bluuebunny/crossref_metadata_2025 huggingface dataset:
Quasinormal modes of black holes in f(Q) gravity
Authors: Gogoi Dhruba Jyoti , Övgün Ali , Koussour M.
Published: August 2023

In this work, we have studied the quasinormal modes of a black hole in a model of the type $$f(Q)=\underset{n}{\sum }a_{n}\left( Q-Q_{0}\right) ^{n} $$

f

(
Q
)

=

∑
n

a
n

Q
-

Q
0

n

in f(Q) gravity by using a recently introduced method known as Bernstein spectral method and confirmed the validity of the method with the help of well known Padé averaged higher order WKB approximation method. Here we have considered scalar perturbation and electromagnetic perturbation in the black hole spacetime and obtained the corresponding quasinormal modes. We see that for a non-vanishing nonmetricity scalar $$Q_0$$

Q
0

, quasinormal frequencies in scalar perturbation are greater than those in electromagnetic perturbation scenarios. On the other hand, the damping rate of gravitational waves is higher for electromagnetic perturbation. To confirm the quasinormal mode behaviour, we have also investigated the time domain profiles for both types of perturbations.
Study of rotating gravastars
Authors: Das Krishna Pada , Debnath Ujjal
Published: August 2023

In this work, we have discussed about a rotating gravastar model and some physical aspects in the presence of an anisotropic fluid source in the framework of General Relativity. We have considered two cases: one is gravastar’s interior fluid rigidly (or slowly) rotates, and the other is gravastar’s interior fluid non-rigidly rotates. We have considered a gravastar with three regions: interior region, thin shell region, and exterior region. We have written the field equations for a spherically symmetric object in which interior fluid rigidly (or slowly) rotates with angular velocity ([Formula: see text]). Next, we have solved the field equations in three regions of a gravastar. To compute the analytical solution within the shell region, we have used the approximation [Formula: see text]. Some physical quantities, like the proper length of the thin shell, energy, and entropy within the shell, have been obtained and discussed graphically. We have evaluated the surface energy density and the surface pressure analytically through the junction conditions between the surfaces of the interior and exterior regions. Next, we have discussed the equation of state parameter of the surface layer, the mass of the thin shell, and the total mass of the gravastar analytically and graphically. Also, we have discussed the stable region of such type gravastar. Again, we constructed the field equations for a spherically symmetric object in which interior fluid rotates non-rigidly. Next, we have discussed these field equations for a gravastar with three regions. Also, we have obtained some physical quantities like the proper length of the thin shell region, energy, entropy, density and angular velocity within the shell region for such type of gravastar. The stability has been discussed through the surface redshift within the shell region, and we get our model stable and physically valid.
Conformal motions of static cylindrically symmetric solutions in f(T, B) gravity
Authors: Malik Shabeela , Hussain Fiaz , Haq Sirajul , Ramzan Muhammad
Published: August 2023

In this paper, we investigate the conformal vector fields (CVFs) of static cylindrically symmetric (SCS) spacetimes in [Formula: see text] gravity, a novel modified teleparallel gravity that connects both [Formula: see text] and [Formula: see text] theories via a boundary term [Formula: see text]. Initially, we employ an algebraic approach to extract some classes that represent SCS solutions in [Formula: see text] gravity. Applying the above-mentioned approach, we find solutions in nine cases. We also investigate the CVFs using the direct integration technique. Following a thorough investigation, we discover that the spacetimes admit proper CVFs in only one case. In rest of the eight cases, the spacetimes either become conformally flat or they admit homothetic vector fields (HVFs) or Killing vector fields (KVFs). The overall dimension of CVFs for the spacetimes under consideration has come out to be 5, 6 or 15. To complete the study, we also compute the energy density and pressure of each model. Corresponding to the resulting models, we discuss the energy conditions in order to check the physical sound of the solutions.
The generalized Fourier’s and Fick laws effects on MHD free convection flows of Maxwell fluids by employing Caputo–Fabrizio time-fractional integral
Authors: Alsaud Huda
Published: August 2023

The relevance of time-dependent magneto-free convection and its consequences for mass and energy transport are being increasingly understood in science. Unfortunately, very little is known about how the fractional generalized technique would affect a complete analysis of Maxwell fluid dynamics over a porous plate. Using the Caputo–Fabrizio time-fractional integral, the Fourier thermal flux law and the fractionally generalized Fick’s equation of mass flow are both generalized. Using the appropriate similarity transformations allows us to characterize the structured governing equations, which are nondimensionalized. The dimensionless energy, concentration, and velocity distribution problem is solved using the Laplace transform method. The graph demonstrates how physical and fractional parameters are affected. Fractional derivatives may be employed to accurately represent the rheology of such fluids. The Maxwell generalized fluid across an oscillating sheet was studied by Zheng et al.3
ENHANCING MECHANICAL PROPERTIES AND MICROSTRUCTURE ON MODIFIED SURFACE AL–MG/CR3C2 BY FRICTION STIR PROCESSING
Authors: CHANAKYAN C. , ALAGARSAMY S. V.
Published: August 2023

Friction Stir Processing (FSP) is a promising solid state method and it is developed from the Friction Stir Welding (FSW) principle. FSP was employed to enhance the surface characteristics by ceramic particulate reinforced with AA5052 aluminum alloy. Initially, the machined square grove was formed on AA5052 and packed with ceramic particulate. In this research, chromium carbide (Cr3C2) is a ceramic material for improving the surface characteristics of the base material. The FSP parameters such as tool rotational speed, traverse speed and axial forces were utilized in this process. The microstructure evolutions of the processed specimens were observed by optical microscope and Field Emission Scanning Electron Microscope (FESEM) with Electron Dispersion Spectroscopy (EDS). The mechanical properties like processed microhardness and tensile strength of AA5052 friction stir processed specimens were analyzed. The various microstructural zones were observed in the processed regions with dispersion of the particulates Cr3C2. The specimen fabricated at 1000 rpm tool rotational speed, 25 mm/min traverse speed and 7 kN axial force exhibits maximum microhardness and tensile strength with homogeneous dispersion of Cr3C2.
Synthesis and Characterization of Multistage Porous Sodalite Nanocrystal Aggregate
Authors: Liu Zhigang , Yu Yaxin , Wang Chunmei , Yang Lirong
Published: August 2023

Using the mixed solution of [Formula: see text]-butanol and ethanol as solvent, the sodalite nanocrystal aggregate was prepared by the solvothermal method. The influences of crystallization temperature, molar ratio Na/Al, crystallization time and silane concentration on the morphology, crystallite size, degree of crystallization and pore structure of the as-prepared samples were investigated by X-ray diffraction (XRD), BET, FTIR, Transmission Electron Microscopy (TEM) and scanning electron microscope (SEM). The results reveal that the sodalite nanocrystals are aggregated by self-assembly into the micropore–mesopore–macropore structure. Higher crystallization temperature and longer crystallization time are conducive to the growth of sodalite nanocrystals. It is a necessary condition for the formation of sodalite nanocrystals to keep high molar ratio Na/Al. The higher the molar ratio Na/Al, the more favorable the crystallization of sodalite nanocrystals. The appropriate concentration of silane agent is conducive to the preparation of smaller crystal-sized sodalite nanocrystals. After removing the silane agent by pickling, the sodalite nanocrystal aggregate is a multistage porous structure with the pore volume of 1.0133[Formula: see text]mL/g and the specific surface area of 449.73[Formula: see text]m2/g.
Green Synthesis, Characterization and Application of Proanthocyanidins-Functionalized Fe3O4 Magnetic Nanocomposites
Authors: Lin Yamei , Liu Shengkai , Sun JiXiang , Li Han , Huang Jin , Bai Jiaxiao , Guo Yaqin , Fu Yujie , Liu Zhiguo
Published: August 2023

In this study, proanthocyanidins-functionalized Fe3O4 magnetic nanocomposites were synthesized by the hydrothermal method. The prepared Fe3O4 nanocomposites were characterized by Fourier transform infrared spectrometer (FTIR), X-ray powder diffractometer (XRD), physical property measurement system (PPMS), particle size analyzer, scanning electron microscope (SEM), and transmission electron microscope (TEM). FTIR results indicated that the obtained products were coated with proanthocyanidins. The SEM and TEM results, as well as particle size distribution analysis, revealed that the obtained products were spherical particles with average diameter of [Formula: see text][Formula: see text]nm. XRD and PPMS characterization confirmed that the Fe3O4 nanoparticles have a cubic spinel structure with magnetic properties. The performance of the Fe3O4 nanocomposites for removing organic dyes in an aqueous solution was investigated. The synthesized products were found to be effective on removing various organic dyes, such as Methylene blue (MB), neutral red (NR) and Rhodamine B (RhB), indicating their considerable potential as efficient dyes adsorbents for wastewater treatment.
Tailoring the microstructure, martensitic transformation temperature and mechanical properties of 4D printed NiTi alloys
Authors: Kang Jingtao , Li Ruidi , Zheng Dan , Liu Xinyan , Lai Duan , Huang Wenjing , Liang Enquan
Published: August 2023

This study explores the control of the microstructure and properties of NiTi alloy through the adjustment of 4D printing process parameters. The results indicate that increasing the scanning speed from 450 mm/s to 750 mm/s leads to a change in the phase composition from near full martensitic to a two-phase structure of austenite and martensite. The increase in scanning speed can also reduce the evaporation of Ni element and lower the phase transformation temperature. [Formula: see text] temperature and [Formula: see text] temperature decrease from 93°C and 63°C at 450 mm/s to 37°C and 12°C at 750 mm/s, respectively. Moreover, the scanning speed can alter the texture characteristics and mechanical behavior of NiTi alloy. The hardness value and critical stress increase with the increase in scanning speed, while the strain distribution during tensile deformation becomes uneven at high scanning speed due to the unevenly distributed dual-phase microstructure. These findings provide insights for the optimization of 4D printing parameters to tailor the properties of NiTi alloy for various applications.
Self-Supervised Dynamic Graph Representation Learning via Temporal Subgraph Contrast
Authors: Chen Ke-Jia , Liu Linsong , Jiang Linpu , Chen Jingqiang
Published: August 2023

Self-supervised learning on graphs has recently drawn a lot of attention due to its independence from labels and its robustness in representation. Current studies on this topic mainly use static information such as graph structures but cannot well capture dynamic information such as timestamps of edges. Realistic graphs are often dynamic, which means the interaction between nodes occurs at a specific time. This article proposes a self-supervised dynamic graph representation learning framework DySubC, which defines a temporal subgraph contrastive learning task to simultaneously learn the structural and evolutional features of a dynamic graph. Specifically, a novel temporal subgraph sampling strategy is firstly proposed, which takes each node of the dynamic graph as the central node and uses both neighborhood structures and edge timestamps to sample the corresponding temporal subgraph. The subgraph representation function is then designed according to the influence of neighborhood nodes on the central node after encoding the nodes in each subgraph. Finally, the structural and temporal contrastive loss are defined to maximize the mutual information between node representation and temporal subgraph representation. Experiments on five real-world datasets demonstrate that (1) DySubC performs better than the related baselines including two graph contrastive learning models and five dynamic graph representation learning models, especially in the link prediction task, and (2) the use of temporal information cannot only sample more effective subgraphs, but also learn better representation by temporal contrastive loss.
Heterogeneous Hypergraph Neural Network for Social Recommendation using Attention Network
Authors: Khan Bilal , Wu Jia , Yang Jian , Ma Xiaoxiao
Published: August 2023

Graph neural networks (GNNs) have been used extensively as a backbone for social recommendation. However, their application to a diverse range of situations is still rather limited. This is because graph structures only leverage pairwise user relationships. They cannot capture the higher-order relationships so common in the real world, and ignoring the interest friends and strangers might have in similar items is severely hampering the expressiveness of the current graph-based recommendation models. Hence, in this paper, we outline a heterogeneous hypergraph neural network for social recommendation called HHGSA that incorporates an attention network to address these issues. The hypergraph is able to represent higher-order relationships through five motifs: friend and stranger item appeal, item similarity, user similarity based on interactions with items, and social relations. Two modules, the attentive vertex aggregation module, and the attentive hyperedge aggregation module, capture user and item attention. In addition, it has been discovered that similar items have identical appeal when displayed to users. A GNN aggregates the user embedding data, including information about the friend and stranger and item embeddings. Finally, information about users and items is aggregated for social recommendations. Extensive experiments on four datasets demonstrate that the HHGSA model outperforms a wide range of baselines and can significantly improve the accuracy of recommendations.
Computing Mellin Representations and Asymptotics of Nested Binomial Sums in a Symbolic Way: The RICA Package
Authors: Blümlein Johannes , Fadeev Nikolai , Schneider Carsten
Published: August 2023

Nested binomial sums form a particular class of sums that arise in the context of particle physics computations at higher orders in perturbation theory within QCD and QED, but that are also mathematically relevant, e.g., in combinatorics. We present the package RICA (Rule Induced Convolutions for Asymptotics), which aims at calculating Mellin representations and asymptotic expansions at infinity of those objects. These representations are of particular interest to perform analytic continuations of such sums.
SLC12A cryo-EM: analysis of relevant ion binding sites, structural domains, and amino acids
Authors: Trejo Fátima , Elizalde Stephanie , Mercado Adriana , Gamba Gerardo , de losHeros Paola
Published: August 2023

The solute carrier family 12A (SLC12A) superfamily of membrane transporters modulates the movement of cations coupled with chloride across the membrane. In doing so, these cotransporters are involved in numerous aspects of human physiology: cell volume regulation, ion homeostasis, blood pressure regulation, and neurological action potential via intracellular chloride concentration modulation. Their physiological characterization has been largely studied; however, understanding the mechanics of their function and the relevance of structural domains or specific amino acids has been a pending task. In recent years, single-particle cryogenic electron microscopy (cryo-EM) has been successfully applied to members of the SLC12A family including all K+:Cl− cotransporters (KCCs), Na+:K+:2Cl− cotransporter NKCC1, and recently Na+:Cl− cotransporter (NCC); revealing structural elements that play key roles in their function. The present review analyzes the data provided by these cryo-EM reports focusing on structural domains and specific amino acids involved in ion binding, domain interactions, and other important SCL12A structural elements. A comparison of cryo-EM data from NKCC1 and KCCs is presented in the light of the two recent NCC cryo-EM studies, to propose insight into structural elements that might also be found in NCC and are necessary for its proper function. In the final sections, the importance of key coordination residues for substrate specificity and their implication on various pathophysiological conditions and genetic disorders is reviewed, as this could provide the basis to correlate structural elements with the development of novel and selective treatments, as well as mechanistic insight into the function and regulation of cation-coupled chloride cotransporters (CCCs).
Cancer-mesothelial and cancer-macrophage interactions in the ovarian cancer microenvironment
Authors: Jazwinska Dorota E. , Kulawiec Diana G. , Zervantonakis Ioannis K.
Published: August 2023

The metastatic ovarian cancer microenvironment is characterized by an intricate interaction network between cancer cells and host cells. This complex heterotypic cancer-host cell crosstalk results in an environment that promotes cancer cell metastasis and treatment resistance, leading to poor patient prognosis and survival. In this review, we focus on two host cell types found in the ovarian cancer microenvironment: mesothelial cells and tumor-associated macrophages. Mesothelial cells make up the protective lining of organs in the abdominal cavity. Cancer cells attach and invade through the mesothelial monolayer to form metastatic lesions. Crosstalk between mesothelial and cancer cells can contribute to metastatic progression and chemotherapy resistance. Tumor-associated macrophages are the most abundant immune cell type in the ovarian cancer microenvironment with heterogeneous subpopulations exhibiting protumor or antitumor functions. Macrophage reprogramming toward a protumor or antitumor state can be influenced by chemotherapy and communication with cancer cells, resulting in cancer cell invasion and treatment resistance. A better understanding of cancer-mesothelial and cancer-macrophage crosstalk will uncover biomarkers of metastatic progression and therapeutic targets to restore chemotherapy sensitivity.
Proteomics identifies the developmental regulation of HKDC1 in liver of pigs and mice
Authors: Martinez-Garza Ursula , Choi Joseph , Scafidi Susana , Wolfgang Michael J.
Published: August 2023

During the perinatal period, unique metabolic adaptations support energetic requirements for rapid growth. To gain insight into perinatal adaptations, quantitative proteomics was performed comparing the livers of Yorkshire pigs at postnatal day 7 and adult. These data revealed differences in the metabolic control of liver function including significant changes in lipid and carbohydrate metabolic pathways. Newborn livers showed an enrichment of proteins in lipid catabolism and gluconeogenesis concomitant with elevated liver carnitine and acylcarnitines levels. Sugar kinases were some of the most dramatically differentially enriched proteins compared with neonatal and adult pigs including galactokinase 1 (Galk1), ketohexokinase (KHK), hexokinase 1 (HK1), and hexokinase 4 (GCK). Interestingly, hexokinase domain containing 1 (HKDC1), a newly identified fifth hexokinase associated with glucose disturbances in pregnant women, was highly enriched in the liver during the prenatal and perinatal periods and continuously declined throughout postnatal development in pigs and mice. These changes were confirmed via Western blot and mRNA expression. These data provide new insights into the developmental and metabolic adaptations in the liver during the transition from the perinatal period to adulthood in multiple mammalian species.
Clock genes regulate skeletal muscle energy metabolism through NAMPT/NAD+/SIRT1 following heavy-load exercise
Authors: Xia Yu , Yao Binyu , Fu Zeting , Li Lunyu , Jin Songlin , Qu Bo , Huang Ying , Ding Haili
Published: August 2023

The biological clock is an invisible “clock” in the organism, which can regulate behavior, physiology, and biochemical reactions. However, the relationship between clock genes and energy metabolism in postexercise skeletal muscle is not well known. The purpose of this study was to determine the mechanisms through which peripheral clock genes regulate energy metabolism in skeletal muscle. We analyzed the rhythm of mRNA expression of the clock genes Bmal1 and Clock in skeletal muscle following heavy-load exercise and measured related indicators of mitochondrial structure and function. We obtained the following experimental results. First, heavy-load exercise induced loss of circadian rhythm of Bmal1 between ZT0 and ZT24, and the circadian rhythm of Clock was not restored between ZT0 and ZT72. Second, analysis of mitochondrial morphology in group E showed abnormal swelling and ridge structure damage at ZT0, which recovered somewhat at ZT24 and ZT48, and the damage had essentially disappeared by ZT72. Third, the expression of NAMPT/NAD+/SIRT1 signaling axis proteins in group E was abnormal at ZT0, the content of NAMPT and the activity of SIRT1 significantly increased, and the content of NAD+ significantly decreased. Fourth, the expression of BMAL1 and PGC-1α in group E significantly increased, whereas the ATP and ADP content, as well as the activities of COXII and COXIV, were significantly changed. Finally, the colocalization of BMAL1 and SIRT1 in group E was significantly upregulated at ZT0. These results suggest that the skeletal muscle clock gene Bmal1 may regulate the energy metabolism level of skeletal muscle after exercise through the NAMPT/NAD+/SIRT1 signaling pathway.
The Underreported Postoperative Suffering after Thyroid Surgery: Dysphagia, Dysphonia, and Neck Pain—A Cross-Sectional Study
Authors: Chawaka Hunduma Jisha , Teshome Zenebe Bekele
Published: August 2023

Background and Aims. Postoperative voice change, difficulty of swallowing, throat pain, and neck pain are the most commonly complaint after thyroid surgery. However, little emphasis is given to the problem, especially a place where the surgical and anesthesia services’ unmet need is highly observed, i.e., the problem gets little attention especially in the countries where the gaps of surgery and anesthesia services are observed. Hence, this study aims to determine the magnitude and associated factors of voice change and related complaints after thyroid surgery. Methods. A cross-sectional study was conducted on 151 patients who had had thyroid surgery from June 1 to December 30, 2021. Data were retrieved during the postoperative period after the patient regains consciousness. Result. Out of 151 participants, 98 (64.9%) patients complained of either voice change or difficulty of swallowing and neck pain after thyroid surgery within 24 hours. Majority (58.3%) of the participants aged more than 30 years with a mean age of 33.7 ± 8.3 years and females 102 (67.5%). Neck pain is the most (52.3%) complained suffering after thyroid surgery, followed by voice change 38.4% and difficulty in swallowing 37.7%. Difficulty in swallowing after thyroid surgery significantly associated with a patient who frequently experience intraoperative hypotension (AOR = 23.24, 95% CI 4.6–116.7, and

p
=
0.01

), type of surgical procedure (total thyroidectomy) (AOR = 8.62, 95% CI 1.21–61.50, and

p
=
0.03

), and larger ETT size (AOR = 4.92, 95% CI 1.34–18.01, and

p
=
0.02

). Postoperative voice change is associated with larger endotracheal tube (AOR = 15.47, 95% CI 3.4–69.5, and

p
≤
0.001

), surgery lasting more than 2 hours (AOR = 7.34, 95% CI 1.5–35.1, and

p
=
0.01

), and intraoperative hypotension (AOR = 23.24, 95% CI 4.6–116.7, and

p
≤
0.001

). Conclusion. The complaint of postthyroidectomy neck pain and throat discomfort is higher than 64.9%. Intraoperative hypotension, blood loss, higher ETT size utilization, and duration of surgical procedure are the identified possible risk factors and have to be minimized as much as possible. Patient reassurance has to be considered during the postoperative time.
A Digital Controller for Reactivity Monitoring and Power Control
Authors: Vo Van-Tai , Nguyen Van-Kien , Le Van-Diep , Phan Quoc-Minh , Phan La-Son , Nguyen Huy-Bach , Nguyen Nhi-Dien
Published: August 2023

This paper introduces a controller unit for reactivity monitoring and automatic power control that was designed and constructed for the 500 kW Dalat Nuclear Research Reactor (DNRR). For power control and reactivity calculations, frequency signals from neutron measurement channels of starting and working ranges of the reactor are used. Two abovementioned independent functions were combined in an Artix-7 FPGA board for determining reactivity values by solving the point reactor kinetics equations with six delayed neutron groups and for stabilizing the reactor power at preset levels by determining the unbalance voltage signal to control the automatic control rod. With real-time calculations, the newly developed controller can monitor the reactor reactivity and control the reactor power online. The developed controller unit’s reactivity measuring and power stabilizing capabilities were assessed using the DNRR in normal operation and assumed emergency conditions and compared with those of the preexisting imported BNO-102R1 module of the DNRR control and protection system, known as ASUZ-14R. The results of the experiments show that the produced FPGA-based unit and the BNO-102R1 unit have the same technical characteristics and features, with the disparities being less than 5% and 1%, respectively, in reactivity measurement and power stabilization. The experimental data of reactivity measurements by the FPGA-based unit and the calculation results were also compared and found that the relative deviations between those are also less than 10%. The developed controller unit is capable of carrying out a variety of training and operational experiments on the DNRR.
Antioxidant and Enzyme Inhibitory Potential of Streptomyces sp. G-18 Grown in Various Media
Authors: Ashok G. C. , Prakash Pradhan Suman , Kumar Karki Krishna , Khadka Aakriti , Bhandari Aishwarya , Prasad Pandey Bishnu
Published: August 2023

Streptomyces are bacteria well known for producing bioactive secondary metabolites which are commonly found in diverse habitats. The biosynthesis of metabolites from Streptomyces is influenced by various factors such as the growth medium, environmental conditions, and gene regulation. This study aimed to investigate the influence of different growth media on biomass production and the antioxidant and enzyme inhibitory potential of a crude extract obtained from Streptomyces sp. G-18 isolated from high altitudinal soil of Nepal. The highest dry weight growth was observed in R2YE medium (184 mg/L), followed by R5 (144 mg/L), YEME (38 mg/L), and R5M media (30 mg/L). The crude extract showed notable antioxidant activities against free radicals. The highest alpha-amylase inhibition was observed in the R2YE medium, and worthy lipase and tyrosinase inhibition was observed in the YEME medium. However, only the R2YE medium exhibited inhibitory potential against elastase and acetylcholinesterase, while crude extracts from R5, YEME, and R5 modified did not show any such activity. Overall, our findings suggest that the production of bioactive secondary metabolites in Streptomyces sp. G-18 was significantly influenced by the growth medium. This strain may be a promising source of enzyme inhibitors with potential applications in the pharmaceutical and cosmetic industries.
Holographic Schwinger Effect with a Rotating Probe D3-Brane
Authors: Xu Hao , Ilyas M. , Huang Yong-Chang
Published: August 2023

This paper, among other things, talks about possible research on the holographic Schwinger effect with a rotating probe D3-brane. We discover that for the zero temperature case in the Schwinger effect, the faster the angular velocity and the farther the distance of the test particle pair at D3-brane, the potential barrier of total potential energy also grows higher and wider. This paper shows that at a finite temperature, when S5 without rotation is close to the horizon, the Schwinger effect fails because the particles remain in an annihilate state, which is an absolute vacuum state. However, the angular velocity in S5 will avoid the existence of an absolute vacuum near the horizon. For both zero and finite temperature states, the achieved results completely agree with the results of the Dirac-Born-Infeld (DBI) action. So the theories in this paper are consistent. All of these show that these theories will play important roles in future pair production research.
Phenotypic Diversity in GNAO1 Patients: A Comprehensive Overview of Variants and Phenotypes
Authors: Sáez González Maria , Kloosterhuis Kes , van de Pol Laura , Baas Frank , Mikkers Harald
Published: August 2023

GNAO1 disorder is a rare autosomal dominant neurodevelopmental syndrome that is clinically manifested by developmental delay, (early onset) epilepsy, and movement disorders. Clinical symptoms appear very heterogeneous in nature and severity, as well as the response of GNAO1 patients to available medication varies. Pathogenic GNAO1 variants have been found mainly scattered throughout the gene although certain mutation hotspots affecting the function of the encoded Gαo proteins exist. GNAO1 variants only partially explain the diverse phenotypic spectrum observed but full stratification has been hampered by the limited number of patients. The aim of this review was to generate a comprehensive overview of the germline variants in GNAO1 and provide insight into the phenotypic diversity of the GNAO1 disorder. We compiled a list of 398 GNAO1 germline variants. In addition, we provide the GNAO1 variants and associated phenotypes of 282 GNAO1 patients reported in case reports, whole genome sequencing studies, genetic variant databases, and 8 novel GNAO1 patients that were not described before. This has resulted in a list of 107 (likely) pathogenic GNAO1 variants. Available phenotypic data was utilized to quantitatively assess the genetic and phenotypic diversity of the GNAO1 disorder and discuss the outcomes. This inventory forms the basis for a GNAO1 variant database that will be updated continuously. Moreover, it will aid genetic diagnostics, medical decision-making, prognostication, and research on the mechanisms underlying the GNAO1 disorder.
Sparassis latifolia Polysaccharide Attenuates Cholesterol in Rats Maintained on a High-Fat, High-Cholesterol Diet
Authors: Cheng Feier , Yang Yaru , Yun Shaojun , Cao Jinling , Chang Mingchang , Cheng Yanfen , Feng Cuiping
Published: August 2023

Sparassis latifolia polysaccharide (SLP) has broad application prospects as a raw material of functional food. This study aimed to investigate the effects of SLP on liver cholesterol metabolism and its mechanism. Sprague–Dawley rats were fed a high-fat, high-cholesterol diet, and various assessments were conducted including hematoxylin and eosin staining, measurement of liver and metabolic indices, and antioxidant analysis. In addition, fluorescence quantitative reverse transcription-polymerase chain reaction was performed to analyze mRNA expression, and gas chromatography-mass spectrometry was employed for screening differential metabolites. The results demonstrated that SLP reduced the abnormal increase in the liver index caused by high fat and cholesterol and improved liver tissue morphology, metabolism level, and antioxidant-related enzyme activities. The polysaccharide regulated the liver sterol metabolism pathway, decreased the mRNA expression levels of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoAR) and sterol O-acyltransferase 1 (SOAT1), upregulated the mRNA expression levels of cholesterol 7α hydroxylase (CYP7α-1) and ABCA1, and increased the contents of propionic acid and butyric acid in the liver. These findings indicated a novel pathway through which SLP prevented hepatic lipid deposition and ameliorated sterol metabolism via regulating the HMG-CoAR-CYP7α-1 axis.
A Novel Constitutively Active
c
.
98
G
>
C
, p.(R33P) Variant in RAB11A Associated with Intellectual Disability Promotes Neuritogenesis and Affects Oligodendroglial Arborization
Authors: Tsuneura Yumi , Kawai Taeko , Yamada Keitaro , Aoki Shintaro , Nakashima Mitsuko , Eda Shima , Matsuki Tohru , Nishikawa Masashi , Nagata Koh-ichi , Enokido Yasushi , Saitsu Hirotomo , Nakayama Atsuo
Published: August 2023

Whole exome sequencing/whole genome sequencing has accelerated the identification of novel genes associated with intellectual disabilities (ID), and RAB11A which encodes an endosomal small GTPase is among them. However, consequent neural abnormalities have not been studied, and pathophysiological mechanisms underlying the ID and other clinical features in patients harboring RAB11A variants remain to be clarified. In this study, we report a novel de novo missense variant in RAB11A, NM_004663.5:

c
.
98
G
>
C

, which would result in NP_004654.1: p.(R33P) substitution, in a Japanese boy with severe ID and hypomyelination. Biochemical analyses indicated that the RAB11A-R33P is a gain-of-function, constitutively active variant. Accordingly, the introduction of the RAB11A-R33P promoted neurite extension in neurons like a known constitutively active variant Rab11A-Q70L. In addition, the RAB11A-R33P induced excessive branching with thinner processes in oligodendrocytes. These results indicate that the gain-of-function RAB11A-R33P variant in association with ID and hypomyelination affects neural cells and can be deleterious to them, especially to oligodendrocytes, and strongly suggest the pathogenic role of the RAB11A-R33P variant in neurodevelopmental impairments, especially in the hypomyelination.
Breast Cancer–Secreted Factors Promote Lung Metastasis by Signaling Systemically to Induce a Fibrotic Premetastatic Niche
Authors: Cohen Noam , Mundhe Dhanashree , Deasy Sarah K. , Adler Omer , Ershaid Nour , Shami Tamar , Levi-Galibov Oshrat , Wassermann Rina , Scherz-Shouval Ruth , Erez Neta
Published: August 2023

Metastatic cancer is largely incurable and is the main cause of cancer-related deaths. The metastatic microenvironment facilitates formation of metastases. Cancer-associated fibroblasts (CAF) are crucial players in generating a hospitable metastatic niche by mediating an inflammatory microenvironment. Fibroblasts also play a central role in modifying the architecture and stiffness of the extracellular matrix (ECM). Resolving the early changes in the metastatic niche could help identify approaches to inhibit metastatic progression. Here, we demonstrate in mouse models of spontaneous breast cancer pulmonary metastasis that fibrotic changes and rewiring of lung fibroblasts occurred at premetastatic stages, suggesting systemic influence by the primary tumor. Activin A (ActA), a TGFβ superfamily member, was secreted from breast tumors and its levels in the blood were highly elevated in tumor-bearing mice. ActA upregulated the expression of profibrotic factors in lung fibroblasts, leading to enhanced collagen deposition in the lung premetastatic niche. ActA signaling was functionally important for lung metastasis, as genetic targeting of ActA in breast cancer cells significantly attenuated lung metastasis and improved survival. Moreover, high levels of ActA in human patients with breast cancer were associated with lung metastatic relapse and poor survival. This study uncovers a novel mechanism by which breast cancer cells systemically rewire the stromal microenvironment in the metastatic niche to facilitate pulmonary metastasis.

Significance:

ActA mediates cross-talk between breast cancer cells and cancer-associated fibroblasts in the lung metastatic niche that enhances fibrosis and metastasis, implicating ActA as a potential therapeutic target to inhibit metastatic relapse.
Supplementary Data Investigator Lists from Niraparib for Advanced Breast Cancer with Germline BRCA1 and BRCA2 Mutations: the EORTC 1307-BCG/BIG5–13/TESARO PR-30–50–10-C BRAVO Study
Authors: Turner Nicholas C. , Balmaña Judith , Poncet Coralie , Goulioti Theodora , Tryfonidis Konstantinos , Honkoop Aafke H. , Zoppoli Gabriele , Razis Evangelia , Johannsson Oskar T. , Colleoni Marco , Tutt Andrew N. , Audeh William , Ignatiadis Michail , Mailliez Audrey , Trédan Olivier , Musolino Antonino , Vuylsteke Peter , Juan-Fita Maria Jose , Macpherson Iain R.J. , Kaufman Bella , Manso Luis , Goldstein Lori J. , Ellard Susan L. , Láng István , Jen Kai Yu , Adam Virginie , Litière Saskia , Erban John , Cameron David A.
Published: August 2023

investigator lists
Estrogen Receptor and Immune Checkpoint Inhibitors: New Partners in Lung Cancer?
Authors: Valencia Karmele , Montuenga Luis M. , Calvo Alfonso
Published: August 2023

The influence of sex on immunotherapy response in patients with non–small cell lung cancer (NSCLC) had been studied with no clear conclusions. An article in this issue reports that a key determinant of response is not sex but the existence of a 17β-estradiol/ERα/PDL1 signaling loop in NSCLC. This intriguing result opens new therapeutic options.

See related article by Anobile et al., p. 3958
Dual Immune Checkpoint Blockade Induces Analogous Alterations in the Dysfunctional CD8+ T-cell and Activated Treg Compartment
Authors: van der Leun Anne M. , Traets Joleen J.H. , Vos Joris L. , Elbers Joris B.W. , Patiwael Sanne , Qiao Xiaohang , Machuca-Ostos Mercedes , Thommen Daniela S. , Haanen John B.A.G. , Schumacher Ton N.M. , Zuur Charlotte L.
Published: August 2023

To dissect the effect of neoadjuvant PD-1 and CTLA4 blockade on intratumoral T cells in treatment-naive head and neck squamous cell carcinoma, we analyzed primary tumor immune infiltrates from responding and nonresponding patients. At baseline, a higher ratio between active (4-1BB/OX40+) and inactive regulatory CD4+ T cells was associated with immunotherapy response. Furthermore, upon therapy, this active regulatory T-cell (Treg) population showed a profound decrease in responding patients. In an analogous process, intratumoral dysfunctional CD8+ T cells displayed decreased expression of activity and dysfunction-related genes in responding patients, whereas in clinical nonresponders, natural killer cells showed an increased cytotoxic profile early upon treatment. These data reveal immunologic changes in response to dual PD-1/CTLA4 blockade, including a parallel remodeling of presumed tumor-reactive Treg and CD8+ T-cell compartments in responding patients, and indicate that the presence of activated Tregs at baseline may be associated with response.

Significance:

In head and neck squamous cell carcinoma, neoadjuvant PD-1/CTLA4 blockade has shown substantial response rates (20%–35%). As recognition of tumor antigens by T cells appears to be a critical driver of therapy response, a better understanding of alterations in T-cell state that are associated with response and resistance is of importance.

This article is featured in Selected Articles from This Issue, p. 2109
Supplementary Table S5 from Development and validation of a 15-gene expression signature with superior prognostic ability in stage II colorectal cancer
Authors: Rokavec Matjaž , Özcan Elif , Neumann Jens , Hermeking Heiko
Published: August 2023

Supplementary Table S5 shows the concordance of the 15-gene and the Oncotype DX colon signatures.
Supplementary Table S4 from Development and validation of a 15-gene expression signature with superior prognostic ability in stage II colorectal cancer
Authors: Rokavec Matjaž , Özcan Elif , Neumann Jens , Hermeking Heiko
Published: August 2023

Supplementary Table S4 shows the concordance of the 15-gene and the Oncotype DX colon signatures.
Supplementary Results from Whole genome CpG-resolution DNA methylation profiling of HNSCC reveals distinct mechanisms of carcinogenesis for fine-scale HPV+ cancer subtypes
Authors: Qin Tingting , Li Shiting , Henry Leanne E , Chou Elysia , Cavalcante Raymond G , Garb Bailey F , D'Silva Nisha J. , Rozek Laura S. , Sartor Maureen A
Published: August 2023

Supplementary Results
Supplementary Methods from Whole genome CpG-resolution DNA methylation profiling of HNSCC reveals distinct mechanisms of carcinogenesis for fine-scale HPV+ cancer subtypes
Authors: Qin Tingting , Li Shiting , Henry Leanne E , Chou Elysia , Cavalcante Raymond G , Garb Bailey F , D'Silva Nisha J. , Rozek Laura S. , Sartor Maureen A
Published: August 2023

Supplementary Methods
Supplementary Figure S2 from Development and validation of a 15-gene expression signature with superior prognostic ability in stage II colorectal cancer
Authors: Rokavec Matjaž , Özcan Elif , Neumann Jens , Hermeking Heiko
Published: August 2023

Supplementary Figure S2 shows the association of the Oncotype DX colon signature with relapse free survival in the pooled stage II cohort.
Supplementary Figure S1 from Development and validation of a 15-gene expression signature with superior prognostic ability in stage II colorectal cancer
Authors: Rokavec Matjaž , Özcan Elif , Neumann Jens , Hermeking Heiko
Published: August 2023

Supplementary Figure S1 shows pathway analysis and clinico-pathological associations of unfavorable prognostic genes.
Supplementary Fig 5 from Whole genome CpG-resolution DNA methylation profiling of HNSCC reveals distinct mechanisms of carcinogenesis for fine-scale HPV+ cancer subtypes
Authors: Qin Tingting , Li Shiting , Henry Leanne E , Chou Elysia , Cavalcante Raymond G , Garb Bailey F , D'Silva Nisha J. , Rozek Laura S. , Sartor Maureen A
Published: August 2023

Correlate GSE testing results from mRNA expression and DNA methylation in the exon, intron regions and keratinization genes visualization.
Supplementary Fig 4 from Whole genome CpG-resolution DNA methylation profiling of HNSCC reveals distinct mechanisms of carcinogenesis for fine-scale HPV+ cancer subtypes
Authors: Qin Tingting , Li Shiting , Henry Leanne E , Chou Elysia , Cavalcante Raymond G , Garb Bailey F , D'Silva Nisha J. , Rozek Laura S. , Sartor Maureen A
Published: August 2023

. Patient-level methylation at repetitive regions, stratified by disease stage (A), by subtype and HPV status across genome (B) or at different genomic regions (C).
Supplementary Fig 2 from Whole genome CpG-resolution DNA methylation profiling of HNSCC reveals distinct mechanisms of carcinogenesis for fine-scale HPV+ cancer subtypes
Authors: Qin Tingting , Li Shiting , Henry Leanne E , Chou Elysia , Cavalcante Raymond G , Garb Bailey F , D'Silva Nisha J. , Rozek Laura S. , Sartor Maureen A
Published: August 2023

Average methylation of tumors and normal epithelial cells at gene body (A), promoter (B), CpG island (C) and repetitive region (D). Samples were grouped by HPVor HPV integration status.
Supplementary Figure 3 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

Sensitivity analysis of the most sensitive model parameters
Supplementary Figure 1 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

Experimental data and model parameter fitting
FIGURE 6 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

Effect on tumor growth of varying sensitive model parameters. A, Grouped histogram of the repeated sensitivity analysis (five times for each parameter), overlapped by four (differently colored) histograms of the most sensitive parameters: mutation probability of luminal cells (Pmut, red), probability of CAFs promoting tumor cell proliferation (CFprom, green), yellow represents the amount of mutations needed before tumor cells affect macrophage differentiation (TUthrshM) and M1 macrophage migration probability (M1pmig, blue). B, The averaged evolution of the amount of tumor cells for 40 simulations that developed cancer for each of the eight subclasses. These classes were based on the “high” or “low” status of sensitive parameters for CAFs, TAMs, and tumor cells. Included is a violin plot depicting the spread of simulated tumor cell amounts. C, An example of tumor development for each group at an early point in the simulation (50 days), the point at which it becomes invasive and the state at the end of the simulation (400 days).
FIGURE 4 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

Initial healthy stage and following eight steps of prostate cancer development as by prostate cancer ABM simulation. A, Healthy prostatic acinus. B, Mutations start to occur in the luminal cells converting them into tumor cells. C, The presence of mutated cells increases the influx of M1 macrophages. D, Mutated cells start to occupy spaces in the basal cell layer. E, Fibroblasts are differentiating toward their tumor-promoting phenotype (CAFs). F, Macrophages are differentiating toward their tumor-promoting phenotype. G, All these factors lead to break down of the basement membrane. H, Mutated cells become more invasive and start undergoing EMT. I, Invasive cancer with cells spreading through the surrounding tissue. The white grid spaces indicate “empty space,” corresponding to the lumen or to the cleaved ECM (e.g. by CAFs).
FIGURE 3 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

Overview of the starting geometry in 3-fold; a pathology slice, schematic representation, and model geometry visualization. A, A histology slice of a healthy prostatic acinus (H&E staining, 400x magnification). B, Schematic representation of the acinus (created with BioRender.com). C, Modeled starting geometry, including a color scheme of all cells included in the starting geometry.
FIGURE 2 from Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model
Authors: Passier Margot , van Genderen Maisa N.G. , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise M. , Bergman Andries M. , Zwart Wilbert , Eduati Federica
Published: August 2023

In silico testing of requirements for tumor maintenance. A, Amount of tumor cells (blue) and percentage of stem cells (orange, dotted) simulated over time under the condition that included only stem cells to maintain tumors. Simulations for six different initial percentages of stem cells (SCstart) are shown. B, Similar plot testing the condition in which the proliferative advantage of mutated tumor cells is the only source for tumor maintenance. Simulations for three different probabilities of acquiring mutations (Pmut) are shown. C, Similar plot testing the condition in which tumor maintenance depends on both stem cells and tumor cells that can gain mutations. Four combinations of initial stem cell percentage and probability of mutation acquisition are shown.