bluuebunny/crossref_metadata_2025 huggingface dataset:
An introduction to phase ordering in scalar active matter
Authors: Meissner Laura , Yeomans Julia M.
Published: August 2024

These notes provide an introduction to phase ordering in dry, scalar active matter. We first briefly review Model A and Model B, the long-standing continuum descriptions of ordering in systems with a non-conserved and conserved scalar order parameter. We then contrast different ways in which the field theories can be extended so that the phase ordering persists, but in systems that are active and do not reach thermodynamic equilibrium. The active models allow a wide range of dynamical steady states not seen in their passive counterparts. These include microphase separation, active foams and travelling density bands.
Tools of Our Tools? Exploring the Cybercene Conjecture
Authors: Schuler Douglas
Published: August 2024

Dek :

Are we seeing the dawning of a new epoch?
A Face Cover Perspective to
ℓ
1
Embeddings of Planar Graphs
Authors: Filtser Arnold
Published: August 2024

It was conjectured by Gupta et al. that every planar graph can be embedded into

\(\ell_{1}\)

with constant distortion. However, given an

\(n\)

-vertex weighted planar graph, the best upper bound on the distortion is only

\(O(\sqrt{\log n})\)

, by Rao. In this article, we study the case where there is a set

\(K\)

of terminals, and the goal is to embed only the terminals into

\(\ell_{1}\)

with low distortion. In a seminal article, Okamura and Seymour showed that if all the terminals lie on a single face, they can be embedded isometrically into

\(\ell_{1}\)

. The more general case, where the set of terminals can be covered by

\(\gamma\)

faces, was studied by Lee and Sidiropoulos and Chekuri et al. The state of the art is an upper bound of

\(O(\log\gamma)\)

by Krauthgamer, Lee and Rika. Our contribution is a further improvement on the upper bound to

\(O(\sqrt{\log\gamma})\)

. Since every planar graph has at most

\(O(n)\)

faces, any further improvement on this result will be a major breakthrough, directly improving upon Rao's long standing upper bound. Moreover, it is well known that the flow-cut gap equals to the distortion of the best embedding into

\(\ell_{1}\)

. Therefore, our result provides a polynomial time

\(O(\sqrt{\log\gamma})\)

-approximation to the sparsest cut problem on planar graphs, for the case where all the demand pairs can be covered by

\(\gamma\)

faces.
Chemical Botany: Bottlebrush Polymers in Materials Science
Authors: Lapkriengkri Intanon , Albanese Kaitlin R. , Rhode Andrew , Cunniff Austin , Pitenis Angela A. , Chabinyc Michael L. , Bates Christopher M.
Published: August 2024

Molecular architectures known as bottlebrush polymers provide unique opportunities to tune the structure and properties of soft materials with applications ranging from rubbers to thin films and composites. This review addresses recent developments and future opportunities in the field with an emphasis on materials science enabled by contemporary bottlebrush chemistry.
The Active Chlorine Mediated Electrochemical Synthesis of Aromatic Nitriles through Cascade Reaction
Authors: Zhu Yinghong , Zhou Minling , Ge Zhanbang , Jiao Yufeng , Wang Menghui , Peng Wujin
Published: August 2024

An efficient and transition-metal-free synthesis strategy of aromatic nitriles from corresponding aldehydes with H2SO4(NH2OH)2 as the nitrogen source and Cl−/ClO− as the redox mediator was developed. The redox Cl−/ClO− showed electrochemical reversibility in acidic condition. The possible mechanism involving the transformation of Cl−, the generation and electrochemical reduction of nitrile oxides based on the results of cyclic voltammetry and constant current electrolysis was proposed.
Review—Machine Learning-Driven Advances in Electrochemical Sensing: A Horizon Scan
Authors: Murugan Kaviya , Gopalakrishnan Karnan , Sakthivel Kogularasu , Subramanian Sakthinathan , Li I-Cheng , Lee Yen-Yi , Chiu Te-Wei , Chang-Chien Guo-Ping
Published: August 2024

The burgeoning intersection of machine learning (ML) with electrochemical sensing heralds a transformative era in analytical science, pushing the boundaries of what’s possible in detecting and quantifying chemical substances with unprecedented precision and efficiency. This convergence has accelerated a number of discoveries, improving electrochemical sensors’ sensitivity, selectivity, and ability to comprehend complicated data streams in real-time. Such advancements are crucial across various applications, from monitoring health biomarkers to detecting environmental pollutants and ensuring industrial safety. Yet, this integration is not without its challenges; it necessitates navigating intricate ethical considerations around data use, ensuring robust data privacy measures, and developing specialized software tools that balance accessibility and security. As the field progresses, addressing these challenges head-on is essential for harnessing the full potential of ML-enhanced electrochemical sensing. This review briefly explores these dimensions, spotlighting the significant technological strides, the ethical landscape, and the dynamic interplay between open-source and proprietary software solutions while also casting a forward gaze at the promising future directions of this interdisciplinary venture.
Tailoring of Novel Amorphous RuS2/ZrS2/MWCNT Nanocomposite Platform as a Dual Sensor for the Detection for Water Pollutant Indigo Carmine
Authors: Sajeevan Bhama , M G Gopika , Murali Aswathy S. , Sreelekshmi G , Saraswathyamma Beena , Govindasamy Mani
Published: August 2024

The present study focuses on synthesizing amorphous nanocomposites of RuS2/ZrS2/MWCNT and exploring their potential for modifying electrodes and detecting indigo carmine dyestuff. Amorphous materials have recently garnered significant attention due to their ability to control material properties through their distinct nature. Transition metal dichalcogenides, or TMDs, are being extensively used in various applications such as catalysis, dye degradation, and so on. Amorphous transition metal sulphides, due to their heightened active sites, exhibit higher performance. This study presents the first-ever successful production of two amorphous metal sulphides that are doped with multi-walled carbon nanotubes. The resulting novel material was used to detect indigo carmine with high efficiency. The detection range was wide, spanning from 0.1 μM to 300.0 μM, and the limit of detection was 0.08 μM. These results demonstrate that the material outperforms most previously reported studies in this field. The technique employed was both simple and innovative, and it was used on both Glassy Carbon Electrode (GCE) and Screen-Printed Electrode (SPE) systems. It was effectively evaluated for the detection of the dye in water samples as well as food and pharmaceutical samples.
Regulation of cancer cell lipid metabolism and oxidative phosphorylation by microenvironmental acidosis
Authors: Rolver Michala G. , Severin Marc , Pedersen Stine F.
Published: August 2024

The expansion of cancer cell mass in solid tumors generates a harsh environment characterized by dynamically varying levels of acidosis, hypoxia, and nutrient deprivation. Because acidosis inhibits glycolytic metabolism and hypoxia inhibits oxidative phosphorylation, cancer cells that survive and grow in these environments must rewire their metabolism and develop a high degree of metabolic plasticity to meet their energetic and biosynthetic demands. Cancer cells frequently upregulate pathways enabling the uptake and utilization of lipids and other nutrients derived from dead or recruited stromal cells, and in particular lipid uptake is strongly enhanced in acidic microenvironments. The resulting lipid accumulation and increased reliance on β-oxidation and mitochondrial metabolism increase susceptibility to oxidative stress, lipotoxicity, and ferroptosis, in turn driving changes that may mitigate such risks. The spatially and temporally heterogeneous tumor microenvironment thus selects for invasive, metabolically flexible, and resilient cancer cells capable of exploiting their local conditions and of seeking out more favorable surroundings. This phenotype relies on the interplay between metabolism, acidosis, and oncogenic mutations, driving metabolic signaling pathways such as peroxisome proliferator-activated receptors (PPARs). Understanding the particular vulnerabilities of such cells may uncover novel therapeutic liabilities of the most aggressive cancer cells.
Electron Spin Resonance Spin Probe Technique for Investigating Non‐TEMPO Radicals Dispersed in Nanospaces of a Crystalline Zn Complex
Authors: Kobayashi Hirokazu , Akiniwa Kento , Iwahori Fumiyasu , Honda Hidehiko , Yamamoto Masato
Published: August 2024

An ESR spin probe technique with non‐TEMPO radicals, such as nitronyl nitroxide (NN), benzonitronyl nitroxide (BzNN), and iminonitroxide (IN) radicals, was used for a porous metal‐organic framework (MOF), [(ZnI2)3(TPT)2] (ZnTPT; TPT = tris(4‐pyridyl)‐1,3,5‐triazine), at room temperature. The principal values of g and hyperfine coupling (A) tensors estimated from spectral reproduction were different from those for organic matrices for some of these radicals. These results indicate that host‐guest interactions occur between the ZnTPT matrix and guest radicals. Thus, when using NN, BzNN, and IN radicals as spin probes for a porous MOF, the interaction between the metal atoms or organic ligands in host materials and guest radicals should be considered. The experimental ESR spectra for the derivatives of NN or BzNN radicals were reproduced only by the rigid‐limit component in the ESR time scale. However, those for the derivatives of IN radicals were approximately reproduced only by rotational diffusion around the z‐axis perpendicular to the plane in the IN group. Interestingly, this reproduction was not around the y‐axis of the principal axes of the g tensors, parallel to the molecular long axis, as previously observed in a few organic matrices. The IN radicals dispersed in the ZnTPT matrix are expected to be accommodated in cylindrical or pseudocylindrical nanospaces sandwiched by the pyridyl or triazine rings of TPT in ZnTPT. These findings show that the ESR spin probe technique using non‐TEMPO radicals can be used to investigate the chemical and biological structures of nanosized materials.
Research on Shortest Path Planning and Smoothing Without Obstacle Collision Based on Moving Carrier
Authors: Di Lingsong , Sun Defeng , Qi Yahui , Xiao Zhicai
Published: August 2024

In response to the challenges of path planning in complex scenarios, to overcome the influence of optimal path determination by the precision of grid map sizes, and to escape the uncertainty in solving by intelligent algorithms, this paper designs a method for obtaining an adjacency matrix based on node planning of shortest path diagrams with polygonal obstacles and then uses the Dijkstra algorithm to get the shortest path. For irregular curved obstacles, an edge straightening method is proposed. To enhance the applicability of the path, this paper introduces the constraint of minimum turning radius. It researches path smoothing under obstacle conditions based on arcs and straight lines, providing practical solutions for different scenarios. Considering the need to maintain a safe distance due to the size of the moving carrier and the deviation in trajectory tracking, this paper conducts an expansion analysis of obstacles. It obtains the trajectory on the arc after edge straight line fitting, followed by further smoothing treatment. The method proposed in this paper demonstrates excellent accuracy and robustness in path planning through simulation verification, proving its practicality and effectiveness in complex environments.
Antifungal, Insecticidal, and Repellent Activities of Rosmarinus officinalis Essential Oil and Molecular Docking of Its Constituents against Acetylcholinesterase and β‐Tubulin
Authors: Houzi Ghizlane , El abdali Youness , Beniaich Ghada , Chebaibi Mohamed , Taibi Mohamed , Elbouzidi Amine , Kaioua Samiha , Asehraou Abdeslam , Addi Mohamed , Chaabane Khalid , Flouchi Rachid , Allali Aimad , Khal-Layoun Soad
Published: August 2024

The aim of this study was to determine the phytochemical composition and evaluate the antifungal and insecticidal properties of Rosmarinus officinalis essential oil (EO). GC‐MS was employed to analyze the phytochemical profile of the EO. The antifungal activity of the EO was assessed by calculating growth inhibition rates for Alternaria alternata, Fusarium oxysporum, and Botrytis cinerea. Repellent capacity and toxicity were evaluated through inhalation and contact tests on Callosobruchus maculatus. Molecular docking techniques were utilized to test the insecticidal and antifungal activities of rosemary EO. The analysis revealed a total of sixteen components in R. officinalis EO, with 1,8‐cineole (40.80%) being the major constituent, followed by α‐pinene (26.18%) and camphor (19.53%). Antifungal evaluation demonstrated a significant inhibitory impact on the mycelial growth of the tested fungi, with complete inhibition observed against B. cinerea. In terms of insecticidal capacity, the EO induced complete mortality of C. maculatus adults at a concentration of 1 μL/L air, with an inhalation test LC50 value of 0.62 μL/L air. Concentration‐dependent reductions were observed in the number of both laid eggs and emerged insects, reaching a 99.36% reduction. The EO also exhibited a moderate effectiveness in repelling insects, with an average repellency rate of 50.83%. In silico analysis identified borneol as the most active molecule against insect acetylcholinesterase (PDB: 6ARY) with a Glide score of −7.254 kcal/mol. α‐Caryophyllene showed the highest activity against B. cinerea β‐tubulin (PDB: 3N2G) with a Glide score of −7.025 kcal/mol. These findings suggest that the EO derived from Moroccan Rosmarinus officinalis has potential as an effective natural agent against pathogenic fungi and could serve as a sustainable and environmentally friendly alternative as a bioinsecticide.
Perspective Exploring Novel Associations of IL‐18 Levels as a Mediator of the Causal Links between Major Depression and Reproductive Health
Authors: Li Mengying , Sun Kaibo , Mei Yunyun , Liu Keyan , Chen Lei , Guo Yihong
Published: August 2024

This research has suggested a link between major depressive disorder (MDD) and infertility, with interleukin‐18 (IL‐18) being proposed as a potential mediator due to its connections to both conditions. A Mendelian randomization (MR) approach was utilized in this study, which drew on genetic data from 500,199 European participants studied for MDD, along with additional IL‐18 and reproductive health data from the FinnGen consortium and GWAS datasets. Single nucleotide polymorphisms were employed as instrumental variables to examine the causal relationships between MDD, genetically predicted IL‐18 levels, and infertility. In our study, bidirectional MR analysis revealed a significant inverse causal relationship between MDD and genetically predicted IL‐18 levels, with a higher genetic predisposition to MDD, correlating with reduced IL‐18 levels (β: −0.40; 95% confidence interval (CI): −0.69 to −0.11; P = 7.09 × 10−3). Additionally, MDD is found to significantly increase the risk of female infertility. Notably, genetically predicted IL‐18 levels demonstrated a protective effect against female infertility (odds ratio (OR): 0.92; 95% CI: 0.86–0.98; P = 1.17 × 10−2). Mediation analysis indicated that genetically predicted IL‐18 levels partially mediated the impact of MDD on female infertility associated with cervical, vaginal, other or unspecified origin, accounting for up to 14.61% of this effect. No evidence of pleiotropy or heterogeneity was detected. The role of genetic predispositions to MDD in influencing genetically predicted IL‐18 levels, and subsequently, female infertility, was highlighted by our study, offering insights into the complex interplay between mental health and reproductive biology. These findings contribute to a deeper understanding of the genetic and molecular pathways influencing these conditions, suggesting new directions for research and potential therapeutic interventions.
Redirecting B7-H3.CAR T Cells to Chemokines Expressed in Osteosarcoma Enhances Homing and Antitumor Activity in Preclinical Models
Authors: Talbot Lindsay J. , Chabot Ashley , Ross Aaron B. , Beckett Alexandra , Nguyen Phuong , Fleming Andrew , Chockley Peter J. , Shepphard Heather , Wang Jian , Gottschalk Stephen , DeRenzo Christopher
Published: August 2024

Purpose:

Clinical efficacy of chimeric antigen receptor (CAR) T cells against pediatric osteosarcoma (OS) has been limited. One strategy to improve efficacy may be to drive chemokine-mediated homing of CAR T cells to tumors. We sought to determine the primary chemokines secreted by OS and evaluate the efficacy of B7-H3.CAR T cells expressing the cognate receptors.

Experimental Design:

We developed a pipeline to identify chemokines secreted by OS by correlating RNA-seq data with chemokine protein detected in media from fresh surgical specimens. We identified CXCR2 and CXCR6 as promising receptors for enhancing CAR T-cell homing against OS. We evaluated the homing kinetics and efficiency of CXCR2- and CXCR6.T cells and homing, cytokine production, and antitumor activity of CXCR2- and CXCR6.B7-H3.CAR T cells in vitro and in vivo.

Results:

T cells transgenically expressing CXCR2 or CXCR6 exhibited ligand-specific enhanced migration over T cells modified with nonfunctional control receptors. Differential homing kinetics were observed, with CXCR2.T-cell homing quickly and plateauing early, whereas CXCR6.T cells took longer to home but achieved a similar plateau. When expressed in B7-H3.CAR T cells, CXCR2- and CXCR6 modification conferred enhanced homing toward OS in vitro and in vivo. CXCR2- and CXCR6-B7-H3.CAR-treated mice experienced prolonged survival in a metastatic model compared with B7-H3.CAR T-cell-treated mice.

Conclusions:

Our patient-based pipeline identified targets for chemokine receptor modification of CAR T cells targeting OS. CXCR2 and CXCR6 expression enhanced the homing and anti-OS activity of B7-H3.CAR T cells. These findings support clinical evaluation of CXCR-modified CAR T cells to improve adoptive cell therapy for patients with OS.
Table S2 from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: August 2024

Primers
Supplementary Data from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: August 2024

Overview of supplementary data
Figure S4 from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: August 2024

M1/M2 macrophages convey differential survival outcomes. M1/M2 gating strategy. CD68 gating of monocytes in culture system.
Figure S1 from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: August 2024

CBX2 binds to promoter regions of cytokine genes and CBX2 is significantly associated with immune signatures.
Figure 4 from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: August 2024

Overexpression of CBX2 leads to an increase in M2-like macrophage activity. A, Diagram of co-culture experimental setup with OVCAR4 CBX2 OE exposed to primary monocytes (from eight unique donors), then analyzed by flow utilizing M1- and M2-like markers. B, Flow cytometry analysis of CBX2 OE compared with control, increase in M2-like macrophages (CD163 and CD206). C and D, Plots of the fold change of M1- and M2-like receptors in control, CBX2 OE, +LPS/INFγ, and IL4/IL10/IL13, in which IL4/IL10/IL13 serves as the control for M2-like stimulation. E, Functional phagocytosis assay of monocytes co-cultured with control OVCAR4 compared with CBX2 OE. F, Functional phagocytosis assay, +LPS (M1 stimulatory) compared with +IL4, +IL10, and +IL13 (M2 stimulatory). Error bars, SEM. Statistical test, unpaired t test. Note: Each dot represents a unique PBMC donor.
Figure 3 from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: August 2024

Modulation of CBX2 leads to shift in macrophage recruitment. A, OVCAR4 CBX2 OE and knockdown confirmation by qPCR. Diagram of protocol with direct co-culture of spheroids with primary monocytes. B, Confocal microscopy with infiltration of monocytes (green) increased with knockdown of CBX2. C, Confocal microscopy with infiltration of monocytes increased with overexpression of CBX2. D, Plots demonstrating the percentage of spheres with monocytes in shCBX2 or overexpression constructs. E, Plots demonstrating the number of spheres with CellTracker-positive monocytes in shCBX2 and overexpression. F, OVCAR4 (control) and CBX2 KO cells co-cultured with fluorescence-tagged primary monocytes (green, white arrowheads). Blue = nuclei. Images (top) are maximum projections of confocal z-stack and form-filling rendering [brown, cancer cells; pink, monocytes (black arrowheads)]. 50-micron grid. G, Quantification of F. H, qPCR of CXCL1 and CXCL8 in siControl (siCTRL) and siCXCL1/siCXCL8. Internal control, HPRT. I, Flow cytometric analysis of digested co-culture spheroids to measure monocyte infiltration. J, Same as F, but with siControl and siCXCL1/8 in cells overexpressing CBX2. K, Quantification of J. Error bars, SEM. Statistical test, unpaired t test and multicomparison ANOVA.
Figure 1 from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: August 2024

CBX2 regulates immune transcriptional profiles. A, Volcano plot of differential gene expression based on shCBX2 vs. shCTRL in the PEO1 cell line. Immunoblot against CBX2 in PEO1 shCTRL and shCBX2 cells. Loading control, β-actin. B, Volcano plot of differential gene expression based on CBX2 KO vs. CTRL in the OVCAR4 cell line. Immunoblot against CBX2 in OVCAR4 CTRL and CBX2 KO. Loading control, β-actin. Asterisks indicate cell lines used for RNA-seq. C, Volcano plot of differential gene expression based on CBX2 OE vs. CTRL in the OVCAR cell line. Immunoblot against CBX2 in OVCAR4 control (CTRL) and CBX2 OE. Loading control, β-actin. D, Overlap of OVCAR4 CBX2 CRISPR knockout vs. OVCAR4 CBX2 OE. Inverse expression top hits: EMT and inflammatory response. E, Evaluation of hallmark pathways identified TNFα signaling via NF-κB inflammatory responses, and IL2 STAT5 signaling pathways. Direct relationship between CBX2 status and CXCL1 and CXCL8 (IL8) noted (black arrows).
Data from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: August 2024

Abstract
Chromobox 2 (CBX2), an epigenetic reader and component of polycomb repressor complex 1, is highly expressed in >75% of high-grade serous carcinoma. Increased CBX2 expression is associated with poorer survival, whereas CBX2 knockdown leads to improved chemotherapy sensitivity. In a high-grade serous carcinoma immune-competent murine model, knockdown of CBX2 decreased tumor progression. We sought to explore the impact of modulation of CBX2 on the tumor immune microenvironment (TIME), understanding that the TIME plays a critical role in disease progression and development of therapy resistance. Exploration of existing datasets demonstrated that elevated CBX2 expression significantly correlated with specific immune cell types in the TIME. RNA sequencing and pathway analysis of differentially expressed genes demonstrated immune signature enrichment. Confocal microscopy and co-culture experiments found that modulation of CBX2 leads to increased recruitment and infiltration of macrophages. Flow cytometry of macrophages cultured with CBX2-overexpressing cells showed increased M2-like macrophages and decreased phagocytosis activity. Cbx2 knockdown in the Trp53-null, Brca2-null ID8 syngeneic murine model (ID8 Trp53−/−Brca2−/−) led to decreased tumor progression compared with the control. NanoString immuno-oncology panel analysis suggested that knockdown in Cbx2 shifts immune cell composition, with an increase in macrophages. Multispectral immunohistochemistry (mIHC) further confirmed an increase in macrophage infiltration. Increased CBX2 expression leads to recruitment and polarization of protumor macrophages, and targeting CBX2 may serve to modulate the TIME to enhance the efficacy of immune therapies.
Significance:
CBX2 expression correlates with the TIME. CBX2 modulation shifts the macrophage population, potentially leading to an immunosuppressive microenvironment, highlighting CBX2 as a target to improve efficacy of immunotherapy.
Single-Cell RNA-Seq Analysis of Hearts in Patients with Fetal Tetralogy of Fallot
Authors: Ding Ye , Zhu Jingai , Xu Geng , Cheng Qing , Zhu Chun
Published: August 2024

Introduction: To explore the cytological characteristics of tetralogy of Fallot (TOF), we collected samples and investigated the differences in the cytological classification between normal fetal hearts and fetal hearts with congenital defects. We then performed single-cell sequencing analysis to search for possible differential genes of disease markers. Methods: Here, the right ventricles of a heart sample with TOF and a healthy human fetal heart sample were analyzed through single-cell sequencing. Data quality control filtering, comparison, quantification, and identification of recovered cells on the raw data were performed using Cell Ranger, thereby ultimately obtaining gene expression matrices for each cell. Subsequently, Seurat was used for cell filtration, standardization, cell subgroup classification, differential expression gene analysis of each subgroup, and marker gene screening. Results: Bioinformatic analysis identified 9,979 and 15,224 cells from the healthy and diseased samples, respectively, with an average read depth of 25,000/cell. The cardiomyocyte cell populations, derived from the abnormal samples identified through the first-level graph-based analysis, were separated into six distinct cell clusters. Conclusion: Our study provides some information on TOF in a fetus, which can offer a new reference for the early detection and treatment of TOF by comparing defective heart cells with normal heart cells.
Real-World Disproportionality Analysis of the Food and Drug Administration Adverse Event Reporting System Database for Asciminib
Authors: Liu Zhijing , Wu Dongzhi , Ke Chengjie , Nian Qichun , Chen Yan , Huang Yaping , Chen Maohua
Published: August 2024

Introduction: Asciminib is primarily utilized for treating Philadelphia chromosome-positive chronic myeloid leukemia in its chronic phase among patients harboring the T315I mutation or those who have been previously treated with at least two tyrosine kinase inhibitors. The safety profile of asciminib across a broad patient population over an extended timeframe remains unverified. This study uses a real-world pharmacovigilance database to evaluate the adverse events (AEs) linked with asciminib, providing valuable insights for clinical drug safety. Methods: Data from the FDA Adverse Event Reporting System (FAERS) database, spanning from October 2021 to December 2023, served as the basis for this analysis. The extent of disproportional events was assessed using sophisticated metrics such as the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean. Results: Within the specified period, the FAERS database documented 3,913,574 AE reports, with asciminib being associated with 966 incidents. Reactions to asciminib spanned 27 system organ categories. Utilizing four distinct analytical algorithms, 663 significant preferred terms exhibiting disproportional frequencies were identified. Notably, this investigation uncovered 26 significant AEs linked to off-label asciminib use, encompassing conditions such as gynecomastia, nephrotic syndrome, orchitis, pyelonephritis, hepatotoxicity, and pancreatitis. The median onset time for asciminib-related AEs was 52.5 days, ranging from 17 to 122.75 days. Conclusion: The study sheds light on additional potential AEs associated with asciminib use, warranting further research to confirm these findings.
The Extract of Humulus japonicus Inhibits Lipogenesis and Promotes Lipolysis via PKA/p38 Signaling
Authors: Sun Jaw Long , Kim Young Jin , Cho Wonjun , Park Sung Su , Abd El-Aty A.M. , Mobarak Enas H. , Jung Tae Woo , Jeong Ji Hoon
Published: August 2024

Introduction: Previous research has shown that an aqueous extract of Humulus japonicus (EH) can ameliorate hypertension, nonalcoholic fatty liver disease, and oxidative stress in adipocytes by activating the thermogenic pathway. However, the effects of an ethanol (30%) extract of EH on obesity are unknown. Methods: Various protein expression levels in fully differentiated 3T3-L1 adipocytes were assessed by Western blotting. Lipid deposition in 3T3-L1 adipocytes was examined by oil red O staining. The MTT assay was used to evaluate adipocyte viability. Caspase 3 activity and glycerol release were determined using commercial assay kits. Results: In this study, we discovered that EH treatment inhibited lipogenesis and promoted lipolysis in both differentiated 3T3-L1 adipocytes and adipose tissue of mice fed a high-fat diet. EH treatment also increased phosphorylated protein kinase A (PKA) levels while reducing p38 phosphorylation. When H89, a PKA inhibitor, was used, the effects of EH on lipogenic lipid accumulation and lipolysis in 3T3-L1 adipocytes were eliminated. Treatment with luteolin 7-O-β-d-glucoside (LU), the major active compound in EH, also suppressed lipid deposition and p38 phosphorylation but enhanced lipolysis in 3T3-L1 adipocytes. These changes were abrogated by H89. Conclusion: These findings indicate that EH containing LU reduces lipogenesis and stimulates lipolysis via the PKA/p38 signaling pathway, leading to an improvement in obesity in mice. Therefore, our study suggested that EH could be a promising therapeutic agent for treating obesity.
Phenotypic Discordance among Siblings with Autosomal Recessive Polycystic Kidney Disease: Case Report and Review of the Literature
Authors: Henein Marc , Russo Felicia , Sentell Zachary T. , Goupil Rémi , Kitzler Thomas M.
Published: August 2024

Missense variants in the PKHD1 gene are associated with the full spectrum of autosomal recessive polycystic kidney disease severity and exhibit variable expressivity. The study of clinical expressivity is limited by the extensive allelic heterogeneity within the PKHD1 gene, which encodes a 4074-amino-acid protein. We report the case of adult siblings with biallelic missense PKHD1 variants, c.4870C>T (p.Arg1624Trp) and c.8206T>G (p.Trp2736Gly), who presented with discordant phenotypes. Patient A developed progressive chronic kidney disease and Caroli syndrome in childhood requiring combined liver and kidney transplantation, while patient B remains minimally affected in the fourth decade of life with normal kidney function and signs of medullary sponge kidney on imaging. We review previously reported cases of phenotypic discordance among siblings and suggest that genotypes composed of at least one hypomorphic missense variant are more likely to lead to phenotypic discordance.
Os fios soltos da história da Arte em ações criativas contemporâneas.
Authors: Rizolli Marcos , Daré Paula Serafim
Published: August 2024

A arte contemporânea rompeu com muitos pressupostos da tradição da história da arte. Este ensaio discorre sobre quatro conceitos que artistas arte contemporâneos se utilizam para fazer releituras de obras consagradas. O texto aborda alguns processos de citação, apropriação, transgressão e intervenção em imagens pretéritas como possibilidade de revisitar cenas da cultura com novas extensões de significados.
Long-Term Incidence of Bradycardia and Pacemaker Implantations Among Cross-Country Skiers: A Cohort Study
Authors: Svedberg Niclas , Sundström Johan , James Stefan , Hållmarker Ulf , Hambraeus Kristina , Andersen Kasper
Published: August 2024

BACKGROUND:

Bradycardia is more common among well-trained athletes than in the general population, but the association with pacemaker implantations is less known. We investigated associations of endurance training with incidence of bradycardia and pacemaker implantations, including sex differences and long-term outcome, in a cohort of endurance trained individuals.

METHODS:

All Swedish skiers who completed >1 race in the cross-country skiing event Vasaloppet between 1989 and 2011 (n=209 108) and a sample of 532 290 nonskiers were followed until first event of bradycardia, pacemaker implantation, or death, depending on end point. The Swedish National Patient Register was used to obtain diagnoses. Cox regression was used to investigate associations of number of completed races and finishing time in Vasaloppet with incidence of bradycardia and pacemaker implantations. In addition, Cox regression was used to investigate associations of pacemaker implantations with death in skiers and nonskiers.

RESULTS:

Male skiers had a higher incidence of bradycardia (adjusted hazard ratio [aHR], 1.19 [95% CI, 1.05–1.34]) and pacemaker implantations (aHR, 1.17 [95% CI, 1.04–1.31]) compared with male nonskiers. Those who completed the most races and had the best performances exhibited the highest incidence. For female skiers in Vasaloppet, the incidence of bradycardia (aHR, 0.98 [95% CI, 0.75–1.30]) and pacemaker implantations (aHR, 0.98 [95% CI, 0.75–1.29]) was not different from that of female nonskiers. The indication for pacemaker differed between skiers and nonskiers, with sick sinus syndrome more common in the former and third-degree atrioventricular block in the latter. Skiers had lower overall mortality rates than nonskiers (aHR, 0.16 [95% CI, 0.15–0.17]). There were no differences in mortality rates by pacemaker status among skiers.

CONCLUSIONS:

In this study, male endurance skiers had a higher incidence of bradycardia and pacemaker implantations compared with nonskiers, a pattern not seen in women. Among male skiers, those who completed the most races and had the fastest finishing times had the highest incidence of bradycardia and pacemaker implantations. Within each group, mortality rates did not differ in relation to pacemaker status. These findings suggest that bradycardia associated with training leads to a higher risk for pacemaker implantation without a detrimental effect on mortality risk.
Association Between Hospital Policy on Local Versus General Anesthesia, and Outcomes of Carotid Endarterectomy
Authors: Kirchhoff Felix , Knappich Christoph , Kallmayer Michael , Bohmann Bianca , Lohe Vanessa , Tsantilas Pavlos , Naher Shamsun , Eckstein Hans‐Henning , Kuehnl Andreas
Published: August 2024

Background

Carotid endarterectomy (CEA) is an established procedure for the treatment of extracranial internal carotid artery stenosis. However, the type of anesthesia during elective CEA is still under debate. This study analyzes the association between the hospital policy on local anesthesia (LA) versus general anesthesia, and the outcome of elective CEA in German hospitals.

Methods

This retrospective analysis is based on the nationwide German statutory carotid quality assurance database for the years 2012 to 2016. Research was funded by Germany's Federal Joint Committee Innovation Fund (funding reference number 01VSF19016). Emergency CEA and carotid stenting procedures were excluded from the analysis. A total of 119 800 patients remained in the analysis. Hospitals were classified on a yearly basis as routine general anesthesia (<10% LA), selective LA (10%–90% LA), or routine LA centers (>90% LA). The primary outcome event was the combined in‐hospital rate of stroke or death. Secondary outcome events were in‐hospital stroke, major stroke or death, death, myocardial infarction, and major adverse cardiovascular events. Univariate and multivariable regression analyses were performed to analyze associations between the primary outcome event and the hospital policy on LA versus general anesthesia as well as clinical or procedural variables.

Results

Patient characteristics did not differ significantly between the groups (age, degree of stenosis, and rate of symptomatic patients). Raw primary outcome event rates were 1.9%, 2.1%, and 1.6% in routine general anesthesia, selective LA, and routine LA centers, respectively. Multivariable analysis revealed a significant lower rate of the primary outcome event for CEA operated under LA (adjusted odds ratio, 0.47 [95% CI, 0.33–0.67];
P
<0.001). Stratified multivariable analysis revealed that the beneficial effect of LA was only present in routine LA centers.

Conclusion

LA is associated with a lower risk of in‐hospital stroke or death after CEA in centers that use LA routinely.
The Transformation of Islamic Property and Evidentiary Law in Colonial-era Morocco: The Case of Shufʿa as Préemption
Authors: Schriber Ari
Published: August 2024

A cornerstone of French land policy in colonial Protectorate Morocco (1912–56) was to restrict jurisdiction of sharīʿa courts while maintaining sharīʿa-based property laws in French courts. This article examines the Islamic property concept of shufʿa (the right of “preemption” or “first-refusal” for co-owned land) as adjudicated in sharīʿa courts and French courts of colonial-era Morocco. Both jurisdictions claimed to uphold the provisions of shufʿa stipulated by the Mālikī legal school of Islamic law; however, the French courts used a codified version—le droit de préemption—while relying on property facts established by the new colonial institution of land registration (Fr., immatriculation foncière; Ar., taḥfīẓ ʿaqārī). By analyzing paradigmatic shufʿa disputes in each jurisdiction, the article argues that evidence and procedure are critical to understanding Islamic law’s encounter with the colonial state. Most importantly, French courts implemented a hybrid version of Islamic property law in which immatriculation supplanted Islamic legal modes of proof making. The French hybrid approach thus constituted a competing version of state sharīʿa that was mutually exclusive with the sharīʿa courts and persisted into the post-colonial period. This discussion more broadly seeks to center property, evidence, and judicial procedure in scholarly narratives concerning twentieth-century Islamic legal history.
New Scheloribates (Acari, Oribatida, Scheloribatidae) from Ethiopia
Authors: ERMILOV SERGEY G. , RYBALOV LEONID B. , KUZMICHEVA EVGENIYA A.
Published: August 2024

Four new species of the genus Scheloribates (Oribatida, Scheloribatidae)—S. (Scheloribates) flexibilis Ermilov sp. nov., S. (S.) monosetosus Ermilov sp. nov., S. (S.) triangulus Ermilov sp. nov., S. (Topobates) tredecim Ermilov sp. nov.—are described, based on adults collected from litter in the afroalpine and bamboo locations in Ethiopia. Scheloribates (S.) flexibilis differs from the related species S. (S.) longisetosus by the length of aggenital, anal and adanal setae and the morphology of setal bothridial head and anterodorsal part of the leg tibia II. Scheloribates (S.) monosetosus differs from the related species S. (S.) concentricus by the length of anal and adanal setae and translamellar line, and the morphology of the setal bothridial head. Scheloribates (S.) triangulus differs from the related species S. (S.) monosetosus by the morphology of ventrodistal part of the leg femora II–IV, number of setae on the leg genu II, the length of the prolamella, and the development of the notogastral seta p1. Scheloribates (T.) tredecim differs from the related species S. (T.) scheloribatoides by the absence of the prolamella, distinctly longer aggenital, anal and adanal setae, and narrower body.
New data on spiders (Arachnida: Araneae) of Iraqi Kurdistan, with new species and records
Authors: ZAMANI ALIREZA , KHUDHUR FARHAD A. , MARUSIK YURI M.
Published: August 2024

Based on a series of specimens collected between 2021 and 2023, this study presents new data on spiders of Iraqi Kurdistan. Despite the small size of the collection (i.e., 74 specimens), the material was found to include five species new to science, which are described and illustrated in this paper: Dysdera goyzha sp. n. (♂♀; Sulaymaniyah) [Dysderidae], D. kurdistanica sp. n. (♂; Sulaymaniyah) [Dysderidae], Palpimanus garmiyanus sp. n. (♂; Sulaymaniyah) [Palpimanidae], Tegenaria sorani sp. n. (♂; Erbil) [Agelenidae], and Zelotes hazarmerdensis sp. n. (♀; Sulaymaniyah) [Gnaphosidae]. Two families (Cheiracanthiidae; Zoropsidae), eleven genera (Agalenatea Archer, 1951 [Araneidae]; Cheiracanthium C.L. Koch, 1839 [Cheiracanthiidae]; Drassodes Westring, 1851 [Gnaphosidae]; Gibbaranea Archer, 1951 [Araneidae]; Mesiotelus Simon, 1897 [Liocranidae]; Micrommata Latreille, 1804 [Sparassidae]; Porrhoclubiona Lohmander, 1944 [Clubionidae]; Rhysodromus Schick, 1965 [Philodromidae]; Steatoda Sundevall, 1833 [Theridiidae]; Trochosa C.L. Koch, 1847 [Lycosidae]; Zoropsis Simon, 1878 [Zoropsidae]) and 18 species are recorded in Iraq for the first time, and five species are newly reported from the Kurdistan Region.
Geography of Knowledge Production in European Urban Studies
Authors: Swianiewicz Paweł , Niedziółka Maria
Published: August 2024

The production of scientific knowledge in urban studies is not evenly distributed. Studies produced in some academic centres are cited more frequently than others and have a larger impact on the academic community. This article traces the spatial concentration of urban studies in European countries over the last decade. On a theoretical level, it refers to the theory of dependent development, distinguishing areas of global core, periphery and semi-periphery, and applying this theory to the production of academic knowledge.Based on the bibliometric data of articles from selected renowned international journals, the article constructs a synthetic index of the centrality of academic knowledge production in urban studies, developed in the academic centres of individual countries. In particular, it draws attention to the peripheral or semi-peripheral position of almost all Central and Eastern European countries.
Transnational and Decolonial Feminist Insights Into the Neoliberalization of Estonian Academia
Authors: Koobak Redi , Marling Raili
Published: August 2024

Since the 1990s Estonia has been characterized by the acceptance of neoliberal values, as an antidote to the Soviet past. Neoliberal practices, like quantification and market- orientation, have permeated most spheres of society, including academia. There has been very little critical reflection on the epistemic inequalities created by this academic model for Estonia as a semi-peripheral country. In this article, the authors aim to place the neoliberalization of academia within a broader framework of colonial practices within global knowledge production, continuing their previous work on the blind spots of transnational feminism  and intersections of feminisms and neoliberalism. Building on insights developed within transnational and decolonial  feminism, the authors propose three interventions into neoliberal academic culture: telling better stories, practicing slow scholarship to tease apart complex colonial entanglements and using creative writing practices.
Retrospective analysis on the occurrence of kidney cysts in mice in a central animal facility in the years 2009–2019
Authors: Becker Katrin
Published: August 2024

Kidney cysts in humans are mainly caused by inheritable polycystic kidney disease. Although they are a regular finding in laboratory mice, their occurrence upon dissection has not been systematically investigated, yet. Therefore, the aim of this report was to investigate on prevalence, phenotype and aetiology of spontaneously occurring kidney cysts in mice by retrospectively analysing the laboratory-receipt tables of the in-house laboratory of a central animal facility in North Rhine-Westphalia, Germany, years 2009–2019. A percentage of 0.4% of dissected mice displayed kidney cysts, with more male than female animals affected and average age equal to that of all dissected animals. Preliminary report in half of the cases was distended abdomen, and a few individuals displayed additional pathologic alterations of kidneys, most commonly dilated renal pelvis, or extrarenal comorbidities. Kidney cysts occurred independently of a renal phenotype of the transgenic strain or presence of infectious agents in health monitoring. To conclude, kidney cysts were characterized as harmless for affected mice but, as inheritability is suggested according with the literature, affected animals should be excluded from breeding.
The Psychopathological Predictors and Effects of Death Anxiety
Authors: Husain Waqar , Malik Manahil Mehmood , Shakeel Amna , Riaz Aliya , Mahnoor  , Jahrami Haitham
Published: August 2024

Death anxiety has been linked to several psychopathological conditions. However, the causes, comorbidity, and differential diagnosis of death anxiety is unexplored. This paper stands out by identifying common predictors of death anxiety and exploring the potential of death anxiety as a predictor for other psychological conditions. The paper reports the findings of four consecutive studies that involved a total of 2291 conveniently selected participants including 861 men and 1430 women. We focused on clarifying both the predictors of death anxiety and the psychopathological consequences emerging from it. Our findings established depression, anxiety, stress, fear of aging, and reduced life satisfaction as predictors of death anxiety. Psychosocial illness, sleep disturbances, aggression, and daily hassles were established as the adverse outcomes of death anxiety. Fear of aging was the most significant predictor of death anxiety and daily hassles emerged as the most significant adverse consequence of death anxiety.