bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the efficacy of biologics with and without methotrexate in the treatment of psoriatic arthritis: a network meta-analysis
Authors: Mease Philip J , Reddy Soumya , Ross Sarah , Lisse Jeffrey R , Reis Paulo , Griffing Kirstin , Sapin Christophe , Vadhariya Aisha , Furst Daniel E
Published: February 2024

Introduction

An important consideration in the treatment of patients with psoriatic arthritis (PsA) is whether the addition of methotrexate (MTX) to biologics has greater efficacy than biologic monotherapy with respect to efficacy outcomes in these patients.

Objectives

To conduct a network meta-analysis (NMA) comparing biologics by treatment class with and without MTX for treatment of adults with active PsA.

Methods

A systematic literature review (SLR) identified randomised, double-blinded, controlled trials, and a Bayesian NMA compared biologics with and without MTX by treatment class (tumour necrosis factor inhibitors (TNFi), interleukin-23 inhibitors (IL-23i) and IL-17i). Efficacy outcomes included American College of Rheumatology 20%, 50% and 70% (ACR20, ACR50 and ACR70) improvement response.

Results

The SLR initially identified 31 studies, of which 17 met feasibility criteria for the NMA by containing the ‘without MTX’ subgroup. For ACR20 efficacy (the most robust assessment examined), all active treatments were significantly better than placebo. No statistically significant differences were demonstrated between biologic monotherapy (for all classes examined) and biologics in combination with MTX for ACR20/50. IL-17i were comparable to IL-23i, and IL-17i were significantly better than TNFi for ACR20. Although limited by fewer trials, TNFi, IL-23i and IL-17i were not statistically different for ACR50/70.

Conclusions

Concomitant use of MTX and biologics did not improve ACR efficacy outcomes versus biologic monotherapy. MTX does not appear to be necessary as a background therapy when biologics are used for the achievement of ACR20/50 responses in patients with PsA.
Validity and score interpretation of the 12-item Psoriatic Arthritis Impact of Disease: an analysis of pooled data from two phase 3 trials of bimekizumab in patients with psoriatic arthritis
Authors: Gossec Laure , Orbai Ana-Maria , Coates Laura C , Gladman Dafna D , Ogdie Alexis , Pelligra Christopher G , Ciaravino Valérie , Ink Barbara , Taieb Vanessa , Lambert Jérémy , de Wit Maarten
Published: February 2024

Objectives

To investigate psychometric performance of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) total and individual item scores in patients with psoriatic arthritis (PsA) and to estimate score change thresholds and scores corresponding to different levels of symptom/impact severity.

Methods

Data up to week 16 from 1252 patients with active PsA enrolled in two randomised controlled trials of bimekizumab (BE OPTIMAL (NCT03895203) and BE COMPLETE (NCT03896581)) were used to assess construct validity (correlations with other patient-reported outcomes), known-groups validity (based on Minimal Disease Activity index, Disease Activity Index for Psoriatic Arthritis and Psoriatic Arthritis Disease Activity Score), reliability (Cronbach’s alpha and intraclass correlation coefficients (ICCs)) and responsiveness (sensitivity to change). Clinically meaningful within-patient improvement thresholds were estimated by anchor-based and distribution-based analyses, and symptom/impact severity thresholds were estimated by receiver operating characteristic curve analyses.

Results

The mean (SD) PsAID-12 total score at baseline was 4.19 (1.94). PsAID-12 scores demonstrated good convergent validity and good known-groups validity. Internal consistency reliability (Cronbach’s alpha 0.95) and test–retest reliability (ICC ≥ 0.70) were also good. Responsiveness was acceptable (correlations ≥0.30 for most scores). Improvement thresholds were estimated at 1.5–2 points for the PsAID-12 total score and 2 or 3 points for item scores. Thresholds for different levels of symptom/impact severity could be derived for most PsAID-12 items.

Conclusions

The PsAID-12 demonstrated robust psychometric properties in a large sample of patients with active PsA, supporting its use as a fit-for-purpose patient-reported outcome in this population. Furthermore, thresholds for score interpretation were derived.
Comparison of the ASAS Health Index in patients classified as radiographic axial spondyloarthritis (axSpA) or non-radiographic axSpA in the ASAS Health Index international validation study
Authors: Fong Warren , Woon Ting Hui , Kwan Yu Heng , Braun Jürgen , van der Heijde Désirée , Boonen Annelies , Kiltz Uta
Published: February 2024

Objectives

To determine if there were differences in the Assessment of SpondyloArthritis international Society Health Index (ASAS HI) scores between patients classified as radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axSpA (nr-axSpA), and to identify factors associated with higher ASAS HI scores in both disease phenotypes.

Methods

This study was an ancillary analysis of the ASAS HI international validation project performed in 23 countries. Patients were included if they were ≥18 years of age and diagnosed with axSpA. Univariable and multivariable analysis were performed to determine if ASAS HI scores differed between the axSpA phenotypes, and to identify other variables associated with ASAS HI scores. We also tested for potential interactions between the axSpA phenotype and significant variables identified through the multivariable regression.

Results

A total of 976 patients were included, with 703 having r-axSpA and 273 nr-axSpA. Patients with r-axSpA reported higher (worse) ASAS HI scores compared with those with nr-axSpA (6.8 (4.4) vs 6.0 (4.0), p=0.02), but the axSpA phenotype was not associated with ASAS HI scores in the multivariable regression (β: −0.19, 95% CI: −0.56 to 0.19). Female gender, having worse physical function (Bath Ankylosing Spondylitis Functional Index), disease activity (Ankylosing Spondylitis Disease Activity Score) and anxiety and depressive symptoms (Hospital Anxiety and Depression Scale) were associated with higher ASAS HI scores. No interactions were found to be significant.

Conclusion

Overall health and functioning are similarly affected in patients with r-axSpA and nr-axSpA. Female patients, having worse physical function, disease activity, anxiety and depressive symptoms were independently associated with higher ASAS HI scores.
Understanding pediatric surgical needs in North Korea: a modeling analysis
Authors: Hsu Phillip J , Yoon Sangchul , Park Kee B
Published: February 2024

Background

Sixty-five percent of children worldwide lack access to surgical care, the majority of whom live in low-income and middle-income countries (LMICs). Developing surgical infrastructure requires information on surgical need; however, this information is often limited in LMICs. North Korea (Democratic People’s Republic of Korea, DPRK) has a low amount of publicly available data. Here, we analyzed available modeled data to understand the causes of pediatric deaths due to conditions treatable with surgery in DPRK.

Methods

We used World Bank data and models from the Institute for Health Metrics and Evaluation to identify causes of pediatric deaths affecting pediatric patients (age <20 years). We compared mortality of disease between DPRK and countries with similar economic status.

Results

Between 1990 and 2019, the number of overall pediatric deaths has decreased. In 2019, 32.2% of all pediatric deaths in DPRK were caused by surgical conditions. The leading categories of surgical conditions were injuries (53.9%), congenital conditions (34.2%), tumors (8.8%), and abdominal conditions (3.2%). DPRK has a lower relative rate of pediatric deaths compared with other LMICs with similar gross domestic product per capita. However, it has a higher relative rate of pediatric deaths due to conditions requiring treatment with surgery. Transport injuries contribute significantly to the high rate of pediatric deaths in DPRK.

Conclusions

Although DPRK may be allocating overall resources toward pediatric healthcare more efficiently than economic peers, DPRK may benefit from improvement in pediatric surgical capacity. Improved availability of data and close international collaboration could be potential solutions to bridge this gap.
The 50th anniversary of the coupled channels Born approximation (CCBA) and the coupled reaction channels (CRC) theories of nucleon transfer reactions (a unique interplay between theory, experiment and computer technology, conducted during the most tumultuous period in modern American society)
Authors: Ascuitto Robert J. , Vaagen Jan S.
Published: February 2024

Nucleon transfer reactions have played a fundamental role in understanding the single-particle components, shell structure and collective properties of atomic nuclei. The conventional distorted wave Born approximation (DWBA) envisioned the nucleon transfer reaction as a one-step process, which proceeds directly from the ground state of the target nucleus to a state of the residual nucleus. The coupled channels Born approximation (CCBA) and coupled reaction channels (CRC) theories evolved because a number of nucleon transfer reaction cross sections could not be reconciled within the DWBA. These coupled channels models revealed that, in addition to the “one-step” process of the DWBA, “multi-step” nucleon transfer processes involving accessary pathways can participate in populating the final nuclear state. In the CCBA, the auxiliary pathways involved inelastic excitations of the target and/or residual nucleus, whereas, in the CRC, the pathways included sequential nucleon transfer passing through nuclear states of an intermediate partition. Coherent addition of contributions from one-step and multi-step nucleon transfer processes resulted in dramatic alterations in reaction cross sections, which were experimentally confirmed. The CCBA and CRC linked the structure of the nuclei participating in a reaction to modalities of nucleon transfer arising during the relative motion between the interacting ions. These complementary theories inexorably changed physicists’ interpretations of nucleon transfer reactions and, in doing so, heralded in the new field of direct heavy-ion reactions.
Harnessing the Power of Statistics and Machine Learning in the Era of Biobank-Scale Whole-Genome Sequencing and Multi-Omics Studies
Authors: Li Xihao
Published: February 2024

Researchers are developing new statistical and machine learning methods to effectively integrate biobank-scale whole-genome sequencing multi-omics and electronic health records data to better understand the molecular basis of complex human diseases.
Unsupervised Learnings of Protein Large Language Models for Make Benefit Glorious Sector of Biotech
Authors: Hartwig Albin
Published: February 2024

Protein language models were nurtured by unlikely parents---corporations. Now that they have come of age, they have been forced to strike out on their own. A common pitfall that biotechnology platforms make is to attempt to solve as many problems, all at once, while in reality solving none. Whether these fledgling protein LLM companies will learn from the mistakes of their industry predecessors remains to be seen.
Eleven Best Practices to Support Learners with Disabilities in the Online Classroom
Authors: Dyer Rebekah , Mandernach Jean
Published: February 2024

Online learning can greatly benefit learners with disabilities, provided that inclusive teaching practices and effective support systems are implemented. This article highlights 11 best practices for supporting these learners, including fostering relationships, identifying individual needs, using proactive teaching strategies, ensuring course alignment, providing emotional safety, implementing differentiation strategies, monitoring engagement, encouraging a growth mindset, establishing preferred communication modes, soliciting feedback, and adjusting teaching methods based on that feedback.
SiG: A Siamese-Based Graph Convolutional Network to Align Knowledge in Autonomous Transportation Systems
Authors: Hao Mai , Cai Ming , Fang Minghui , You Linlin
Published: February 2024

Domain knowledge is gradually renovating its attributes to exhibit distinct features in autonomy, propelled by the shift of modern transportation systems (TS) toward autonomous TS (ATS) comprising three progressive generations. The knowledge graph (KG) and its corresponding versions can help depict the evolving TS. Given that KG versions exhibit asymmetry primarily due to variations in evolved knowledge, it is imperative to harmonize the evolved knowledge embodied by the entity across disparate KG versions. Hence, this article proposes a siamese-based graph convolutional network (GCN) model, namely
SiG
, to address unresolved issues of low accuracy, efficiency, and effectiveness in aligning asymmetric KGs. SiG can optimize entity alignment in ATS and support the analysis of future-stage ATS development. Such a goal is attained through (a) generating unified KGs to enhance data quality, (b) defining graph split to facilitate entire-graph computation, (c) enhancing a GCN to extract intrinsic features, and (d) designing a siamese network to train asymmetric KGs. The evaluation results suggest that SiG surpasses other commonly employed models, resulting in average improvements of 23.90% and 37.89% in accuracy and efficiency, respectively. These findings have significant implications for TS evolution analysis and offer a novel perspective for research on complex systems limited by continuously updated knowledge.
Bayesian Strategy Networks Based Soft Actor-Critic Learning
Authors: Yang Qin , Parasuraman Ramviyas
Published: February 2024

A strategy refers to the rules that the agent chooses the available actions to achieve goals. Adopting reasonable strategies is challenging but crucial for an intelligent agent with limited resources working in hazardous, unstructured, and dynamic environments to improve the system’s utility, decrease the overall cost, and increase mission success probability. This article proposes a novel hierarchical strategy decomposition approach based on Bayesian chaining to separate an intricate policy into several simple sub-policies and organize their relationships as Bayesian strategy networks (BSN). We integrate this approach into the state-of-the-art DRL method—soft actor-critic (SAC), and build the corresponding Bayesian soft actor-critic (BSAC) model by organizing several sub-policies as a joint policy. Our method achieves the state-of-the-art performance on the standard continuous control benchmarks in the OpenAI Gym environment. The results demonstrate that the promising potential of the BSAC method significantly improves training efficiency. Furthermore, we extend the topic to the Multi-Agent systems (MAS), discussing the potential research fields and directions.
Hepatic glucagon action: beyond glucose mobilization
Authors: Kajani Sarina , Laker Rhianna C. , Ratkova Ekaterina , Will Sarah , Rhodes Christopher J.
Published: February 2024

Glucagon’s ability to promote hepatic glucose production has been known for over a century, with initial observations touting this hormone as a diabetogenic agent. However, glucagon receptor agonism [when balanced with an incretin, including glucagon-like peptide 1 (GLP-1) to dampen glucose excursions] is now being developed as a promising therapeutic target in the treatment of metabolic diseases, like metabolic dysfunction-associated steatotic disease/metabolic dysfunction-associated steatohepatitis (MASLD/MASH), and may also have benefit for obesity and chronic kidney disease. Conventionally regarded as the opposing tag-team partner of the anabolic mediator insulin, glucagon is gradually emerging as more than just a “catabolic hormone.” Glucagon action on glucose homeostasis within the liver has been well characterized. However, growing evidence, in part thanks to new and sensitive “omics” technologies, has implicated glucagon as more than just a “glucose liberator.” Elucidation of glucagon’s capacity to increase fatty acid oxidation while attenuating endogenous lipid synthesis speaks to the dichotomous nature of the hormone. Furthermore, glucagon action is not limited to just glucose homeostasis and lipid metabolism, as traditionally reported. Glucagon plays key regulatory roles in hepatic amino acid and ketone body metabolism, as well as mitochondrial turnover and function, indicating broader glucagon signaling consequences for metabolic homeostasis mediated by the liver. Here we examine the broadening role of glucagon signaling within the hepatocyte and question the current dogma, to appreciate glucagon as more than just that “catabolic hormone.”
Changes in the Step Counts of University Students Living in Hokkaido during the COVID-19 Pandemic
Authors: Mizumoto Atsushi , Echizen Kotomi , Tsuji Reiya , Takata Yuichi
Published: February 2024

Background. Coronavirus disease (COVID-19) countermeasures, such as lockdowns, have been reported to reduce people’s physical activity levels. Purpose. To determine changes in the step counts among university students before and after the COVID-19 pandemic and identify the risk factors for decreased step counts. Materials and Methods. An online questionnaire was sent by e-mail to 1,851 students enrolled in a university in Hokkaido, Japan; of these, 127 participated. The questionnaire items were average monthly step counts from October 2019 to March 2022, type of residence, part-time job, club activities, personal demographics, height, and weight. The average step counts in October/November 2019 (before the pandemic) were used as the baseline, and changes in step counts were studied at five time points (every 6 months): April/May 2020 (first state of emergency declared), October/November 2020 (period of contained infection), April/May 2021 (second state of emergency declared), and October/November 2021 (period of contained infection). We also examined changes in the number of steps due to different lifestyle factors and factors that contributed to decreased step counts during the study period. Results. Significantly lower step counts than those at baseline were observed in April/May 2020 and April/May 2021; however, there was no significant difference in October/November 2020 and October/November 2021 compared with baseline. In addition, significantly lower step counts were observed in April/May 2020 than in April/May 2021. The risk of decreased step counts was significantly associated with nonparticipation in club activities, even after adjustment for other variables. Conclusion. The step counts of university students decreased significantly during the declaration of a state of emergency and recovered to pre-pandemic levels after the declaration was lifted. Lifestyle status revealed differences in the number of steps taken before and after the pandemic. Nonparticipation in club activities was identified as a major risk factor for a decrease in step counts.
Evaluation of Lemon Peel Juice Fermentation Methods and Its Impact on Hyperlipidemia and Health Management
Authors: Hsu Chang-Lu , Tsai Chin-Fa , Chen Pei-Chun , Chen Tzu-Chun , Cho Tsai-Yi , Hung Jeng-Fung , Chen Yi-Jinn Lillian
Published: February 2024

Excessive body fat is a major contributor to obesity, which is related to high blood, total cholesterol, and triglycerides. Lemons (Citrus limon) are renowned for their antioxidant and lipid-lowering properties. First, sugar-free fermentation demonstrated better results in lowering sugar content and was identified as the preferred fermentation method. Next, the effect of two doses of sugar-free fermented lemon peel juice (SF-FLPJ) on obesity was investigated. Sprague Dawley (male rats) were randomly divided into 4 groups and fed a standard feed or high-fat diet (HFD) to induce fatness for eight weeks. The two groups of rats fed an HFD were administered SF-FLPJ at 0.45 or 0.9 g/kg body weight daily for eight weeks. The obese rats administered 0.9 g/kg (body weight/day) of SF-FLPJ exhibited significant reductions in body fat mass and percentage; they also had lower blood cholesterol and triglyceride levels than the other groups. Additionally, the rats displayed diminished liver fat accumulation. The results suggest that SF-FLPJ can be a supplement in managing body fat, contributing positively to addressing obesity within the context of health management, and reducing obesity-associated issues.
Interleukin‐18 Gene Polymorphisms and Rheumatoid Arthritis Susceptibility: An Umbrella Review of Meta‐Analyses
Authors: Chen Yuehong , Ye Yali , Liu Huan , Luo Zhongling , Li Qianwei , Xie Qibing
Published: February 2024

This study systematically analyzes the association between interleukin‐18 (IL‐18) gene polymorphisms and rheumatoid arthritis (RA) susceptibility. The electronic databases Ovid MEDLINE, Ovid Excerpta Medica Database, and Cochrane Library were searched to identify meta‐analyses that included case–control studies reporting IL‐18 gene polymorphisms and RA susceptibility. Data were reanalyzed using Review Manager Software 5.1, and Mantel–Haenszel random effects were applied for the five genetic models: allelic, recessive, dominant, homozygote, and heterozygote. The effect size of odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated. A total of seven meta‐analyses with poor quality were included. The IL‐18 polymorphisms ‐607 A/C, ‐137 C/G, ‐920 T/C, and ‐105 C/A have been reported. With weak evidence, IL‐18 ‐607 A/C polymorphisms were associated with a reduced risk of RA susceptibility using the allele model (OR = 0.76, 95% CI: 0.61 − 0.93, p = 0.01), dominant model (OR = 0.67, 95% CI: 0.50 − 0.90, p = 0.008), homozygote model (OR = 0.57, 95% CI: 0.35 − 0.91, p = 0.02), and heterozygote model (OR = 0.71, 95% CI: 0.54 − 0.93, p = 0.01) in the overall population. IL‐18 gene polymorphisms and RA susceptibility are affected by ethnicity: With weak evidence, IL‐18 ‐137 C/G polymorphisms were related to reduce RA susceptibility in the Asian population (allele model: OR = 0.59, 95% CI: 0.40 − 0.88, p = 0.01; dominant model: OR = 0.57, 95% CI: 0.37 − 0.89, p = 0.01; heterozygote model: OR = 0.60, 95% CI: 0.38 − 0.94, p = 0.03). IL‐18 ‐607 A/C gene polymorphisms are a protective factor for RA susceptibility in the overall population, and IL‐18 −137 C/G gene polymorphisms are a protective factor for RA susceptibility in the Asian population. Further studies are needed to confirm these results owing to the limitations of the included studies.
An Estimation of Digital Learning Culture Index of Secondary Education in Nigeria
Authors: Guobadia Frank Enoruomwanse , Ekuobase Godspower Osaretin
Published: February 2024

The socioeconomic vulnerability of youths in developing economies is a challenge that can be mitigated by quality education and digital learning skills. However, it is increasingly demanding for developing economies still struggling with universal access to preadult education to provide their youths with quality education. Mitigating this challenge, therefore, will require a social reengineering of the educational system of developing economies. Critical to this, reengineering is a comprehensive appraisal of their educational system’s support for digital learning. We set two objectives for this study: (i) examine the digital learning culture (DLC) of secondary education in Nigeria—a typical developing economy and (ii) estimate the digital learning culture index (DLCI) of secondary education in readiness for a lifelong learning skill among the Nigerian youths. Data were collected using the questionnaire survey and the stratified random sampling technique. A total of 2,107 students’ questionnaire feedback and 666 secondary schoolteachers’ questionnaire feedback at all secondary education levels across communities in the six geopolitical zones of Nigeria were analyzed. The DLCI of secondary education in Nigeria has been estimated to be 0.21. The results revealed two key findings: (1) evidence of sharp divides in DLC of secondary education among the communities in Nigeria and (2) statistical evidence that secondary education in the North-East zone of Nigeria has a higher DLCI than all other zones in the country except for the South-East zone.
Classification Performance Analysis of Decision Tree‐Based Algorithms with Noisy Class Variable
Authors: Alharbi Abdulmajeed Atiah
Published: February 2024

Class noise is a common issue that affects the performance of classification techniques on real‐world data sets. Class noise appears when a class variable in data sets has incorrect class labels. In the case of noisy data, the robustness of classification techniques against noise could be more important than the performance results on noise‐free data sets. The decision tree method is one of the most popular techniques for classification tasks. The C4.5, CART, and random forest (RF) algorithms are considered to be three of the most used algorithms in decision trees. The aim of this paper is to reach conclusions on which decision tree algorithm is better to use for building decision trees in terms of its performance and robustness against class noise. In order to achieve this aim, we study and compare the performance of the models when applied to class variables with noise. The results obtained indicate that the RF algorithm is more robust to data sets with noisy class variable than other algorithms.
A Control Architecture for Regulating Voltage and Power Flows in a Networked Microgrid System
Authors: John Thomas , Khan Umar
Published: February 2024

This paper presents a unique control system to regulate power exchanges and load bus voltage in a networked microgrid (NMG) system comprising AC and DC microgrids. During the islanding of a microgrid in this NMG system, load voltage and power balance can get disturbed. A control system and associated converter and inverter control methods are presented to rectify these issues. An efficient model predictive control (MPC) method, which gives a tracking error of 50% lower than a conventional proportional-integral (PI) controller, is used to control multiple inverters in the NMG system. Simulation studies are conducted to test the NMG in islanding and load change scenarios. With the help of these studies, it is verified that the MPC-controlled inverters can provide better tracking accuracy in achieving desired power flows in the NMG system.
The Role of Cholesterol during the Ovarian Maturation and Lipid Metabolism of Female Chinese Mitten Crab (Eriocheir sinensis)
Authors: Guo Huixing , Hua Haokun , Wang Jianfeng , Qiang Wei , Xiang Xiaoe , Liu Wenbin , Jiang Guangzhen
Published: February 2024

In previous study, we found that the cholesterol requirement of Eriocheir sinensis was 0.27%, to further investigate the effects of cholesterol on health status, ovarian maturation, and lipid metabolism of female Eriocheir sinensis broodstock. Two diets containing 0% and 0.25% (actually 0.05% and 0.27%) cholesterol were fed to the female crabs (average weight: 49.21 ± 0.11 g) for 4 months and sampled once a month. The results showed that the body weight (BW), survival rate (SR), meat yield (MY), condition factor (CF), hepatosomatic index (HSI), and gonadosomatic index (GSI) of Eriocheir sinensis were significantly affected by treatment time and compared with the cholesterol deficient group, supplementing cholesterol significantly increased BW, HSI, and GSI (P < 0.05). In addition, long‐term lack of cholesterol will lead to a significant decrease in the activity of ACP, AKP, and SOD and a significant increase in the content of MDA. The histological results showed that cholesterol significantly increased the volume of oocytes (P < 0.05). Further studies found that 0.27% cholesterol significantly increased the transcription levels of vtg and vgr in hepatopancreas and ovaries, which may be the main reason for the increase of oocyte size (P < 0.05). When fed with 0.27% cholesterol diet, the contents of nutrients in hepatopancreas and ovaries increased significantly, especially lipids and cholesterol (P < 0.05). Through the analysis of mRNA expression level of genes related to lipid metabolism, it was found that cholesterol enhanced the transcription level of genes related to lipid synthesis and transport in hepatopancreas, thereby promoting the accumulation of lipid in the organism. Furthermore, compared with control group, the levels of juvenile hormone (JH), 17β‐estradiol (E2), methyl farnesoate (MF), and ecdysone in the organism were significantly increased after feeding a diet with 0.27% cholesterol (P < 0.05). In summary, supplementing an appropriate amount of cholesterol in the diet can improve the growth performance of Eriocheir sinensis broodstock, enhance the body’s antioxidant and immune system, and promote the accumulation of nutrients in the ovaries, thereby promoting ovarian maturation.
Effects of Antarctic Krill Meal in Diet on Reproductive Performance and Embryo Quality of Eriocheir sinensis
Authors: Huang Xiaorong , Tan Ru , Geng Zhi , Zhang Tao , Feng Guangpeng , Yang Gang , Zhao Feng , Zhuang Ping
Published: February 2024

A 60‐day feeding trial was conducted to evaluate the impact of dietary Antarctic krill meal on the reproductive performance and embryo quality of the Chinese mitten crab, Eriocheir sinensis. Three diets were formulated, incorporating varying levels of Antarctic krill meal at 0% (Diet K0), 10% (Diet K10), and 20% (Diet K20), with a control group fed razor clam Sinonovacula constricta. Each diet was randomly assigned to three replicate tanks, each stocked with 5 males and 10 females. Male and female weights were 145.38 ± 8.01 and 102.57 ± 9.73 g, respectively. The results revealed no significant differences in weight gain rate, specific growth rate, and survival rate. However, the hepatopancreatic weight and hepatopancreas index of female crabs in each group decreased, while gonadal weight and gonadosomatic index increased significantly after 60 days, with Diet K20 showing the highest values. Egg production and fecundity of female crabs reached their peak in Diet K20, with no significant differences in reproductive indices among all groups. The phospholipid content in Diet K20 was significantly higher than in the other groups (P < 0.05). Cholesterol contents in Diet K0 and the control group were significantly higher than in Diet K10 and K20 (P < 0.05). No significant differences were observed in egg diameter, egg weight, moisture, crude protein, and crude fat between the groups. The content of C20 : 2 and C20 : 4n6 was highest in Diet K0, with a significant difference compared to Diet K10 (P < 0.05). However, no significant differences were found in the total content of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids among all groups. Based on the research findings, it is recommended that the optimal level of Antarctic krill meal in diets is 20%.
Figure 4 from Deep Learning Enables Spatial Mapping of the Mosaic Microenvironment of Myeloma Bone Marrow Trephine Biopsies
Authors: Hagos Yeman Brhane , Lecat Catherine S.Y. , Patel Dominic , Mikolajczak Anna , Castillo Simon P. , Lyon Emma J. , Foster Kane , Tran Thien-An , Lee Lydia S.H. , Rodriguez-Justo Manuel , Yong Kwee L. , Yuan Yinyin
Published: February 2024

Studying bone physiology using MoSaicNet. A, Proportion of different compartments of BM trephine digital images. B–E, One stacked bar represents a sample. Box plots showing the difference in %bone between samples from NDMM and posttreatment (B), MGUS and NDMM (C), different age groups (median age = 58.0 years; D), and gender groups (E). F, Scatter plot showing the number of bone superpixels in 17 clusters from MGUS, NDMM, and posttreatment samples. The size of the dots represents the percentage of superpixels. The color represents the number of slides in each cluster. G, Correlation of percentage of superpixels in each cluster between different patient groups. A point represents a cluster. H, Scatter plot of slide-level heterogeneity of bone features measured by features variance (Supplementary Materials and Methods). A point represents a patient/slide. I and J, Box plots showing differences in bone density heterogeneity between NDMM and posttreatment (I), and between MGUS and NDMM (J). K–N, Box plots showing the difference in bone thickness between samples from NDMM and posttreatment (K), MGUS and NDMM (L), and different age groups (median age = 58.0 years; M) and gender (N).
Supplementary Video S3 from Osteoclast Cancer Cell Metabolic Cross-talk Confers PARP Inhibitor Resistance in Bone Metastatic Breast Cancer
Authors: Fan Huijuan , Xu Zhanao , Yao Ke , Zheng Bingxin , Zhang Yuan , Wang Xuxiang , Zhang Tengjiang , Li Xuan , Hu Haitian , Yue Bin , Hu Zeping , Zheng Hanqiu
Published: February 2024

Supplementary Video S3 is related to Figure 5 (Zoledronate-only group).
Supplementary Data from Neuronal Activity Promotes Glioma Progression by Inducing Proneural-to-Mesenchymal Transition in Glioma Stem Cells
Authors: Guo Xiaofan , Qiu Wei , Wang Chaochao , Qi Yanhua , Li Boyan , Wang Shaobo , Zhao Rongrong , Cheng Bo , Han Xiao , Du Hao , Gao Zijie , Pan Ziwen , Zhao Shulin , Li Gang , Xue Hao
Published: February 2024

Figure S1. Original western blots 1
Supplementary Data from Neuronal Activity Promotes Glioma Progression by Inducing Proneural-to-Mesenchymal Transition in Glioma Stem Cells
Authors: Guo Xiaofan , Qiu Wei , Wang Chaochao , Qi Yanhua , Li Boyan , Wang Shaobo , Zhao Rongrong , Cheng Bo , Han Xiao , Du Hao , Gao Zijie , Pan Ziwen , Zhao Shulin , Li Gang , Xue Hao
Published: February 2024

Figure S6. A-NDEs promote the PMT of GSCs in vitro
Supplementary Figure S2 from Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies
Authors: Carneiro Benedito A. , Cavalcante Ludimila , Mahalingam Devalingam , Saeed Anwaar , Safran Howard , Ma Wen Wee , Coveler Andrew L. , Powell Steven , Bastos Bruno , Davis Elizabeth , Sahai Vaibhav , Mikrut William , Longstreth James , Smith Sheri , Weisskittel Taylor , Li Hu , Borden Brittany A. , Harvey R. Donald , Sahebjam Solmaz , Cervantes Andrés , Koukol Austin , Mazar Andrew P. , Steeghs Neeltje , Kurzrock Razelle , Giles Francis J. , Munster Pamela
Published: February 2024

Plasma Elraglusib (9-ING-41) Concentrationsr 5.0 mg/kg Elraglusib plus Carboplatin regimen
Supplementary Figure S1 from Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies
Authors: Carneiro Benedito A. , Cavalcante Ludimila , Mahalingam Devalingam , Saeed Anwaar , Safran Howard , Ma Wen Wee , Coveler Andrew L. , Powell Steven , Bastos Bruno , Davis Elizabeth , Sahai Vaibhav , Mikrut William , Longstreth James , Smith Sheri , Weisskittel Taylor , Li Hu , Borden Brittany A. , Harvey R. Donald , Sahebjam Solmaz , Cervantes Andrés , Koukol Austin , Mazar Andrew P. , Steeghs Neeltje , Kurzrock Razelle , Giles Francis J. , Munster Pamela
Published: February 2024

Plasma Elraglusib (9-ING-41) Concentrations: Elraglusib plus Carboplatin Regimen
Supplementary Figure 3 from Neoadjuvant Selicrelumab, an Agonist CD40 Antibody, Induces Changes in the Tumor Microenvironment in Patients with Resectable Pancreatic Cancer
Authors: Byrne Katelyn T. , Betts Courtney B. , Mick Rosemarie , Sivagnanam Shamilene , Bajor David L. , Laheru Daniel A. , Chiorean E. Gabriela , O'Hara Mark H. , Liudahl Shannon M. , Newcomb Craig , Alanio Cécile , Ferreira Ana P. , Park Byung S. , Ohtani Takuya , Huffman Austin P. , Väyrynen Sara A. , Dias Costa Andressa , Kaiser Judith C. , Lacroix Andreanne M. , Redlinger Colleen , Stern Martin , Nowak Jonathan A. , Wherry E. John , Cheever Martin A. , Wolpin Brian M. , Furth Emma E. , Jaffee Elizabeth M. , Coussens Lisa M. , Vonderheide Robert H.
Published: February 2024

Figure S3 shows representative mIHC images of tumors correlating to the three main cluster groups discussed in Figure 3D, and the density of immune cell subsets described in Figure 3F.
Supplementary Table S6-1 from Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models
Authors: Friese-Hamim Manja , Ortiz Ruiz Maria J. , Bogatyrova Olga , Keil Marina , Rohdich Felix , Blume Beatrix , Leuthner Birgitta , Czauderna Frank , Hahn Diane , Jabs Julia , Jaehrling Frank , Heinrich Timo , Kellner Roland , Chan Katherine , Tong Amy H.Y. , Wienke Dirk , Moffat Jason , Blaukat Andree , Zenke Frank T.
Published: February 2024

ELISA data for increasing dilutions of unpurified, purified antibody MKV-3-165-11 and flow through fraction
Supplementary Figure S11-7 from Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models
Authors: Friese-Hamim Manja , Ortiz Ruiz Maria J. , Bogatyrova Olga , Keil Marina , Rohdich Felix , Blume Beatrix , Leuthner Birgitta , Czauderna Frank , Hahn Diane , Jabs Julia , Jaehrling Frank , Heinrich Timo , Kellner Roland , Chan Katherine , Tong Amy H.Y. , Wienke Dirk , Moffat Jason , Blaukat Andree , Zenke Frank T.
Published: February 2024

Body weight curves for RCC PDX model RXF-2796-bearing mice treated with vehicle, M8891 (100 mg/kg, daily, per os), axitinib (4 mg/kg, twice daily, per os), or the combination are shown
Table S1 from CD38 x ICAM-1 Bispecific Antibody Is a Novel Approach for Treating Multiple Myeloma and Lymphoma
Authors: Chen Xiaocheng , Wong Oi Kwan , Reiman Lauren , Sherbenou Daniel W. , Post Leonard
Published: February 2024

Cell line information
Figure S3 from CD38 x ICAM-1 Bispecific Antibody Is a Novel Approach for Treating Multiple Myeloma and Lymphoma
Authors: Chen Xiaocheng , Wong Oi Kwan , Reiman Lauren , Sherbenou Daniel W. , Post Leonard
Published: February 2024

ELISA Binding to recombinant CD38 and ICAM-1
Figure S1 from CD38 x ICAM-1 Bispecific Antibody Is a Novel Approach for Treating Multiple Myeloma and Lymphoma
Authors: Chen Xiaocheng , Wong Oi Kwan , Reiman Lauren , Sherbenou Daniel W. , Post Leonard
Published: February 2024

CD38 and ICAM-1 expression levels by FACS
Data from TAS0612, a Novel RSK, AKT, and S6K Inhibitor, Exhibits Antitumor Effects in Preclinical Tumor Models
Authors: Ichikawa Koji , Ito Satoshi , Kato Emi , Abe Naomi , Machida Takumitsu , Iwasaki Junya , Tanaka Gotaro , Araki Hikari , Wakayama Kentaro , Jona Hideki , Sugimoto Tetsuya , Miyadera Kazutaka , Ohkubo Shuichi
Published: February 2024

Abstract
The MAPK and PI3K pathways are involved in cancer growth and survival; however, the clinical efficacy of single inhibitors of each pathway is limited or transient owing to resistance mechanisms, such as feedback signaling and/or reexpression of receptor-type tyrosine kinases (RTK). This study identified a potent and novel kinase inhibitor, TAS0612, and characterized its properties. We found that TAS0612 is a potent, orally available compound that can inhibit p90RSK (RSK), AKT, and p70S6K (S6K) as a single agent and showed a strong correlation with the growth inhibition of cancer cells with PTEN loss or mutations, regardless of the presence of KRAS and BRAF mutations. Additional RSK inhibitory activity may differentiate the sensitivity profile of TAS0612 from that of signaling inhibitors that target only the PI3K pathway. Moreover, TAS0612 demonstrated broad-spectrum activity against tumor models wherein inhibition of MAPK or PI3K pathways was insufficient to exert antitumor effects. TAS0612 exhibited a stronger growth-inhibitory activity against the cancer cell lines and tumor models with dysregulated signaling with the genetic abnormalities described above than treatment with inhibitors against AKT, PI3K, MEK, BRAF, and EGFR/HER2. In addition, TAS0612 demonstrated the persistence of blockade of downstream growth and antiapoptotic signals, despite activation of upstream effectors in the signaling pathway and FoxO-dependent reexpression of HER3. In conclusion, TAS0612 with RSK/AKT/S6K inhibitory activity may provide a novel therapeutic strategy for patients with cancer to improve clinical responses and overcome resistance mechanisms.
Abstract A015: Mutations in mismatch repair genes that alter subcellular localization of the protein predict resistance to standard therapy but response to cell cycle inhibitors
Authors: Mazumder Aloran , Haricharan Svasti
Published: February 2024

Hormone positive breast cancer is one of the most common cancer types in U.S. Every year, over 150,000 patients are detected with this cancer type of which, >40,000 patients will go on to die of their disease. We recently identified defects in a principal mismatch repair (MMR) gene, MLH1, as a driver of resistance to standard-care treatment and poor patient outcomes. Moreover, we demonstrated increased sensitivity to palbociclib, a CDK4/6 inhibitor, in experimental model systems in vitro and in vivo and in clinical trial data. MLH1 is mutated in 5-10% of treatment-resistant tumors, i.e., 4,000 patient tumors every year. However, most of these mutations are missense and variants of unknown significance (VUS). The impact of these mutations on mismatch repair capability and on treatment resistance remains uncertain. Here, we use experimental model systems (ER+/HER2- breast cancer cells, organoid models, and patient tumors) to study how variants of MLH1 and its subcellular localization predicts resistance to standard endocrine therapy but sensitivity to cell cycle inhibitors. We also assessed the ability of nuclear MLH1 to induce activation of G1/S cell cycle checkpoints by activating Chk2. Currently, there are few tests available in the clinic to predict response to therapies early in the timeline of hormone positive breast cancer patients. Due to the nature of the disease, this can result in years of overtreatment. Overtreatment comes at great financial, physical, and emotional cost to patients and their families. We for the first time show that stalling nuclear translocation of MLH1 inhibits Chk2 activation which counterbalances CDK4/6 activity. Therefore, cytoplasmic Mlh1 may be first in-class biomarker for CDK4/6 response in cancer types.

Citation Format: Aloran Mazumder, Svasti Haricharan. Mutations in mismatch repair genes that alter subcellular localization of the protein predict resistance to standard therapy but response to cell cycle inhibitors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A015.
Abstract A034: 3D in-vitro model picturing cancer-stromal cell crosstalk & bone metastasis
Authors: Ghosh Shrinwanti
Published: February 2024

Breast cancer is presently the most prevalent malignancy and the second leading cause of tumor-related deaths among women. Approximately 75% of patients with advanced breast cancer will develop bone metastasis. Despite the significant improvement in treating primary breast cancer, the 5-year survival rate for metastatic breast cancer remains at 25%. While we recognize the critical importance of cancer cells and Tumor Microenvironment (TME) communication, the field still suffers from a lack of a proper model system to reconstitute 3D multi-cellular TME in-vitro, especially for bone metastasis. Most of the current 3D in-vitro breast cancer models are composed of cancer cells only and are unable to mimic the complex cellular homeostasis within the TME. To address this deficiency along with the tumor heterogeneity, we aimed to develop a unique 3D multi-cellular culture system using patient-derived (PD) cancer cells. In this study, we implemented the “hanging drop” method to create 3D Tumor Spheroids (TSs). This method was not only sufficient to build the 3D structure, but also significantly enhanced patient-derived cancer cell line establishment rate up to 75%. 3D TSs maintained their histopathological characteristics and original hormone receptor status. Over time, TSs exhibited intratumoral hypoxia leading to significant induction of VEGF expression and EMT showcasing the quality of the system. To investigate the complex interrelation between the tumor and TME, we cultured TSs with Endothelial Cells (ECs) and pericytes to introduce the vascular component. To probe these tumor-stromal interactions, we incorporated Cancer-Associated Fibroblasts (CAFs) into TSs and observed the successful growth of Multi-Cellular Tumor Spheroids (MCTSs) alongside the tubular structure. Analysis of our data revealed that the presence of stromal cells in TME enhanced tumor survival. In this study, we define how CAFs aid in the formation of vascular structures of ECs. Recent studies also have found that the effects of CAFs are significantly high in aggressive TNBC and HER2+ cell lines compared to HR+. The long-term goal of this current study is to explore bone-mimicking nano-clay-based 3D scaffold culture systems to investigate the development of metastatic tumors and to understand the influence of bone TME on cellular responses in-vitro.

Citation Format: Shrinwanti Ghosh. 3D in-vitro model picturing cancer-stromal cell crosstalk & bone metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A034.
Abstract B013: Understanding the anti-metastatic activity of estrogen receptor β in inflammatory breast cancer
Authors: Karagounis Ilias , Tastsoglou Spyros , Nagandla Harika , Ueno Naoto , Maity Amit , Hatzigeorgiou Artemis , Thomas Christoforos
Published: February 2024

Inflammatory breast cancer (IBC) is a highly metastatic breast carcinoma with high frequency of estrogen receptor a (ERα) negativity. We previously explored the second ER subtype, (ERβ) and reported expression in IBC tissues and correlation with reduced metastasis in patients. We have also seen decreased metastasis of IBC tumors in vivo when ERβ was expressed or activated by agonists. Mechanistically, we found that ablation of ERβ in IBC cells increased actin-based cell migration and activated gene expression that promote Rho GTP signaling and cytoskeleton reorganization. Because migratory cells undergo metabolic and epigenetic adaptations that enable them to evade immune surveillance and progress to metastasis, we have now followed an integrated approach to fully understand the role of ERβ as a driver of interconnected transcriptional programs that function to inhibit aggressive phenotypes. We have mapped ERβ binding sites in IBC cells and interrogated this information with gene expression data to identify downstream targets that prevent IBC cells from gaining metastatic traits. Through analysis of cells that express endogenous ERβ and upon its activation by agonists we have defined how a physiologically relevant receptor interacts with the cancer genome to adjust differentiation, metabolism and tumor host interactions to mitigate the metastatic propensity of IBC cells. We compared target genes in normal and malignant tissues and associated their expression with clinical outcomes to strengthen their biological relevance and evaluate their potential use as molecular targets. Our findings thus offer ample opportunities to advance our understanding about endocrine mechanisms that operate within the tumor microenvironment to regulate metastasis with the potential to discover novel targets for therapy intervention.

Citation Format: Ilias Karagounis, Spyros Tastsoglou, Harika Nagandla, Naoto Ueno, Amit Maity, Artemis Hatzigeorgiou, Christoforos Thomas. Understanding the anti-metastatic activity of estrogen receptor β in inflammatory breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B013.