bluuebunny/crossref_metadata_2025 huggingface dataset:
Ferritin From Striped Stem Borer (Chilo suppressalis) Oral Secretion Acts as an Effector Helping to Maintain Iron Homoeostasis and Impair Defenses in Rice
Authors: Yu Shan , Li Shuai , Li Jing , Wang Chen‐Yang , Yang Lei , Li Jing , Meng Yue , Tan Xin‐Yang , Jing Mao‐Feng , Luo Guang‐Hua , Fang Ji‐Chao , Ji Rui
Published: January 2025

The striped stem borer (Chilo suppressalis, SSB) is a highly destructive insect pest in rice (Oryza sativa). SSB oral secretions (OSs) can induce plant defense responses in rice. However, the specific effectors in SSB OSs that mediate these interactions with rice remain poorly understood. In this study, hallmarks of ferroptosis‐like plant defense response, such as the reprogramming of ferroptosis‐related genes, reduced glutathione levels, accumulation of ferric ion, and enhanced lipid peroxidation by reactive oxygen species (ROS), were detected in rice subjected to SSB infestation and SSB OSs treatment. Furthermore, we identified and characterized a protein from SSB OSs, the ferritin CsFer1, which plays a critical role in the regulation of plant iron homoeostasis. CsFer1 was shown to possess Fe2+ binding capacity and ferroxidase activity. Through recombinant CsFer1 protein treatment, overexpression of CsFer1 in rice and SSB larvae with silencing CsFer1 feeding in rice, we found that CsFer1 helped maintain iron homoeostasis under SSB infestation, suppressing H2O2 and JA accumulation, ultimately compromising rice resistance to herbivorous pests. Moreover, such a phenomenon about the regulation of iron homoeostasis and suppression of insect resistance was observed in the CsFer1 overexpressed tobacco. Collectively, these findings suggest that CsFer1 functions as an effector involved in the regulation of iron homoeostasis‐ and lipid peroxidation‐related plant defense during plant‐insect interaction.
Does public sector performance information impact stakeholders? Evidence from a meta‐analysis
Authors: Meng Xue , Li Chaoping
Published: January 2025

Performance information (PI) has received significant attention in public administration research. However, evaluating the impact of public sector PI on stakeholders is challenging due to varying empirical results. Drawing on information propagation theory, as well as social and cognitive psychology, we conduct a meta‐analysis to examine the effect of public sector PI. Using 461 effect sizes from 75 studies, the meta‐analysis reveals PI's positive effects on stakeholder attitudes, behaviors, and perceptions of performance. Moreover, the effects tend to be stronger when PI is sent by third parties, received by citizens, delivered with positive valence, presented in absolute forms, and disseminated in law enforcement administrative subfields and in societies characterized by low power distance. The findings reinforce the significance of public sector PI and illuminate the complex interplay between it and stakeholder responses.
Symplectomorphisms and spherical objects in the conifold smoothing
Authors: Keating Ailsa , Smith Ivan
Published: January 2025

Let $X$ denote the ‘conifold smoothing’, the symplectic Weinstein manifold which is the complement of a smooth conic in $T^*S^3$ or, equivalently, the plumbing of two copies of $T^*S^3$ along a Hopf link. Let $Y$ denote the ‘conifold resolution’, by which we mean the complement of a smooth divisor in $\mathcal {O}(-1) \oplus \mathcal {O}(-1) \to \mathbb {P}^1$. We prove that the compactly supported symplectic mapping class group of $X$ splits off a copy of an infinite-rank free group, in particular is infinitely generated; and we classify spherical objects in the bounded derived category $D(Y)$ (the three-dimensional ‘affine $A_1$-case’). Our results build on work of Chan, Pomerleano and Ueda and Toda, and both theorems make essential use of working on the ‘other side’ of the mirror.
Tribological Impact of Carbon Black Nanoparticles Obtained From Recycled Waste Tires as Additive to Motor Oil
Authors: Alazemi Abdullah A. , Buarki Farah , Alajmi Abdullah F.
Published: January 2025

Used tires are commonly stockpiled at landfills, taking up a vast space of land and leading to serious environmental issues, which makes recycling and finding better waste management strategies necessary. This study explores the potential role of recycled material extracted from waste tires in the lubrication industry by examining different properties of motor oil with the addition of carbon black (CB) particles obtained from used tires via the pyrolysis process. The CB particles have been added to motor oil at various concentrations (0.5, 1, 2, and 4 wt%), and several properties of the oil–CB lubricant mixture, such as tribological, rheological, and lubrication, have been investigated. After testing different concentration samples, the 2 wt% of CB in the motor oil showed the best tribological and rheological behavior compared to other samples. The improvement in motor oil performance with the addition of CB was evident in the mixed lubrication regime, with a more than 20% reduction in frictional and wear losses compared to the reference motor oil. This improvement in the oil's lubrication performance is attributed to the presence of CB particles between sliding surfaces operating as a third body that helps reduce the contact pressure and minimize solid–solid asperities contact. Therefore, this work demonstrates the viable role of carbon black recycled material in improving the lubrication properties of current motor oils.
Dynamic Characteristics of Hydrostatic Thrust Bearing With Tilting Oil Pad Under Eccentric Load
Authors: Yu Xiaodong , Du Boyu , Meng Xiuli , Qiao Wenzhuo , Sun Yankun , Ma Wenjie , Sun Kaixuan , Dai Ruichun , Jia Wentao , Jiao Jianhua , Wang Junfeng , Jiang Hui
Published: January 2025

During the processing of heavy machine tools, due to the effect of eccentric load, the oil film thickness changes, which directly affects the lubrication performance of the bearing. Therefore, this study takes the tiltable double rectangular oil pad hydrostatic thrust bearing as the research object and explores its dynamic characteristics. The study involves the analysis of oil film displacement response under eccentric loading conditions at different offset distances, loads, and sudden loads. Through analysis, the oil film damping coefficient and oil film dynamic stiffness of each oil cavity can be determined under different offset distances and loads. The research results show that the change in oil film thickness has a significant effect on the oil film stiffness. As the oil film thickness increases, the stiffness decreases, the ability to resist deformation becomes weaker, and the displacement response time becomes longer. Moreover, the dynamic stiffness is affected by the offset distance and the loading frequency. When the offset distance is 200 mm, the load is 24 tons, and the loading frequency is 50 rad/s, the oil film stiffness of the oil cavity 1 reaches 180 × 108 N/m. It is worth noting that the increase in dynamic stiffness of the sinking side is significantly greater than that of the floating side. Ultimately, this study provides a theoretical reference for evaluating the stability of hydrostatic thrust-bearing systems under eccentric loads.
Dual Actuator Control Strategy for Temperature Stability in High-Temperature Solar Receivers
Authors: Verstraete Sofie , Abedini Hamed , Alsahlani Assaad , Ophoff Cedric , Ozalp Nesrin
Published: January 2025

Fluctuations in incoming solar energy adversely affect the temperature stability within solar receivers, leading to a decrease in thermal efficiency. Therefore, it is essential to design a control system with the capability to maintain quasi-steady temperatures inside the reactor consistently throughout the day. This study introduces a dual-actuator control technology to regulate the temperature within a high-temperature cylindrical cavity-type gas receiver. The actuating system comprises two primary components. The first component involves a variable aperture mechanism, executed through a rotary mechanism made of stainless steel. This mechanism features seven holes of fixed diameters arranged in a half-circle configuration. The rotary mechanism is powered by a stepper motor regulated by a feedback control system. The second actuator is a mass flow controller (MFC) responsible for meticulous adjustment of the inlet gas flow directed toward the solar receiver. The direct normal irradiance (DNI) is simulated using a 10 kW high-flux solar simulator (HFSS) with a variable power supply ranging from 80 to 200 A. This setup enables the simulation of different operational conditions. The dual-actuator method concurrently adjusts both gas flowrate and aperture size. While utilizing each of these methods individually can achieve reasonable temperature control performance, the hybrid approach leverages the strengths of both control methods, resulting in a significant improvement in the temperature regulation performance of the solar receiver. Two control strategies, namely, proportional integral (PI) and model predictive control (MPC), were implemented to regulate the temperature inside a cavity-type gas receiver. Experimental tests indicate that the incorporating the dual-actuator controller is a promising technique, and its application can be extended to include additional parameters for utilization in a multi-input multi-output (MIMO) control system.
Effects of leading-edge serration shape on noise reduction in rod-airfoil interactions
Authors: Yu Fu-Yang , Wan Zhen-Hua , Hu Ya-Sen , Sun De-Jun , Lu Xi-Yun
Published: January 2025

Leading-edge serrations inspired by owls exhibit the capability to control airfoil-turbulence interaction noise, but the design principle of the serration shape is still an open issue. To this end, we designed five types of serration shapes with different combinations of curvature, namely, triangular, ogee, anti-ogee, feather-like, and anti-feather-like. These curves are applied to serrated modifications with different bluntness levels (sharp or blunt) and amplitudes (0.05, 0.075, and 0.1 chord length). Considering these serration shapes, 30 cases with various curved types, bluntness levels, and amplitudes are investigated using compressible large-eddy simulation and the acoustic analogy of Ffowcs-Williams and Hawkings on a rod-airfoil configuration. The outcomes reveal a general trend where increased amplitude and blunted serrations are more effective in noise mitigation. Notably, the blunt feather-like (FB) serrations demonstrate the maximum noise reduction capacity across all amplitude levels, decreasing the overall sound power level by up to 2.1 dB. Through multi-process acoustic analysis, source characteristics responsible for generating noise are diagnosed. It is found that noise reduction primarily stems from the change in the source distribution and destructive interference among sound sources, consistent with prior studies. Generally, the serration shape would significantly affect the source distribution and sound interference without altering the fundamental noise reduction mechanisms. The FB shape exhibits the highest concentration of sources at its peaks and roots among all shapes. The presence of concentrated sources in these locations enhances destructive interference, effectively reducing noise emissions. The superior noise-reduction feature of FB serrations should be attributed to both the concentration of sources and the destructive interference. This extensive examination underscores the importance of serration design, especially the potential of FB serrations, in noise control strategies for rod-airfoil configurations, contributing to advancements in aeroacoustic engineering.
Features of Selective Reflection of High-Intensity Laser Radiation Using Rubidium Nanocell
Authors: Sargsyan A. D. , Sarkisyan D. H.
Published: January 2025

The effect of selective reflection (SR) of laser radiation from the boundary of 87Rb D2-line atomic vapors and a dielectric window was studied using a nanocell (NC) with a vapor column thickness of ~300 nm. The formation of an SR with a spectral width of 25 MHz, located on atomic transitions, is demonstrated. This is a record narrowing of the 670 MHz Doppler width by a factor of 27 using single-pass geometry. The SR signal reaches several percent of the intensity of its forming radiation, and the SR amplitude’s linear dependence is maintained up to 100 mW/cm2, which is almost two orders of magnitude greater than the saturation intensity of optical processes when using centimeter-long cells with atomic vapors. Such a high saturation intensity value is achieved by using the nanocell.
Cost-utility analysis of combination medical therapies in chronic coronary syndrome: a comparative study using real-world and patient-level data from Iran
Authors: Davari Majid , Fatemi Behzad , Sadeghipour Parham , Kebriaeezadeh Abbas , Maracy Mohammad Reza , Soleymani Fatemeh , Naderi Nasim , Zartab Saman
Published: January 2025

Objectives

The main objective was to evaluate the cost-effectiveness of various medical therapy combinations in managing chronic coronary syndrome (CCS) in Iran, based on real-world and patient-level data.

Design

A cost-utility analysis employing a Markov model was conducted using data from a retrospective cohort study.

Setting

The study was conducted in the healthcare setting of Iran, focusing on primary and secondary care.

Participants

Patients with CCS were included in the study. Numbers entering and completing the study were reported, with clear definitions of selection, entry and exclusion criteria.

Interventions

All combinations of recommended medical therapies for CCS were permitted. Ultimately, taking into account the sample size and study power, a comparison was made between the combination therapy of β-blockers (BB), long-acting nitroglycerin (LAN), aspirin (ASA) and statin versus the group receiving only BB, ASA and statin.

Primary and secondary outcome measures

The primary outcome measure was the incremental cost-effectiveness ratio, along with an initial evaluation of disability-adjusted life-years (DALYs) and costs related to the interventions.

Results

The BB/LAN/ASA/statin combination was cost-saving and effective, averting 0.02 DALYs and saving $172 compared with BB/ASA/statin. This combination was cost-effective in over 97% of the probabilistic sensitivity analysis results.

Conclusions

Incorporating LAN into the combination therapy of BB, ASA and statin is cost-effective in Iran. This finding provides evidence for policymakers on resource allocation in low-income countries.
Degree of housing damage caused by the Great East Japan Earthquake and all-cause mortality in the community-based cohort study of the Tohoku Medical Megabank Project
Authors: Nakaya Naoki , Nakaya Kumi , Kogure Mana , Kotozaki Yuka , Hatanaka Rieko , Chiba Ippei , Tokioka Sayuri , Takase Masato , Nagaie Satoshi , Ohmomo Hideki , Nasu Takahito , Fuse Nobuo , Tanno Kozo , Hozawa Atsushi
Published: January 2025

Background

Natural disasters may have negative health effects on survivors. However, long-term observations on this are lacking. Therefore, this study investigated the association between the degree of housing damage caused by the Great East Japan Earthquake (GEJE) and all-cause mortality using the data from the cohort study conducted by the Tohoku Medical Megabank (TMM) Project in disaster-stricken areas.

Methods

The community-based cohort study of the TMM Project which conducted a baseline survey from May 2013 to March 2016 collected data using questionnaires and blood and urine tests. The present large-scale prospective cohort study was a follow-up survey in which the degree of house damage and all-cause mortality were analysed using Cox proportional hazards regression, adjusting for sex, age and other potentially confounding variables. The degree of house damage was categorised into ‘did not live in the disaster area’, ‘no damage’, ‘small-scale damage’ and ‘large-scale damage’. Among the 58 320 participants, 1763 deaths were confirmed during the follow-up which averaged 6.5 years.

Results

The multivariate analysis showed a hazard ratio (95% CI) of 0.96 (0.82 to 1.13) for those who did not live in the disaster area, 0.98 (0.87 to 1.10) for small-scale damage and 0.98 (0.85 to 1.14) for large-scale damage, compared with no damage, but no significant association with all-cause mortality was observed.

Conclusion

The results of this large-scale prospective cohort study of GEJE survivors showed no significant relationship between the degree of house damage and all-cause mortality. Further long-term follow-up studies are needed to examine the long-term health effects of natural disasters on survivors.
Direct measurement of the 19F(p,$$\alpha $$)16O reaction using the LHASA detector array
Authors: Petruse T. , Guardo G. L. , Lattuada D. , Cognata M. La , Balabanski D. L. , Aciksoz E. , Acosta L. , Capponi L. , Carbone D. , Cherubini S. , Choudhury D. , D’Agata G. , Pietro A. Di , Figuera P. , Gulino M. , Kilik A. I. , Commara M. La , Lamia L. , Matei C. , Palmerini S. , Pizzone R. G. , Romano S. , Söderström P.-A. , Sparta R. , Tumino A. , Viñals S.
Published: January 2025

The low-energy 19F(p,

$$\alpha $$

α

)16O reaction has significant implications for nuclear astrophysics. The 19F(p,

$$\alpha $$

α

)16O reaction occurs via three channels: (p,

$$\alpha _0$$

α
0

), (p,

$$\alpha _\pi $$

α
π

), and (p,

$$\alpha _\gamma $$

α
γ

). At lower temperatures, below 0.15 GK, the (p,

$$\alpha _0$$

α
0

) channel is the dominant contributor of the reaction. The 19F(p,

$$\alpha _{0}$$

α
0

)16O reaction cross section in the energy range of 400–900 keV was studied in this work. Recent data in the literature reveals a roughly 1.4 increase compared to prior findings reported in the NACRE (Nuclear Astrophysics Compilation of REactions) compilation. Therefore, we present new additional result of the study published in EPJA [22] employing a silicon strip detector array (LHASA - Large High-resolution Array of Silicon for Astrophysics). The anguar distributions, the reaction cross sections and the astrophysical S-factors of the (p,

$$\alpha _0$$

α
0

) channel were obtained through this experiment. Our findings resolve the discrepancies that exist between the two previously available data sets in the literature.
Conditional Generative Models for Synthetic Tabular Data: Applications for Precision Medicine and Diverse Representations
Authors: Liu Kara , Altman Russ B.
Published: January 2025

Tabular medical datasets, like electronic health records (EHRs), biobanks, and structured clinical trial data, are rich sources of information with the potential to advance precision medicine and optimize patient care. However, real-world medical datasets have limited patient diversity and cannot simulate hypothetical outcomes, both of which are necessary for equitable and effective medical research. Fueled by recent advancements in machine learning, generative models offer a promising solution to these data limitations by generating enhanced synthetic data. This review highlights the potential of conditional generative models (CGMs) to create patient-specific synthetic data for a variety of precision medicine applications. We survey CGM approaches that tackle two medical applications: correcting for data representation biases and simulating digital health twins. We additionally explore how the surveyed methods handle modeling tabular medical data and briefly discuss evaluation criteria. Finally, we summarize the technical, medical, and ethical challenges that must be addressed before CGMs can be effectively and safely deployed in the medical field.
Machine Learning for Sparse Nonlinear Modeling and Control
Authors: Brunton Steven L. , Zolman Nicholas , Kutz J. Nathan , Fasel Urban
Published: January 2025

Machine learning is rapidly advancing nearly every field of science and engineering, and control theory is no exception. In particular, it has shown incredible promise for handling several of the main challenges facing modern dynamics and control, including complexity, unmodeled dynamics, strong nonlinearity, and hidden variables. However, machine learning models are often expensive to train and deploy, fail to generalize beyond the training data, and suffer from a lack of explainability, interpretability, and guarantees, all of which limit their use in real-world and safety-critical control applications. Sparse nonlinear modeling and control techniques are a powerful class of machine learning that promote parsimony through sparse optimization, providing data-efficient models that are more interpretable and generalizable and have proven effective for control. In this review, we explore the use of sparse optimization in the context of machine learning to develop compact models and controllers that are easy to train, require significantly less data, and make low-latency predictions. In particular, we focus on applications in model predictive control and reinforcement learning, two of the foundational algorithms in control theory.
A menu for microbes: unraveling appetite regulation and weight dynamics through the microbiota-brain connection across the lifespan
Authors: Ribeiro Gabriela , Schellekens Harriët , Cuesta-Marti Cristina , Maneschy Ivie , Ismael Shámila , Cuevas-Sierra Amanda , Martínez J. Alfredo , Silvestre Marta P. , Marques Cláudia , Moreira-Rosário André , Faria Ana , Moreno Luis A. , Calhau Conceição
Published: January 2025

Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior. Therefore, the role of the microbiota-gut-brain axis in appetite and obesity is receiving increased attention. Omics approaches such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics in appetite and weight regulation offer new opportunities for featuring obesity phenotypes. Furthermore, gut-microbiota-targeted approaches such as pre-, pro-, post-, and synbiotic, personalized nutrition, and fecal microbiota transplantation are novel avenues for precision treatments. The aim of this narrative review is 1) to provide an overview of the role of the microbiota-gut-brain axis in appetite regulation across the lifespan and 2) to discuss the potential of omics and gut microbiota-targeted approaches to deepen understanding of appetite regulation and obesity.
Supplementary Table 3 from Ephrin A1 Stimulates CCL2 Secretion to Facilitate Premetastatic Niche Formation and Promote Gastric Cancer Liver Metastasis
Authors: Cui Yun , Chang Yongxia , Ma Xixi , Sun Meng , Huang Yuliang , Yang Feng , Li Shuang , Zhuo Wei , Liu Wei , Yang Bo , Lin Aifu , Ou Guangshuo , Yang Yuehong , Xie Shanshan , Zhou Tianhua
Published: January 2025

All cytokines tested in human cytokine array
Table S3 from PHGDH Induction by MAPK Is Essential for Melanoma Formation and Creates an Actionable Metabolic Vulnerability
Authors: Jasani Neel , Xu Xiaonan , Posorske Benjamin , Kim Yumi , Wang Kaizhen , Vera Olga , Tsai Kenneth Y. , DeNicola Gina M. , Karreth Florian A.
Published: January 2025

Table S3
Supplementary Table 9 from FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma
Authors: Jessa Selin , De Cola Antonella , Chandarana Bhavyaa , McNicholas Michael , Hébert Steven , Ptack Adam , Faury Damien , Tsai Jessica W. , Korshunov Andrey , Phoenix Timothy N. , Ellezam Benjamin , Jones David T.W. , Taylor Michael D. , Bandopadhayay Pratiti , Pathania Manav , Jabado Nada , Kleinman Claudia L.
Published: January 2025

Cell type specific gene signatures derived from reference datasets, used for enrichment scoring.
Supplemental Figure S7 from The EP3–ZNF488 Axis Promotes Self-Renewal of Glioma Stem-Like Cells to Induce Resistance to Tumor Treating Fields
Authors: Chen Dongjiang , Le Son B. , Manektalia Harshit , Liu Tianyi , Hutchinson Tarun E. , O’Dell Adam , Salhia Bodour , Tran David D.
Published: January 2025

EP3 inhibition and overexpression reverses and induces TTFields resistance, respectively, in GBM cells. (Supporting Main Figure 2)
Supplementary Table 6 from FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma
Authors: Jessa Selin , De Cola Antonella , Chandarana Bhavyaa , McNicholas Michael , Hébert Steven , Ptack Adam , Faury Damien , Tsai Jessica W. , Korshunov Andrey , Phoenix Timothy N. , Ellezam Benjamin , Jones David T.W. , Taylor Michael D. , Bandopadhayay Pratiti , Pathania Manav , Jabado Nada , Kleinman Claudia L.
Published: January 2025

Summary of reference datasets for the normal brain and adrenal gland used in this study.
Supplementary Table 5 from FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma
Authors: Jessa Selin , De Cola Antonella , Chandarana Bhavyaa , McNicholas Michael , Hébert Steven , Ptack Adam , Faury Damien , Tsai Jessica W. , Korshunov Andrey , Phoenix Timothy N. , Ellezam Benjamin , Jones David T.W. , Taylor Michael D. , Bandopadhayay Pratiti , Pathania Manav , Jabado Nada , Kleinman Claudia L.
Published: January 2025

Quality control metrics and processing parameters for single-cell data for murine models.
Supplemental Figure S10 from The EP3–ZNF488 Axis Promotes Self-Renewal of Glioma Stem-Like Cells to Induce Resistance to Tumor Treating Fields
Authors: Chen Dongjiang , Le Son B. , Manektalia Harshit , Liu Tianyi , Hutchinson Tarun E. , O’Dell Adam , Salhia Bodour , Tran David D.
Published: January 2025

ZNF488 is required to maintain TTFields resistance in GSC and GBM cells. (Supporting Main Figure 6)
Supplementary Figure 3 from FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma
Authors: Jessa Selin , De Cola Antonella , Chandarana Bhavyaa , McNicholas Michael , Hébert Steven , Ptack Adam , Faury Damien , Tsai Jessica W. , Korshunov Andrey , Phoenix Timothy N. , Ellezam Benjamin , Jones David T.W. , Taylor Michael D. , Bandopadhayay Pratiti , Pathania Manav , Jabado Nada , Kleinman Claudia L.
Published: January 2025

NB-FOXR2 express a transcription factor fingerprint of the medial ganglionic eminence.
Supplementary Data from ACE2 Enhances Sensitivity to PD-L1 Blockade by Inhibiting Macrophage-Induced Immunosuppression and Angiogenesis
Authors: Xie Peiyi , Guo Lei , Yu Qiang , Zhao Yufei , Yu Mincheng , Wang Hui , Wu Mengyuan , Xu Wenxin , Xu Min , Zhu Xiao-Dong , Xu Yongfeng , Xiao Yong-Sheng , Huang Cheng , Zhou Jian , Fan Jia , Hung Mien-Chie , Sun Huichuan , Ye Qing-Hai , Zhang Bo , Li Hui
Published: January 2025

Supplementary materials and methods, Supplementary Figures and figure legends, Supplementary Tables
Supplementary Figure 1 from FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma
Authors: Jessa Selin , De Cola Antonella , Chandarana Bhavyaa , McNicholas Michael , Hébert Steven , Ptack Adam , Faury Damien , Tsai Jessica W. , Korshunov Andrey , Phoenix Timothy N. , Ellezam Benjamin , Jones David T.W. , Taylor Michael D. , Bandopadhayay Pratiti , Pathania Manav , Jabado Nada , Kleinman Claudia L.
Published: January 2025

Quality control (QC) metrics and copy-number variation for scRNAseq datasets of NB-FOXR2 patient tumors.
Figure 5 from FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma
Authors: Jessa Selin , De Cola Antonella , Chandarana Bhavyaa , McNicholas Michael , Hébert Steven , Ptack Adam , Faury Damien , Tsai Jessica W. , Korshunov Andrey , Phoenix Timothy N. , Ellezam Benjamin , Jones David T.W. , Taylor Michael D. , Bandopadhayay Pratiti , Pathania Manav , Jabado Nada , Kleinman Claudia L.
Published: January 2025

Foxr2 is oncogenic in the ventral telencephalon in mice. A, Schematic describing the IUE-based strategy to model FOXR2-driven brain tumors. PiggyBac and CRISPR vectors are delivered into neural stem cells in the GEs at E12.5. After birth, mice develop tumors and are euthanized when neurologic symptoms become apparent. B, Representative brightfield (BF) and fluorescence (GFP) images of a GFP+ Foxr2-driven tumor (top, whole brain; bottom, coronal section). C, Kaplan–Meier survival curves of tumor-bearing mice carrying Foxr2 overexpression alone (Foxr2 alone, n = 6) or in combination with p53 LOF (Foxr2 p53LOF, n = 6). Statistical comparisons using the log-rank Mantel–Cox test are described in Supplementary Table S1. D, Immunofluorescence of Foxr2 alone tissue in coronal sections from the striatum. Lesions driven by Foxr2 overexpression alone are GFP+ and colocalize with V5. Cells harboring Foxr2 overexpression alone possess low levels of Ki67 and Olig2. However, cells in these lesions are positive for NeuN, DCX, and GFAP. Scale bar, 50 μm. E, IHC detection of hematoxylin and eosin (H&E), GFP, and Ki67 in coronal forebrain sections from Foxr2 p53LOF tumor-bearing symptomatic mice. Tumor cells are GFP+. Scale bars, 1 mm in the low-magnification panels and 100 μm in the high-magnification panels. F, Immunofluorescence for GFP, Foxr2-V5, Ki67, Olig2, NeuN, DCX, and GFAP in coronal forebrain sections from Foxr2 p53LOF tumor-bearing symptomatic mice. Cells within the tumor in the striatum are GFP+, colocalize with V5, and many are actively proliferating, as indicated by the presence of Ki67. Individual tumor cells are also positive for Olig2, NeuN, DCX, and GFAP. Scale bar, 50 μm.
Supplementary Figure 1 from KRAS Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition
Authors: Fey Sigrid K. , Najumudeen Arafath K. , Watt Dale M. , Millett Laura M. , Ford Catriona A. , Gilroy Kathryn , Simpson Rosalin J. , McLay Kathy , Upstill-Goddard Rosanna , Chang David , Clark William , Nixon Colin , Birch Joanna L. , Barry Simon T. , Morton Jennifer P. , Campbell Andrew D. , Sansom Owen J.
Published: January 2025

Increased fibrosis in wild-type Kras deficient PanINs.
Data from PHGDH Induction by MAPK Is Essential for Melanoma Formation and Creates an Actionable Metabolic Vulnerability
Authors: Jasani Neel , Xu Xiaonan , Posorske Benjamin , Kim Yumi , Wang Kaizhen , Vera Olga , Tsai Kenneth Y. , DeNicola Gina M. , Karreth Florian A.
Published: January 2025

Abstract
Overexpression of phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in the serine synthesis pathway, promotes melanomagenesis, melanoma cell proliferation, and survival of metastases in serine-low environments such as the brain. Here, we found that PHGDH is universally increased in melanoma cells and required for melanomagenesis. Although PHGDH amplification explained PHGDH overexpression in a subset of melanomas, oncogenic BRAFV600E also promoted PHGDH transcription through mTORC1-mediated translation of ATF4. Importantly, depletion of PHGDH in genetic mouse melanoma models blocked tumor formation. In addition to BRAFV600E-mediated upregulation, PHGDH was further induced by exogenous serine restriction. Surprisingly, BRAFV600E inhibition diminished serine restriction–mediated PHGDH expression by preventing ATF4 induction. Consequently, melanoma cells could be specifically starved of serine by combining BRAFV600E inhibition with exogenous serine restriction, which promoted cell death in vitro and attenuated melanoma growth in vivo. In summary, this study identified that PHGDH is essential for melanomagenesis and regulated by BRAFV600E, revealing a targetable vulnerability in BRAFV600E-mutant melanoma.

Significance: BRAFV600E promotes the expression of the serine synthesis enzyme PHGDH, which is required for melanoma formation, and can be targeted to sensitize melanoma to dietary serine restriction, providing a melanoma cell–specific treatment strategy.
Data from BEEx Is an Open-Source Tool That Evaluates Batch Effects in Medical Images to Enable Multicenter Studies
Authors: Wu Yuxin , Xu Xiongjun , Cheng Yuan , Zhang Xiuming , Liu Fanxi , Li Zhenhui , Hu Lei , Madabhushi Anant , Gao Peng , Liu Zaiyi , Lu Cheng
Published: January 2025

Abstract
The batch effect is a nonbiological variation that arises from technical differences across different batches of data during the data generation process for acquisition-related reasons, such as collection of images at different sites or using different scanners. This phenomenon can affect the robustness and generalizability of computational pathology- or radiology-based cancer diagnostic models, especially in multicenter studies. To address this issue, we developed an open-source platform, Batch Effect Explorer (BEEx), that is designed to qualitatively and quantitatively determine whether batch effects exist among medical image datasets from different sites. A suite of tools was incorporated into BEEx that provide visualization and quantitative metrics based on intensity, gradient, and texture features to allow users to determine whether there are any image variables or combinations of variables that can distinguish datasets from different sites in an unsupervised manner. BEEx was designed to support various medical imaging techniques, including microscopy and radiology. Four use cases clearly demonstrated the ability of BEEx to identify batch effects and validated the effectiveness of rectification methods for batch effect reduction. Overall, BEEx is a scalable and versatile framework designed to read, process, and analyze a wide range of medical images to facilitate the identification and mitigation of batch effects, which can enhance the reliability and validity of image-based studies.

Significance: BEEx is a prescreening tool for image-based analyses that allows researchers to evaluate batch effects in multicenter studies and determine their origin and magnitude to facilitate development of accurate AI–based cancer models.
Table 1 from First-in-Human Study of 23ME-00610, an Antagonistic Antibody for Genetically Validated CD200R1 Immune Checkpoint, in Participants with Advanced Solid Malignancies
Authors: Kummar Shivaani , Razak Albiruni Abdul , Laurie Scott , Glatt Dylan M. , Kell Sariah , Diep Anh N. , Schmidt Maike , Hom Clifford , German Chris , Shringarpure Suyash S. , Majeed Sophia R. , Rasco Drew
Published: January 2025

Baseline patient and disease characteristics
Figure S3 from First-in-Human Study of 23ME-00610, an Antagonistic Antibody for Genetically Validated CD200R1 Immune Checkpoint, in Participants with Advanced Solid Malignancies
Authors: Kummar Shivaani , Razak Albiruni Abdul , Laurie Scott , Glatt Dylan M. , Kell Sariah , Diep Anh N. , Schmidt Maike , Hom Clifford , German Chris , Shringarpure Suyash S. , Majeed Sophia R. , Rasco Drew
Published: January 2025

Supplemental Figure S3
Figure 3 from First-in-Human Study of 23ME-00610, an Antagonistic Antibody for Genetically Validated CD200R1 Immune Checkpoint, in Participants with Advanced Solid Malignancies
Authors: Kummar Shivaani , Razak Albiruni Abdul , Laurie Scott , Glatt Dylan M. , Kell Sariah , Diep Anh N. , Schmidt Maike , Hom Clifford , German Chris , Shringarpure Suyash S. , Majeed Sophia R. , Rasco Drew
Published: January 2025

CD200 and CD200R1 expression in participant tumors. A, Representative photomicrographs of H&E, CD200, and CD200R1 IHC-stained sections of tumor from a patient with a well-differentiated neuroendocrine tumor (patient in Fig. 2C) whose target lesions shrank 39% from baseline assessments. B, Distribution of CD200 H-scores and CD200R1-positive immune cells (% positive cells) at baseline. Pink data points present the CD200 H-score and CD200R1 %–positive immune cell value for the patient tumor shown in A [CD200 H-score of 155; CD200R1 %–positive immune cells of <1%]. C, Baseline CD200 tumor cell membrane staining intensity and frequency (%) for 19 patients with evaluable archival tumor tissue that received pharmacologic active doses of 23ME-00610 (≥60 mg) and sorted by PR, SD, or PD. ASPS, alveolar soft part sarcoma; CESC, cervical squamous cell carcinoma; ccSCA, clear cell chondrosarcoma; H&E, hematoxylin and eosin; LSA, leiomyosarcoma; NSCLC, non–small cell lung cancer; SKCM, cutaneous melanoma; THCA, papillary thyroid carcinoma.
Figure 1 from First-in-Human Study of 23ME-00610, an Antagonistic Antibody for Genetically Validated CD200R1 Immune Checkpoint, in Participants with Advanced Solid Malignancies
Authors: Kummar Shivaani , Razak Albiruni Abdul , Laurie Scott , Glatt Dylan M. , Kell Sariah , Diep Anh N. , Schmidt Maike , Hom Clifford , German Chris , Shringarpure Suyash S. , Majeed Sophia R. , Rasco Drew
Published: January 2025

Single-dose serum PK and peripheral target engagement for 23ME-00610 in patients with cancer by dose level. Sample size for participants with evaluable data by dose cohorts: 1,400 mg (N = 8), 600 mg (N = 8), 200 mg (N = 3),60 mg (N = 4), 20 mg (N = 3), 6 mg (N = 1), and 2 mg (N = 1). A, Geometric mean and geometric SD for cycle 1 serum 23ME-00610 concentration–time data by dose level. Below limit of quantitation (BLQ) values were set to missing, and data were plotted only if more than half of the evaluable data was quantifiable [greater than the lower limit of quantitation (LLOQ)] and not missing. EC90 in tumor PK target (dotted reference line) based on in vitro tumor-killing assay and 10% tumor-to-serum partition. B, Median RO by dose level for cycle 1. The RO assay is qualitative and measures 23ME-00610 bound to the target receptor CD200R1 on the target cell of interest. At least 60% RO (shaded in green) is considered saturated, in which less than 60% RO is considered not saturated. C, Median-free soluble CD200R1 by dose level from cycle 1 day 1 predose to cycle 4 day 1 predose (63 study days). The assay lower limit of detection (following a 20-fold minimum required dilution) is 312 pg/mL (dotted reference line). BLQ values were plotted at the LLOQ. All patients for dose levels ≥60 mg were BLQ at day 21 and day 63. D, Median total soluble CD200R1 (sum of free soluble CD200R1 and 23ME-00610–bound soluble CD200R1) by dose level from cycle 1 day 1 predose to cycle 4 day 1 predose (63 study days). The assay lower limit of detection (following a 20-fold minimum required dilution) is 312 pg/mL (dotted reference line).
Data from First-in-Human Study of 23ME-00610, an Antagonistic Antibody for Genetically Validated CD200R1 Immune Checkpoint, in Participants with Advanced Solid Malignancies
Authors: Kummar Shivaani , Razak Albiruni Abdul , Laurie Scott , Glatt Dylan M. , Kell Sariah , Diep Anh N. , Schmidt Maike , Hom Clifford , German Chris , Shringarpure Suyash S. , Majeed Sophia R. , Rasco Drew
Published: January 2025

AbstractPurpose:
In this phase 1 portion of a first-in-human phase 1/2a study (NCT05199272), 23ME-00610 was evaluated in participants with advanced solid malignancies to determine its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). Exploratory biomarkers were evaluated to examine potential correlates of efficacy and safety.
Patients and Methods:
Eligible participants (≥18 years) were administered 23ME-00610 intravenously every 3 weeks (Q3W) using an accelerated titration design followed by a traditional 3 + 3 design, with an initial dose level of 2 mg.
Results:
Twenty-eight participants were enrolled across seven cohorts and received a median of four cycles of 23ME-00610. No treatment-related serious adverse events (AE) were observed, and the maximum tolerated dose was not reached. Overall, the PK of 23ME-00610 was linear and dose proportional for doses ≥60 mg, with a median terminal half-life of 13 days at 1,400 mg. Peripheral saturation of CD200R1 was observed for doses ≥60 mg. Immune-related AEs, including rash, pruritus, and hypothyroidism, were predicted by phenome-wide association studies and observed for doses ≥60 mg. A confirmed partial response was observed in a participant with well-differentiated pancreatic neuroendocrine cancer whose tumor was among those with the highest tumor CD200 expression.
Conclusions:
23ME-00610 has mild-to-moderate on-target AEs and PK/PD consistent with tumor target saturation and dosing every 3 weeks. The trend for clinical benefit in participants with tumor CD200 expression suggests that 23ME-00610 inhibits CD200R1 signaling and may reverse CD200-mediated immune evasion. Based on PK/PD, safety, and preliminary antitumor activity, 1,400 mg Q3W was selected as the dose for further study.
Significance:
Genome-wide association studies (GWAS) of the 23andMe genetic database identified CD200R1 as a promising therapeutic target for cancer. This phase 1 study of 23ME-00610, a CD200R1 antagonist IgG1, showed acceptable safety and tolerability, PK supporting Q3W dosing, and PD and preliminary clinical activity supporting an initial recommended phase 2 dose of 1,400 mg.
Approach to the Do-Not-Resuscitate patient in the periendoscopic period – survey about the current Portuguese reality
Authors: Franco Ana Rita , Lima Pedro , Simão Inês Rodrigues , Mendes Raquel R. , Mascarenhas André , Feld Lauren D. , Barosa Rita , Chagas Cristina
Published: January 2025

Background and Aims: Cardiopulmonary arrest is a rare but possible complication of endoscopic procedures, particularly when performed under sedation and/or analgesia. Hospitalized patients, and probably those with a Do Not Resuscitate (DNR) order, present a higher risk of severe cardiopulmonary complications during endoscopy. The request for endoscopic examination, particularly urgent procedures, is becoming increasingly more frequent in patients with Do-Not-Resuscitate orders. This study aimed to assess current practices, concepts and guideline awareness of nationally surveyed Portuguese gastroenterologists regarding the approach to code status for DNR patients in the periendoscopic period.
Methods: Online anonymous and self-administered survey was adapted to the Portuguese reality and was conducted to assess gastroenterologists and gastroenterology trainees’ basic demographics data and details about current practice, personal opinions and knowledge of existing guidelines concerning the reversal of periprocedural DNR orders.
Results: One hundred and forty five gastroenterologists, including 26 trainees (17.9%), responded to the survey. In patients with a DNR order, code status is rarely discussed (<25% of cases) with the patient/legal representative (66.9%, n=97) or hospitalist (58.6%, n=85) and the DNR order is also rarely reversed (reversal in all (100% of cases) or most cases (75-99% of cases) in 8.3% n=12). Most respondents were unaware of the procedures necessary for DNR prescription in Portugal (81.3%, n=118), as well as existing guidelines on DNR reversal (96.5%, n=140). Regarding personal beliefs, the majority considered that in these patients, the DNR order should be reversed to an intermediate option that includes limited resuscitation maneuvers (62.1%, n=90) and that the urgency of a procedure should not influence the decision to reverse DNR (n=89, 61.4%). There was consensus on the need for recommendations on this topic for gastroenterologists (97.9%, n=142).

Conclusion: Portuguese gastroenterologists usually do not revisit the DNR order before endoscopic procedures as a matter of course and consequently do not reverse it. Furthermore, we found significant variation in practices and beliefs among Portuguese gastroenterologists in their approach to the patient w
Netflix, cosmopolitismo e a construção de um ethos discursivo de diversidade
Authors: Prudencio Natalia Engler
Published: January 2025

Este artigo tem por objetivo discutir como a noção de diversidade tem sido tematizada na construção de marca da Netflix. Para tanto, nos valemos da noção de ethos discursivo e a analisamos a construção de um ethos discursivo de diversidade em um comunicado de imprensa em que a companhia mobiliza essa noção. Conclui-se que a construção desse ethos discursivo de diversidade seria uma estratégia da plataforma para estratificar seu público transnacionalmente diante de um mercado globalizado e se diferenciar da concorrência, posicionando a marca como agente de mudanças em sua indústria e a ligando a um modo de ser cosmopolita e comprometido com a diversidade de identidades de seu público e de seus criadores.
Abstract 199: Association of the Monocyte‐to‐HDL ratio (MHR) with the diagnosis and prognosis of Acute Ischemic Stroke: A systematic review with meta‐analysis
Authors: Luna G. , Rios-Garcia W. , Váscones-Román F. F. , Quispe-Vicuña C. , Velazco-Muñoz J. , Carbajal-García G. , Alegre-Cordero I.
Published: January 2025

Objective

To summarize the current evidence on the diagnostic and prognostic value of Monocyte‐to‐HDL ratio (MHR) on acute ischemic stroke (AIS)

Background

Recently, the MHR has been studied as a potential biomarker for assessing the prognosis of different diseases.

Design/Methods

We searched 5 databases (PubMed, Embase, Scopus, Web of Science and Google Scholar) until June 2024. We included observational studies that evaluated the association between MHR and AIS. A meta‐analysis using a random‐effects model to estimate pooled effects was planned for each outcome and a narrative synthesis when this was not possible. The Newcastle‐Ottawa scale was used to assess the risk of bias and GRADE criteria were used to identify the certainty of evidence.

Results

11 studies (7 cohorts, 3 cross‐sectionals and 1 case‐control) were included. With high uncertainty, a meta‐analysis of 4 studies showed a significantly increased risk of AIS in patients with a higher MHR (MD: 2.14, 95%CI: 1.75 to 2.54, I2: 100%, 4 studies). Regarding AIS prognosis, two separate meta‐analysis were conducted on 30‐day mortality and functional outcome. With high uncertainty, the MHR was found to be higher in deceased patients within 30 days of AIS onset (MD: 3.22, 95%CI: ‐3.28 to 9.72, I2: 99%, 2 studies), and higher in patients with mRS score > 2 at 90 days (MD: 0.15, 95%CI: ‐0.05 to 0.34, I2: 87%, 2 studies). Additionally, all studies reported a low risk of bias.

Conclusions

With high uncertainty, we found that MHR is a useful tool for the diagnosis and prediction of poor outcomes in AIS. However, we need more studies, especially prospective ones, in order to improve the evidence regarding this index.
Insect-based chitin and chitosan from whole body sources and rearing by-products: extraction, physicochemical, structural and bioactivity characterisation
Authors: Navarro P. , Ribeiro J.C. , Luı́s Â. , Domingues F. , Anjos O. , Cunha L.M.
Published: January 2025

Fractionation of edible insects and their rearing by-products can lead to expanded industrial applications and extraction of value-added products. The main goal of this study was to extract chitin and synthesise chitosan from three different insect sources – Tenebrio molitor larvae, adult Acheta domesticus and A. domesticus rearing by-products (legs and wings). Furthermore, the physicochemical, structural, and bioactive properties of insect-derived chitin and chitosan were characterised and compared to commercial crustacean-based samples. Chitin was isolated from defatted sources through chemical hydrolysis followed by decolourisation and was deacetylated with a strong alkaline solution to synthesise chitosan. Notably, A. domesticus rearing by-products yielded the highest chitin and chitosan content. Chitin and chitosan derived from insects exhibited physicochemical and structural characteristics consistent with the α-polymorphic form, similar to the commercial samples. Differences were found in surface morphology, with insect-derived samples presenting large and irregular flakes and porosity, while the crustacean-derived samples presented irregularly arranged fibres and a more regular and smoother surface. As for antioxidant activity, although all chitosan samples demonstrated poor DPPH radical scavenging activity, this study showed for the first time that insect-derived chitosan presents lipid peroxidation inhibition ability. All chitosan samples presented antimicrobial activity against different pathogenic bacteria, with K. pneumoniae being the most susceptible strain. Nevertheless, there is potential for enhancement of the biological properties through modifications on the molecular weight and deacetylation degree. This research introduces the potential of cricket-rearing by-products as sustainable sources of chitosan with functional bioactive properties.