bluuebunny/crossref_metadata_2025 huggingface dataset:
RBOHF activates stomatal immunity by modulating both reactive oxygen species and apoplastic pH dynamics in Arabidopsis
Authors: Arnaud Dominique , Deeks Michael J. , Smirnoff Nicholas
Published: July 2023

Stomatal defences are important for plants to prevent pathogen entry and further colonisation of leaves. Apoplastic reactive oxygen species (ROS) generated by NADPH oxidases and apoplastic peroxidases play an important role in activating stomatal closure upon perception of bacteria. However, downstream events, particularly the factors influencing cytosolic hydrogen peroxide (H2O2) signatures in guard cells are poorly understood. We used the H2O2 sensor roGFP2‐Orp1 and a ROS‐specific fluorescein probe to study intracellular oxidative events during stomatal immune response using Arabidopsis mutants involved in the apoplastic ROS burst. Surprisingly, the NADPH oxidase mutant rbohF showed over‐oxidation of roGFP2‐Orp1 by a pathogen‐associated molecular pattern (PAMP) in guard cells. However, stomatal closure was not tightly correlated with high roGFP2‐Orp1 oxidation. In contrast, RBOHF was necessary for PAMP‐mediated ROS production measured by a fluorescein‐based probe in guard cells. Unlike previous reports, the rbohF mutant, but not rbohD, was impaired in PAMP‐triggered stomatal closure resulting in defects in stomatal defences against bacteria. Interestingly, RBOHF also participated in PAMP‐induced apoplastic alkalinisation. The rbohF mutants were also partly impaired in H2O2‐mediated stomatal closure at 100 μm while higher H2O2 concentration up to 1 mm did not promote stomatal closure in wild‐type plants. Our results provide novel insights on the interplay between apoplastic and cytosolic ROS dynamics and highlight the importance of RBOHF in plant immunity.
Numerical Assessment of Hydraulic Properties of Triply Periodic Minimal Surfaces Structures
Authors: Piatti Cecilia , Savoldi Laura , Fathi Nima
Published: July 2023

The present work is devoted to evaluating the hydraulic properties of Triply Periodic Minimal Surfaces (TPMS) structures, a generation of porous structures developed using the periodicity of trigonometric equations to generate triply periodic minimal surfaces. The thorough computational and experimental analysis coupled with verification assessment is key to using these product structures in thermal hydraulics especially to address industrial requirements. Here the hydraulic properties are computed by performing three-dimensional CFD analyses using Star-CCM+. Gyroid TPMS was hydraulically analyzed with a water flow in three-channel configurations (circular, square, and rectangular section), with the same hydraulic diameter and length, respectively 5.08cm and 10cm. Their porosity values range from 80% to 93% depending on the unit cell dimensions (chosen values were 10mm, 15mm, 20mm, 25mm, and 30mm). The CFD models for the rectangular TPMS contain the maximum epistemic uncertainty of 19% following the ASME VV 20 codes. In preparation for the forthcoming test campaign, the hydraulic characteristic of the different channels is assessed comparatively, and the friction factors are computed and compared to reach a basic understanding of the parametric effect of channel shape and cell size.
Practical guide for in-house solid-state nanopore fabrication and characterization
Authors: Dominic Anumol , Sajeer Parambath Muhammad , Nasa Simran , Varma Manoj
Published: July 2023

Solid-state nanopores are considered a better alternative to biological nanopores for several sensing applications due to their better chemical, mechanical, and temperature stability. In addition to sequencing, nanopores currently also find applications in education, biomarker identification, quantification, single-molecule chemistry, and DNA computing. Nanopore technology’s simplicity and wide interdisciplinary applications have raised further interest among industry and scientific community worldwide. However, further development in solid-state nanopore technology and exploring its applications presents the need to have the capability to fabricate them in-house. This will be a more financially viable and flexible approach, especially in resource-limited situations. In order to do an in-house fabrication of solid-state nanopores, two key steps are involved. The first step is to fabricate suspended thin films, and the second one is the drilling of pores in these suspended thin membranes. Successful implementation of these two steps involves tedious optimization and characterization of the fabricated chips and nanopores. In this work, we describe the nanopore fabrication process in a ready-to-follow step-by-step guide and present solutions for several practical difficulties faced during the silicon nitride pore fabrication process. This work will help anyone new to this field and make the pore fabrication process more accessible.
Terbinafine-Resistant Dermatophytes and the Presence of Trichophyton indotineae in North America
Authors: Cañete-Gibas Connie F. , Mele James , Patterson Hoja P. , Sanders Carmita J. , Ferrer Dora , Garcia Victor , Fan Hongxin , David Marjorie , Wiederhold Nathan P.
Published: July 2023

Dermatophytes are common causes of skin, hair, and nail infections in humans. The most common species causing infections in humans are
Trichophyton rubrum
,
Trichophyton mentagrophytes
, and
Trichophyton interdigitale
.
Diffraction-Limited Focusing of Acoustic Waves by a Mesoscopic Flat Janus Lens
Authors: Minin O. V. , Zhou S. , Baranov P. F. , Minin I. V.
Published: July 2023

Anisotropic focusing by a mesoscopic (Mie size parameter of about 18) acoustic cubic lens based on V-shaped plate structures has been simulated numerically and confirmed experimentally. It has been shown for the first time that this lens with an edge dimension of about three wavelengths ensures the focusing of an acoustic wave in air into a diffraction-limited region. In the inverse geometry of the structure, the lens completely reflects the incident acoustic wave.
Chiral Separation Effect in a Quark–Gluon Plasma
Authors: Khaidukov Z. V.
Published: July 2023

An expression for the chiral separation effect in a quark–gluon plasma has been derived using the method of field correlators by expanding in Landau levels.
Association between Medicare eligibility at age 65 years and in-hospital treatment patterns and health outcomes for patients with trauma: regression discontinuity approach
Authors: Bhaumik Deepon , Ndumele Chima D , Scott John W , Wallace Jacob
Published: July 2023

Objective

To determine whether health systems in the United States modify treatment or discharge decisions for otherwise similar patients based on health insurance coverage.

Design

Regression discontinuity approach.

Setting

American College of Surgeons’ National Trauma Data Bank, 2007-17.

Participants

Adults aged between 50 and 79 years with a total of 1 586 577 trauma encounters at level I and level II trauma centers in the US.

Interventions

Eligibility for Medicare at age 65 years.

Main outcome measures

The main outcome measure was change in health insurance coverage, complications, in-hospital mortality, processes of care in the trauma bay, treatment patterns during hospital admission, and discharge locations at age 65 years.

Results

1 586 577 trauma encounters were included. At age 65, a discontinuous increase of 9.6 percentage points (95% confidence interval 9.1 to 10.1) was observed in the share of patients with health insurance coverage through Medicare at age 65 years. Entry to Medicare at age 65 was also associated with a decrease in length of hospital stay for each encounter, of 0.33 days (95% confidence interval −0.42 to −0.24 days), or nearly 5%), which coincided with an increase in discharges to nursing homes (1.56 percentage points, 95% confidence interval 0.94 to 2.16 percentage points) and transfers to other inpatient facilities (0.57 percentage points, 0.33 to 0.80 percentage points), and a large decrease in discharges to home (1.99 percentage points, −2.73 to −1.27 percentage points). Relatively small (or no) changes were observed in treatment patterns during the patients’ hospital admission, including no changes in potentially life saving treatments (eg, blood transfusions) or mortality.

Conclusions

The findings suggest that differences in treatment for otherwise similar patients with trauma with different forms of insurance coverage arose during the discharge planning process, with little evidence that health systems modified treatment decisions based on patients’ coverage.
The responses of Cannabis sativa to environmental stress: a balancing act
Authors: Payment Josephine , Cvetkovska Marina
Published: July 2023

Cannabis sativa L. is one of the oldest cultivated crops, used for its fiber and medicinal properties. The cannabis plant synthesizes a myriad of secondary metabolites, but the most valuable products from a medical and commercial standpoint are cannabinoids. Despite significant advances in elucidating the biochemistry and genetics that govern cannabinoid accumulation, we still do not have conclusive evidence for the role of these secondary metabolites in the physiology of C. sativa. In line with known functions of other secondary metabolites, the protective functions of cannabinoids against temperature stress, poor micronutrient soil content, drought, ultraviolet B radiation, and as antimicrobial agents have been suggested, but are yet to be conclusively demonstrated. Recent research suggests that the environment has a major effect on cannabis growth and productivity, but the relationship between stress, cannabinoid accumulation, and plant health is complex. Here, we summarize the current insights on how abiotic and biotic stresses affect C. sativa biology. We also examine the available evidence to support the hypothesis for the protective function of cannabinoids against environmental stressors. Maintaining optimal growth and high cannabinoid synthesis is a balancing act, one that can only be achieved by better understanding of the effects of the environment on the cannabis plant.
NuHamil : A numerical code to generate nuclear two- and three-body matrix elements from chiral effective field theory
Authors: Miyagi Takayuki
Published: July 2023

The applicability of nuclear ab initio calculations has rapidly extended over the past decades. However, starting research projects is still challenging due to the required numerical expertise in the generation of underlying nuclear interaction matrix elements and many-body calculations. To ease the first issue, in this paper we introduce the numerical code to generate the nucleon-nucleon (NN) and three-nucleon (3N) matrix elements expressed in a spherical harmonic-oscillator basis, inputs of many-body calculations. The ground-state energies for the selected doubly closed shell nuclei are calculated with the no-core shell-model (NCSM) and in-medium similarity renormalization group (IMSRG). The code is written in modern Fortran, and OpenMP+MPI hybrid parallelization is available for the 3N matrix-element calculations.
Bayesian inference of W-boson mass
Authors: Rallapalli Aaseesh , Desai Shantanu
Published: July 2023

We use a Bayesian regression technique (similar to a recent analysis by Rinaldi et al.) to obtain a central estimate for the W-boson mass using four different combinations of datasets compiled by the PDG including the 2022 CDF result. We use three different priors on the unknown intrinsic scatter and also a non-parametric hierarchical Dirichlet Process Gaussian Mixture model to obtain a world average for W-boson mass. We also evaluate the statistical significance of the discrepancy with respect to the Standard model for each of the datasets. We find that for all the combination of datasets and the aformentioned prior choices, the discrepancy with respect to the Standard Model value for the W-mass is less than 3$$\sigma $$
σ
. We also checked that if we use a narrow prior on the intrinsic scatter, we get a discrepancy of about 3.8$$\sigma $$
σ
compared to the Standard model value.
Performance of the MALTA telescope
Authors: van Rijnbach Milou , Gustavino Giuliano , Allport Phil , Tortajada Ignacio Asensi , Berlea Dumitru Vlad , Bortoletto Daniela , Buttar Craig , Charbon Edoardo , Dachs Florian , Dao Valerio , Dobrijevic Dominik , de Acedo Leyre Flores Sanz , Gabrielli Andrea , Gazi Martin , Gonella Laura , Gonzalez Vicente , Guidon Stefan , LeBlanc Matt , Pernegger Heinz , Piro Francesco , Riedler Petra , Sandaker Heidi , Sharma Abhishek , Sanchez Carlos Solans , Snoeys Walter , Suligoj Tomislav , Nunez Marcos Vazquez , Weick Julian , Worm Steven , Zoubir Abdelhak M.
Published: July 2023

MALTA is part of the Depleted Monolithic Active Pixel sensors designed in Tower 180 nm CMOS imaging technology. A custom telescope with six MALTA planes has been developed for test beam campaigns at SPS, CERN, with the ability to host several devices under test. The telescope system has a dedicated custom readout, online monitoring integrated into DAQ with realtime hit map, time distribution and event hit multiplicity. It hosts a dedicated fully configurable trigger system enabling to trigger on coincidence between telescope planes and timing reference from a scintillator. The excellent time resolution performance allows for fast track reconstruction, due to the possibility to retain a low hit multiplicity per event which reduces the combinatorics. This paper reviews the architecture of the system and its performance during the 2021 and 2022 test beam campaign at the SPS North Area.
Topology in thermodynamics of regular black strings with Kaluza–Klein reduction
Authors: Hung Tran N. , Nam Cao H.
Published: July 2023

We study the topological defects in the thermodynamics of regular black strings (from a four-dimensional perspective) that is symmetric under the double Wick rotation and constructed in the high-dimensional spacetime with an extra dimension compactified on a circle. We observe that the thermodynamic phases of regular black strings can be topologically classified by the positive and negative winding numbers (at the defects) which correspond to the thermodynamically stable and unstable branches. This topological classification implies a phase transition due to the decay of a thermodynamically unstable regular black string to another which is thermodynamically stable. We confirm these topological properties of the thermodynamics of regular black strings by investigating their free energy, heat capacity, and Ruppeiner scalar curvature of the state space. The Ruppeiner scalar curvature of regular black strings is found to be always negative, implying that the interactions among the microstructures of regular black strings are only attractive.
A six-component integrable hierarchy and its Hamiltonian formulation
Authors: Ma Wen-Xiu
Published: July 2023

The aim of this paper is to construct a six-component integrable hierarchy associated with a matrix spatial spectral problem of arbitrary order. The adopted method is the zero curvature formulation. The corresponding Hamiltonian formulation is furnished by using the trace identity, which guarantees the Liouville integrability for the resulting hierarchy. Two illustrative examples of integrable equations of lower orders are six-component coupled nonlinear Schrödinger equations and modified Korteweg–de Vries equations.
A density functional theory study of the CiN and the CiNOicomplexes in silicon
Authors: Kuganathan N. , Christopoulos S.-R. G. , Papadopoulou K. , Sgourou E. N. , Chroneos A. , Londos C. A.
Published: July 2023

Nitrogen (N) is an important impurity in silicon (Si), which associates with impurities as well as with other defects to form defect complexes. The knowledge of the properties and behavior of defect structures containing carbon (C), N and oxygen (O) is important for the Si–based electronic technology. Here, we employ density functional theory (DFT) calculations to investigate the association of nitrogen with carbon and oxygen defects to form the CiN and CiNOidefects. We provide evidence of the formation of these defects and additional details of their structure, their density of states (DOS) and Bader charges. Therefore, CiN and CiNOidefects are now well characterized.
A Dimension Coupling Method for Three-Dimensional Helmholtz and Poisson’s Equations
Authors: Cheng Heng , Xing Zebin , Zhang Jiao , Liu Fengbin
Published: July 2023

In this study, by introducing the finite element method (FEM) into the improved element-free Galerkin (IEFG) method, the dimension coupling method (DCM) is proposed for solving three-dimensional (3D) Helmholtz and Poisson’s equations efficiently. The dimensional splitting method is introduced into the corresponding governing equations, thus 3D equations can be split into a series of 2D ones. The IEFG method is selected to discretize those 2D forms, thus the discretized equations are derived easily by using the weak forms. In the third direction, the FEM is selected to couple those discretized equations, thus the final linear equation of 3D equation is derived. In numerical examples, the good convergence of the DCM for Helmholtz and Poisson’s equations is shown. The solutions of numerical examples show that the computational efficiency of the IEFG method is improved significantly without losing the computational accuracy when the DCM is used. In addition, the DCM can enhance the computational efficiency of the hybrid element-free Galerkin (HEFG) method significantly without too many layers when the natural boundary conditions exist in the splitting direction.
Improve description of electronic structure of layer material Bi2O2Te: A DFT+ U + V calculation
Authors: Quang Tran Van , Trinh Chu Duc
Published: July 2023

The conventional first-principles density-functional theory (DFT) predicts a negative bandgap of the thermoelectric semiconductor Bi2O2Te, which needs to be corrected. To enable a higher-level precise calculation, in this report, we include the self-consistent on-site [Formula: see text] and inter-site [Formula: see text] interactions in our studies, the so-called [Formula: see text] method, and demonstrate that it significantly improves the description of excited states of Bi2O2Te. The on-site interactions of Te-p and O-p play an essential role and substantially improve the band gap of Bi2O2Te. Inter-site interaction between Bi-s, Bi-p, and O-p within the [Bi2O2] layer and between the intercalated Te layer and the [Bi2O2] layer further increases the band gap. Thermoelectric coefficient calculations show a significant Seebeck coefficient and the power factor in p-type doping, which originates from the intercalated Te layer.
Unsupervised Graph Representation Learning with Cluster-aware Self-training and Refining
Authors: Zhu Yanqiao , Xu Yichen , Yu Feng , Liu Qiang , Wu Shu
Published: July 2023

Unsupervised graph representation learning aims to learn low-dimensional node embeddings without supervision while preserving graph topological structures and node attributive features. Previous Graph Neural Networks (GNN) require a large number of labeled nodes, which may not be accessible in real-world applications. To this end, we present a novel unsupervised graph neural network model with Cluster-aware Self-training and Refining (
CLEAR
). Specifically, in the proposed
CLEAR
model, we perform clustering on the node embeddings and update the model parameters by predicting the cluster assignments. To avoid degenerate solutions of clustering, we formulate the graph clustering problem as an optimal transport problem and leverage a balanced clustering strategy. Moreover, we observe that graphs often contain inter-class edges, which mislead the GNN model to aggregate noisy information from neighborhood nodes. Therefore, we propose to refine the graph topology by strengthening intra-class edges and reducing node connections between different classes based on cluster labels, which better preserves cluster structures in the embedding space. We conduct comprehensive experiments on two benchmark tasks using real-world datasets. The results demonstrate the superior performance of the proposed model over baseline methods. Notably, our model gains over 7% improvements in terms of accuracy on node clustering over state-of-the-arts.
Human pulmonary microvascular endothelial cell DDAH1-mediated nitric oxide production promotes pulmonary smooth muscle cell apoptosis in co-culture
Authors: Almazroue Hanadi , Jin Yi , Nelin Leif D. , Barba John C. , Milton Avante D. , Trittmann Jennifer K.
Published: July 2023

BPD-PH is characterized by vascular remodeling. NO is an apoptotic mediator made in the pulmonary endothelium by eNOS. ADMA is an endogenous eNOS inhibitor metabolized by DDAH1. EC-DDAH1 overexpression resulted in greater cleaved caspase-3 and caspase-8 protein expression and lower viable cell numbers in co-cultured SMC. After NO sequestration, SMC viable cell numbers partially recovered despite EC-DDAH1 overexpression. EC-DDAH1-mediated NO production positively regulates SMC apoptosis, which may prevent/attenuate aberrant pulmonary vascular proliferation/remodeling in BPD-PH.
Seizure as Presenting Symptom of Multisystem Inflammatory Syndrome in Children
Authors: D’Ambrosio Eleonora S. , Gauguet Stefanie , Miller Christine , McMahon Erin , Driscoll Christopher , Mohanty Mugdha , Guggina Thomas
Published: July 2023

We describe the case of a 13-year-old girl who presented with a new-onset seizure and fever and subsequently developed severe cardiac dysfunction, coronary artery dilation, and shock due to the surprising diagnosis of multisystem inflammatory syndrome in children (MIS-C). Although the clinical entity we now call MIS-C was first mentioned in the medical literature in April 2020, the full picture of this disease process is still evolving. Neurologic involvement has been described in cases with MIS-C; however, seizures are not a typical presenting symptom. Additionally, because children infected with SARS-CoV-2 are often asymptomatic, a documented preceding COVID-19 infection might not be available to raise suspicion of MIS-C early on. Febrile seizures, meningitis, and encephalitis are childhood illnesses that pediatricians are generally familiar with, but associating these clinical pictures with MIS-C is uncommon. Given the possibility of rapid clinical cardiogenic decline, as seen in our patient, a prompt diagnosis and appropriate monitoring and treatment are of utmost importance. This case report aims to raise awareness that new-onset seizures with fevers can be early or the first presenting symptoms in children with MIS-C, and further workup and close monitoring may be required.
A Breast Cancer Image Classification Algorithm with 2c Multiclass Support Vector Machine
Authors: Wajeed Mohammed Abdul , Tiwari Shivam , Gupta Rajat , Ahmad Aamir Junaid , Agarwal Seema , Jamal Sajjad Shaukat , Hinga Simon Karanja
Published: July 2023

Breast cancer is the most frequent type of cancer in women; however, early identification has reduced the mortality rate associated with the condition. Studies have demonstrated that the earlier this sickness is detected by mammography, the lower the death rate. Breast mammography is a critical technique in the early identification of breast cancer since it can detect abnormalities in the breast months or years before a patient is aware of the presence of such abnormalities. Mammography is a type of breast scanning used in medical imaging that involves using x‐rays to image the breasts. It is a method that produces high‐resolution digital pictures of the breasts known as mammography. Immediately following the capture of digital images and transmission of those images to a piece of high‐tech digital mammography equipment, our radiologists evaluate the photos to establish the specific position and degree of the sickness in the breast. When compared to the many classifiers typically used in the literature, the suggested Multiclass Support Vector Machine (MSVM) approach produces promising results, according to the authors. This method may pave the way for developing more advanced statistical characteristics based on most cancer prognostic models shortly. It is demonstrated in this paper that the suggested 2C algorithm with MSVM outperforms a decision tree model in terms of accuracy, which follows prior findings. According to our findings, new screening mammography technologies can increase the accuracy and accessibility of screening mammography around the world.
Preclinical Demonstration of a Novel Treatment with High Efficacy and No Detectable Toxicity for Inflammatory Skin Conditions including Psoriasis
Authors: Vanden Heuvel John P. , Zhou Shuling , Patel Anisha B. , Kamerow Harry N. , Baran Peter , Ford John P.
Published: July 2023

Although the management options for psoriasis have progressed with the use of systemic agents, there are few efficacious nonsteroidal topical therapies for patients with limited or lower grade disease. The effects of allopurinol (Allo) and glutathione (GSH) were examined in two different in vitro models for psoriasis. In the first model, human immortalized keratinocytes (HaCaT) were treated with M5 cocktail (IL‐17A, IL‐22, oncostatin M, IL‐1α, and TNF‐α) in four interventional groups (control, Allo, oxypurinol (Oxy), and methotrexate (MTX)). The number of live and dead cells was determined after treatment for 48 and 72 hrs. Allo decreased cell proliferation (total cells) without increasing cell death compared to both its xanthine oxidase inhibiting metabolite Oxy and a standard agent in clinical use, MTX. In the second model, a human psoriatic skin equivalent (PSE) culture system, cells were treated with vehicle control, Allo and GSH (as monotherapies and in combination), and vitamin D (VitD) for 2 and 6 days followed by histological analysis and altered gene expression. The combined exposure to Allo and GSH was equivalent to a standard antipsoriasis agent VitD in the inhibition of both proliferative and replicative markers. Histologic examination of the tissue at 6 days of exposure to VitD resulted in loss of the integrity of the squamous/epithelial continuity whereas tissue integrity was preserved with Allo and GSH exposure. The additional exposure of GSH to Allo reversed the increased thickness of the dermis layer caused by Allo exposure alone. Taken together, this data shows that topical Allo and GSH may have a synergistic effect with low toxicity and constitute a therapeutic advantage over current nonsteroidal therapies in the treatment of inflammatory skin conditions marked by increased cell proliferation such as psoriasis.
Antiproliferative, Antiangiogenic, and Antimigrastatic Effects of Oroxylum indicum (L.) Kurz Extract on Breast Cancer Cell
Authors: Chiraatthakit Benjamas , Dunkunthod Benjawan , Suksaweang Sanong , Eumkeb Griangsak
Published: July 2023

Breast cancer recurrence continues to pose a major clinical problem, despite significant advancements in early diagnosis and an aggressive mode of treatment. This study aimed at investigating the anticancer activity of Oroxylum indicum extract (OIE) by assessing cell proliferation, cell migration, and angiogenesis in metastatic breast cancer MDA‐MB‐231 cell lines. This study also estimated the phytochemical profiles of OIE by LC‐QTOF‐MS. The extract was found to contain six identified flavonoid substances, and baicalein was the most abundant substance in the extract. Cell proliferation capacity was performed by cell counting kit‐8 (CCK‐8) and colony formation assays. The effect of OIE on cell migration was determined using wound healing and transwell assays. Meanwhile, MDA‐MB‐231‐induced angiogenesis on chick chorioallantoic membrane (CAM) was applied to investigate the ex vivo antiangiogenesis activity of the extracts. OIE at concentrations lower than 600 μg/mL had no cytotoxic effects against MDA‐MB‐231 cells. OIE was found to inhibit the long‐term colony formation ability of MDA‐MB‐231 cells in a concentration‐dependent manner. Antimigration and antiangiogenesis activities were further investigated using noncytotoxic concentrations of OIE ranging from 25 to 150 μg/mL. OIE greatly reduced the migration of MDA‐MB‐231 breast cancer cells in a dose‐dependent manner. OIE significantly suppressed the MDA‐MB‐231‐induced angiogenesis, and there was no substantial toxic effect on natural angiogenesis. Interestingly, the concentration of OIE at 150 μg/mL was as practically potent as pazopanib, the positive anticancer drug, at 4.37 μg/mL in inhibiting MDA‐MB‐231 cell migration and angiogenesis induced by these cells. Therefore, the inhibitory effects of OIE in cell proliferation and cell migration, together with antiangiogenesis in MDA‐MB‐231 breast cancer cells, suggesting that OIE has the potential to be a novel adjunct candidate for breast cancer chemotherapeutic agents.
Solubilized Pancreatic Extracellular Matrix from Juvenile Pigs Protects Isolated Human Islets from Hypoxia-Induced Damage: A Viable Option for Clinical Islet Transplantation
Authors: Brandhorst Heide , Krishtul Stasia , Brandhorst Daniel , Baruch Limor , Machluf Marcelle , Johnson Paul R. V.
Published: July 2023

The pancreatic extracellular matrix (ECM) is an enormously complex construct. Previous studies underline the challenges to identify the optimal combinations and ratios of individual ECM proteins for promoting survival and function of isolated and transplanted islets. This study aimed on assessing the efficiency of solubilized natural ECM extracted from juvenile pigs, an unlimited donor source. Isolated human islets were cultured under a hypoxic atmosphere (2% oxygen) in media supplemented with either solubilized porcine pancreatic ECM (ppECM) or a mixture of human ECM proteins composed of collagen-IV, laminin-521, and nidogen-1 (hEPM). Control islets were cultured under identical conditions without ECM-compounds. Reactive oxygen species production increased three-fold in controls but was reduced by hEPM or ppECM. Early apoptosis remained on preculture levels when islets were treated with hEPM or ppECM. Preculture viability was preserved when hEPM or ppECM was administered. Whilst controls failed to respond to glucose challenge, treatment with hEPM or ppECM preserved the physiological insulin response. In summary, overall survival was significantly highest in ppECM-treated islets. This study presents a new approach to protect human islets from hypoxia-induced damage by supplementing media with ppECM extracted from an unlimited donor source. The findings may also serve as starting point for a novel encapsulation technique to protect isolated human islets.
An Open-Source Framework for Modeling RC Shear Walls Using Deep Neural Networks
Authors: Solorzano German , Plevris Vagelis
Published: July 2023

Reinforced concrete (RC) shear walls macroscopic models are simplified strategies able to simulate the complex nonlinear behavior of RC shear walls to some extent, but their efficacy and robustness are limited. In contrast, microscopic models are sophisticated finite element method (FEM) models that are far more accurate and reliable. However, their elevated computational cost turns them unfeasible for most practical applications. In this study, a data-driven surrogate model for analyzing RC shear walls is developed using deep neural networks (DNNs). The surrogate model is trained with thousands of FEM simulations to predict the characteristic curve obtained when a static nonlinear pushover analysis is performed. The surrogate model is extensively tested and found to exhibit a high degree of accuracy in its predictions while being extremely faster than the detailed FEM analysis. The complete framework that made this study possible is provided as an open-source project. The project is developed in Python and includes a parametric FEM model of an RC shear wall in OpenSeesPy, the training and validation of the DNN model in TensorFlow, and an application with an interactive graphical user interface to test the methodology and visualize the results.
Growth, Biochemical Characteristics, Flesh Quality, and Gut Microbiota of the Pacific White Shrimp (Penaeus vannamei) Fed a Defatted Superworm (Zophobas atratus) Larvae Meal
Authors: Lin Hongxing , Liang Xiaolong , Han Fenglu , Luo Xiaolong , Li Erchao
Published: July 2023

This study evaluated the effects of defatted superworm (Zophobas atratus) larvae meal (DBWLM) as an alternative protein ingredient for juvenile Pacific white shrimp (Penaeus vannamei). Six isonitrogenous and isolipidic experimental diets were characterized by replacing 0%, 15%, 30%, 45%, 60%, and 75% fish meal (DBWLM0, DBWLM15, DBWLM30, DBWLM45, DBWLM60, and DBWLM75, respectively) with DBWLM on a w/w basis and feeding them to juvenile shrimp (0.34 ± 0.04 g) for 56 days. The results showed that the replacement of up to 75% fish meal by DBWLM had no negative effect on the growth performance of P. vannamei. The survival of shrimp in the DBWLM30 group was the highest, and the weight gain, specific growth rate, feed conversion ratio, condition factor, and apparent digestibility coefficients of dry matter in the DBWLM15 group were the highest. The substitution of DBWLM for fish meal significantly increased the elasticity of flesh, improved the total content of umami amino acids in flesh (aspartic acid, glutamic acid, glycine, and alanine), promoted lipid metabolism in shrimp, and reduced serum lipid levels. With the increase in DBWLM level, serum acid phosphatase, alkaline phosphatase activity, and intestinal inflammatory gene expression (IGF-1 and IL-6) were inhibited, malondialdehyde content decreased, and total antioxidant capacity level and superoxide dismutase activity increased significantly. Histological sections of the hepatopancreas showed that when 60% or more fish meal was replaced, the hepatopancreas atrophied and had irregular lumen distortion, but the cell membrane was not damaged. Microbiome analysis showed that the abundance of Bacteroidetes and Firmicutes increased and the abundance of Proteobacteria decreased in the DBWLM replacement group, and it was rich in “metabolism”-related functional pathways. It is worth mentioning that the expression of amino-acid-related enzymes was upregulated in the DBWLM15 and DBWLM30 groups, and the DBWLM75 group inhibited the biosynthesis of steroids and hormones. To conclude, the replacement of 15%–45% fish meal with DBWLM can result in better growth and immune status, improved meat elasticity, and reduced inflammation in P. vannamei. However, it is recommended that the replacement level should not exceed 60%, otherwise it will cause atrophy of hepatopancreas cells.
Performance Optimization of Chemical and Green Coagulants in Tannery Wastewater Treatment: A Response Surface Methodology Approach
Authors: Appiah-Brempong Miriam , Michelle Korkor Essandoh Helen , Yaw Asiedu Nana , Kwame Dadzie Samuel , Yao Momade Francis
Published: July 2023

Vegetable tannery wastewater, highly laden with recalcitrant organics, is not easily treatable through biological processes. This study focuses on the use of response surface methodology in optimizing a coagulation-flocculation process for pretreatment of vegetable tannery wastewater. This study also assessed the possibility of replacing chemical coagulants such as aluminum sulphate with green alternatives such as cassava starch and orange peel powder. The effects of coagulant dosage and pH on three key wastewater quality parameters (chemical oxygen demand (COD) and total suspended solids (TSS)’s removal efficiencies as well as sludge volume index (SVI)) were also assessed. Quadratic models developed for all the three responses were adequate. The optimal conditions were attained at a pH of 3.17 and a dosage of 2.76 g/L for cassava starch coagulant, pH of 3.74 and a dosage of 5.16 g/L for orange peel powder coagulant, and pH of 6.09 and a dosage of 11.60 g/L for aluminum sulphate. The COD and TSS removal efficiencies as well as SVI achieved under these optimal conditions were 37.25%, 73.95%, and 14.80 mL/g, respectively, for cassava starch coagulant; 17.97%, 66.08%, and 19.87 mL/g, respectively, for orange peel powder coagulant; and 38.51%, 76.06%, and 29.57 mL/g, respectively, for aluminum sulphate. The outperformance of cassava starch over orange peel powder and its comparable results with aluminum sulphate makes the former a more environment-friendly alternative to aluminum sulphate for treatment of tannery wastewater.
Metastasis Unleashed: Hyposialylation Empowers Chemo-Evasive Circulating Tumor Cell Clusters in Breast Cancer
Authors: Gvozdenovic Ana , Aceto Nicola
Published: July 2023

Therapy resistance is frequently observed in cancer patients with distant metastases and effective management of metastatic disease remains challenging. Unraveling the cellular mechanisms and molecular targets fueling metastatic spread is crucial for advancing cancer therapies. In a recent issue of Cancer Discovery, Dashzeveg and colleagues revealed that loss of terminal sialylation in glycoproteins within circulating tumor cell clusters is a dynamic process that contributes to cellular dormancy, facilitates evasion of chemotherapy, and enhances metastatic seeding. Furthermore, the study identifies the glycoprotein podocalyxin (PODXL) as a potential target for counteracting the metastasis of quiescent tumor cells associated with paclitaxel treatment in triple-negative breast cancer.
Heterochromatin-Dependent Replication Stress: A Lesson from IDH1/2 Mutants
Authors: Zou Lee
Published: July 2023

Oncogenic point mutants of isocitrate dehydrogenases 1 and 2 (IDH2) generate 2-hydroxyglutarate, which inhibits lysine demethylases and increases heterochromatin. Tumor cells expressing IDH mutants are sensitive to PARP inhibitors (PARPi), offering an opportunity to eliminate IDH-driven tumor cells in therapy. Expression of an oncogenic IDH1 mutant in cells leads to aberrant heterochromatin formation at DNA breaks and impairs DNA repair through homologous recombination (HR), providing a possible explanation for the PARPi sensitivity of IDH mutant cells. However, a recent study published in Molecular Cell shows that IDH mutant tumors do not display the genomic alterations associated with HR defects. Instead, IDH mutants induce heterochromatin-dependent DNA replication stress. Furthermore, PARP is activated by the replication stress induced by IDH mutants and required for suppressing the ensuing DNA damage, providing an alternative model to explain the susceptibility of IDH mutant cells to PARPis. This study presents a new example of oncogene-induced and heterochromatin-dependent replication stress, and a role of PARP in the response to the stress, extending the molecular basis for PARP-targeted therapy.
Caveolin Gene Expression Predicts Clinical Outcomes for Early-Stage HER2-Negative Breast Cancer Treated with Paclitaxel-Based Chemotherapy in the GeparSepto Trial
Authors: Williams Terence M. , Schneeweiss Andreas , Jackisch Christian , Shen Changxian , Weber Karsten E. , Fasching Peter A. , Denkert Carsten , Furlanetto Jenny , Heinmöller Ernst , Schmatloch Sabine , Karn Thomas , Szeto Christopher W. , van Mackelenbergh Marion T. , Nekljudova Valentina , Stickeler Elmar , Soon-Shiong Patrick , Schem Christian , Mairinger Thomas , Müller Volkmar , Marme Frederik , Untch Michael , Loibl Sibylle
Published: July 2023

Purpose:

Caveolin-1 and -2 (CAV1/2) dysregulation are implicated in driving cancer progression and may predict response to nab-paclitaxel. We explored the prognostic and predictive potential of CAV1/2 expression for patients with early-stage HER2-negative breast cancer receiving neoadjuvant paclitaxel-based chemotherapy regimens, followed by epirubicin and cyclophosphamide.

Experimental Design:

We correlated tumor CAV1/2 RNA expression with pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) in the GeparSepto trial, which randomized patients to neoadjuvant paclitaxel- versus nab-paclitaxel–based chemotherapy.

Results:

RNA sequencing data were available for 279 patients, of which 74 (26.5%) were hormone receptor (HR)–negative, thus triple-negative breast cancer (TNBC). Patients treated with nab-paclitaxel with high CAV1/2 had higher probability of obtaining a pCR [CAV1 OR, 4.92; 95% confidence interval (CI), 1.70–14.22; P = 0.003; CAV2 OR, 5.39; 95% CI, 1.76–16.47; P = 0.003] as compared with patients with high CAV1/2 treated with solvent-based paclitaxel (CAV1 OR, 0.33; 95% CI, 0.11–0.95; P = 0.040; CAV2 OR, 0.37; 95% CI, 0.12–1.13; P = 0.082). High CAV1 expression was significantly associated with worse DFS and OS in paclitaxel-treated patients (DFS HR, 2.29; 95% CI, 1.08–4.87; P = 0.030; OS HR, 4.97; 95% CI, 1.73–14.31; P = 0.003). High CAV2 was associated with worse DFS and OS in all patients (DFS HR, 2.12; 95% CI, 1.23–3.63; P = 0.006; OS HR, 2.51; 95% CI, 1.22–5.17; P = 0.013), in paclitaxel-treated patients (DFS HR, 2.47; 95% CI, 1.12–5.43; P = 0.025; OS HR, 4.24; 95% CI, 1.48–12.09; P = 0.007) and in patients with TNBC (DFS HR, 4.68; 95% CI, 1.48–14.85; P = 0.009; OS HR, 10.43; 95% CI, 1.22–89.28; P = 0.032).

Conclusions:

Our findings indicate high CAV1/2 expression is associated with worse DFS and OS in paclitaxel-treated patients. Conversely, in nab-paclitaxel–treated patients, high CAV1/2 expression is associated with increased pCR and no significant detriment to DFS or OS compared with low CAV1/2 expression.
A Novel HOXA10-Associated 5-Gene–Based Prognostic Signature for Stratification of Short-term Survivors of Pancreatic Ductal Adenocarcinoma
Authors: Kisling Sophia G. , Atri Pranita , Shah Ashu , Cox Jesse L. , Sharma Sunandini , Smith Lynette M. , Ghersi Dario , Batra Surinder K.
Published: July 2023

Purpose:

Despite the significant association of molecular subtypes with poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC), few efforts have been made to identify the underlying pathway(s) responsible for this prognosis. Identifying a clinically relevant prognosis-based gene signature may be the key to improving patient outcomes.

Experimental Design:

We analyzed the transcriptomic profiles of treatment-naïve surgically resected short-term survivor (STS) and long-term survivor (LTS) tumors (GSE62452) for expression and survival, followed by validation in several datasets. These results were corroborated by IHC analysis of PDAC-resected STS and LTS tumors. The mechanism of this differential survival was investigated using CIBERSORT and pathway analyses.

Results:

We identified a short-surviving prognostic subtype of PDAC with a high degree of significance (P = 0.018). One hundred thirty genes in this novel subtype were found to be regulated by a master regulator, homeobox gene HOXA10, and a 5-gene signature derived from these genes, including BANF1, EIF4G1, MRPS10, PDIA4, and TYMS, exhibited differential expression in STSs and a strong association with poor survival. This signature was further associated with the proportion of T cells and macrophages found in STSs and LTSs, demonstrating a potential role in PDAC immunosuppression. Pathway analyses corroborated these findings, revealing that this HOXA10-driven prognostic signature is associated with immune suppression and enhanced tumorigenesis.

Conclusions:

Overall, these findings reveal the presence of a HOXA10-associated prognostic subtype that can be used to differentiate between STS and LTS patients of PDAC and inform on the molecular interactions that play a role in this poor prognosis.
Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Thummalapalli Rohit , Ricciuti Biagio , Bandlamudi Chaitanya , Muldoon Daniel , Rizvi Hira , Elkrief Arielle , Luo Jia , Alessi Joao V. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Hong Lingzhi , Zhang Jianjun , Heymach John V. , Gibbons Don L. , Plodkowski Andrew J. , Ravichandran Vignesh , Donoghue Mark T.A. , Vanderbilt Chad , Ladanyi Marc , Rudin Charles M. , Kris Mark G. , Riely Gregory J. , Chaft Jamie E. , Hellmann Matthew D. , Vokes Natalie I. , Awad Mark M. , Schoenfeld Adam J.
Published: July 2023

Purpose:

We sought to identify features of patients with advanced non–small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICI), and how these might differ from features predictive of short-term response (STR).

Experimental Design:

We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs between 2011 and 2022. LTR and STR were defined as response ≥ 24 months and response < 12 months, respectively. Tumor programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), next-generation sequencing (NGS), and whole-exome sequencing (WES) data were analyzed to identify characteristics enriched in patients achieving LTR compared with STR and non-LTR.

Results:

Among 3,118 patients, 8% achieved LTR and 7% achieved STR, with 5-year overall survival (OS) of 81% and 18% among LTR and STR patients, respectively. High TMB (≥50th percentile) enriched for LTR compared with STR (P = 0.001) and non-LTR (P < 0.001). Whereas PD-L1 ≥ 50% enriched for LTR compared with non-LTR (P < 0.001), PD-L1 ≥ 50% did not enrich for LTR compared with STR (P = 0.181). Nonsquamous histology (P = 0.040) and increasing depth of response [median best overall response (BOR) −65% vs. −46%, P < 0.001] also associated with LTR compared with STR; no individual genomic alterations were uniquely enriched among LTR patients.

Conclusions:

Among patients with advanced NSCLC treated with ICIs, distinct features including high TMB, nonsquamous histology, and depth of radiographic improvement distinguish patients poised to achieve LTR compared with initial response followed by progression, whereas high PD-L1 does not.
S-531011, a Novel Anti-Human CCR8 Antibody, Induces Potent Antitumor Responses through Depletion of Tumor-Infiltrating CCR8-Expressing Regulatory T Cells
Authors: Nagira Yoji , Nagira Morio , Nagai Ryohei , Nogami Wataru , Hirata Michinari , Ueyama Azumi , Yoshida Tetsuya , Yoshikawa Mai , Shinonome Satomi , Yoshida Hiroshi , Haruna Miya , Miwa Hiroto , Chatani Natsumi , Ohkura Naganari , Wada Hisashi , Tanaka Hidekazu
Published: July 2023

Although regulatory T cells (Treg) are inhibitory immune cells that are essential for maintaining immune homeostasis, Tregs that infiltrate tumor tissue promote tumor growth by suppressing antitumor immunity. Selective reduction of tumor-infiltrating Tregs is, therefore, expected to activate antitumor immunity without affecting immune homeostasis. We previously reported that selective Treg depletion targeted by a C-C motif chemokine receptor 8 (CCR8) resulted in induction of strong antitumor immunity without any obvious autoimmunity in mouse models. Thus, herein, we developed a novel humanized anti-CCR8 monoclonal antibody, S-531011, aimed as a cancer immunotherapy strategy for patients with cancer. S-531011 exclusively recognized human CCR8 among all chemokine receptors and showed potent antibody-dependent cell-mediated cytotoxicity activity toward CCR8+ cells and neutralization activity against CCR8-mediated signaling. We observed that S-531011 reduced tumor-infiltrating CCR8+ Tregs and induced potent antitumor activity in a tumor-bearing human-CCR8 knock-in mouse model. Moreover, combination therapy with S-531011 and anti-mouse programmed cell death 1 (PD-1) antibody strongly suppressed tumor growth compared with anti–PD-1 antibody alone with no observable adverse effects. S-531011 also depleted human tumor-infiltrating Tregs, but not Tregs derived from human peripheral blood mononuclear cells. These results suggest that S-531011 is a promising drug for inducing antitumor immunity without severe side effects in the clinical setting.