bluuebunny/crossref_metadata_2025 huggingface dataset:
The Conditional Distributivity for Uni-Nullnorms Over Uninorms
Authors: Zhang Xin , Qin Feng , Bi Han-Yu
Published: April 2023

The conditional distributivity of aggregation operators has always been the focus of research because it is crucial for various areas including integration theory, utility theory and so on. Therefore, this article is mainly devoted to dealing with the conditional distributivity of a uni-nullnorm over a uninorm with the continuous underlying operators and also gives the full characterization of each pair [Formula: see text] satisfying this property. Moreover, it extends the previous research results since they are now on a much wider class of uninorms.
A Genetic Algorithm for Solving Nonlinear Optimization Problem with Max-Archimedean Bipolar Fuzzy Relation Equations
Authors: Tiwari Vijay Lakshmi , Thapar Antika , Bansal Richa
Published: April 2023

This paper discusses a nonlinear optimization problem with the system of max-Archimedean bipolar fuzzy relation equations as constraints. Some results related to the structure of the solution set of max-Archimedean bipolar fuzzy relation equations are proved. Using these results, a genetic algorithm is proposed to solve the problem for obtaining optimal or converging solutions. The effectiveness of the algorithm is also compared with other methods found in the literature. The previous methods require conversion of the problem into 0-1 mixed integer optimization problem solvable by some nonlinear optimization solvers and thereby, the computational work may increase with the size of the problem. Some test problems are developed to evaluate the performance of the proposed algorithm.
KNOWLEDGE CAPITAL AND INNOVATION ACROSS FIRMS IN ASIAN ECONOMIES: A BALANCED INVESTMENT APPROACH
Authors: KHALIL MUHAMMAD AZHAR , NIMMANUNTA KRIDSDA
Published: April 2023

The difference between knowledge capital and innovation and their combined impact on firm market performance remains a puzzle. Firms can utilise their accumulated stock of knowledge to create value, and at the same time, allocate their resources each year to create innovation, hoping to sustain their performance and make a better future. Using time fixed effects panel regression with industry and country dummies, this study investigates how knowledge capital and innovation impact firm performance by analysing the sample of 2,958 listed companies of Asian countries during 2015–2019. We observe that different sectors exhibit strong variations in their levels of knowledge capital and innovation. This study finds that more knowledge capital negatively impacts firm performance, but up to a certain point. The U-shaped relationship found suggests that learning and accumulating capabilities to exploit knowledge capitals’ potential is essential to achieve higher firm value. We also find that firms’ more spending on innovation positively impacts firm performance, but only up to a certain level. An inverted U-shaped relationship found suggests a balanced investment in innovation activities to attain improved firm performance. Implications for management and potential for further research are provided.
Long silence on the East Anatolian Fault Zone (Southern Turkey) ends with devastating double earthquakes (6 February 2023) over a seismic gap: implications for the seismic potential in the Eastern Mediterranean region
Authors: Karabulut Hayrullah , Güvercin Sezim Ezgi , Hollingsworth James , Konca Ali Özgün
Published: April 2023

On 6 February 2023, an earthquake with magnitude M
w
c
. 7.0 on the Narlı Fault, a fault sub-parallel to the East Anatolian Fault Zone (EAFZ), initiated a chain of large earthquakes on the EAFZ. The earthquakes occurred in a seismic gap with low geodetic strain rates and low background seismicity, where deformation is distributed across a wide fault zone and a long recurrence time of historical earthquakes. The
c.
50 km long rupture of the Narlı Fault towards Pazarcık led to an M
w
7.8 left-lateral strike-slip earthquake breaking a
c.
300 km section of the
c.
600 km long EAFZ bilaterally with a total duration of more than 80 s. Toward the SW, the rupture propagated on the
c.
100 km long Amanos segment with a peak surface offset of 5 m, before diminishing toward the Hatay graben. In the NE direction, the rupture reached a peak surface offset of 7 m before sharply declining at the termination of the 2020 M
w
6.8 Sivrice earthquake rupture. A second large earthquake with M
w
7.6 occurred 9 h later on the Çardak Fault, located at the western margin of (and sub-parallel to) the EAFZ and breaking the surface with almost 9 m of left-lateral slip (average of
c.
4 m). Following these large earthquakes, the increase in the regional stress led to a rapid seismic activation in a broad region from central to eastern Anatolia, loading the faults at various scales and increasing seismic hazard. Two weeks after the initiation of the seismic crisis, a third earthquake with M
w
6.4 occurred at the southern boundary of the Hatay graben, near the southwestern termination of the Amanos rupture. The earthquakes caused significant loss of human life, devastating 12 cities. We evaluate the observations prior to the ruptures, and present preliminary seismological results with surface displacements from sub-pixel correlation of optical satellite images and the stress perturbations computed on the nearby faults based on preliminary slip models. The re-evaluation of the seismic potential in light of the recent and historical earthquakes provides some new insight on seismic hazard assessment. The recent series of events on the EAFZ is an important reminder that large faults can generate very large earthquakes on multiple segments. The seismic potential of large earthquakes on these fault zones can be estimated only by considering multiple seismic cycles and moment deficits from very large earthquakes.

Supplementary material
: Supplementary figures and tables are available at
https://doi.org/10.6084/m9.figshare.c.6567094
Learning Analytics: An Opportunity for Education
Authors: Baker Ryan S.
Published: April 2023

How analytics is transforming the future for millions of learners.
Building Inclusive and Equitable Artificial Intelligence for Education
Authors: Roscoe Rod D.
Published: April 2023

Four "who-ristic" questions to ask yourself when designing artificially intelligent educational technologies that will actually benefit people.
Making Speech Recognition Work for Children: An Interview with Amelia Kelly
Authors: Adair Amy , Koh Joewie J.
Published: April 2023

What does it take to build new AI technologies for education? Dr. Amelia Kelly, chief technology officer at SoapBox Labs, shares her experience with us in this interview.
Inq-ITS: Creating Rigorous Assessment and Real-Time Support of Science Learning
Authors: Gobert Janice D.
Published: April 2023

This article is an example of how theoretical frameworks about how people learn science were used in combination with computational techniques to develop authentic assessments and intelligent tutoring for science.
ChatGPT for Next Generation Science Learning
Authors: Zhai Xiaoming
Published: April 2023

This article pilots ChatGPT in tackling the most challenging part of science learning and found it successful in automation of assessment development, grading, learning guidance, and recommendation of learning materials.
Placement of Microservices-based IoT Applications in Fog Computing: A Taxonomy and Future Directions
Authors: Pallewatta Samodha , Kostakos Vassilis , Buyya Rajkumar
Published: April 2023

The Fog computing paradigm utilises distributed, heterogeneous and resource-constrained devices at the edge of the network for efficient deployment of latency-critical and bandwidth-hungry IoT application services. Moreover, MicroService Architecture (MSA) is increasingly adopted to keep up with the rapid development and deployment needs of fast-evolving IoT applications. Due to the fine-grained modularity of the microservices and their independently deployable and scalable nature, MSA exhibits great potential in harnessing Fog and Cloud resources, thus giving rise to novel paradigms like Osmotic computing. The loosely coupled nature of the microservices, aided by the container orchestrators and service mesh technologies, enables the dynamic composition of distributed and scalable microservices to achieve diverse performance requirements of the IoT applications using distributed Fog resources. To this end, efficient placement of microservice plays a vital role, and scalable placement algorithms are required to utilise the said characteristics of the MSA while overcoming novel challenges introduced by the architecture. Thus, we present a comprehensive taxonomy of recent literature on microservices-based IoT applications placement within Fog computing environments. Furthermore, we organise multiple taxonomies to capture the main aspects of the placement problem, analyse and classify related works, identify research gaps within each category, and discuss future research directions.
IoT Based Smart Baby Monitoring System with Emotion Recognition Using Machine Learning
Authors: Alam Hina , Burhan Muhammad , Gillani Anusha , Haq Ihtisham ul , Arshed Muhammad Asad , Shafi Muhammad , Ahmad Saeed
Published: April 2023

Child care is necessary for parents, but nowadays taking care of a child has become a lot more challenging, especially for working mothers. It has become increasingly difficult for parents to continuously monitor their baby’s condition. Thus, a smart baby monitoring system based on IoT and machine learning is implemented to overcome the monitoring issues and provide intimation to parents in real-time. In the proposed system, the necessary monitoring features like room temperature and humidity, cry detection, and face detection were monitored by exploiting different sensors. The sensor data is transferred to the Blynk server via controllers with an Internet connection. The system is also capable of detecting the facial emotions of the registered babies by using a machine learning model. Parents can monitor the live activities and emotions of their child through the external web camera and can swing the baby cradle remotely upon cry detection using their mobile application. They can also check the real-time room temperature and humidity level. In case an abnormal action is detected, a notification is sent to the parent’s mobile application to take action thus, making the baby monitoring system a relief for all working parents to manage their time efficiently while taking care of their babies simultaneously.
Mechanical and Thermal Adsorption Actions on Epoxy Hybrid Composite Layered with Various Sequences of Alkali-Treated Jute and Carbon Fibre
Authors: Sasikumar R. , Venkadeshwaran K. , Kannan C. Ramesh , De Poures Melvin Victor , Aruna M. , Mukilarasan N. , Kaliyaperumal Gopal , Murugan Arundeep
Published: April 2023

Structural applications are accomplished by using a lightweight epoxy matrix bonded with natural jute fibre/synthetic carbon fibre to enhance the physical, mechanical, and thermal properties obtained by different sequences of alkali-treated jute fibre (J.F.)/carbon fibre (C.F.) through conventional hand layup technique. The sequences of the sample are named as H1, H2, H3, and H4 layers of JF/JF/JF/JF, CF/CF/CF/CF, JF/CF/CF/JF, and CF/JF/JF/CF. Influences of JF/CF on physical, mechanical, and thermal adsorption properties of the epoxy composite are evaluated and compared. The mechanical tensile performance of the jute fibre-covered (JF/CF/CF/JF) composite H3 sample is augmented by 29% compared to the H4 sample. Similarly, the CF/JF/JF/CF combinations exhibited a higher impact strength of 129.71 KJ/m2. The maximum hardness of 47.12Hv was found on the four-layered carbon fibre. The thermal adsorption actions on developed composites are evaluated by thermogravimetric apparatus (TGA). It is confirmed that the presence of JF/CF in epoxy composites can endure stability at a higher temperature.
Identification of Inflammatory Gene in the Congenital Heart Surgery Patients following Cardiopulmonary Bypass via the Way of WGCNA and Machine Learning Algorithms
Authors: Cai Liang , Zhang Bingdong
Published: April 2023

Performing cardiopulmonary bypass (CPB) to reduce ischemic injury during surgery is a common approach to cardiac surgery. However, this procedure can lead to systemic inflammation and multiorgan dysfunction. Therefore, elucidating the molecular mechanisms of CPB-induced inflammatory cytokine release is essential as a critical first step in identifying new targets for therapeutic intervention. The GSE143780 dataset which is mRNA sequencing from total circulating leukocytes of the neonatorum was downloaded from the Gene Expression Omnibus (GEO) database. A total of 21 key module genes were obtained by analyzing the intersection of differentially expressed gene (DEG) and gene coexpression network analysis (WGCNA), and then, 4 genes (TRAF3IP2-AS1, PPARGC1B, CD4, and PDLIM5) were further confirmed after the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) screening and were used as hub genes for CPB-induced inflammatory cytokine release in patients with congenital heart defects. The enrichment analysis revealed 21 key module genes mainly related to the functions of developmental cell growth, regulation of monocyte differentiation, regulation of myeloid leukocyte differentiation, ERK1 and ERK2 cascade, volume-sensitive anion channel activity, and estrogen receptor binding. The result of gene set enrichment analysis (GSEA) showed that the hub genes were related to different physiological functions of cells. The ceRNA network established for hub genes includes 3 hub genes (PPARGC1B, CD4, and PDLIM5), 55 lncRNAs, and 34 miRNAs. In addition, 4 hub genes have 215 potential therapeutic agents. Finally, expression validation of the four hub genes revealed that they were all significantly low expressed in the surgical samples than before.
MAFLD in Patients with Cushing’s Disease Is Negatively Associated with Low Free Thyroxine Levels Rather than with Cortisol or TSH Levels
Authors: Chen Kuangyang , Chen Lijiao , Dai Jiarong , Ye Hongying
Published: April 2023

Purpose. This study aims to analyze the clinical characteristic of metabolic associated fatty liver disease (MAFLD) in patients with active Cushing’s disease (CD) and determine associations of thyroid hormones with MAFLD. Methods. Patients with active CD were included in this cross-sectional study. All subjects were assessed for hepatic steatosis by abdominal ultrasonography and thyroid functions. Demographic and clinical characteristic parameters were collected for correlation analysis and logistic analysis. Results. 290 individuals with active CD were included in Huashan hospital from January 2014 to February 2022. We found that the prevalence of CD with MAFLD was 33.79%. The MAFLD group had a lower level of FT4 and a higher level of FT3/FT4 but no difference in levels of cortisol, 24 h UFC, TSH, TT4, TT3, and FT3. Correlation analysis showed positive associations of TSH, TT4, TT3, FT3, and FT3/FT4 with BMI. In age-, BMI-, sex-, cortisol-, and 24 h UFC-adjusted analysis, FT4 was independently associated with MAFLD in patients with CD. This association remained similar even after adjusting for the presence of metabolic syndrome components. Conclusion. Lower FT4 levels were associated with higher risk of MAFLD in patients with CD. FT4 may be used as a helpful indicator to predict MAFLD and provide novel ideas for the treatment of MAFLD in patients with CD in the future.
Dynamic Response Analysis of Orthotropic Saturated Subgrade-Pavement Slab
Authors: Zhang Chunli , Yang Xinxin , Cheng Qing , Sun Zhuojun , Li Jie
Published: April 2023

Based on the Kirchhoff thin plate theory, a three-dimensional spatial mechanical model of the subgrade pavement with an infinite elastic plate on the orthotropic saturated foundation in the rectangular coordinate system is established, and the differential equations under a moving harmonic load are derived. The partial differential equations are solved by using coordinate transform and Fourier transform, and the analytical solutions of the dynamic responses of the plate and foundation are obtained. A three-dimensional spatial finite element model of subgrade-pavement is established by ABAQUS finite element software. The correctness of the method is verified by comparing the theoretical solution with the finite element solution. The influence of foundation parameters on plate displacement and vertical normal stress of soil is further studied. The results show that considering the orthogonal anisotropy of saturated soil, the dynamic response of subgrade-pavement slab interaction can be described more accurately.
Potential for Introduction of African Swine Fever Virus into High-Biosecurity Pig Farms by Flying Hematophagous Insects
Authors: Stelder Jonno Jorn , Olesen Ann Sofie , Belsham Graham J. , Rasmussen Thomas Bruun , Bøtner Anette , Kjær Lene Jung , Boklund Anette Ella , Bødker René
Published: April 2023

Background. DNA of African swine fever virus (ASFV) has previously been detected in hematophagous insects on ASF outbreak farms. However, it remains unclear whether the viral DNA derived from blood meals that originated from pigs on the outbreak farm or was introduced from infected domestic pigs or wild boar sources located outside of the outbreak farm. Methods. We caught 644 hematophagous insects on the windows at two non-outbreak high-biosecurity pig farms (i.e., without ASFV-infected pigs) using plastic meshes coated with sticky glue, as well as 3576 hematophagous insects using H-traps on or around the farms. Using PCR analyses, we identified which insects were present, whether these hematophagous insects carried blood from an external (exogenous) source and if the blood contained ASFV DNA. Results. We found blood meals with ASFV DNA in one pool of five Haematopota spp. in the H-traps. From the window traps, we found 0–2.7% of Haematopota spp., Stomoxys calcitrans, and Aedes spp. carrying blood meals from exogenous sources into the farms. Some insects carried bovine blood; the closest registered source for this was 2500m from the pig farm. Conclusion. Hematophagous insects carrying ASFV-positive blood meals or blood meals from exogenous sources seem to be attracted to high-biosecurity pig farms and attempt to enter them through their windows. Despite the small percentage of insects carrying blood and the small amounts carried by each insect, the large numbers of insects result in a sufficient volume of exogenous blood, potentially containing ASFV, to constitute a non-negligible risk for ASFV-introduction into unprotected pig stables. This study is the first to provide quantitative data on the number of hematophagous insects trying to enter high-biosecurity pig farms. It is also the first to provide information about the origin of their blood meals, indicating that insect-borne introduction of blood containing ASFV into high-biosecurity pig farms is possible and, therefore, could potentially be responsible for some of the outbreaks observed during the summer peaks of infection.
On a Multistable Type of Free Boundary Problem with a Flux at the Boundary
Authors: Ren Haitao , Cai Jingjing , Xu Li
Published: April 2023

This paper studies the free boundary problem of a multistable equation with a Robin boundary condition, which may be used to describe the spreading of the invasive species with the solution representing the density of species and the free boundary representing the boundary of the spreading region. The Robin boundary condition

u

x

t
,
0

=
τ
u

t
,
0

means that there is a flux of species at

x
=
0

. By studying the asymptotic properties of the bounded solution, we obtain the following two situations: (i) four types of survival states: the solution is either big spreading (the solution converges to a big stationary solution defined on the half-line) or small spreading (the solution converges to a small stationary solution defined on the half-line) or small equilibrium state (the survival interval

0
,
h

t

tends to a finite interval and the solution tends to a small compactly supported solution) or vanishing happens (the solution and the interval

0
,
h

t

shrinks to 0 as

t
⟶
T

for

T
<
+
∞

); (ii) a trichotomous survival states of solutions: big spreading, big equilibrium state, and vanishing.
Separation of Amino Acids, Dyes, and Pigments Using Novel Pressurized Circular TLC Assembly for Secure Medical Imaging Applications
Authors: Dar Amara , Ahmad Muhammad Nayab , Samin Ghufrana , Jahangir Muhammad Muzammil , Rehman Rabia , Anwar Jamil , Al-thagafi Zahrah T. , Meraf Zelalem , Jaber Mustafa Musa
Published: April 2023

A novel pressurized flow system for circular thin-layer chromatography (PC-TLC) has been successfully established and employed for the separation of amino acids, dyes, and pigments for safe medical imaging applications. In this system, the mobile phase is applied to a regular TLC plate through the tube and needle of an intravenous infusion set. The needle was fused in a hole underneath the center of the plate, while the second side end of the tube was connected to a microburette containing the solvent. This new assembly proved itself better in terms of separation time (within 5 minutes) and controlled flow of the solvent and horizontal movement of analyte components over chromatograms with better separation and Rf values (glutamine: 0.26, valine: 0.44, phenylalanine: 0.60, chlorophyll a: 0.52, chlorophyll b: 0.43, xanthophyll: 0.18, carotenoid: 0.97, and pheophytin: 0.60) when a number of samples of amino acids, dyes, and pigments were separated by the developed apparatus and the conventional TLC procedure. The developed method was found distinctly rapid, precise, and eco-friendly (less solvent consuming) as compared to traditional ascending TLC.
Supplementary Table 7 from Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC)
Authors: Wang Shuo , Onyeaghala Guillaume C. , Pankratz Nathan , Nelson Heather H. , Thyagarajan Bharat , Tang Weihong , Norby Faye L. , Ugoji Chinenye , Joshu Corinne E. , Gomez Christian R. , Couper David J. , Coresh Josef , Platz Elizabeth A. , Prizment Anna E.
Published: April 2023

Supplemental Table 7 shows the association of sMICA and sMICB levels (continuous variables) and pre-selected SNPsa with risk of CRC stratified by family history of CRC.
Supplemental Table 1 from Five-year Survival Trends for Young Adult Cancers Diagnosed from 2002 to 2014 in Taiwan and the United States
Authors: Tsai Yu-Han , Teng Yu-Tung , Kuan Tai-Chuan , Liu Jason J.
Published: April 2023

APC values for five-year age-standardized relative survival trends with more than one joinpoint segment
Supplementary Table 5 from Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC)
Authors: Wang Shuo , Onyeaghala Guillaume C. , Pankratz Nathan , Nelson Heather H. , Thyagarajan Bharat , Tang Weihong , Norby Faye L. , Ugoji Chinenye , Joshu Corinne E. , Gomez Christian R. , Couper David J. , Coresh Josef , Platz Elizabeth A. , Prizment Anna E.
Published: April 2023

Supplemental table 5 shows the associations between pre-selected SNPs and risk of CRC with and without adjustment for sMICA and sMICB levels.
Supplementary Table 3 from Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC)
Authors: Wang Shuo , Onyeaghala Guillaume C. , Pankratz Nathan , Nelson Heather H. , Thyagarajan Bharat , Tang Weihong , Norby Faye L. , Ugoji Chinenye , Joshu Corinne E. , Gomez Christian R. , Couper David J. , Coresh Josef , Platz Elizabeth A. , Prizment Anna E.
Published: April 2023

Supplemental Table 3 shows the associations between pre-selected SNPs and CRC risk stratified by sex, race, or diabetes status.
Figure S4 from Trend in Cervical Cancer Incidence and Mortality Rates in China, 2006–2030: A Bayesian Age-Period-Cohort Modeling Study
Authors: Yuan Meiwen , Zhao Xuelian , Wang Honghao , Hu Shangying , Zhao Fanghui
Published: April 2023

Figure S4 age-period-cohort effect on cervical cancer mortality rates in China between 2006 to 2016.
Figure S3 from Trend in Cervical Cancer Incidence and Mortality Rates in China, 2006–2030: A Bayesian Age-Period-Cohort Modeling Study
Authors: Yuan Meiwen , Zhao Xuelian , Wang Honghao , Hu Shangying , Zhao Fanghui
Published: April 2023

Figure S3 shows age-period-cohort effect on cervical cancer incidence rates in China between 2006 to 2016.
Supplemental Table 3 from Measurement of Ovarian Tumor Immune Profiles by Multiplex Immunohistochemistry: Implications for Epidemiologic Studies
Authors: Hathaway Cassandra A. , Conejo-Garcia Jose R. , Fridley Brooke L. , Rosner Bernard , Saeed-Vafa Daryoush , Moran Segura Carlos , Nguyen Jonathan V. , Hecht Jonathan L. , Sasamoto Naoko , Terry Kathryn L. , Tworoger Shelley S. , Townsend Mary K.
Published: April 2023

Supplemental Table 3 shows case characteristics included on tissue microarrays in NHS and NHSII
Supplemental Figure 1 from Measurement of Ovarian Tumor Immune Profiles by Multiplex Immunohistochemistry: Implications for Epidemiologic Studies
Authors: Hathaway Cassandra A. , Conejo-Garcia Jose R. , Fridley Brooke L. , Rosner Bernard , Saeed-Vafa Daryoush , Moran Segura Carlos , Nguyen Jonathan V. , Hecht Jonathan L. , Sasamoto Naoko , Terry Kathryn L. , Tworoger Shelley S. , Townsend Mary K.
Published: April 2023

Supplemental Figure 1 provides representative images from the T cell panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.
Data from Low-Carbohydrate Diet Score and the Risk of Colorectal Cancer: Findings from the Singapore Chinese Health Study
Authors: Yu Yi-Chuan , Paragomi Pedram , Jin Aizhen , Wang Renwei , Schoen Robert E. , Koh Woon-Puay , Yuan Jian-Min , Luu Hung N.
Published: April 2023

AbstractBackground:
Colorectal cancer is common cancer with a high mortality rate. Low-carbohydrate diet (LCD) score holistically evaluates the LCD pattern from carbohydrate, protein, and fat intake. Epidemiologic data of LCD–colorectal cancer association are sparse.
Methods:
We evaluated the associations between LCD (i.e., total, animal- and plant-based) and colorectal cancer risk in the Singapore Chinese Health Study, a population-based prospective cohort study including 61,321 Chinese in Singapore who were 45 to 74 years old at baseline. Cox proportional hazard regression model was used to determine the HRs and respective 95% confidence intervals (CI) for colorectal cancer associated with LCD after adjusting for potential confounders, including age, sex, BMI, physical activity, family history of colorectal cancer, etc.
Results:
After an average of 19.5 years of follow-up, 2,520 participants developed colorectal cancer (1,608 colon cancer and 912 rectal cancer). Overall, the association between total or plant-based LCD scores with the risk of colorectal, colon, or rectal cancer was null (all Ptrend ≥ 0.28). The animal-based LCD was modestly associated with colon cancer risk (Ptrend = 0.02), but not with rectal cancer. Compared with the lowest quartile, HRs (95% CIs) of colon cancer for quartiles 2, 3, and 4 of animal-based LCD were 1.12 (0.98–1.29), 1.27 (1.10–1.46), and 1.14 (0.99–1.31), respectively.
Conclusions:
A low-level carbohydrate diet with a high level of animal protein and fat was associated with a moderate increase in the risk of colon cancer among Chinese Singaporeans.
Impact:
High consumption of animal protein/fat and low consumption of carbohydrates may increase colon cancer risk.
Data from Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC)
Authors: Wang Shuo , Onyeaghala Guillaume C. , Pankratz Nathan , Nelson Heather H. , Thyagarajan Bharat , Tang Weihong , Norby Faye L. , Ugoji Chinenye , Joshu Corinne E. , Gomez Christian R. , Couper David J. , Coresh Josef , Platz Elizabeth A. , Prizment Anna E.
Published: April 2023

AbstractBackground:
The MHC class I chain-related protein A (MICA) and protein B (MICB) participate in tumor immunosurveillance and may be important in colorectal cancer, but have not been examined in colorectal cancer development.
Methods:
sMICA and sMICB blood levels were measured by SomaScan in Visit 2 (1990–92, baseline) and Visit 3 (1993–95) samples in cancer-free participants in the Atherosclerosis Risk in Communities Study. We selected rs1051792, rs1063635, rs2516448, rs3763288, rs1131896, rs2596542, and rs2395029 that were located in or in the vicinity of MICA or MICB and were associated with cancer or autoimmune diseases in published studies. SNPs were genotyped by the Affymetrix Genome-Wide Human SNP Array. We applied linear and Cox proportional hazards regressions to examine the associations of preselected SNPs with sMICA and sMICB levels and colorectal cancer risk (236 colorectal cancers, 8,609 participants) and of sMICA and sMICB levels with colorectal cancer risk (312 colorectal cancers, 10,834 participants). In genetic analyses, estimates adjusted for ancestry markers were meta-analyzed.
Results:
Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-A, rs2596542-T, and rs2395029-G were significantly associated with decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and MICB, was also associated with increased sMICB levels. Rs2596542-T was significantly associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males (HR = 0.68; 95% confidence interval, 0.49–0.96) but not in females (Pinteraction = 0.08).
Conclusions:
Rs2596542-T associated with lower sMICA levels was associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males.
Impact:
These findings support an importance of immunosurveillance in colorectal cancer.
Data from Trend in Cervical Cancer Incidence and Mortality Rates in China, 2006–2030: A Bayesian Age-Period-Cohort Modeling Study
Authors: Yuan Meiwen , Zhao Xuelian , Wang Honghao , Hu Shangying , Zhao Fanghui
Published: April 2023

AbstractBackground:
There are no studies extrapolating the incidence and mortality of cervical cancer in China by comparing incidence and deaths pattern between geographic and age groups.
Methods:
We applied age-period-cohort models to assess region-level trends in incidence and mortality from 2006 to 2016, with piecewise linear regression in a Bayesian framework to predict these trends to 2030.
Results:
Between 2006 and 2016, age-standardized incidence rates (ASIR) for females aged 15 to 84 years increased by 3.7% (95% confidence interval, 3.1%–4.3%) annually from 11.01 to 16.41 per 100,000 females in China. In the 25 to 39 age groups, the incidence rates decreased in urban regions and inversely increased in rural regions. The age-standardized mortality rates (ASMR) increased from 3.18 to 4.83, with annual increases of about 3.6% (1.5%–5.8%). From 2017 to 2030, the ASIR is expected to increase from 17.13 (15.91–18.46) to 23.22 (20.02–27.01) by 2.5% per year (P < 0.05). Meanwhile, the average age at diagnosis is predicted to grow from 53.1 to 60.5 years. In the 15 to 54 age groups, the incidence rates decreased in urban regions but increased in rural regions. The ASMR is expected to increase consistently from 4.82 (4.38–5.31) to 9.13 (7.35–11.39) by 5.0% per year (P < 0.05).
Conclusions:
Cervical cancer incidence and mortality rates are projected to increase in China. In addition, the urban–rural incidence gap is estimated to widen further among young women.
Impact:
Cervical cancer prevention should consider the trend and diversity in incidence patterns between urban and rural regions.
Table S1 from PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer
Authors: Gupta Santosh , Halabi Susan , Yang Qian , Roy Akash , Tubbs Alisa , Gore Yamini , George Daniel J. , Nanus David M. , Antonarakis Emmanuel S. , Danila Daniel C. , Szmulewitz Russell Z. , Wenstrup Richard , Armstrong Andrew J.
Published: April 2023

Comparison of CTC enumeration and PSMA+ CTC expression in 57 baseline and paired progression samples from the PROPHECY study. All the CTC parameters (mean, median, and range) were represent in CTC/mL.
Figure S3 from PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer
Authors: Gupta Santosh , Halabi Susan , Yang Qian , Roy Akash , Tubbs Alisa , Gore Yamini , George Daniel J. , Nanus David M. , Antonarakis Emmanuel S. , Danila Daniel C. , Szmulewitz Russell Z. , Wenstrup Richard , Armstrong Andrew J.
Published: April 2023

Waterfall plots depicting A) the proportion of men achieving a 50% or greater PSA decline from baseline, confirmed with a subsequent value (confirmed PSA50) and B) best overall objective radiographic responses among response evaluable subjects at baseline, by RECIST 1.1 criteria.
Preclinical Profile of BYON3521 Predicts an Effective and Safe MET Antibody–Drug Conjugate
Authors: Groothuis Patrick G. , Jacobs Daniëlle C.H. , Hermens Inge A.T. , Damming Désirée , Berentsen Kim , Mattaar-Hepp Ellen , Stokman Marloes E.M. , Boekel Tinie van , Rouwette Myrthe , van der Vleuten Monique A.J. , Sesink Aloys , Dijcks Fred A. , Coumans Ruud G.E. , Schouten Jan , Glaudemans Dirk H. , Wijk Daniëlle van , Blomenröhr Marion , Kappers Wendela A. , Ubink Ruud , van der Lee Miranda M.C. , Dokter Wim H.A.
Published: April 2023

MET, the cell-surface receptor for the hepatocyte growth factor/scatter factor, which is widely overexpressed in various solid cancer types, is an attractive target for the development of antibody-based therapeutics. BYON3521 is a novel site-specifically conjugated duocarmycin-based antibody–drug conjugate (ADC), comprising a humanized cysteine-engineered IgG1 monoclonal antibody with low pmol/L binding affinity towards both human and cynomolgus MET. In vitro studies showed that BYON3521 internalizes efficiently upon MET binding and induces both target- and bystander-mediated cell killing. BYON3521 showed good potency and full efficacy in MET-amplified and high MET–expressing cancer cell lines; in moderate and low MET–expressing cancer cell lines good potencies and partial efficacy were observed. In mouse xenograft models, BYON3521 showed significant antitumor activity upon single-dose administration in multiple non-MET–amplified tumor types with low, moderate, and high MET expression, including complete tumor remissions in models with moderate MET expression. In the repeat-dose Good Laboratory Practice (GLP) safety assessment in cynomolgus monkeys, BYON3521 was well tolerated and based on the observed toxicities and their reversibility, the highest non-severely toxic dose was set at 15 mg/kg. A human pharmacokinetics (PK) model was derived from the PK data from the cynomolgus safety assessments, and the minimal efficacious dose in humans is estimated to be in the range of 3 to 4 mg/kg. In all, our nonclinical data suggests that BYON3521 is a safe ADC with potential for clinical benefit in patients. A first-in-human dose-escalation study is currently ongoing to determine the maximum tolerated dose and recommended dose for expansion (NCT05323045).
Figure S6 from UBE2C-mediated Autophagy Inhibition via Ubiquitination of SIRT1 Contributes to Endometrial Cancer Progression
Authors: Zhao Rong , Liu Yan , Wang Ziwei , Zhang Jun , Zhang Wei , Zhou Xing , Tsedendorj Sevjid , Enkhtur Amarsanaa , Feng Dilu , Wang Hongbo
Published: April 2023

Figure S6
Figure S6 from Interdependence of SS18-SSX–driven YAP1 and β-Catenin Activation in Synovial Sarcoma
Authors: Isfort Ilka , Berthold Ruth , Heinst Lorena , Wardelmann Eva , Larsson Olle , Trautmann Marcel , Hartmann Wolfgang
Published: April 2023

Figure S6 shows that the mutual activation of YAP1/TAZ and β-catenin in SySa cells is impeded by knockdown of BAF complex subunits.
Figure S3 from Interdependence of SS18-SSX–driven YAP1 and β-Catenin Activation in Synovial Sarcoma
Authors: Isfort Ilka , Berthold Ruth , Heinst Lorena , Wardelmann Eva , Larsson Olle , Trautmann Marcel , Hartmann Wolfgang
Published: April 2023

Figure S3 shows a reciprocal regulation of YAP1/TAZ-TEAD and β-catenin-TCF in SySa cells via luciferase assays.
Figure S2 from Interdependence of SS18-SSX–driven YAP1 and β-Catenin Activation in Synovial Sarcoma
Authors: Isfort Ilka , Berthold Ruth , Heinst Lorena , Wardelmann Eva , Larsson Olle , Trautmann Marcel , Hartmann Wolfgang
Published: April 2023

Figure S2 shows that inhibition of YAP1, TAZ or β-catenin via siRNA-mediated knockdown or inhibitor treatment reduces each other's transcriptional activity.
Supplementary Tables 1-5 from FOXA1 Reprogramming Dictates Retinoid X Receptor Response in ESR1-Mutant Breast Cancer
Authors: Wu Yang , Li Zheqi , Wedn Abdalla M. , Casey Allison N. , Brown Daniel , Rao Shalini V. , Omarjee Soleilmane , Hooda Jagmohan , Carroll Jason S. , Gertz Jason , Atkinson Jennifer M. , Lee Adrian V. , Oesterreich Steffi
Published: April 2023

Table S1. Data Sets UsedTable S2. FOXA1 and ER Chip-seq peaksTable S3. DE genesTable S4. Enriched FOXA1 peak motifsTable S5. Enriched IPA pathways
Table S1 from USP10 Regulates ZEB1 Ubiquitination and Protein Stability to Inhibit ZEB1-Mediated Colorectal Cancer Metastasis
Authors: Sun Lei , Yu Jia , Guinney Justin , Qin Bo , Sinicrope Frank A.
Published: April 2023

Deubiquitinases identified from the Biogrid database that may potentially interact with ZEB1.
Supplementary Figure Legend from USP10 Regulates ZEB1 Ubiquitination and Protein Stability to Inhibit ZEB1-Mediated Colorectal Cancer Metastasis
Authors: Sun Lei , Yu Jia , Guinney Justin , Qin Bo , Sinicrope Frank A.
Published: April 2023

Supplementary Figure 1 legend
Data from Interdependence of SS18-SSX-driven YAP1 and β-catenin activation in synovial sarcoma
Authors: Isfort Ilka , Berthold Ruth , Heinst Lorena , Wardelmann Eva , Larsson Olle , Trautmann Marcel , Hartmann Wolfgang
Published: April 2023

Abstract
Synovial sarcoma (SySa), a rare malignant soft tissue tumor, is characterized by a specific chromosomal translocation t(X;18). The resulting chimeric SS18-SSX fusion protein drives SySa pathogenesis by integrating into the BAF complex and dysregulating gene transcription. Since previous functional analyses revealed a connection between SS18-SSX and the activity of the transcriptional co-regulators YAP1/TAZ and β-catenin, respectively, this study examined a potential interdependence between these essential effector proteins in SySa. In a large cohort of SySa tissue specimens, immunohistochemical analyses revealed a substantial subset of SySa with concurrent nuclear accumulation of YAP1/TAZ and β‑catenin. In vitro, small molecule inhibitor treatment, RNAi-mediated knockdown and vector-based overexpression assays demonstrated that YAP1, TAZ and β-catenin transcriptional activity is not only stimulated by the SS18-SSX fusion protein, but that they also mutually enhance each other’s activation. These analyses showed the highest cooperative effect with overexpression of YAP1 in combination with β-catenin. Co-immunoprecipitation experiments detected nuclear interactions between YAP1, β-catenin and the SS18-SSX fusion protein, the latter being an integral part of the BAF complex. Disruption of BAF complex assembly affected the coregulation of YAP1 and β-catenin, indicating that this chromatin remodeling complex plays a crucial role for interdependent YAP1 and β-catenin activation in SySa cells.

Implications: This study provides deeper insights into SySa tumor biology demonstrating a mutual dependence between YAP1/TAZ and β-catenin transcriptional activity and a complex interplay with the SS18-SSX fusion protein within the BAF complex.
Data from USP10 regulates ZEB1 ubiquitination and protein stability to inhibit ZEB1-mediated colorectal cancer metastasis
Authors: Sun Lei , Yu Jia , Guinney Justin , Qin Bo , Sinicrope Frank A.
Published: April 2023

Abstract
Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor that can promote tumor invasion and metastasis by inducing epithelial to mesenchymal transition (EMT). To date, regulation of ZEB1 by RAS/RAF signaling remains unclear, and few studies have examined post translation modification of ZEB1 including its ubiquitination. In human colorectal cancer (CRC) cell lines with RAS/RAF/MEK/ERK activation, an interaction of ZEB1 with the deubiquitinase ubiquitin-specific protease 10 (USP10) was identified whereby USP10 modifies ZEB1 ubiquitination and promotes its proteasomal degradation. Regulation of the USP10-ZEB1 interaction by MEK-ERK signaling was shown whereby constitutive activation of ERK can phosphorylate USP10 at Ser236 to impair its interaction with ZEB1 and enable ZEB1 protein stabilization. Stabilized ZEB1 was shown to promote CRC metastatic colonization in a mouse tail vein injection model. Conversely, MEK-ERK inhibition blocked USP10 phosphorylation and enhanced the USP10-ZEB1 interaction shown to suppress ZEB1-mediated tumor cell migration and metastasis. In conclusion, we demonstrate a novel function of USP10 in the regulation of ZEB1 protein stability and its ability to mediate tumor metastasis in a preclinical model.

Implications: The MEK-ERK regulated interaction of USP10 with ZEB1 can promote the proteasomal degradation of ZEB1 and thereby suppress its demonstrated ability to mediate tumor metastasis.
Data from HDAC3 Inhibition Promotes Antitumor Immunity by Enhancing CXCL10-Mediated Chemotaxis and Recruiting of Immune Cells
Authors: Li Lili , Hao Shumin , Gao Meiling , Liu Junxiao , Xu Xin , Huang Jianfei , Cheng Genhong , Yang Heng
Published: April 2023

Abstract
It is generally believed that histone deacetylase (HDAC) inhibitors, which represent a new class of anticancer agents, exert their antitumor activity by directly causing cell-cycle arrest and apoptosis of tumor cells. However, in this study, we demonstrated that class I HDAC inhibitors, such as Entinostat and Panobinostat, effectively suppressed tumor growth in immunocompetent but not immunodeficient mice. Further studies with Hdac1, 2, or 3 knockout tumor cells indicated that tumor-specific inactivation of HDAC3 suppressed tumor growth by activating antitumor immunity. Specifically, we found that HDAC3 could directly bind to promotor regions and inhibit the expression of CXCL9, 10, and 11 chemokines. Hdac3-deficient tumor cells expressed high levels of these chemokines, which suppressed tumor growth in immunocompetent mice by recruiting CXCR3+ T cells into the tumor microenvironment (TME). Furthermore, the inverse correlation between HDAC3 and CXCL10 expression in hepatocellular carcinoma tumor tissues also suggested HDAC3 might be involved in antitumor immune regulation and patient survival. Thus, our studies have illustrated that HDAC3 inhibition suppresses tumor growth by enhancing immune cell infiltration into the TME. This antitumor mechanism may be helpful in guiding HDAC3 inhibitor–based treatment.
Data from Myeloid-derived suppressor–cell dynamics control outcomes in the metastatic niche
Authors: Kreger Jesse , Roussos Torres Evanthia T. , MacLean Adam L.
Published: April 2023

Abstract
Myeloid-derived suppressor cells (MDSCs) play a prominent role in the tumor microenvironment. A quantitative understanding of the tumor–MDSC interactions that influence disease progression is critical, and currently lacking. We developed a mathematical model of metastatic growth and progression in immune-rich tumor microenvironments. We modeled the tumor–immune dynamics with stochastic delay differential equations and studied the impact of delays in MDSC activation/recruitment on tumor growth outcomes. In the lung environment, when the circulating level of MDSCs was low, the MDSC delay had a pronounced impact on the probability of new metastatic establishment: blocking MDSC recruitment could reduce the probability of metastasis by as much as 50%. To predict patient-specific MDSC responses we fit to the model individual tumors treated with immune checkpoint inhibitors via Bayesian parameter inference. We reveal that control of the inhibition rate of natural killer (NK) cells by MDSCs had a larger influence on tumor outcomes than controlling the tumor growth rate directly. Posterior classification of tumor outcomes demonstrates that incorporating knowledge of the MDSC responses improved predictive accuracy from 63% to 82%. Investigation of the MDSC dynamics in an environment low in NK cells and abundant in cytotoxic T cells revealed, in contrast, that small MDSC delays no longer impacted metastatic growth dynamics. Our results illustrate the importance of MDSC dynamics in the tumor microenvironment overall and predict interventions promoting shifts toward less immune-suppressed states. We propose that there is a pressing need to consider MDSCs more often in analyses of tumor microenvironments.
Data from SWI/SNF complex genomic alterations as a predictive biomarker for response to immune checkpoint inhibitors in multiple cancers
Authors: Wang Di , Wang Jianchao , Zhou Dongmei , Wu Zhixian , Liu Wei , Chen Yanping , Chen Gang , Zhang Jing
Published: April 2023

Abstract
Whether there is an association between SWI/SNF genomic alterations in tumors and response to immune checkpoint inhibitors (ICIs) remains unclear because prior studies have focused on either an individual gene or a predefined set of genes. Herein, using mutational and clinical data from 832 ICI-treated patients who underwent whole-exome sequencing, including sequencing of all 31 genes of the SWI/SNF complex, we found that SWI/SNF complex alterations were associated with significantly improved overall survival (OS) in melanoma, clear cell renal cell carcinoma, and gastrointestinal cancer, as well as improved progression-free survival (PFS) in non-small cell lung cancer. Including tumor mutational burden as a variable, the multivariate Cox regression analysis showed SWI/SNF genomic alterations had prognostic value in melanoma (HR 0.63 [95% CI 0.47–0.85], p = 0.003), clear cell renal cell carcinoma (HR 0.62 [95% CI 0.46–0.85], p = 0.003) and gastrointestinal cancer (HR 0.42 [95% CI 0.18–1.01], p = 0.053). Further, we used the random forest method for variable screening, identifying 14 genes as a SWI/SNF signature for potential clinical application. Significant correlations were observed between SWI/SNF signature alterations and improved OS and PFS in all cohorts. This suggests that SWI/SNF gene alterations are associated with better clinical outcomes in ICI-treated patients and may serve as a predictive marker for ICI therapy in multiple cancers.