bluuebunny/crossref_metadata_2025 huggingface dataset:
Delta opioid peptide [D-ala2, D-leu5]-Enkephalin’s ability to enhance mitophagy via TRPV4 to relieve ischemia/reperfusion injury in brain microvascular endothelial cells
Authors: Deng Zhongfang , Chen Xiaoyu , Zhang Ran , Kong Lingchao , Fang Yang , Guo Jizheng , Shen Bing , Zhang Lesha
Published: May 2024

Background

Local brain tissue can suffer from ischaemia/reperfusion (I/R) injury, which lead to vascular endothelial damage. The peptide δ opioid receptor (δOR) agonist [D-ala2, D-leu5]-Enkephalin (DADLE) can reduce apoptosis caused by acute I/R injury in brain microvascular endothelial cells (BMECs).

Objective

This study aims to explore the mechanism by which DADLE enhances the level of mitophagy in BMECs by upregulating the expression of transient receptor potential vanilloid subtype 4 (TRPV4).

Methods

BMECs were extracted and made to undergo oxygen-glucose deprivation/reoxygenation (OGD/R) accompanied by DADLE. RNA-seq analysis revealed that DADLE induced increased TRPV4 expression. The CCK-8 method was used to assess the cellular viability; quantitative PCR (qPCR) was used to determine the mRNA expression ofDrp1; western blot was used to determine the expression of TRPV4 and autophagy-related proteins; and calcium imaging was used to detect the calcium influx. Autophagosomes in in the cells’ mitochondria were observed by using transmission electron microscopy. ELISA was used to measure ATP content, and a JC-1 fluorescent probe was used to detect mitochondrial membrane potential.

Results

When compared with the OGD/R group, OGD/R+DADLE group showed significantly enhanced cellular viability; increased expression of TRPV4, Beclin-1, LC3-II/I, PINK1 and Parkin; decreased p62 expression; a marked rise in calcium influx; further increases in mitophagy, an increase in ATP synthesis and an elevation of mitochondrial membrane potential. These protective effects of DADLE can be blocked by a TRPV4 inhibitor HC067047 or RNAi of TRPV4.

Conclusion

DADLE can promote mitophagy in BMECs through TRPV4, improving mitochondrial function and relieving I/R injury.
Precision pest control using purpose-built uncrewed aerial system (UAS) technology and a novel bait pod system
Authors: Morley Craig G. , Solaris Philip , Quinn Greg O. , Ross Kathryn E. , Peterson Bruce J.
Published: May 2024

Controlling invasive species is imperative due to their significant roles in spreading diseases, preying on threatened species, and diminishing biodiversity. Crewed aircraft are proficient at dispersing toxic bait across vast expanses to combat small pest mammals such as possums and rats. However, their utility diminishes significantly in small, remote areas typified by rugged terrain due to impracticality and prohibitive costs. Similarly, while ground control operations are effective in compact, easily reachable locations, they encounter formidable obstacles like costly labour expenses, safety hazards, and the peril of worker injuries while navigating treacherous landscapes. An innovative approach to address these limitations is to use uncrewed aerial systems that are unhampered by the terrain to deploy bait at precise locations. Our team engineered a purpose-built system designed specifically for deploying bait using innovative bait pods. Two field trials were conducted in New Zealand to validate our systems’ efficacy, assessing deployment precision and accuracy against predefined ground targets. While the initial trial yielded mixed results, significant improvements were observed in the subsequent trial, featuring enhancements to the bait pod design. The median deployment accuracy achieved was 1.91 m from the target ( n = 63), with no statistically significant difference in deployment accuracy between open and forested areas ( p = 0.76). This advanced system permits the precise placement of bait pods to any location, facilitating effective pest control within complex landscapes, challenging terrain, and dense vegetation. With its smart functionality and adaptability, this system can be utilised across various aircraft and autopilot systems to ensure maximum accuracy and efficiency in delivering bait pods for pest control operations. Therefore, this innovative tool possesses tremendous potential for managing small mammalian invasive species, particularly in specialised environments such as reserves, gullies, and islands, complementing existing pest control strategies to expedite the restoration of ecosystems and safeguard biodiversity.
Molecular dynamics exploration of the temperature-dependent elastic, mechanical, and anisotropic properties of hcp ruthenium
Authors: Güler E. , Uğur Ş. , Güler M. , Uğur G.
Published: May 2024

Molecular dynamics calculations were performed for the hitherto unclarified temperature-dependent elastic, mechanical, and anisotropic properties of the hexagonal closed pack (hcp) ruthenium (Ru) between 0 and 1200 K. All elastic stiffness constants were found to decrease with increasing temperature. Under the examined temperature range, hcp Ru obeys Born stability conditions. Further, both Pugh ratio analyses and calculated Poisson ratio values mutually suggest the brittle character of hcp Ru between 0 and 1200 K. The intricate hardness behavior of hcp Ru was also obtained and discussed throughout the work. For the considered temperature range, hcp Ru exhibits apparent elastic anisotropy that exponentially increases with increasing temperature. Moreover, presently obtained ground state (T = 0 K and P = 0 GPa) theoretical data for hcp Ru agree well with the former experimental and theoretical data. The present findings on the temperature-dependent characteristics of this metal may further inspire future applied works.

Graphical abstract
Shape isomers: status and perspectives across the nuclear chart
Authors: Leoni S. , Fornal B. , Mărginean N. , Wilson J. N.
Published: May 2024

The paper reviews the searches for shape isomers, which are “extreme” example of shape-coexistence phenomena in nuclei. They may appear when highly deformed structures, well localized in the nuclear Potential Energy Surface (PES) in the deformation space, undergo a significant change in shape to match the final state shape, thus leading to a substantially hindered $$\gamma$$
γ
decay. This is in sharp contrast to the vast majority of shape-coexistence phenomena, where significant mixing in the initial and final state wave functions is found. So far, the most spectacular examples of shape isomerism are known in fissioning systems in the actinides, although only scarce experimental information is available from experiments conducted more than 20 years ago. Searches in lighter mass regions, guided by theory predictions based on different approaches and experimental investigations on superdeformed systems, are also presented. They point to $$^{64,66}$$

64
,
66

Ni as additional examples of prolate deformed shape-isomer-like structures, although with much reduced hindrance with respect to the actinides. Their origin is strictly related to the action of the monopole component of the tensor force of the nucleon-nucleon interaction, which is expected to favor the appearance of deep secondary minima also in the PES of Sn nuclei with masses 112–118. Perspectives in current searches of shape isomerism with modern detection systems, in the actinides regions and in lighter masses, are discussed.
Subsurface maturation in a saline aquifer CCS project development. Experience from the Northern Lights project, offshore Norway
Authors: Meneguolo Renata , Thompson Nicholas , Acuna Catalina , Furre Anne-Kari , Milovanova Elvira
Published: May 2024

The Northern Lights full-scale commercial CO
2
transport and storage project is open to multi-industry capture plants, in a business still under development. The geological sequestration concept of a sloping saline aquifer raised several subsurface challenges related to timeline, data availability and development constrains, which all affected the decision process. The subsurface focus on storage security required the different disciplines to perform adjustments to the established workflows available from the hydrocarbon industry. A risk management-focused approach, front-end loading and early emphasis on containment were paramount. Here we share the experience from the Northern Lights subsurface maturation process and highlight the crucial contribution from the different disciplines in a challenging new industry.
Long-term risk assessment of subsurface carbon storage: analogues, workflows and quantification
Authors: Jenkins Creties , Pestman Pieter , Carragher Peter , Constable Rosalie
Published: May 2024

A key aspect of transferrable oil and gas expertise to subsurface CO
2
storage (SCS) relates to risk assessment. While initial subsurface risk and volume assessments for SCS projects are similar to oil and gas prospect evaluations, full life-cycle risk assessment requires evaluation of the current knowledge of the storage complex and future potential events that may have impacts over long time frames. It is important to learn from past water, gas, and CO
2
injection and storage projects, examples of which are reviewed here. The concepts of aleatory and epistemic risk and uncertainty are discussed, and the use of standard risk matrices for evaluation of long-term, low-frequency but potentially high-impact events is challenged. Drawing on the large volume of previous work, this paper highlights key elements for development of a robust risking framework, including thorough project framing and implementation of a staged approach to project execution. The paper assesses methods for ensuring all potential hazards are captured and addresses the challenges of defining a quantitative risking scale suitable for long-term SCS projects. Example quantitative risk profiles can be used to calculate the timing and duration of ‘Peak Risk’, augment monitoring and mitigation planning for management of risk and capital exposure, and help to ensure successful project outcomes.

Thematic collection:
This article is part of the Geoscience workflows for CO
2
storage collection available at:
https://www.lyellcollection.org/topic/collections/geoscience-workflows-for-CO2-storage
About this title - Geology, Tectonics and Natural Resources of Arabia and its Surroundings
Authors: Scharf A. , Al-Kindi M. , Racey A.
Published: May 2024

The diverse and excellently exposed geology and tectonics of the Arabian Plate and its surroundings provide a natural laboratory for scientific research as well as for the exploration of its natural resources. This volume offers a range of chapters improving our geological understanding of the region and its energy/mineral resources.
The Proterozoic–Cambrian salt detachment zone at Lakhar Kuh, Iran: a seismic-scale analogue for salt stringers, detachment folding and multiphase structural development
Authors: Morley Christopher K. , Back Stefan
Published: May 2024

In the Middle East, significant evaporite units formed in the latest Precambrian–Cambrian, Triassic, Jurassic, Cretaceous and Cenozoic. The Precambrian–Cambrian period gave rise to the Ara Salt carbonate stringer plays, southern Oman and the giant Zagros anticline traps (Hormuz Formation). While outcrops of salt diapirs are common, basal detachment exposures are extremely rare. The Lakar Kuh area of Central Iran reveals the Precambrian–Cambrian basal salt detachment, on satellite images, in natural cross-section view through the entire Phanerozoic sedimentary section east of Ravar. This view illustrates how older diapiric structures (pillows and normal faults) were the focus of later contractional folds, particularly in the Jurassic and Cenozoic. The salt detachment zone contains many floating blocks (stringers) of clastic, carbonate and igneous rocks. Some blocks were stoped from the overlying beds, while most were layers originally interbedded with the evaporites. Block size, distribution and orientation is highly variable, and folding is infrequent. Lakar Kuh encompasses several key themes generally pertinent to structural geology and salt system research: the presence of sedimentary stringers within evaporites, multiple detachment levels within a thick (>5 km) stratigraphic section, detachment folding, multiphase salt activity, reactivation of older structures by newer ones and multi-stage development of salt bodies.
Probabilistic Unitary Synthesis with Optimal Accuracy
Authors: Akibue Seiseki , Kato Go , Tani Seiichiro
Published: May 2024

The purpose of unitary synthesis is to find a gate sequence that optimally approximates a target unitary transformation. A new synthesis approach, called probabilistic synthesis, has been introduced, and its superiority has been demonstrated over traditional deterministic approaches with respect to approximation error and gate length. However, the optimality of current probabilistic synthesis algorithms is unknown. We obtain the tight lower bound on the approximation error obtained by the optimal probabilistic synthesis, which guarantees the sub-optimality of current algorithms. We also show its tight upper bound, which improves and unifies current upper bounds depending on the class of target unitaries. These two bounds reveal the fundamental relationship of approximation error between probabilistic approximation and deterministic approximation of unitary transformations. From a computational point of view, we show that the optimal probability distribution can be computed by the semidefinite program (SDP) we construct. We also construct an efficient probabilistic synthesis algorithm for single-qubit unitaries, rigorously estimate its time complexity, and show that it reduces the approximation error quadratically compared with deterministic algorithms.
Effects of Gas-Dissolved Water for Ceria Nanoparticles on the SiO2 Film Surface in Post-CMP Cleaning
Authors: Park Kihong , Jeon Wookyung , Liu Pengzhan , Jeon Sanghuck , Hong Seokjun , Park Sanghyeon , Kim Taesung
Published: May 2024

As a trend of using colloidal and smaller ceria nanoparticles (CNPs) at the shallow trench isolation (STI) chemical mechanical polishing (CMP) in semiconductor manufacturing, post-CMP cleaning challenges in the removal of residual CNPs on the SiO2 film surface became much more challenging. We investigated the reduction/oxidation of ceria nanoparticles (CNPs) by hydrogen gas-dissolved water (H2 GDW), carbon dioxide gas-dissolved water (CO2 GDW), and oxygen gas-dissolved water (O2 GDW). The concentration of Ce3+ on the CNPs changed from 18.64% to 19.48%, 20.31% to 21.94%, and 21.27% to 19.22%, respectively, after immersion in H2 GDW, CO2 GDW, and O2 GDW for 3 to 12 h. Following the Ce3+ concentration of the CNP surface, adhesion energies between CNPs immersed in H2 GDW, CO2 GDW, and O2 GDW for 6 h with SiO2 surface were 6.06E-16 J, 6.18E-16 J, and 4.83E-16 J. Cleaning experiments under megasonic conditions revealed the efficacy of H2 GDW and O2 GDW in removing residual CNPs from SiO2 surfaces. The residual cerium (Ce) ion concentrations remaining on the SiO2 film surface after cleaning, were 0.06, 0.41, and 0.10 ppb for H2 GDW, CO2 GDW, and O2 GDW, respectively.
Effect of Novel pH Regulators on Copper film Chemical Mechanical Polishing for Ruthenium-Based Copper Interconnect under Weak Alkalinity Conditions
Authors: Dong Changxin , Niu Xinhuan , Liu Jianghao , Zhan Ni , Zou Yida , He Chao , Li Xinjie , Luo Fu , Shi Yunhui , Cheng Jiabao
Published: May 2024

For Ruthenium (Ru)-based copper (Cu) interconnects Cu film chemical mechanical polishing (CMP), it is crucial to select appropriate pH regulators in the slurry to ensure the chemical reactions and maintain the stability of the polishing chemical environment. In this study, the effects of inorganic pH regulator KOH, organic pH regulator diethanolamine (DEA), and 2-amino-2-methyl-1-propanol (AMP) on CMP and slurry properties of Cu film were compared. It was found when using AMP as a pH regulator, the Cu/Ru removal rate selectivity (RRS) can reach 598:1, the surface roughness of Cu film decreased to 0.76 nm, and the slurry can remain stable for at least 7 d. The performance order of the three pH regulators is AMP＞KOH＞DEA. Meanwhile, through experimental results and test analysis, it has been confirmed that AMP can also play a multifunctional role as a complexing agent, dispersant, and surfactant. Therefore, AMP can replace KOH as a new pH regulator in weak alkaline slurries. This result plays an important role in guiding the selection of organic pH regulators in the optimization of Cu film CMP slurry.
Leveraging digital assets: lessons from a 14-year-old isotope tracer course for professional scientists
Authors: Malabanan Eann , McGuinness Owen P. , Oliver Kendra H.
Published: May 2024

We examined impact of leveraging digital assets to support virtual engagement for an in-person program. Using survey data of a 14-year-old program for scientific professionals, we compared pre- and postpandemic in-person programs. Through incorporating digital assets, we found increased survey satisfaction compared to prepandemic in-person programs. These findings highlight how incorporating new digital engagement strategies benefits even the most successful professional development programs.
Kidney collecting duct-derived vasopressin is not essential for appropriate concentration or dilution of urine
Authors: Zuchowski Yvonne , Carty Joshua S. , Trapani Jonathan B. , Watts Jason A. , Bock Fabian , Zhang Mingzhi , Terker Andrew S. , Zent Roy , Delpire Eric , Harris Raymond C. , Arroyo Juan Pablo
Published: May 2024

Hypothalamic vasopressin is required for appropriate urinary concentration. However, whether collecting duct-derived vasopressin is involved remains unknown. We developed a novel transgenic mouse model to induce tissue-specific deletion of vasopressin and showed that collecting duct-derived vasopressin is not required to concentrate or dilute urine.
Differential effects of exercise intensity and tolerable duration on exercise-induced diaphragm and expiratory muscle fatigue
Authors: Hardy Tim A. , Chadwick Matt R. , Ferguson Carrie , Cross Troy J. , Taylor Bryan J.
Published: May 2024

Exercise-induced respiratory muscle fatigue contributes to limiting exercise tolerance. Accordingly, better understanding the exercise conditions under which respiratory muscle fatigue occurs is warranted. Although heavy-intensity as well as short- and long-duration severe-intensity exercise performed to intolerance elicit diaphragm and expiratory muscle fatigue, we find, for the first time, that the relationship between exercise intensity, exercise duration, and the magnitude of exercise-induced fatigue is different for the diaphragm compared with the expiratory muscles.
Fetal sex and the relative reactivity of human umbilical vein and arteries are key determinants in potential beneficial effects of phosphodiesterase inhibitors
Authors: Peyter Anne-Christine , Beaumann Manon , Delhaes Flavien , Joye Sébastien , Menétrey Steeve , Baud David , Tolsa Jean-François
Published: May 2024

The effects of phosphodiesterase inhibition on the umbilical circulation depend on the presence of intrauterine growth restriction, the fetal sex, vessel type, and vasoconstrictors implicated. The human umbilical vascular tone regulation is complex and depends on the amount and activity of specific proteins but also probably on the subcellular organization mediating protein interactions. Therefore, therapeutic interventions using phosphodiesterase inhibitors to improve the placental-fetal circulation should consider fetal sex and both umbilical vein and artery reactivity.
The use of accelerometers to improve estimation of the thermic effect of food in whole room calorimetry studies
Authors: Purcell Sarah A. , LaMunion Samuel R. , Chen Kong Y. , Rynders Corey A. , Thomas Elizabeth A. , Melanson Edward L.
Published: May 2024

Two research-grade accelerometers can effectively estimate spontaneous physical activity and improve the estimation of thermic effect of food (TEF) in whole room calorimeters. The activPAL demonstrates strong group-level accuracy and reasonable individual-level agreement in estimating wakeful TEF, whereas a hip-worn Actigraph is an acceptable approach for estimating 24-h TEF. These results highlight the promising potential of accelerometers in advancing energy balance research by improving the assessment of TEF within whole room calorimeters.
Different descending pathways mediate early and late portions of lower limb responses to transcranial magnetic stimulation
Authors: Shemmell Jonathan , Falling Carrie , MacKinnon Colum D. , Stapley Paul J. , Ribeiro Daniel Cury , Stinear James W.
Published: May 2024

Early and late portions of the response to transcranial magnetic stimulation (TMS) in a lower limb postural muscle are modulated independently by cortical suppression, late motor evoked potentials (MEPs) being facilitated during cortical inhibition. These results suggest a cortico-brain stem transmission pathway for late portions of the TMS-induced MEP.
A versatile delivery vehicle for cellular oxygen and fuels or metabolic sensor? A review and perspective on the functions of myoglobin
Authors: Adepu Kiran Kumar , Anishkin Andriy , Adams Sean H. , Chintapalli Sree V.
Published: May 2024

A canonical view of the primary physiological function of myoglobin (Mb) is that it is an oxygen (O2) storage protein supporting mitochondrial oxidative phosphorylation, especially as the tissue O2 partial pressure (Po2) drops and Mb off-loads O2. Besides O2 storage/transport, recent findings support functions for Mb in lipid trafficking and sequestration, interacting with cellular glycolytic metabolites such as lactate (LAC) and pyruvate (PYR), and “ectopic” expression in some types of cancer cells and in brown adipose tissue (BAT). Data from Mb knockout (Mb−/−) mice and biochemical models suggest additional metabolic roles for Mb, especially regulation of nitric oxide (NO) pools, modulation of BAT bioenergetics, thermogenesis, and lipid storage phenotypes. From these and other findings in the literature over many decades, Mb’s function is not confined to delivering O2 in support of oxidative phosphorylation but may serve as an O2 sensor that modulates intracellular Po2- and NO-responsive molecular signaling pathways. This paradigm reflects a fundamental change in how oxidative metabolism and cell regulation are viewed in Mb-expressing cells such as skeletal muscle, heart, brown adipocytes, and select cancer cells. Here, we review historic and emerging views related to the physiological roles for Mb and present working models illustrating the possible importance of interactions between Mb, gases, and small-molecule metabolites in regulation of cell signaling and bioenergetics.
Alginate Nanoparticles Containing Cuminum cyminum and Zataria multiflora Essential Oils with Promising Anticancer and Antibacterial Effects
Authors: Osanloo Mahmoud , Ranjbar Razieh , Zarenezhad Elham
Published: May 2024

Cancer and bacterial infections are major global health concerns driving the need for innovative medicines. This study investigated alginate nanoparticles loaded with essential oils (EOs) from Cuminum cyminum and Zataria multiflora as potential drug delivery systems. The nanoparticles were comprehensively characterized using techniques such as gas chromatography-mass spectrometry (GC-MS), dynamic light scattering (DLS), zetasizer, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and ultraviolet-visible spectroscopy (UV-Vis). Their biological properties against two human skin cancer cell lines (A-375 and A-431) and three bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) were also evaluated. Alginate nanoparticles containing C. cyminum and Z. multiflora EOs exhibited sizes of 160 ± 8 nm and 151 ± 10 nm, respectively. Their zeta potentials and encapsulation efficiencies were −18 ± 1 mV and 79 ± 4%, as well as −27 ± 2 mV and 86 ± 5%, respectively. The IC50 values against the tested cell lines and bacteria revealed superior efficacy for nanoparticles containing Z. multiflora EO. Considering the proper efficacy of the proposed nanoparticles, the straightforward preparation method and low cost suggest their potential for further in vivo studies.
Supplementary Figure S4 from Breast Cancer Stem Cells Secrete MIF to Mediate Tumor Metabolic Reprogramming That Drives Immune Evasion
Authors: Yan Linlin , Wu Mingming , Wang Tianyu , Yuan Hui , Zhang Xiao , Zhang Huafeng , Li Tao , Pandey Vijay , Han Xinghua , Lobie Peter E. , Zhu Tao
Published: May 2024

Supplementary Figure S4 shows that MIF secreted by BCSCs to enhance the glycolysis of breast cancer cells.
Data from Breast Cancer Stem Cells Secrete MIF to Mediate Tumor Metabolic Reprogramming That Drives Immune Evasion
Authors: Yan Linlin , Wu Mingming , Wang Tianyu , Yuan Hui , Zhang Xiao , Zhang Huafeng , Li Tao , Pandey Vijay , Han Xinghua , Lobie Peter E. , Zhu Tao
Published: May 2024

Abstract
Reprogramming of energy metabolism exerts pivotal functions in cancer progression and immune surveillance. Identification of the mechanisms mediating metabolic changes in cancer may lead to improved strategies to suppress tumor growth and stimulate antitumor immunity. Here, it was observed that the secretomes of hypoxic breast cancer cells and breast cancer stem cells (BCSC) induced reprogramming of metabolic pathways, particularly glycolysis, in normoxic breast cancer cells. Screening of the BCSC secretome identified MIF as a pivotal factor potentiating glycolysis. Mechanistically, MIF increased c-MYC–mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Consequently, targeting MIF improved the therapeutic efficacy of immune checkpoint blockade in triple-negative breast cancer. Collectively, this study proposes MIF as an attractive therapeutic target to circumvent metabolic reprogramming and immunosuppression in breast cancer.
Significance:
MIF secreted by breast cancer stem cells induces metabolic reprogramming in bulk tumor cells and engenders an immunosuppressive microenvironment, identifying MIF targeting as a strategy to improve immunotherapy efficacy in breast cancer.
Supplementary Table S1 from Severity of Complications and Duration of Type 2 Diabetes and the Risk of Cancer: A Population-Based Study
Authors: Hu Yu-Wen , Yeh Chiu-Mei , Liu Chia-Jen , Chen Tzeng-Ji , Huang Nicole , Chou Yiing-Jenq
Published: May 2024

Supplementary Table S1: Monthly Bulletin of Interior Statistics, 1.6 Population by 5-year Age Group
Figure S5 from Prognostic Value of Pretreatment Plasma C-Reactive Protein in Patients with Early-Stage Breast Cancer
Authors: Andersen Høgni H. , Bojesen Stig E. , Johansen Julia S. , Ejlertsen Bent , Berg Tobias , Tuxen Malgorzata , Madsen Kasper , Danø Hella , Flyger Henrik , Jensen Maj-Britt , Nielsen Dorte L.
Published: May 2024

Continuous CRP and overall survival
Supplementary Figure S13 from Serum Lipidome Profiling Reveals a Distinct Signature of Ovarian Cancer in Korean Women
Authors: Sah Samyukta , Bifarin Olatomiwa O. , Moore Samuel G. , Gaul David A. , Chung Hyewon , Kwon Sun Young , Cho Hanbyoul , Cho Chi-Heum , Kim Jae-Hoon , Kim Jaeyeon , Fernández Facundo M.
Published: May 2024

Supplementary Figure S13 shows Brief outline of the comparisons performed in this study.
Supplementary Figure S11 from Serum Lipidome Profiling Reveals a Distinct Signature of Ovarian Cancer in Korean Women
Authors: Sah Samyukta , Bifarin Olatomiwa O. , Moore Samuel G. , Gaul David A. , Chung Hyewon , Kwon Sun Young , Cho Hanbyoul , Cho Chi-Heum , Kim Jae-Hoon , Kim Jaeyeon , Fernández Facundo M.
Published: May 2024

Supplementary Figure S11 shows Unsupervised Principal Component Analysis (PCA) using annotated lipids as input.
Data from Diffsig: Associating Risk Factors with Mutational Signatures
Authors: Park Ji-Eun , Smith Markia A. , Van Alsten Sarah C. , Walens Andrea , Wu Di , Hoadley Katherine A. , Troester Melissa A. , Love Michael I.
Published: May 2024

AbstractBackground:
Somatic mutational signatures elucidate molecular vulnerabilities to therapy, and therefore detecting signatures and classifying tumors with respect to signatures has clinical value. However, identifying the etiology of the mutational signatures remains a statistical challenge, with both small sample sizes and high variability in classification algorithms posing barriers. As a result, few signatures have been strongly linked to particular risk factors.
Methods:
Here, we develop a statistical model, Diffsig, for estimating the association of one or more continuous or categorical risk factors with DNA mutational signatures. Diffsig takes into account the uncertainty associated with assigning signatures to samples as well as multiple risk factors' simultaneous effect on observed DNA mutations.
Results:
We applied Diffsig to breast cancer data to assess relationships between five established breast-relevant mutational signatures and etiologic variables, confirming known mechanisms of cancer development. In simulation, our model was capable of accurately estimating expected associations in a variety of contexts.
Conclusions:
Diffsig allows researchers to quantify and perform inference on the associations of risk factors with mutational signatures.
Impact:
We expect Diffsig to provide more robust associations of risk factors with signatures to lead to better understanding of the tumor development process and improved models of tumorigenesis.
Supplementary Table from Breast Cancer Index and Prediction of Extended Aromatase Inhibitor Therapy Benefit in Hormone Receptor-Positive Breast Cancer from the NRG Oncology/NSABP B-42 Trial
Authors: Mamounas Eleftherios P. , Bandos Hanna , Rastogi Priya , Zhang Yi , Treuner Kai , Lucas Peter C. , Geyer Charles E. , Fehrenbacher Louis , Chia Stephen K. , Brufsky Adam M. , Walshe Janice M. , Soori Gamini S. , Dakhil Shaker , Paik Soonmyung , Swain Sandra M. , Sgroi Dennis C. , Schnabel Catherine A. , Wolmark Norman
Published: May 2024

Supplementary Table from Breast Cancer Index and Prediction of Extended Aromatase Inhibitor Therapy Benefit in Hormone Receptor-Positive Breast Cancer from the NRG Oncology/NSABP B-42 Trial
Supplementary Table 1 from Belzutifan for von Hippel–Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study
Authors: Else Tobias , Jonasch Eric , Iliopoulos Othon , Beckermann Kathryn E. , Narayan Vivek , Maughan Benjamin L. , Oudard Stephane , Maranchie Jodi K. , Iversen Ane B. , Goldberg Cynthia M. , Fu Wei , Perini Rodolfo F. , Liu Yanfang , Linehan W. Marston , Srinivasan Ramaprasad
Published: May 2024

Supplementary Table 1. Representativeness of Study Participants.
Supplementary Figure S1 from Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Authors: Sheth Sangini S. , Oh Ji Eun , Bellone Stefania , Siegel Eric R. , Greenman Michelle , Mutlu Levent , McNamara Blair , Pathy Shefali , Clark Mitchell , Azodi Masoud , Altwerger Gary , Andikyan Vaagn , Huang Gloria , Ratner Elena , Kim Daniel J. , Iwasaki Akiko , Levi Angelique W. , Buza Natalia , Hui Pei , Flaherty Sean , Schwartz Peter E. , Santin Alessandro D.
Published: May 2024

Representative microscopic images of paired cervical biopsies at enrollment at 6 months follow-up.
Supplementary Figure S1 from Molecular and Pathologic Characterization of YAP1-Expressing Small Cell Lung Cancer Cell Lines Leads to Reclassification as SMARCA4-Deficient Malignancies
Authors: Ng Jin , Cai Ling , Girard Luc , Prall Owen W.J. , Rajan Neeha , Khoo Christine , Batrouney Ahida , Byrne David J. , Boyd Danielle K. , Kersbergen Ariena J. , Christie Michael , Minna John D. , Burr Marian L. , Sutherland Kate D.
Published: May 2024

Characterisation of SMARCA4 mutations in lung cancer cell lines from the CCLE.
Supplementary Figure S6 from Radiotherapy Enhances Metastasis Through Immune Suppression by Inducing PD-L1 and MDSC in Distal Sites
Authors: Hou Yuzhu , Yang Kaiting , Wang Liangliang , Wang Jiaai , Huang Xiaona , Piffkó András , Luo Sean Z. , Yu Xinshuang , Rao Enyu , Martinez Carlos , Bugno Jason , Mack Matthias , Vokes Everett E. , Pitroda Sean P. , Chmura Steven J. , Weichselbaum Ralph R. , Liang Hua Laura
Published: May 2024

Supplementary Figure 6. CXCL10 induces PD-L1 expression
Supplemental Table 6 from Broad Next-Generation Integrated Sequencing of Myelofibrosis Identifies Disease-Specific and Age-Related Genomic Alterations
Authors: Kandarpa Malathi , Robinson Dan , Wu Yi-Mi , Qin Tingting , Pettit Kristen , Li Qing , Luker Gary , Sartor Maureen , Chinnaiyan Arul , Talpaz Moshe
Published: May 2024

Supplemental Table 6. Germline variants in MF cohort
Supplemental Figure 4 from Broad Next-Generation Integrated Sequencing of Myelofibrosis Identifies Disease-Specific and Age-Related Genomic Alterations
Authors: Kandarpa Malathi , Robinson Dan , Wu Yi-Mi , Qin Tingting , Pettit Kristen , Li Qing , Luker Gary , Sartor Maureen , Chinnaiyan Arul , Talpaz Moshe
Published: May 2024

Supplemental Figure 4. A. Unsupervised hierarchical clustering of expressed genes in 129 MPN samples. Gene expression in ET, PV, PrePMF and MF cells or enriched CD34-positive hematopoietic stem cells was studied by RNAseq. The heatmap depicts the top 2% genes in the gene expression dataset including MF, ET, PV and PrePMF. Other than the CD34 positive cell type we did not find any clustering of samples with specific disease phenotype. B. Unsupervised hierarchical clustering of expressed genes in 65 MF samples. The heatmap depicts the top 2% genes in the gene expression dataset for MF mononuclear cell samples. There were no distinguishable gene expression cohorts that show association with disease phenotype.
Supplementary Video S10 from Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma
Authors: Wehrli Marc , Guinn Samantha , Birocchi Filippo , Kuo Adam , Sun Yi , Larson Rebecca C. , Almazan Antonio J. , Scarfò Irene , Bouffard Amanda A. , Bailey Stefanie R. , Anekal Praju Vikas , Montero Llopis Paula , Nieman Linda T. , Song Yuhui , Xu Katherine H. , Berger Trisha R. , Kann Michael C. , Leick Mark B. , Silva Harrison , Salas-Benito Diego , Kienka Tamina , Grauwet Korneel , Armstrong Todd D. , Zhang Rui , Zhu Qingfeng , Fu Juan , Schmidts Andrea , Korell Felix , Jan Max , Choi Bryan D. , Liss Andrew S. , Boland Genevieve M. , Ting David T. , Burkhart Richard A. , Jenkins Russell W. , Zheng Lei , Jaffee Elizabeth M. , Zimmerman Jacquelyn W. , Maus Marcela V.
Published: May 2024

Supplementary Video S10. UTD T cells on AsPC1
Supplementary Figure S3 from Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma
Authors: Wehrli Marc , Guinn Samantha , Birocchi Filippo , Kuo Adam , Sun Yi , Larson Rebecca C. , Almazan Antonio J. , Scarfò Irene , Bouffard Amanda A. , Bailey Stefanie R. , Anekal Praju Vikas , Montero Llopis Paula , Nieman Linda T. , Song Yuhui , Xu Katherine H. , Berger Trisha R. , Kann Michael C. , Leick Mark B. , Silva Harrison , Salas-Benito Diego , Kienka Tamina , Grauwet Korneel , Armstrong Todd D. , Zhang Rui , Zhu Qingfeng , Fu Juan , Schmidts Andrea , Korell Felix , Jan Max , Choi Bryan D. , Liss Andrew S. , Boland Genevieve M. , Ting David T. , Burkhart Richard A. , Jenkins Russell W. , Zheng Lei , Jaffee Elizabeth M. , Zimmerman Jacquelyn W. , Maus Marcela V.
Published: May 2024

Supplementary Figure S3. ASPC-1 and CAF repeat stimulation initiates a different transcription profile of meso^FAP and meso^CD19 CAR T-cells over time.
Data from Optimizing Cervical Target Volume in Patients with Nasopharyngeal Cancer Based On Nodal Drainage Distance
Authors: Liu Yang , Yan Wenbin , Hu Chaosu , Huang Xiaodong , Wang Kai , Qu Yuan , Chen Xuesong , Wu Runye , Zhang Ye , Zhang Jianghu , Luo Jingwei , Li Yexiong , Wang Jingbo , Yi Junlin
Published: May 2024

AbstractPurpose:
To determine the potential nodal drainage distances of nasopharyngeal carcinoma (NPC) by investigating spatial distribution of metastatic lymph nodes (LN).
Experimental Design:
Patients with NPC harboring at least two ipsilateral metastatic LNs were enrolled. LN spreading distances were analyzed in nonrestricted direction, cranial-to-caudal direction, and between the two most caudal LNs. Euclidean distance (ED) and vertical distance (VD) between any two LNs were computed. The nearest-neighbor ED and VD covering 95% of LNs or patients (p95-ED and p95-VD) were considered drainage distances, and were further validated by independent internal and external cohorts with recurrent LNs.
Results:
In all, 5,836 metastatic LNs in 948 patients were contoured. Corresponding to the three scenarios, per-LN level, the p95-EDs were 2.83, 3.28, and 3.55 cm, and p95-VDs were 2.17, 2.32, and 2.63 cm, respectively. Per-patient level, the p95-EDs were 3.25, 3.95, and 3.81 cm, and p95-VDs were 2.67, 2.81, and 2.73 cm, respectively. In internal validation, over 95% of recurred LNs occurred within ED of 2.91 cm and VD of 0.82 cm to the neighbor LN, and the corresponding distances in external validation were 2.77 and 0.67 cm, respectively.
Conclusions:
In NPC, the maximum LN drainage distance was 3.95 cm without considering the direction. Specifically, in cranial-to-caudal direction, the sufficient vertical drainage distance was 2.81 cm, indicating that a 3-cm extension from the most inferior node may be rational as caudal border of the prophylactic clinical target volume (CTV). These findings promote in-depth understanding of nodal spreading patterns, uncovering paramount evidence for individualized CTV.
Data from FDG PET/CT Imaging 1 Week after a Single Dose of Pembrolizumab Predicts Treatment Response in Patients with Advanced Melanoma
Authors: Anderson Thomas M. , Chang Bryan H. , Huang Alexander C. , Xu Xiaowei , Yoon Daniel , Shang Catherine G. , Mick Rosemarie , Schubert Erin , McGettigan Suzanne , Kreider Kristin , Xu Wei , Wherry E. John , Schuchter Lynn M. , Amaravadi Ravi K. , Mitchell Tara C. , Farwell Michael D.
Published: May 2024

AbstractPurpose:
Immunologic response to anti–programmed cell death protein 1 (PD-1) therapy can occur rapidly with T-cell responses detectable in as little as one week. Given that activated immune cells are FDG avid, we hypothesized that an early FDG PET/CT obtained approximately 1 week after starting pembrolizumab could be used to visualize a metabolic flare (MF), with increased tumor FDG activity due to infiltration by activated immune cells, or a metabolic response (MR), due to tumor cell death, that would predict response.
Patients and Methods:
Nineteen patients with advanced melanoma scheduled to receive pembrolizumab were prospectively enrolled. FDG PET/CT imaging was performed at baseline and approximately 1 week after starting treatment. FDG PET/CT scans were evaluated for changes in maximum standardized uptake value (SUVmax) and thresholds were identified by ROC analysis; MF was defined as >70% increase in tumor SUVmax, and MR as >30% decrease in tumor SUVmax.
Results:
An MF or MR was identified in 6 of 11 (55%) responders and 0 of 8 (0%) nonresponders, with an objective response rate (ORR) of 100% in the MF-MR group and an ORR of 38% in the stable metabolism (SM) group. An MF or MR was associated with T-cell reinvigoration in the peripheral blood and immune infiltration in the tumor. Overall survival at 3 years was 83% in the MF-MR group and 62% in the SM group. Median progression-free survival (PFS) was >38 months (median not reached) in the MF-MR group and 2.8 months (95% confidence interval, 0.3–5.2) in the SM group (P = 0.017).
Conclusions:
Early FDG PET/CT can identify metabolic changes in melanoma metastases that are potentially predictive of response to pembrolizumab and significantly correlated with PFS.
Abstract PO1-07-03: An Accurate Breast Cancer Diagnosis Method Using a Multi-Feature Fusion Neural Network on Contrast-Enhanced Spectral Mammography
Authors: Song Yipeng , Jiang Wei
Published: May 2024

Objectives: Our study aims to develop an accurate and comprehensive deep neural network capable of classifying CESM images to aid in the early detection and diagnosis of breast cancer in clinical settings. Methods: We enrolled diagnostic CESM examinations conducted between January 1, 2019 and January 17, 2021. We developed and tested the performance of a multi-feature fusion network for breast lesion classification by combining low-energy (LE) and dual-energy subtracted (DES) images, dual-view, and bilateral information using a large and diverse CESM dataset. We have evaluated the ability of the proposed network to generalize on external datasets and the results were reported using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: In the study period 1973CESMs were included. Mean age was 53 years ± 12 (standard deviation). In the internal test dataset, the model with CESM (LE +DES) inputs combined not only bilateral information (left and right breasts) but also dualview information (CC and MLO), achieved best diagnosis performance with AUC of 0.96 [95% confidence interval (CI): 0.95–0.97], accuracy of 0.9 [95% confidence interval (CI): 0.88–0.92], sensitivity of 0.84 [95% confidence interval (CI): 0.80–0.88] and specificity of 0.93 [95% confidence interval (CI): 0.91–0.95], while the model with LE inputs only got an AUC of 0.94 [95% (CI): 0.93–0.95], accuracy of 0.88 [95% confidence interval (CI): 0.86–0.90], sensitivity of 0.79 [95% confidence interval (CI): 0.74–0.83] and specificity of 0.93 [95% confidence interval (CI): 0.91–0.95] (external dataset: an AUC of 0.90 [95% (CI): 0.85–0.94], accuracy of 0.84 [95% confidence interval (CI): 0.78–0.89], sensitivity of 0.77 [95% confidence interval (CI): 0.61–0.88] and specificity of 0.87 [95% confidence interval (CI):0.80–0.92]). Conclusion: CESM is a promising technique in breast cancer diagnosis due to its high feasibility and potential. The results demonstrate that left-right breast fusion and dual-view fusion are helpful for accurate diagnosis on CESM images. Specifically, dual-energy subtracted (DES) images generated by CESM improve diagnostic accuracy when compared to low-energy (LE) images alone. Keywords: Contrast-enhanced spectral mammography; Deep neural network; Breast cancer diagnosis; Multi-feature fusion

Citation Format: Yipeng Song, Wei Jiang. An Accurate Breast Cancer Diagnosis Method Using a Multi-Feature Fusion Neural Network on Contrast-Enhanced Spectral Mammography [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-03.
Abstract PO1-24-10: B cell–mediated immunity predicts survival of patients with ER-positive breast cancer
Authors: Lee Seungbok , Kang Byung-Hee , Lee Han-Byoel , Han Wonshik , Kim In Ah
Published: May 2024

Background: The estrogen receptor-positive (ER+) breast cancer (BC), which constitutes the majority of BC cases, exhibits highly heterogeneous clinical behavior. To aid precision treatments, we aimed to find molecular subtypes of ER+ BC representing the tumor microenvironment.

Methods: We analyzed RNA-seq data of 113 BC patients and classified them according to the PAM50 intrinsic subtypes using gene expression profiles. Among them, we further focused on 48 patients with luminal-type (ER+) BC for subclassification. The Cancer Genome Atlas (TCGA) data of BC patients were utilized as a validation dataset to verify the new classification.

Results: Principal component analysis clearly divided the patients into two subgroups separately from the luminal A and B classification. The top differentially expressed genes between the subgroups were distinctly characterized by immunoglobulin and B cell–related genes. We could also cluster a separate cohort of patients with luminal-type BC from TCGA into two subgroups based on the expression of a B cell–specific gene set, and patients with high B cell immune activity had better prognoses than other patients.

Conclusions: Our transcriptomic approach defines a novel molecular phenotype of B cell immunity in ER+ BC that may help to predict disease prognosis. Although further researches are required, B cell immunity for ER+ BC patients may be helpful for identifying patients who are good responder to chemotherapy or immunotherapy. Work supported by grants from the National Research Foundation of Korea (NRF-2023R1A2C3003782)

Citation Format: Seungbok Lee, Byung-Hee Kang, Han-Byoel Lee, Wonshik Han, In Ah Kim. B cell–mediated immunity predicts survival of patients with ER-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-24-10.
Abstract PO2-03-03: The Significance of Cavity Shave Margins in Breast Carcinoma on Margin Status and Re-excision Rates
Authors: Zaiem Fadi , Numi Anna , Kheil Mira , AbuJamea Asem , Jain Deepti , Abbas Omar , Larson Lauren , Suleiman Noor , Al-Juburi Saleh , Awada Sanaa , Almsaddi Ragad , Jang Hyejeong , Kim Seongho , Salem Nagla , Choi Lydia , Bandyopadhyay Sudeshna , Jaiman Sunil , Ali-Fehmi Rouba
Published: May 2024

Context: The comparative outcomes of breast conserving surgery (BCS) with and without cavity shave margins are not well established. We aim to evaluate the impact of each procedure on final margin status and rate of re-excision.

Design: A total of 529 breast cancer cases from our institution between 2013-2015 were included. Demographic and clinicopathological data including procedure type, tumor type, grade, margins status, and re-excision rates were collected. H&E slides of positive margins (tumor on ink) were reviewed by two pathologists. Appropriate statistical analysis was performed.

Results: Out of 529 breast cancer cases, 125 were Ductal Carcinoma in situ (DCIS), 152 were Invasive Ductal Carcinoma (IDC) and 252 had both pathologies. The median age of patients was 59 years (range: 24-90). Patients who underwent excision with shave margins were 162 (35 DCIS, 56 IDC, 71 both) while excision without shave margins were 367 (90 DCIS, 96 IDC, 181 both). Re-excision rates were significantly lower 1) in patients who underwent BCS with cavity shave margins compared to those without (OR 0.32, p< 0.001) and 2) in patients who did not require lymph node excision compared to those who did (OR 4.26, p< 0.001). Additionally, patients who had DCIS had a higher rate of re-excision than those with invasive cancer only (OR 5.17, P< .001). After adjusting for type of tumor, patients who underwent cavity shaving compared to those who did not, no significant difference was seen in tumor at margins (OR 0.73, p=0.282) or tumor within 2mm (OR 1.14, p=0.512) from margins. However, patients with IDC who underwent cavity shave had a higher proportion of negative tumor at the margins (76.5% vs. 67.0%; p=0.051). We found that patients who had an invasive carcinoma (IC) had a lower risk of having tumor at the margin or within 2 mm from the margin than those with DCIS or DCIS+IC, (p< .05).

Conclusions: Our data shows that BCS with cavity shave margins is superior with regards to negative margin and re-excision rates when compared to without cavity shave margins.

Citation Format: Fadi Zaiem, Anna Numi, Mira Kheil, Asem AbuJamea, Deepti Jain, Omar Abbas, Lauren Larson, Noor Suleiman, Saleh Al-Juburi, Sanaa Awada, Ragad Almsaddi, Hyejeong Jang, Seongho Kim, Nagla Salem, Lydia Choi, Sudeshna Bandyopadhyay, Sunil Jaiman, Rouba Ali-Fehmi. The Significance of Cavity Shave Margins in Breast Carcinoma on Margin Status and Re-excision Rates [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-03-03.