bluuebunny/crossref_metadata_2025 huggingface dataset:
What’s the big IDEA? Incorporating inclusion, diversity, equity, and access (IDEA) in population health nutrition research and practice
Authors: Baranowski Maria , Webb Nikki , Slater Joyce
Published: February 2024

Historically, the constructs of inclusion, diversity, equity, and access (IDEA) have not been sufficiently considered or included in population health nutrition research and practice. Consequently, current nutrition assessment benchmarks and knowledge translation tools may not accurately or adequately reflect diversity in the Canadian population or produce meaningful dietary guidance. The purpose of this current opinion paper is to introduce the population health nutrition research and practice framework and explore the current application of IDEA within this framework. Recommendations are offered to incorporate the constructs of IDEA along the continuum of future nutrition research and services to improve population nutritional health.
Primordial black holes and secondary gravitational waves from generalized power-law non-canonical inflation with quartic potential
Authors: Heydari Soma , Karami Kayoomars
Published: February 2024

Here, generation of PBHs and secondary GWs from non-canonical inflation with quartic potential have been probed. It is illustrated that, quartic potential in non-canonical setup with a generalized power-law Lagrangian density can source a consistent inflationary era with the latest observational data. Besides, we show that our model satisfies the swampland criteria. At the same time, defining a peaked function of inflaton field as non-canonical mass scale parameter $$M(\phi )$$

M
(
ϕ
)

of the Lagrangian, gives rise to slow down the inflaton in a while. In this span, namely Ultra-Slow-Roll (USR) stage, the amplitude of the curvature perturbations on small scales enlarges versus CMB scales. It has been illustrated that, further to the peaked aspect of the chosen non-canonical mass scale parameter, the amount of $$\alpha $$
α
parameter of the Lagrangian has enlarging impact on the amplitude of the scalar perturbations. As a consequence of adjusting three parameter Cases of this model, three Cases of PBHs in proper mass scopes to explain LIGO-VIRGO events, microlensing events in OGLE data and DM content in its totality, could be produced. In the end, power-law behavior of the current density parameter of gravitational waves $$\Omega _{\mathrm{GW_0}}$$

Ω

GW
0

in terms of frequency has been examined. Also, the logarithmic power index as $$n=3-2/\ln (f_c/f)$$

n
=
3
-
2
/
ln
(

f
c

/
f
)

in the infrared regime is obtained.
Four Novel Dual Discrete Memristor-Coupled Hyperchaotic Maps
Authors: Zhang Shaohua , Wang Cong , Zhang Hongli
Published: February 2024

Unlike the high-dimensional hyperchaotic system based on a continuous memristor, the low-dimensional map coupled by discrete memristor (DM) and traditional chaotic map can also generate hyperchaos. However, the hyperchaotic map constructed by two DMs has not attracted much attention. To this end, a generalized two-dimensional dual DM-coupled hyperchaotic mapping model is reported in this paper, and four specific maps are provided. The proposed maps have line invariant points, which can be interpreted as allowing arbitrary real values for the initial condition associated with the DM, and the stability is investigated in detail. Furthermore, the coupling strength-dependent and initial condition-dependent complex dynamics of four maps are studied by numerical simulations, and the dynamical performance is evaluated from the perspective of quantitative analysis. It is shown that the considered maps are capable of exhibiting the three characteristic fingerprints of memristors in arbitrary parameter spaces, and this characteristic has gained attention for the first time. In particular, the complete control of the considered maps by variable substitution is performed, which can generate arbitrary switched hyperchaotic behaviors. In addition, four pseudo-random number generators are designed based on the proposed maps, and the randomness is tested by using the NIST SP800-22 software. In general, the proposed maps can not only generate abundant dynamical behaviors, but also enrich the DM circuits and provide a reference for applications based on chaos. Finally, the developed digital hardware circuit implementation platform verifies the results of the numerical method.
2D Generating Surfaces and Dividing Surfaces in Hamiltonian Systems with Three Degrees of Freedom
Authors: Katsanikas Matthaios , Wiggins Stephen
Published: February 2024

In our previous work, we developed two methods for generalizing the construction of a periodic orbit dividing surface for a Hamiltonian system with three or more degrees of freedom. Starting with a periodic orbit, we extend it to form a torus or cylinder, which then becomes a higher-dimensional object within the energy surface (see [Katsanikas & Wiggins, 2021a, 2021b, 2023a, 2023b]). In this paper, we present two methods to construct dividing surfaces not from periodic orbits but by using 2D surfaces (2D geometrical objects) in a Hamiltonian system with three degrees of freedom. To illustrate the algorithm for this construction, we provide benchmark examples of three-degree-of-freedom Hamiltonian systems. Specifically, we employ the uncoupled and coupled cases of the quadratic normal form of a Hamiltonian system with three degrees of freedom.
Supporting Safety Analysis of Image-processing DNNs through Clustering-based Approaches
Authors: Attaoui Mohammed Oualid , Fahmy Hazem , Pastore Fabrizio , Briand Lionel
Published: February 2024

The adoption of
deep neural networks (DNNs)
in safety-critical contexts is often prevented by the lack of effective means to explain their results, especially when they are erroneous. In our previous work, we proposed a white-box approach (HUDD) and a black-box approach (SAFE) to automatically characterize DNN failures. They both identify clusters of similar images from a potentially large set of images leading to DNN failures. However, the analysis pipelines for HUDD and SAFE were instantiated in specific ways according to common practices, deferring the analysis of other pipelines to future work.

In this article, we report on an empirical evaluation of 99 different pipelines for root cause analysis of DNN failures. They combine transfer learning, autoencoders, heatmaps of neuron relevance, dimensionality reduction techniques, and different clustering algorithms. Our results show that the best pipeline combines transfer learning, DBSCAN, and UMAP. It leads to clusters almost exclusively capturing images of the same failure scenario, thus facilitating root cause analysis. Further, it generates distinct clusters for each root cause of failure, thus enabling engineers to detect all the unsafe scenarios. Interestingly, these results hold even for failure scenarios that are only observed in a small percentage of the failing images.
Token-Event-Role Structure-Based Multi-Channel Document-Level Event Extraction
Authors: Wan Qizhi , Wan Changxuan , Xiao Keli , Xiong Hui , Liu Dexi , Liu Xiping , Hu Rong
Published: February 2024

Document-level event extraction is a long-standing challenging information retrieval problem involving a sequence of sub-tasks: entity extraction, event type judgment, and event type-specific multi-event extraction. However, addressing the problem as multiple learning tasks leads to increased model complexity. Also, existing methods insufficiently utilize the correlation of entities crossing different events, resulting in limited event extraction performance. This article introduces a novel framework for document-level event extraction, incorporating a new data structure called token-event-role and a multi-channel argument role prediction module. The proposed data structure enables our model to uncover the primary role of tokens in multiple events, facilitating a more comprehensive understanding of event relationships. By leveraging the multi-channel prediction module, we transform entity and multi-event extraction into a single task of predicting token–event pairs, thereby reducing the overall parameter size and enhancing model efficiency. The results demonstrate that our approach outperforms the state-of-the-art method by 9.5 percentage points in terms of the
F
1 score, highlighting its superior performance in event extraction. Furthermore, an ablation study confirms the significant value of the proposed data structure in improving event extraction tasks, further validating its importance in enhancing the overall performance of the framework.
Web Application Security: A Pragmatic Exposé
Authors: Aladi Clement C.
Published: February 2024

Many individuals, organizations, and industries rely on web applications for the daily operations of their businesses. With the increasing deployment and dependence on these applications, significant attention has been directed toward developing more accurate and secure mechanisms to safeguard them from malicious web-based attacks. The slow adoption of the latest security protocols, coupled with the utilization of inaccurate and inadequately tested security measures, has hindered the establishment of efficient and effective security measures for web apps. This article reviews recent research and their recommendations for web security over the last 4 years. It identifies code injection as one of the recent most prevalent web-based attacks. The recommendations presented in this article offer a practical guide, enabling individuals and security personnel across various industries and organizations to implement tested and proven security measures for web applications. Furthermore, it serves as a roadmap for security developers, aiding them in creating more accurate and quantifiable measures and mechanisms for web security.
Explicating Geo-Tagging Behavior on Social Media: Role of Interpersonal Competence, Self-Regulation, Online Affiliation, and Privacy Calculus
Authors: Bhagat Sarbottam , Kim Dan J.
Published: February 2024

Geo-tagging features in social media apps allow users to announce their precise location with great ease and convenience, but geo-tagging poses some serious risks to users' privacy since it involves revelation of one's physical location, a form of personal data, to other users within and across social networks, making them vulnerable to various online and offline attacks, ranging from users being stalked to their identities being stolen. Despite these risks, geo-tagging is increasingly becoming a popular culture in the virtual realm of social media. This study explores why individuals geo-tag on social media by drawing from self-determination theory and privacy calculus to illustrate the underlying factors that influence users to engage in geo-tagging behavior on social media platforms. Based on an online survey administered to 834 active users of social media, this study contends that users' interpersonal competence and self-regulation influence their online affiliation need, which, in turn, affects their geo-tagging behavior. Additionally, we find that perceived benefit and risk have moderation effects on the association between users' online affiliation need and their geo-tagging behavior.
A Trust-Enhanced Patent Recommendation Approach to University-Industry Technology Transfer
Authors: Chen Yuwen , Zhu Peihu , Ma Jian , Huang Xiaoming , Qin Jin
Published: February 2024

Technology transfer enables the technology from legal owners to be used by others, and it is essential for technology innovation in modern society. However, transferring technology from academia to industry has become a challenging task due to the "cultural divide" problem, where researchers in universities tend to focus on knowledge discovery, while companies focus on making profits with application of proven technologies. This creates a mistrust problem for companies to use academic patents invented by universities. Various recommendation methods have been proposed for technology transfer purposes, but few have addressed the trust issue caused by the cultural divide. This paper proposes a multidimensional trust-enhanced recommendation approach to promote academic patent trading. The approach extracts patent information, users' online interactions, and technology transfer information for recommendation calculation. It includes 1) measuring the degree of connectivity between companies and patents by the Personalized PageRank model; 2) measuring the trustworthiness of a potential patent transaction from the aspects of patent quality, inventor, and university; and 3) adopting a logistic regression model to integrate the above measurements. The results of our user-based experiment show that the proposed recommendation approach obtains higher average hit rate and higher willingness scores than current recommendation methods.
Mitigating Algorithm Aversion in Recruiting: A Study on Explainable AI for Conversational Agents
Authors: Fleiß Jürgen , Bäck Elisabeth , Thalmann Stefan
Published: February 2024

The use of conversational agents (CAs) based on artificial intelligence (AI) is becoming more common in the field of recruiting. Organizations are now adopting AI-based CAs for applicant (pre-)selection, but negative news coverage, especially the black-box character of AI, has hindered adoption. So far, little is known about the contextual factors influencing users' perception of AI-based CAs in general and the effect of provided explanations by explainable AI (XAI) in particular. While research on algorithm aversion provides some initial explanations, information regarding the effects of different XAI approaches on different types of decisions on the attitudes of (potential) applicants is scarce. Therefore, in this study, we use a quantitative, quota-representative study (n = 490) to assess the acceptance of CAs in recruiting. By applying an experimental within-subject design, we provide a more nuanced perspective on why and when providing explanations increases user acceptance. We also show that contextual factors such as the type of assessed skills are major determinants of this effect, and we conclude that XAI is not a "one-size-fits-all approach." Based on the insight that contextual factors of the decision problem are more important than the type of XAI approach itself, we argue that the use and the effects of explainability in recruiting need a more nuanced perspective, focusing on the fit of explanations with the user's characteristics and preferences.
How Do Job Seekers Respond to Cybervetting? An Exploration of Threats, Fear, and Access Control
Authors: Wakefield Robin L. , Wakefield Lane T.
Published: February 2024

The cybervetting activities of potential employers present a significant threat to job-seeking social media users because their content becomes vulnerable to unwanted access and scrutiny. Without control over access, personal information may be gathered from social media and used in ways that harm the job seeker. Access control is a critical element of information privacy that has not received much attention but can help explain individuals' privacy behaviors. We use a protection motivation framework and a fear appeal to examine how job-seeking SNS users respond to cybervetting. We analyze the responses of 375 job-seeking SNS users to understand the relationships among threat perceptions, fear, coping responses, access control, and intention to implement and use an ephemeral application. We argue that when confronted by cybervetting, job-seeking SNS users are favorable toward using an ephemeral application because it bolsters privacy and meets the psychological need for control over access. Our results show that access control moderates the fear response to cybervetting, it is prompted by users' coping responses, and it helps explain why response efficacy and self-efficacy are predictive of behavioral intention.
Bridging the Gap Between Pouch and Coin Cell Electrochemical Performance in Lithium Metal Batteries
Authors: Soulen Charles , Lam Nicholas , Holoubek John , Liu Ping
Published: February 2024

In lithium metal battery research, coin cells (CC) are the most widely used laboratory instrument in academic settings. However, results thus obtained often don’t translate into pouch cell (PC) performance, which is regarded as a more reliable indicator for commercial relevance. Using both experimental and computational results, we show here that the root cause lies in the pressure distribution in these two cell formats. CCs suffer from a severe pressure inhomogeneity due to the geometry of the wave spring used to apply pressure to the cell stack. Replacing the wave spring with an elastic rubber disc applies a laterally uniform force to the cell stack, resulting in a homogeneous pressure distribution. Li||Cu half cells and Cu||LiNi0.5Mn0.3Co0.2O2 anode-free full cells using the updated structure show performance metrics on par with chemically identical PCs while traditional CCs underperform. Our solution to this common problem retains the quick, easy fabrication of CCs while producing results comparable to the PC-level.
Extraction-Less Amperometric Detection of Tetrodotoxin in Seawater
Authors: Robertson Stuart J. , Cheng Jinping , Shao Minhua
Published: February 2024

Tetrodotoxin (TTX), a potent neurotoxin, has recently been detected in marine fauna and waters in multiple locations outside its historical range and is projected to increase in both stability and bioavailability in acidifying oceans. We report the first biosensor designed to detect sub-ng ml−1 concentrations of TTX directly in natural seawater. The compact sensor chip employs a competitive enzyme strategy with a glucose oxidase-TTX conjugate that generates an amperometric response in the presence of a ferricyanide redox mediator. The biorecognition layer synthesis is confirmed by attenuated total reflection Fourier transform infrared spectroscopy. Cyclic voltammetry and electrochemical impedance spectroscopy are used to probe the stability and hydrophilicity of the biorecognition layer. We investigate the effects of nonspecific adsorption on sensor results and find that bovine serum albumen is an excellent blocking agent for preventing NSA when incubating with filtered seawater samples. The biosensor has a limit of detection of 0.053 ng ml−1 and a sensitivity of 87 nA ng−1 ml. Requiring no extraction or preconcentration steps with a time-to-results of under an hour, our biosensor provides a new tool for detecting TTX in natural waters, which can lead to more proactive monitoring and higher throughput testing.
Research on the Influence of Characteristics of the Annular Connecting Pipe on the Transmission Loss of the Expanded Exhaust Muffler
Authors: Cheng Yue , Yuan Wenhua , Fu Jun , Ma Yi , Zheng Wei
Published: February 2024

In order to broaden the muffler frequency band in the low‐frequency range of the exhaust muffler and to achieve the purpose of broadband noise reduction, in this paper, a model of an annular connecting pipe muffler is proposed using the finite element method (FEM) to simulate the nonreflection boundary condition and to solve the transmission loss (TL). In addition, the experimental value is obtained by the spatial five‐point measurement method and compared with the simulated value, and the validity and reliability of the solution model are verified. Compared with a simple expansion muffler, the average TL of the annular connecting pipe muffler is increased by 11.86 dB, and the maximum TL is increased by 18.31 dB, effectively widening the muffler frequency area, and the overall performance is effectively improved. Finally, the influence of structural factors is analyzed, including the width (W) of the annular connecting pipe, the length (L) of the annular connecting pipe, and the length ratio (m) of the front and rear chambers on the TL and on the width of the anechoic frequency band. The results reveal that the width and length of the annular connecting pipe and front‐to‐back cavity length ratio are the most significant factors to influence the TL, muffler frequency band, and elimination or reduction of the passing frequency, respectively.
A Novel Technique for High-Performance Grid Integrated with Restricted Placement of PV-DG considering Load Change
Authors: Soliman Ayman M. , Emara Safaa M. , Hassan Amir Y.
Published: February 2024

The distributed generation (DG) units’ penetrations in power systems are becoming more prevalent. The majority of recent studies are now focusing on how to best position and size PV-DG units to further improve grid performance. In actuality, and as a result of ideal design requirements, the size and position of the PV are chosen and executed, and no luxury for a change. In this work, the PV-DG unit sizing and location were determined and placed beforehand. Also, load change is a fact and is to be highly considered in the grid. Studying the grid performance and how to enhance it under these conditions is the main objective of this study. This examination was executed using an IEEE 15 bus system in a MATLAB environment. Distribution lines were proposed to connect the PV-DG from its restricted location to the required bus. The purpose of this study is therefore to evaluate the grid’s performance with various actual loads on each bus while connecting a PV-DG unit through a distribution line while taking the available transfer capacity (ATC) of the network into account to find the optimally connected bus. The results said that the optimally connected bus is changed by changing the load which is not doable on land. The results obtained indicate that breaking up PV-DG units into smaller units in the same location and connecting them to every bus was the best option for improving grid performance.
Supplementary Figure S2 from Unsatisfactory Fecal Immunochemical Tests for Colorectal Cancer Screening: Prevalence, Reasons, and Subsequent Testing
Authors: Liu Po-Hong , Nair Rasmi G. , Skinner Celette Sugg , Murphy Caitlin C. , Kim Eric J. , Ortiz Cynthia , Wang Lei , Hu Ellen , Lykken Jacquelyn M. , Levin Theodore R. , Green Beverly B. , Hahn Erin E. , Santini Noel , Halm Ethan A.
Published: February 2024

This figure shows prevalence of unsatisfactory FIT over the study period
Supplemental Table 3 from The Association between State-Level Structural Racism and Alcohol and Tobacco Use Behaviors among a National Probability Sample of Black Americans
Authors: Woodard Nathaniel , Butler James , Ghosh Debarchana , Green Kerry M. , Knott Cheryl L.
Published: February 2024

Supplemental Table 3 reports the correlation matrix of structural racism measures, drinking and smoking behaviors, and demographic variables
Supplementary Table S6 from Genetic Factors and Long-term Treatment-Related Neurocognitive Deficits, Anxiety, and Depression in Childhood Leukemia Survivors: An Exome-Wide Association Study
Authors: Petrykey Kateryna , Lippé Sarah , Sultan Serge , Robaey Philippe , Drouin Simon , Affret-Bertout Laurence , Beaulieu Patrick , St-Onge Pascal , Baedke Jessica L. , Yasui Yutaka , Hudson Melissa M. , Laverdière Caroline , Sinnett Daniel , Krajinovic Maja
Published: February 2024

Multivariable regression analysis for the Moderate-severe anxiety, whole cohort.
Supplementary Table S3 from Genetic Factors and Long-term Treatment-Related Neurocognitive Deficits, Anxiety, and Depression in Childhood Leukemia Survivors: An Exome-Wide Association Study
Authors: Petrykey Kateryna , Lippé Sarah , Sultan Serge , Robaey Philippe , Drouin Simon , Affret-Bertout Laurence , Beaulieu Patrick , St-Onge Pascal , Baedke Jessica L. , Yasui Yutaka , Hudson Melissa M. , Laverdière Caroline , Sinnett Daniel , Krajinovic Maja
Published: February 2024

PLINK results for the Moderate-severe depression.
Figure S1 from Potential for Cure by Stage across the Cancer Spectrum in the United States
Authors: Hubbell Earl , Clarke Christina A. , Smedby Karin E. , Adami Hans-Olov , Chang Ellen T.
Published: February 2024

Cure fraction (with 95% confidence interval indicated by error
bars) by cancer type and stage at diagnosis among cases aged 40–79 years at diagnosis
in 2006–2015, followed for mortality through 2020, Surveillance, Epidemiology, and End
Results (SEER) 17 registries
Supplementary Figure S5 from Community-Level Factors Associated with Hepatocellular Carcinoma Incidence and Mortality: An Observational Registry Study
Authors: Mezzacappa Catherine , Rossi Raiza , Jaffe Ariel , Taddei Tamar H. , Strazzabosco Mario
Published: February 2024

Supplementary Figure S5: Correlation between average annual cases of HCC (y-axis) and proportion of adults 18-64 uninsured (x-axis).
Supplementary Figure 1 from Increase in the Life Expectancy of Patients with Cancer in the United States
Authors: Devasia Theresa P. , Howlader Nadia , Dewar Ron A. , Stevens Jennifer L. , Mittu Karen , Mariotto Angela B.
Published: February 2024

Illustration of loss in expectation of life for DLBCL for 55-year-old women diagnosed with DLBCL. The figure shows general population and cancer cohort survival curves and shows that the LEL is the difference in area underneath the two survival curves.
Supplementary Figure S1 from Decline in the Incidence of Distant Recurrence of Breast Cancer: A Population-Based Health Record Linkage Study, Australia 2001–2016
Authors: Lord Sarah J. , Daniels Benjamin , O'Connell Dianne L. , Kiely Belinda E. , Beith Jane , Smith Andrea L. , Pearson Sallie-Anne , Chiew Kim-Lin , Bulsara Max K. , Houssami Nehmat
Published: February 2024

Supplementary Figure S1: Timeline of Pharmaceutical Benefits Scheme subsidization of adjuvant taxanes and targeted therapies for breast cancer in Australia, 1995-2016.
Supplementary Table S4 from The Influence of Smoking and Occupational Risk Factors on DNA Methylation in the AHRR and F2RL3 Genes
Authors: Pelland-St-Pierre Laura , Pham Michael C. , Nguyen Alice Quynh Huong , Pasquet Romain , Taylor Sherryl A. , Bosson-Rieutort Delphine , Koushik Anita , Ho Vikki
Published: February 2024

Supplementary Table S4 shows regression coefficients that denote the difference in average DNA methylation level, as derived from the mean methylation ratios across all estimated CpG sites in the AHRR gene, and their associated 95%CI relative to the reference group. Multivariable models included adjustment for age, sex (not for stratified models), phase of blood sampling, education level, ethnicity, and smoking (CSI - cumulative smoking index). FWI of 0 was used to classify those as never exposed, >0-population median value as ‘Low exposure’ and ≥population median value as ‘High exposure.’
Supplementary Table S3 from The Influence of Smoking and Occupational Risk Factors on DNA Methylation in the AHRR and F2RL3 Genes
Authors: Pelland-St-Pierre Laura , Pham Michael C. , Nguyen Alice Quynh Huong , Pasquet Romain , Taylor Sherryl A. , Bosson-Rieutort Delphine , Koushik Anita , Ho Vikki
Published: February 2024

Supplementary Table S3 shows for the continuous representation of smoking (CSI), regression coefficients that denote the difference in average DNA methylation levels, as derived from the mean methylation ratios across all estimated CpG sites, per standard deviation increase in CSI, and their associated 95%CI relative to the reference group. For categorical representations of smoking (i.e., former and current smokers), regression coefficients denote the difference in average DNA methylation level, as derived from the mean methylation ratios across all estimated CpG sites, and their associated 95%CI relative to the reference group. Multivariable models included adjustment for age, sex, phase of blood sampling, education level, and ethnicity.
Supplementary Figure S5 from The Influence of Smoking and Occupational Risk Factors on DNA Methylation in the AHRR and F2RL3 Genes
Authors: Pelland-St-Pierre Laura , Pham Michael C. , Nguyen Alice Quynh Huong , Pasquet Romain , Taylor Sherryl A. , Bosson-Rieutort Delphine , Koushik Anita , Ho Vikki
Published: February 2024

Supplementary Figure S5 shows the correlation coefficients on the lower triangle of the matrix. The upper triangle of the matrix uses circles to represent correlation coefficients: where a larger circle represents a stronger correlation, and a smaller circle represents a weaker correlation. Also, on the right of the matrix is the color scale for the circles: where blue
represents a positive correlation while red represents a negative correlation.
Data from Evaluating the Impact of Race and Ethnicity on Health-Related Quality of Life Disparities in Patients with Esophageal Cancer: A SEER-MHOS National Database Study
Authors: Wu Trudy C. , Farrell Matthew J. , Karimi-Mostowfi Nicki , Chaballout Basil H. , Akingbemi Wisdom O. , Grogan Tristan R. , Raldow Ann C.
Published: February 2024

AbstractBackground:
It is unclear whether health-related quality of life (HRQOL) disparities exist between racial/ethnic groups in older patients with esophageal cancer, pre- and post-diagnosis.
Methods:
Using the SEER-MHOS (Surveillance, Epidemiology, and End Results and Medicare Health Outcomes Survey) national database, we included patients ages 65-years-old or greater with esophageal cancer diagnosed from 1996 to 2017. HRQOL data within 36 months before and after diagnosis were measured by the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the SF-36 and VR-12 instruments. Total combined score (TCS) was reflected by both PCS and MCS.
Results:
We identified 1,312 patients, with evaluable data on 873 patients pre-diagnosis and 439 post-diagnosis. On pre-diagnosis cohort MVA, the MCS was better for White over Hispanic patients (54.1 vs. 48.6, P = 0.012). On post-diagnosis cohort MVA, PCS was better for Hispanic compared with White (39.8 vs. 34.5, P = 0.036) patients, MCS was better for Asian compared with White (48.9 vs. 40.9, P = 0.034) patients, and TCS better for Asian compared with White (92.6 vs. 76.7, P = 0.003) patients.
Conclusions:
In older patients with esophageal cancer, White patients had better mental HRQOL as compared with Hispanic patients pre-diagnosis. However, post-diagnosis, White patients had worse mental and physical HRQOL compared with Asian and Hispanic patients, respectively, suggesting a greater negative impact on self-reported HRQOL in White patients with esophageal cancer.
Impact:
To our knowledge, this study is the first to explore HRQOL differences in patients with esophageal cancer of various racial and ethnic groups and warrants further validation in future studies.
Choosing Wisely: Applying Value-Based Economic Principles to Population Science Research Investment
Authors: Frick Kevin D. , Helzlsouer Kathy J.
Published: February 2024

Scientific research requires a substantial investment of time, effort, and money by researchers and funders. The funding that would be needed for all meritorious proposals far exceeds available resources. Major funding organizations use a multistep process for allocating research dollars that follows and extends beyond scientific peer review with considerations including mission priority, budget, and potential duplication of past or ongoing research activities. At the level of programmatic review, the process tends to be less proscribed than scientific review, but considerations relate to and are akin to basic value-driven economic principles. We propose a framework that encompasses the elements of programmatic review and provide examples of how the economic principles of opportunity costs, diminishing marginal productivity, sunk costs, economic optimization, return on investment, and option value apply to both research planning and funding decisions. Examples use cancer control population science research, as the nature of observational and interventional research involves large population studies (large sample size, recruitment, and often long-duration follow-up costs) which demand a high level of resource utilization; the same principles can be applied throughout medical and population health research. Awareness of the aspects of programmatic review and context to focus discussion regarding funding decisions may help guide research planning, decision-making, and increase transparency of the overall review process.
Trends of Prostate Cancer Morbidity in Low-Incidence Countries from 1990–2019
Authors: Jiang Jinjiang , Chen Bo , Tang Bo , Yang Jie , Zhang Ting , Li Jinze , Tan Daqing , Wei Qiang
Published: February 2024

Background:

Our study was designed to elucidate the morbidity trends of prostate cancer in low-incidence countries.

Methods:

Data on prostate cancer were extracted from the 2019 Global Burden of Disease study. A cluster analysis of growth rates stratified by age was conducted, and correlation analyses were performed between age-standardized incidence rates (ASIR), estimated annual percent change (EAPC), and socio-demographic index (SDI).

Results:

Among 35 low-incidence countries for prostate cancer, predominantly located in Asia and North Africa, the SDI ranged from low to high-middle levels. Higher SDI regions exhibited considerably higher ASIR. With the exception of Kyrgyzstan, Kiribati, and Samoa that experienced a decrease in ASIR, the remaining 32 countries displayed an upward morbidity trend since 1990, with all their EAPCs exceeding the global average. In addition, men ages 90 years and above consistently exhibited the highest ASIR for prostate cancer. The most notable growth rate of ASIR was observed in individuals ages 20 to 44 years.

Conclusions:

Overall, low-incidence countries generally witnessed an increase in prostate cancer morbidity, albeit at levels lower than those seen in Western countries. Individuals ages 90 years and above consistently maintained the highest ASIR since 1990. Notably, more substantial increase of ASIR in younger age was also observed in low-incidence countries.

Impact:

This study offers a comprehensive overview of prostate cancer morbidity in low-incidence countries worldwide from 1990 to 2019. Future research should delve into the associations between incidence, clinical stages, PSA screening, environmental factors, lifestyle, and genetic risk in these low-incidence countries.
Cracking the Genomic Code of CDK4/6 Inhibitor Resistance
Authors: Wander Seth A. , Bardia Aditya
Published: February 2024

The therapeutic approach to metastatic hormone receptor–positive, human epidermal growth factor-2–negative metastatic breast cancer (HR+/HER2− MBC) has evolved rapidly over recent years. The cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have become first-line targeted agents of choice, in combination with an antiestrogen. Simultaneously, the clinical landscape of therapeutic options has been rapidly shifting, with novel antiestrogens, signal transduction inhibitors, and next-generation CDK inhibitors in various stages of development. Given these dynamic changes, understanding the genomic and molecular landscape of resistance to currently available antiestrogen therapy and CDK4/6 inhibitors represents a major focus of translational breast cancer research globally.

See related article by Goetz et al., p. 2233
Understanding Mechanisms of Response to CAR T-cell Therapy through Single-Cell Sequencing: Insights and Challenges
Authors: Haradhvala Nicholas J. , Maus Marcela V.
Published: February 2024

Single-cell RNA sequencing has emerged as a powerful technique to understand the molecular features of chimeric antigen receptor (CAR) T cells that associate with clinical outcomes. Here we discuss the common themes that have emerged from across single-cell studies of CAR T-cell therapy, and summarize the challenges in interpreting this complex data type.
Table S3 from FPFT-2216, a Novel Anti-lymphoma Compound, Induces Simultaneous Degradation of IKZF1/3 and CK1α to Activate p53 and Inhibit NFκB Signaling
Authors: Kanaoka Daiki , Yamada Mitsuo , Yokoyama Hironori , Nishino Satoko , Kunimura Naoshi , Satoyoshi Hiroshi , Wakabayashi Shota , Urabe Kazunori , Ishii Takafumi , Nakanishi Masato
Published: February 2024

Table S3 shows patients information on DLBCL PDX models used in this study.
Data from FPFT-2216, a Novel Anti-lymphoma Compound, Induces Simultaneous Degradation of IKZF1/3 and CK1α to Activate p53 and Inhibit NFκB Signaling
Authors: Kanaoka Daiki , Yamada Mitsuo , Yokoyama Hironori , Nishino Satoko , Kunimura Naoshi , Satoyoshi Hiroshi , Wakabayashi Shota , Urabe Kazunori , Ishii Takafumi , Nakanishi Masato
Published: February 2024

Abstract
Reducing casein kinase 1α (CK1α) expression inhibits the growth of multiple cancer cell lines, making it a potential therapeutic target for cancer. Herein, we evaluated the antitumor activity of FPFT-2216—a novel low molecular weight compound—in lymphoid tumors and elucidated its molecular mechanism of action. In addition, we determined whether targeting CK1α with FPFT-2216 is useful for treating hematopoietic malignancies. FPFT-2216 strongly degraded CK1α and IKAROS family zinc finger 1/3 (IKZF1/3) via proteasomal degradation. FPFT-2216 exhibited stronger inhibitory effects on human lymphoma cell proliferation than known thalidomide derivatives and induced upregulation of p53 and its transcriptional targets, namely, p21 and MDM2. Combining FPFT-2216 with an MDM2 inhibitor exhibited synergistic antiproliferative activity and induced rapid tumor regression in immunodeficient mice subcutaneously transplanted with a human lymphoma cell line. Nearly all tumors in mice disappeared after 10 days; this was continuously observed in 5 of 7 mice up to 24 days after the final FPFT-2216 administration. FPFT-2216 also enhanced the antitumor activity of rituximab and showed antitumor activity in a patient-derived diffuse large B-cell lymphoma xenograft model. Furthermore, FPFT-2216 decreased the activity of the CARD11/BCL10/MALT1 (CBM) complex and inhibited IκBα and NFκB phosphorylation. These effects were mediated through CK1α degradation and were stronger than those of known IKZF1/3 degraders. In conclusion, FPFT-2216 inhibits tumor growth by activating the p53 signaling pathway and inhibiting the CBM complex/NFκB pathway via CK1α degradation. Therefore, FPFT-2216 may represent an effective therapeutic agent for hematopoietic malignancies, such as lymphoma.
Significance:
We found potential vulnerability to CK1α degradation in certain lymphoma cells refractory to IKZF1/3 degraders. Targeting CK1α with FPFT-2216 could inhibit the growth of these cells by activating p53 signaling. Our study demonstrates the potential therapeutic application of CK1α degraders, such as FPFT-2216, for treating lymphoma.
Brain Shift during Staged Deep Brain Stimulation for Movement Disorders
Authors: Chee Keanu , Hirt Lisa , Mendlen Madelyn , Machnik Jannika , Razmara Ashkaun , Bayman Eric , Thompson John A. , Kramer Daniel R.
Published: February 2024

Introduction: Deep brain stimulation (DBS) is a routine neurosurgical procedure utilized to treat various movement disorders including Parkinson’s disease (PD), essential tremor (ET), and dystonia. Treatment efficacy is dependent on stereotactic accuracy of lead placement into the deep brain target of interest. However, brain shift attributed to pneumocephalus can introduce unpredictable inaccuracies during DBS lead placement. This study aimed to determine whether intracranial air is associated with brain shift in patients undergoing staged DBS surgery. Methods: We retrospectively evaluated 46 patients who underwent staged DBS surgery for PD, ET, and dystonia. Due to the staged nature of DBS surgery at our institution, the first electrode placement is used as a concrete fiducial marker for movement in the target location. Postoperative computed tomography (CT) images after the first electrode implantation, as well as preoperative, and postoperative CT images after the second electrode implantation were collected. Images were analyzed in stereotactic targeting software (BrainLab); intracranial air was manually segmented, and electrode shift was measured in the x, y, and z plane, as well as a Euclidian distance on each set of merged CT scans. A Pearson correlation analysis was used to determine the relationship between intracranial air and brain shift, and student’s t test was used to compare means between patients with and without radiographic evidence of intracranial air. Results: Thirty-six patients had pneumocephalus after the first electrode implantation, while 35 had pneumocephalus after the second electrode implantation. Accumulation of intracranial air following the first electrode implantation (4.49 ± 6.05 cm3) was significantly correlated with brain shift along the y axis (0.04 ± 0.35 mm; r (34) = 0.36; p = 0.03), as well as the Euclidean distance of deviation (0.57 ± 0.33 mm; r (34) = 0.33; p = 0.05) indicating statistically significant shift on the ipsilateral side. However, there was no significant correlation between intracranial air and brain shift following the second electrode implantation, suggesting contralateral shift is minimal. Furthermore, there was no significant difference in brain shift between patients with and without radiographic evidence of intracranial air following both electrode implantation surgeries. Conclusion: Despite observing volumes as high as 22.0 cm3 in patients with radiographic evidence of pneumocephalus, there was no significant difference in brain shift when compared to patients without pneumocephalus. Furthermore, the mean magnitude of brain shift was <1.0 mm regardless of whether pneumocephalus was presenting, suggesting that intracranial air accumulation may not produce clinical significant brain shift in our patients.
Variations in Patterns of Prescribing Durvalumab in Stage III Lung Cancer: A Survey of Australian Medical Oncologists
Authors: Nindra Udit , Bray Victoria , Karikios Deme , Shafiei Mohsen , Subramaniam Shalini , Ding Pei , Kao Steven , Pal Abhijit
Published: February 2024

Introduction: Local Australian guidelines for the optimal management of stage III unresectable non-small cell lung cancer (NSCLC) are lacking. The American Society of Clinical Oncology (ASCO) guidelines recommend consolidation durvalumab for all patients with unresectable stage III NSCLC, irrespective of their PD-L1 expression or driver mutation status. The European Society of Medical Oncology (ESMO) differs, with consolidation durvalumab only recommended in those patients whose tumours express PD-L1. Methods: Due to differing global guidelines, we conducted an Australia and New Zealand wide survey of medical oncologists specialising in thoracic cancer to determine the variations in patterns of prescribing durvalumab in stage III unresectable NSCLC. This survey was done electronically and sponsored by the Thoracic Oncology Group of Australia (TOGA). Results: Thirty-two medical oncologists completed the survey. In patients with EGFR-mutated stage III unresectable NSCLC, 6% of respondents stated that they prescribed durvalumab for all patients, while an additional 6% strongly recommended treatment. Forty-four percent suggested little benefit of consolidation durvalumab in this cohort, with an additional 19% advocating for observation only. In patients with PD-L1 negative (0%) stage III unresectable NSCLC, 13% of respondents prescribed durvalumab for all patients, while an additional 56% strongly recommended treatment. Interestingly, 18%, 10%, and 10% of prescribers discussed self-funded oral tyrosine kinase inhibitor therapy in patients with EGFR, ALK, or ROS-1-mutated NSCLC respectively as a substitute for consolidation durvalumab. Conclusion: Overall, the clinical practice of Australian and New Zealand Medical Oncologists is variable, but remains consistent with either the ASCO or ESMO guidelines. Local practice guidelines are required to ensure consistency in prescribing patterns across Australia, as well as providing evidence for self-funded treatments outside standard of care.
Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism in SARS-CoV-2
Authors: Caguana-Vélez Oswaldo Antonio , Khilzi Karys , Piccari Lucilla , Rodríguez-Sevilla Juan Jose , Badenes-Bonet Diana , Gonzalez-Garcia Jose , Chalela Roberto , Arita Mariela , Rodó-Pin Anna , Herranz Anna , Admetlló Mireia , Villar-Garcia Judit , Molina Lluis , Zuccarino Flavio , Gea Joaquin , Balcells Eva , Rodríguez-Chiaradia Diego A.
Published: February 2024

Introduction: Chronic thromboembolic pulmonary disease (CTEPD) consists of persistent pulmonary vascular obstruction on imaging and involves long-term functional limitations, with or without chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to evaluate the incidence and risk factors of both persistent pulmonary vascular defects and CTEPH after hospitalization in patients with COVID-19 and PE during a 2-year follow-up. Methods: A prospective observational study was carried out in a tertiary hospital center. Patients were hospitalized between March 2020 and December 2021 with a diagnosis of PE during SARS-CoV-2 infection. Patients received anticoagulant treatment for at least 3 months and were followed up for 2 years. Between the third and fourth months after discharge, all patients were evaluated for the presence of residual thrombotic defects by CTPA and/or perfusion pulmonary scintigraphy. Clinical findings, lung function tests with DLCO, exercise capacity, and echocardiograms were also assessed. Results: Of the 133 patients included, 18% had persistent thrombotic defects on lung imaging at follow-up. The incidence of CTEPD was 0.75% at 2 years of follow-up. Patients with persistent defects were significantly older, had a higher prevalence of systemic arterial hypertension, higher D-dimer and NT-proBNP levels, and more severe PE at diagnosis. Furthermore, there was a higher prevalence of right ventricular dysfunction on echocardiogram at diagnosis of PE (25.0% vs. 2.7%, p = 0.006). This was the only variable independently related to persistent defects in multivariate analyses (OR: 8.13 [95% CI: 1.82–36.32], p = 0.006). Conclusion: The persistence of thrombotic defects after PE is a common finding after SARS-CoV-2 infection, affecting 18% of the population. However, the incidence of CTEPH appears to be lower (0.75%) in COVID-19-related PE compared to that previously observed in PE unrelated to COVID-19.
Sex-Specific Behavioural Deficits in Adulthood following Acute Activation of the GABAA Receptor in the Neonatal Mouse
Authors: Goikolea-Vives Ane , Fernandes Cathy , Thomas Michael S.C. , Thornton Claire , Stolp Helen B.
Published: February 2024

Introduction: Sex differences exist in the prevalence of neurodevelopmental disorders (NDDs). Part of the aetiology of NDDs has been proposed to be alterations in the balance between excitatory and inhibitory neurotransmission, leading to the question of whether males and females respond differently to altered neurotransmitter balance. We investigated whether pharmacological alteration of GABAA signalling in early development results in sex-dependent changes in adult behaviours associated with NDDs. Methods: Male and female C57BL/6J mice received intraperitoneal injections of 0.5 mg/kg muscimol or saline on postnatal days (P) 3–5 and were subjected to behavioural testing, specifically open field, light/dark box, marble-burying, sucralose preference, social interaction, and olfactory habituation/dishabituation tests between P60 and P90. Results: Early postnatal administration of muscimol resulted in reduced anxiety in the light/dark box test in both male and female adult mice. Muscimol reduced sucralose preference in males, but not females, whereas female mice showed reduced social behaviours. Regional alterations in cortical thickness were observed in the weeks following GABAA receptor activation, pointing to an evolving structural difference in the brain underlying adult behaviour. Conclusions: We conclude that activation of the GABAA receptor in the first week of life resulted in long-lasting changes in a range of behaviours in adulthood following altered neurodevelopment. Sex of the individual affected the nature and severity of these abnormalities, explaining part of the varied pathophysiology and neurodevelopmental diagnosis that derive from excitatory/inhibitory imbalance.