogenic Cellular Phenotypes in Malignant Peripheral Nerve Sheath Tumors
Authors: Rad Ellie , Dodd Kayleigh , Thomas Laura , Upadhyaya Meena , Tee Andrew
Published: January 2024

Abstract
Therapeutic options are limited for neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNST) and clinical trials using drug agents have so far been unsuccessful. This lack of clinical success is likely attributed to high levels of intratumoral molecular heterogeneity and variations in signal transduction within MPNSTs. To better explore the variance of malignant signaling properties within heterogeneous MPNSTs, four MPNST cell lines (ST8814, S462, S1844.1, and S1507.2) were used. The data demonstrate that small-molecule inhibition of the MET proto-oncogene and mTOR had variable outcome when preventing wound healing, cell migration, and invasion, with the S462 cells being highly resistant to both. Of interest, targeted inhibition of the STAT3 transcription factor suppressed wound healing, cell migration, invasion, and tumor formation in all four MPNST lines, which demonstrates that unlike MET and mTOR, STAT3 functions as a common driver of tumorigenesis in NF1-MPNSTs. Of clinical importance, STAT3 knockdown was sufficient to block the expression of hypoxia-inducible factor (HIF)1α, HIF2α, and VEGF-A in all four MPNST lines. Finally, the data demonstrate that wound healing, cell migration, invasion, and tumor formation through STAT3 are highly dependent on HIF signaling, where knockdown of HIF1α ablated these oncogenic facets of STAT3.

Implications: This research reveals that aberrant STAT3 and HIF1a activity drives tumor progression in MPNSTs, indicating that inhibition of the STAT3/HIF1α/VEGF-A signaling axis is a viable treatment strategy. Mol Cancer Res; 13(7); 1149–60. ©2015 AACR.
Data from Targeting mTORC1–Mediated Metabolic Addiction Overcomes Fludarabine Resistance in Malignant B Cells
Authors: Sharma Arishya , Janocha Allison J. , Hill Brian T. , Smith Mitchell R. , Erzurum Serpil C. , Almasan Alexandru
Published: January 2024

Abstract
MTOR complex-1(mTORC1) activation occurs frequently in cancers, yet clinical efficacy of rapalogs is limited because of the associated activation of upstream survival pathways. An alternative approach is to inhibit downstream of mTORC1; therefore, acquired resistance to fludarabine (Flu), a purine analogue and antimetabolite chemotherapy, active agent for chronic lymphocytic leukemia (CLL) was investigated. Elevated phospho-p70S6K, also known as RPS6KB1 (ribosomal protein S6 kinase, 70kDa, polypeptide 1) (T389), an mTORC1 activation marker, predicted Flu resistance in a panel of B-cell lines, isogenic Flu-resistant (FluR) derivatives, and primary human CLL cells. Consistent with the anabolic role of mTORC1, FluR cells had higher rates of glycolysis and oxidative phosphorylation than Flu-sensitive (FluS) cells. Rapalogs (everolimus and rapamycin) induced moderate cell death in FluR and primary CLL cells, and everolimus significantly inhibited glycolysis and oxidative phosphorylation in FluR cells. Strikingly, the higher oxidative phosphorylation in FluR cells was not coupled to higher ATP synthesis. Instead, it contributed primarily to an essential, dihydroorotate dehydrogenase catalyzed, step in de novo pyrimidine biosynthesis. mTORC1 promotes pyrimidine biosynthesis by p70S6 kinase–mediated phosphorylation of CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase; Ser1859) and favors S-phase cell-cycle progression. We found increased phospho-CAD (S1859) and higher S-phase population in FluR cells. Pharmacological inhibition of de novo pyrimidine biosynthesis using N-phosphonacetyl-l-aspartate and leflunomide, RNAi-mediated knockdown of p70S6K, and inhibition of mitochondrial respiration were selectively cytotoxic to FluR, but not FluS, cells. These results reveal a novel link between mTORC1-mediated metabolic reprogramming and Flu resistance identifying mitochondrial respiration and de novo pyrimidine biosynthesis as potential therapeutic targets.

Implications: This study provides the first evidence for mTORC1/p70S6K-dependent regulation of pyrimidine biosynthesis in a relevant disease setting. Mol Cancer Res; 12(9); 1205–15. ©2014 AACR.
Data from Therapeutic Targeting of Nuclear γ-Tubulin in RB1-Negative Tumors
Authors: Lindström Lisa , Villoutreix Bruno O. , Lehn Sophie , Hellsten Rebecka , Nilsson Elise , Crneta Enisa , Olsson Roger , Alvarado-Kristensson Maria
Published: January 2024

Abstract
In addition to its cytosolic function, γ-tubulin is a chromatin-associated protein. Reduced levels of nuclear γ-tubulin increase the activity of E2 promoter-binding factors (E2F) and raise the levels of retinoblastoma (RB1) tumor suppressor protein. In tumor cells lacking RB1 expression, decreased γ-tubulin levels induce cell death. Consequently, impairment of the nuclear activity of γ-tubulin has been suggested as a strategy for targeted chemotherapy of RB1-deficient tumors; thus, tubulin inhibitors were tested to identify compounds that interfere with γ-tubulin. Interestingly, citral increased E2F activity but impaired microtubule dynamics while citral analogues, such citral dimethyl acetal (CDA), increased E2F activity without affecting microtubules. The cytotoxic effect of CDA on tumor cells was attenuated by increased expression of either RB1 or γ-tubulin, and increased by reduced levels of either RB1 or γ-tubulin. Mechanistic study, in silico and in vitro, demonstrated that CDA prevents GTP binding to γ-tubulin and suggested that the FDA-approved drug dimethyl fumarate is also a γ-tubulin inhibitor. Finally, in vivo growth of xenograft tumors carrying defects in the RB1 signaling pathway were inhibited by CDA treatment. These results demonstrate that inhibition of γ-tubulin has the potential to specifically target tumor cells and may aid in the design of safer and more efficient chemotherapeutic regimes.

Implications: The in vivo antitumorigenic activity of γ-tubulin inhibitors paves the way for the development of a novel broad range targeted anticancer therapy that causes fewer side effects. Mol Cancer Res; 13(7); 1073–82. ©2015 AACR.
Data from Structure, Dynamics, and Functionality of Tankyrase Inhibitor-Induced Degradasomes
Authors: Thorvaldsen Tor Espen , Pedersen Nina Marie , Wenzel Eva M. , Schultz Sebastian W. , Brech Andreas , Liestøl Knut , Waaler Jo , Krauss Stefan , Stenmark Harald
Published: January 2024

Abstract
Tankyrase (TNKS) enzymes, due to their poly(ADP-ribose) polymerase activity, have emerged as potential targets in experimental cancer therapy. However, the functional consequences of TNKS inhibition remain incompletely resolved because of the binding promiscuity of TNKS. One of the hallmarks of small-molecule TNKS inhibitors (TNKSi) is the stabilization of AXIN, which plays a pivotal role in the WNT/β-catenin signaling pathway. The present study focused on the known ability of TNKSi to induce cytoplasmic puncta (degradasomes) consisting of components of the signal-limiting WNT/β-catenin destruction complex. Using the colorectal cancer cell line SW480 stably transfected with GFP-TNKS1, it was demonstrated that a TNKS-specific inhibitor (G007-LK) induces highly dynamic and mobile degradasomes that contain phosphorylated β-catenin, ubiquitin, and β-TrCP. Likewise, G007-LK was found to induce similar degradasomes in other colorectal cancer cell lines expressing wild-type or truncated versions of the degradasome component APC. Super-resolution and electron microscopy revealed that the induced degradasomes in SW480 cells are membrane-free structures that consist of a filamentous assembly of high electron densities and discrete subdomains of various destruction complex components. Fluorescence recovery after photobleaching experiments further demonstrated that β-catenin–mCherry was rapidly turned over in the G007-LK-induced degradasomes, whereas GFP-TNKS1 remained stable. In conclusion, TNKS inhibition attenuates WNT/β-catenin signaling by promoting dynamic assemblies of functional active destruction complexes into a TNKS-containing scaffold even in the presence of an APC truncation.

Implications: This study demonstrates that β-catenin is rapidly turned over in highly dynamic assemblies of WNT destruction complexes (degradasomes) upon tankyrase inhibition and provides a direct mechanistic link between degradasome formation and reduced WNT signaling in colorectal cancer cells. Mol Cancer Res; 13(11); 1487–501. ©2015 AACR.
Data from PTK6 Potentiates Gemcitabine-Induced Apoptosis by Prolonging S-phase and Enhancing DNA Damage in Pancreatic Cancer
Authors: Ono Hiroaki , Basson Marc D. , Ito Hiromichi
Published: January 2024

Abstract
Protein Tyrosine Kinase 6 (PTK6) is a non-receptor–type tyrosine kinase known to be expressed in various cancers, including pancreatic cancer. The role of PTK6 in cancer chemoresistance remains unclear. Therefore, it was hypothesized that PTK6 mechanistically regulates gemcitabine resistance in pancreatic cancer. Gemcitabine treatment stimulated endogenous PTK6 overexpression in MIAPaCa2 and Panc1 cells. PTK6 gene silencing increased cell survival after gemcitabine treatment and decreased apoptosis, whereas PTK6 overexpression decreased cell survival and increased apoptosis. Selection for gemcitabine resistance revealed substantially lower PTK6 expression in the gemcitabine-resistant subclones compared with the parental lines, while restoring PTK6 rescued gemcitabine sensitivity. Gemcitabine induced phosphorylation of H2AX (γ-H2AX) and ataxia-telangiectasia mutated kinase (pATM), specific markers for DNA double-strand breaks. Both gemcitabine-induced phosphorylation of H2AX and ATM were reduced by PTK6 knockdown and increased by PTK6 overexpression. PTK6 overexpression also increased the S-phase fraction 48 hours after gemcitabine treatment. Although gemcitabine activated both caspase-8 (CASP8) and caspase-9 (CASP9), the effect of PTK6 on gemcitabine-induced apoptosis required CASP8 but not CASP9. In mouse xenografts, PTK6 overexpression in subcutaneous tumors attenuated tumor growth after gemcitabine treatment. In conclusion, PTK6 prolongs S-phase and increases the ability of gemcitabine to cause DNA damage in vitro and in vivo.

Implications: PTK6 affects cell cycle and DNA damage, thus making it an important therapeutic target to improve the outcomes of patients with pancreatic cancer. Mol Cancer Res; 13(8); 1174–84. ©2015 AACR.
Data from Prometastatic NEDD9 Regulates Individual Cell Migration via Caveolin-1–Dependent Trafficking of Integrins
Authors: Kozyulina Polina Y. , Loskutov Yuriy V. , Kozyreva Varvara K. , Rajulapati Anuradha , Ice Ryan J. , Jones Brandon C. , Pugacheva Elena N.
Published: January 2024

Abstract
The dissemination of tumor cells relies on efficient cell adhesion and migration, which in turn depends upon endocytic trafficking of integrins. In the current work, it was found that depletion of the prometastatic protein, NEDD9, in breast cancer cells results in a significant decrease in individual cell migration due to impaired trafficking of ligand-bound integrins. NEDD9 deficiency does not affect the expression or internalization of integrins but heightens caveolae-dependent trafficking of ligand-bound integrins to early endosomes. Increase in mobility of ligand-bound integrins is concomitant with an increase in tyrosine phosphorylation of caveolin-1 (CAV1) and volume of CAV1-vesicles. NEDD9 directly binds to CAV1 and colocalizes within CAV1 vesicles. In the absence of NEDD9, the trafficking of ligand-bound integrins from early to late endosomes is impaired, resulting in a significant decrease in degradation of ligand–integrin complexes and an increase in recycling of ligand-bound integrins from early endosomes back to the plasma membrane without ligand disengagement, thus leading to low adhesion and migration. Reexpression of NEDD9 or decrease in the amount of active, tyrosine 14 phosphorylated (Tyr14) CAV1 in NEDD9-depleted cells rescues the integrin trafficking deficiency and restores cellular adhesion and migration capacity. Collectively, these findings indicate that NEDD9 orchestrates trafficking of ligand-bound integrins through the attenuation of CAV1 activity.

Implications: This study provides valuable new insight into the potential therapeutic benefit of NEDD9 depletion to reduce dissemination of tumor cells and discovers a new regulatory role of NEDD9 in promoting migration through modulation of CAV1-dependent trafficking of integrins. Mol Cancer Res; 13(3); 423–38. ©2014 AACR.
Neuropsychological Assessments of Cognitive Impairment in Major Depressive Disorder: A Systematic Review and Meta-Analysis with Meta-Regression
Authors: Rhee Taeho Greg , Shim Sung Ryul , Manning Kevin J. , Tennen Howard A. , Kaster Tyler S. , d’Andrea Giacomo , Forester Brent P. , Nierenberg Andrew A. , McIntyre Roger S. , Steffens David C.
Published: January 2024

Introduction: Cognitive dysfunction or deficits are common in patients with major depressive disorder (MDD). The current study systematically reviews and meta-analyzes multiple domains of cognitive impairment in patients with MDD. Methods: PubMed/MEDLINE, PsycINFO, Cochrane Library, Embase, Web of Science, and Google Scholar were searched from inception through May 17, 2023, with no language limits. Studies with the following inclusion criteria were included: (1) patients with a diagnosis of MDD using standardized diagnostic criteria; (2) healthy controls (i.e., those without MDD); (3) neuropsychological assessments of cognitive impairment using Cambridge Neuropsychological Test Automated Battery (CANTAB); and (4) reports of sufficient data to quantify standardized effect sizes. Hedges’ g standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were used to quantify effect sizes of cognitive impairments in MDD. SMDs were estimated using a fixed- or random-effects models. Results: Overall, 33 studies consisting of 2,596 subjects (n = 1,337 for patients with MDD and n = 1,259 for healthy controls) were included. Patients with MDD, when compared to healthy controls, had moderate cognitive deficits (SMD, −0.39 [95% CI, −0.47 to −0.31]). In our subgroup analyses, patients with treatment-resistant depression (SMD, −0.56 [95% CI, −0.78 to −0.34]) and older adults with MDD (SMD, −0.51 [95% CI, −0.66 to −0.36]) had greater cognitive deficits than healthy controls. The effect size was small among unmedicated patients with MDD (SMD, −0.19 [95% CI, −0.37 to −0.00]), and we did not find any statistical difference among children. Cognitive deficits were consistently found in all domains, except the reaction time. No publication bias was reported. Conclusion: Because cognitive impairment in MDD can persist in remission or increase the risk of major neurodegenerative disorders, remediation of cognitive impairment in addition to alleviation of depressive symptoms should be an important goal when treating patients with MDD.