bluuebunny/crossref_metadata_2025 huggingface dataset:
Pliability and Approximating Max-CSPs
Authors: Romero Miguel , Wrochna Marcin , Živný Stanislav
Published: October 2023

We identify a sufficient condition,
treewidth-pliability
, that gives a polynomial-time algorithm for an arbitrarily good approximation of the optimal value in a large class of Max-2-CSPs parameterised by the class of allowed constraint graphs (with arbitrary constraints on an unbounded alphabet). Our result applies more generally to the maximum homomorphism problem between two rational-valued structures.

The condition unifies the two main approaches for designing a polynomial-time approximation scheme. One is Baker’s layering technique, which applies to sparse graphs such as planar or excluded-minor graphs. The other is based on Szemerédi’s regularity lemma and applies to dense graphs. We extend the applicability of both techniques to new classes of Max-CSPs. However, we prove that the condition cannot be used to find solutions (as opposed to approximating the optimal value) in general.

Treewidth-pliability turns out to be a robust notion that can be defined in several equivalent ways, including characterisations via size, treedepth, or the Hadwiger number. We show connections to the notions of fractional-treewidth-fragility from structural graph theory, hyperfiniteness from the area of property testing, and regularity partitions from the theory of dense graph limits. These may be of independent interest. In particular, we show that a monotone class of graphs is hyperfinite if and only if it is fractionally-treewidth-fragile and has bounded degree.
Conceptual Design of Solid-State Li-Battery for Urban Air Mobility
Authors: Toghyani S. , Cistjakov W. , Baakes F. , Krewer U.
Published: October 2023

The negative impact of internal combustion engines on the environment is a major concern in metropolitan areas due to the continued rapid growth and high overall level in the number of vehicles, population, and traffic congestion. Electric vertical take-off and landing (eVTOL) aircraft promises a new era for urban regional transportation and air mobility to address the challenges mentioned above. Nonetheless, providing electrical energy storage systems, like batteries, is one of the key issues with such aircraft. Here, the non-flammable technology of all-solid-state Li batteries with high theoretical gravimetric energy is an attractive option. Modelling allows for a knowledge-driven assessment of the potential of this technology. We here used a combination of a pseudo-2-dimensional cell model with a microstructure surrogate model approach to acquire a better understanding of the effect of the cathode microstructure on the internal process limitations. This model is incorporated into a global optimisation algorithm to predict optimum battery size with respect to the dynamic load demand of eVTOL. When carbon black and active materials are premixed, the battery performs better than when solid electrolyte and active materials are premixed, particularly for low amounts of carbon black in the cathode combination, i.e., 5%. Further, results indicate that future electrification of transportation powertrains would necessitate optimising the composition and distribution of electrode components to fulfil the high demands for power and energy density. By enhancing transport through the microstructure and improving the material’s intrinsic conductivity, it is possible to significantly increase the effective diffusivity and conductivity of ASSB, and hence the mission range.
Tailoring the Properties of Bulk BaTiO3Based Perovskites by Heteroatom-Doping towards Multifunctional Applications: A Review
Authors: Rahman M. Atikur , Hasan Zahid , Islam Jahidul , Das D. K. , Chowdhury Faisal I. , Khandaker Mayeen Uddin , Zabed Hossain M. , Bradley D. A. , Osman Hamid , Ullah Md. Habib
Published: October 2023

Dielectric barium titanate-based perovskite (BaTiO3) has emerged as one of the most popular multilayer ceramic materials for its versatile properties. However, the intrinsic properties, particularly the dielectric, ferroelectric, piezoelectric, and electrical properties of natural barium titanate perovskite (BTP) are not as attractive as required for its multifunctional applications. In recent years, the doping technique has been widely studied for improving the desirable properties of BTP ceramic to expand its practical applications in various advanced technologies. Considering the latest research and developments, this review aims to discuss the synthesis techniques of hetero-atom doped BTP, together with doping status, such as doping sites, doped content, and surface-to-volume ratio. We also critically analyze the effects of co-factors (e.g., sintering temperature, grain size, Curie temperature, and compositions of hetero-atoms) on the structural, and electronic properties of BTP. In addition, optimization of the doping requirements for obtaining the desired improvements of the target properties is also discussed, coupled with providing a comprehensive discussion on the synthesis pathways. Subsequently, diverse applications of the heteroatom-doped BTP are exemplified. Finally, major challenges and future outlooks are highlighted from the perspective of different applications of BTP.
Neuraminidase inhibition improves endothelial function in diabetic mice
Authors: Foote Christopher A. , Ramirez-Perez Francisco I. , Smith James A. , Ghiarone Thaysa , Morales-Quinones Mariana , McMillan Neil J. , Augenreich Marc A. , Power Gavin , Burr Katherine , Aroor Annayya R. , Bender Shawn B. , Manrique-Acevedo Camila , Padilla Jaume , Martinez-Lemus Luis A.
Published: October 2023

This work identifies neuraminidase as a key mediator of endothelial dysfunction in type 2 diabetes that may serve as a biomarker for impaired endothelial function and predictive of development and progression of cardiovascular pathologies associated with type 2 diabetes (T2D). Data show that intervention with the neuraminidase inhibitor zanamivir at effective plasma concentrations may represent a novel pharmacological strategy for restoring the glycocalyx and ameliorating endothelial dysfunction.
Biaxial Tensile Mechanical Properties of HTPB Solid Propellant
Authors: Jin Li , Fang Qinzhi , Yan Xingwei , Hu Qinwei
Published: October 2023

The purpose of this work is to study the effects of different loading rate ratios and loading speeds on the biaxial tension of hydroxyl-terminated polybutadiene (HTPB) solid propellant. A proper kind of biaxial tensile specimen with which the stresses in its central part can be obtained with the loads acted on each loading direction is designed and used in the study, and the strains in its central parts are obtained with the digital image correlation (DIC) method. The stress and strain relationship at each direction can be obtained by experiments. The uniaxial stress vs. strain curves and the biaxial stress vs. strain curves were obtained, and it was found that the loading speed remarkably influenced the biaxial tensile behaviors of HTPB propellant. The Mises equivalent stress and strain could be used to describe the biaxial tension stress and strain state, and the exponential constitutive model obtained in the study could be used to predict the stress vs. strain curve under different test conditions.
Characterizations of Lie
n
-Centralizers on Certain Trivial Extension Algebras
Authors: Li Xiaokui , Yuan He , Zhang Qian
Published: October 2023

In this paper, we describe the structure of Lie

n

-centralizers of a trivial extension algebra. We then present some conditions under which a Lie

n

-centralizer on a trivial extension algebra is proper. As an application, we consider Lie

n

-centralizers on a triangular algebra.
The Effect of Low-Level Indoor Exposure Toluene on Orienting Network
Authors: Zhan Changqing , Pan Liping , Wang Jiajing , Cui Mingrui , Yu Peiran , Liu Jie , Zhang Xin , Wang Zukun , Zhao Lei , Liu Junjie , Song Yijun
Published: October 2023

Objective. The aim is to explore the effect and mechanism of indoor toluene exposure on orienting network. Methods. Twenty-two healthy adults were exposed to 0 ppb, 17.5 ppb, 35 ppb, and 70 ppb toluene for 4 hours, respectively. All subjects underwent attention network behavioral test, and their electroencephalographic activity was recorded simultaneously. The causal connection strengths of orienting network were calculated through direct transform function (DTF) methods. The DTF values of orienting networks among four groups were compared. Results. (1) The DTF values of parietal outflow (DTF_outflow) in 70 ppb toluene condition were higher than those of the 0 ppb, 17.5 ppb, and 35 ppb conditions, respectively. (2) The DTFCZ-FZ and DTFCZ-FP2 values of 70 ppb toluene condition were found to be lower as compared to 0 ppb condition. The DTFCZ-FP2 values of 70 ppb condition were lower as compared to those of the 17.5 ppb condition. Furthermore, DTFP3-FP2, DTFP4-FP1, and DTFP4-FZ values of 70 ppb condition were higher as compared to those of the 0 ppb condition. The DTFP3-FP2 values of 70 ppb condition were higher as compared to those of the 17.5 ppb condition. The DTFP4-FP1 values of the 70 ppb condition were higher as compared to those of the 17.5 and 35 ppb conditions. Conclusion. Even short-term exposure to indoor toluene at low concentrations significantly impacts orienting network.
Examining Dynamics of Emerging Nipah Viral Infection with Direct and Indirect Transmission Patterns: A Simulation-Based Analysis via Fractional and Fractal-Fractional Derivatives
Authors: Li Shuo , Ullah Saif , AlQahtani Salman A. , Asamoah Joshua Kiddy K.
Published: October 2023

In this study, we examine the transmission dynamics of global Nipah virus infection under direct (human-to-human) and indirect (contaminated foods-to-human) transmission routes via the Caputo fractional and fractional-fractal modeling approaches. The model is vigorously analyzed both theoretically and numerically. The possible equilibrium points of the system and their existence are investigated based on the reproduction number. The model exhibits three equilibrium points, namely, infection-free, infected flying foxes free, and endemic. Furthermore, novel numerical schemes are derived for the models in fractional and fractal-fractional cases. Finally, an extensive simulation is conducted to validate the theoretical results and provide an impact of the model on the disease incidence. We believe that this study will help to incorporate such mathematical techniques to examine the complex dynamics and control the spread of such infectious diseases.
Diagnostic Accuracy of Corneal and Epithelial Thickness Map Parameters to Detect Keratoconus and Suspect Keratoconus
Authors: Salman Abdelrahman , Mazzotta Cosimo , Kailani Obeda , Ghabra Marwan , Omran Rana , Balamoun Ashraf Armia , Darwish Taym , Shaaban Rafea , Alhaji Hala
Published: October 2023

Aim. To establish the diagnostic accuracy of corneal and epithelial thickness measurements obtained by spectral‐domain optical coherence tomography (SD‐OCT) in detecting keratoconus (KC) and suspect keratoconus (SKC). Methods. This retrospective study reviewed the data of 144 eyes separated into three groups by the Sirius automated corneal classification software: normal (N) (n = 65), SKC (n = 43), and KC (n = 36). Corneal thickness (CT) and epithelial thickness (ET) in the central (0–2 mm) and paracentral (2–5 mm) zones were obtained with the Cirrus high‐definition OCT. Areas under the curve (AUC) of receiver operator characteristic (ROC) curves were compared across groups to estimate their discrimination capacity. Results. ROC curve analysis revealed excellent predictive ability for ET variables: minimum (Min) ET (0_2), minimum‐maximum (Min‐Max) ET (0_2), superonasal‐inferotemporal (SN‐IT) ET (2_5), Min‐Max ET (2_5), and Min ET (2_5) to detect keratoconus (AUC > 0.9, all). Min‐Max CT (0_2) was the only CT parameter with excellent ability to discriminate between KC and N eyes (AUC = 0.94; cutoff = ≤−32 μm). However, both ET and CT variables were not strong enough (AUC < 0.8, all) to differentiate between SKC and N eyes, with the highest diagnostic power for Min‐Max ET (2_5) (AUC = 0.71; cutoff = ≤−9 μm) and central corneal thickness (CCT) (AUC = 0.76; cutoff = ≤533 μm). Conclusion. These results demonstrate that OCT‐derived CT and ET are able to differentiate between KC and N eyes, with a high level of certainty. However, Min‐Max ET (2_5) was the parameter with the highest ability to detect suspect keratoconus.
Benchmark for Nonlinear Consolidation of a Soil Deposit by Considering Depth-Dependent Initial Effective Pressure
Authors: Wang Lu
Published: October 2023

Analytical solutions for 1D nonlinear consolidation of soils are widely applied to calculate consolidation settlement for their simplicity and convenience. Furthermore, analytical solutions can provide valid benchmark for numerical solutions of nonlinear consolidation. However, the existing analytical solutions for 1D nonlinear consolidation assume the initial effective stress to remain constant in the whole deposit. In practice, the initial effective stress increases with depth in a soil deposit. The existing analytical solutions for 1D nonlinear consolidation are lack of consideration about the variation of initial effective stress along with depth, so there is no benchmark for evaluating the corresponding numerical calculation. In this study, an analytical solution for nonlinear consolidation is developed under a special case, considering the linear increase of initial effective stress with the depth, which provides a benchmark for the corresponding numerical calculation of nonlinear consolidation. To facilitate the verification of the reliability of the numerical calculations of nonlinear consolidation, the pore pressure dissipation curves and settlement curves with time for conditions of PTIB (the case for a permeable top surface and an impermeable bottom surface is referred to as PTIB) and PTPB (the case for a permeable top surface and a permeable bottom surface is named as PTPB) are provided in this paper, thus providing some validation data for future calculations of nonlinear consolidation considering a linear increase in the initial effective stress with depth.
Fast Prediction for Criminal Suspects through Neighbor Mutual Information‐Based Latent Network
Authors: Jhee Jong Ho , Kim Myung Jun , Park Myeonggeon , Yeon Jeongheun , Shin Hyunjung
Published: October 2023

One of the interesting characteristics of crime data is that criminal cases are often interrelated. Criminal acts may be similar, and similar incidents may occur consecutively by the same offender or by the same criminal group. Among many machine learning algorithms, network‐based approaches are well‐suited to reflect these associative characteristics. Applying machine learning to criminal networks composed of cases and their associates can predict potential suspects. This narrows the scope of an investigation, saving time and cost. However, inference from criminal networks is not straightforward as it requires being able to process complex information entangled with case‐to‐case, person‐to‐person, and case‐to‐person connections. Besides, being useful at a crime scene requires urgency. However, predictions from network‐based machine learning algorithms are generally slow when the data is large and complex in structure. These limitations are an immediate barrier to any practical use of the criminal network geared by machine learning. In this study, we propose a criminal network‐based suspect prediction framework. The network we designed has a unique structure, such as a sandwich panel, in which one side is a network of crime cases and the other side is a network of people such as victims, criminals, and witnesses. The two networks are connected by relationships between the case and the persons involved in the case. The proposed method is then further developed into a fast inference algorithm for large‐scale criminal networks. Experiments on benchmark data showed that the fast inference algorithm significantly reduced execution time while still being competitive in performance comparisons of the original algorithm and other existing approaches. Based on actual crime data provided by the Korean National Police, several examples of how the proposed method is applied are shown.
Progressively Enhancing Stemness of Adoptively Transferred T Cells with PI3Kδ Blockade Improves Metabolism and Antitumor Immunity
Authors: Rangel Rivera Guillermo O. , Dwyer Connor J. , Knochelmann Hannah M. , Smith Aubrey S. , Aksoy Bülent Arman , Cole Anna C. , Wyatt Megan M. , Kumaresan Soundharya , Thaxton Jessica E. , Lesinski Gregory B. , Paulos Chrystal M.
Published: October 2023

Generating stem-like memory T cells (TSCM) is a potential strategy to improve adoptive immunotherapy. Elucidating optimal ways to modulate signaling pathways that enrich TSCM properties could identify approaches to achieve this goal. We discovered herein that blocking the PI3Kδ pathway pharmaceutically to varying degrees can generate T cells with increasingly heightened stemness properties, based on the progressive enrichment of the transcription factors Tcf1 and Lef1. T cells with enhanced stemness features exhibited metabolic plasticity, marked by improved mitochondrial function and glucose uptake after tumor recognition. Conversely, T cells with low or medium stemness were less metabolically dynamic, vulnerable to antigen-induced cell death, and expressed more inhibitory checkpoint receptors. Only T-cell receptor–specific or chimeric antigen receptor (CAR)-specific T cells with high stemness persisted in vivo and mounted protective immunity to tumors. Likewise, the strongest level of PI3Kδ blockade in vitro generated human tumor-infiltrating lymphocytes and CAR T cells with elevated stemness properties, in turn bolstering their capacity to regress human solid tumors. The stemness level of T cells in vitro was important, ultimately impacting their efficacy in mice bearing three distinct solid tumors. Lef1 and Tcf1 sustained antitumor protection by donor high CD8+ TSCM or CD4+ Th17SCM, as deletion of either one compromised the therapeutic efficacy. Collectively, these findings highlight the importance of strategic modulation of PI3Kδ signaling in T cells to induce stemness and lasting protective responses to solid tumors.

Significance:

Elevating T-cell stemness by progressively blocking PI3Kδ signaling during ex vivo manufacturing of adoptive cell therapies alters metabolic and functional properties to enhance antitumor immunity dependent on Tcf1 and Lef1.
Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: October 2023

Purpose:

In the CASPIAN trial, first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small cell lung cancer (ES-SCLC). We report exploratory analyses of CASPIAN outcomes by programmed cell death ligand-1 (PD-L1) expression and tissue tumor mutational burden (tTMB).

Experimental Design:

Patients were randomized (1:1:1) to durvalumab (1,500 mg) plus EP, durvalumab plus tremelimumab (75 mg) plus EP, or EP alone. Treatment effects in PD-L1 and tTMB subgroups were estimated using an unstratified Cox proportional hazards model.

Results:

The PD-L1 and tTMB biomarker-evaluable populations (BEP) comprised 54.4% (438/805) and 35.2% (283/805) of the intention-to-treat population, respectively. PD-L1 prevalence was low: 5.7%, 25.8%, and 28.3% had PD-L1 expression on ≥1% tumor cells (TC), ≥1% immune cells (IC), and ≥1% TCs or ICs, respectively. OS benefit with durvalumab plus EP versus EP was similar across PD-L1 subgroups, with HRs all falling within the 95% confidence interval (CI) for the PD-L1 BEP (0.47‒0.79). OS benefit with durvalumab plus tremelimumab plus EP versus EP was greater in PD-L1 ≥1% versus <1% subgroups, although CIs overlapped. There was no evidence of an interaction between tTMB and treatment effect on OS (durvalumab plus EP vs. EP, P = 0.916; durvalumab plus tremelimumab plus EP vs. EP, P = 0.672).

Conclusions:

OS benefit with first-line durvalumab plus EP in patients with ES-SCLC was observed regardless of PD-L1 or tTMB status. PD-L1 expression may prove to be a useful biomarker for combined treatment with PD-(L)1 and CTLA-4 inhibition, although this requires confirmation with an independent dataset.

See related commentary by Rolfo and Russo, p. 652
Fibroblast Activation Protein-Targeted Radioligand Therapy with 177Lu-EB-FAPI for Metastatic Radioiodine-Refractory Thyroid Cancer: First-in-Human, Dose-Escalation Study
Authors: Fu Hao , Huang Jingxiong , Zhao Tianzhi , Wang Hongjian , Chen Yuhang , Xu Weizhi , Pang Yizhen , Guo Wei , Sun Long , Wu Hua , Xu Pengfei , Su Bishan , Zhang Jingjing , Chen Xiaoyuan , Chen Haojun
Published: October 2023

Purpose:

Fibroblast activation protein (FAP) is a promising target for tumor treatment. In this study, we aimed to investigate the safety and efficacy of the albumin binder-conjugated FAP-targeted radiopharmaceutical, 177Lu-EB-FAPI (177Lu-LNC1004), in patients with metastatic radioiodine-refractory thyroid cancer (mRAIR-TC).

Patients and Methods:

This open-label, non-randomized, first-in-human, dose-escalation, investigator-initiated trial had a 3+3 design and involved a 6-week 177Lu-LNC1004 treatment cycle in patients with mRAIR-TC at 2.22 GBq initially, with subsequent cohorts receiving an incremental 50% dose increase until dose-limiting toxicity (DLT) was observed.

Results:

177Lu-LNC1004 administration was well tolerated, with no life-threatening adverse events observed. No patients experienced DLT in Group A (2.22 GBq/cycle). One patient experienced grade 4 thrombocytopenia in Group B (3.33 GBq/cycle); hence, another three patients were enrolled, none of whom experienced DLT. Two patients experienced grade 3 and 4 hematotoxicity in Group C (4.99 GBq/cycle). The mean whole-body effective dose was 0.17 ± 0.04 mSv/MBq. Intense 177Lu-LNC1004 uptake and prolonged tumor retention resulted in high mean absorbed tumor doses (8.50 ± 12.36 Gy/GBq). The mean effective half-lives for the whole-body and tumor lesions were 90.20 ± 7.68 and 92.46 ± 9.66 hours, respectively. According to RECIST, partial response, stable disease, and progressive disease were observed in 3 (25%), 7 (58%), and 2 (17%) patients, respectively. The objective response and disease control rates were 25% and 83%, respectively.

Conclusions:

FAP-targeted radioligand therapy with 177Lu-LNC1004 at 3.33 GBq/cycle was well tolerated in patients with advanced mRAIR-TC, with high radiation dose delivery to the tumor lesions, encouraging therapeutic efficacy, and acceptable side effects.
Supplementary Table 5 from Piperacetazine Directly Binds to the PAX3::FOXO1 Fusion Protein and Inhibits Its Transcriptional Activity
Authors: Nakazawa Kay , Shaw Taryn , Song Young K. , Kouassi-Brou Marilyn , Molotkova Anna , Tiwari Purushottam B. , Chou Hsien-Chao , Wen Xinyu , Wei Jun S. , Deniz Emre , Toretsky Jeffrey A. , Keller Charles , Barr Frederic G. , Khan Javed , Üren Aykut
Published: October 2023

Supplementary Table 5
Supplementary Figure 2 from Piperacetazine Directly Binds to the PAX3::FOXO1 Fusion Protein and Inhibits Its Transcriptional Activity
Authors: Nakazawa Kay , Shaw Taryn , Song Young K. , Kouassi-Brou Marilyn , Molotkova Anna , Tiwari Purushottam B. , Chou Hsien-Chao , Wen Xinyu , Wei Jun S. , Deniz Emre , Toretsky Jeffrey A. , Keller Charles , Barr Frederic G. , Khan Javed , Üren Aykut
Published: October 2023

Luciferase assay performed to measure the effect of piperacetazine on PAX7::FOXO1 activity.
The ERBB2 Exonic Variant Pro1170Ala Modulates Mitogen-Activated Protein Kinase Signaling Cascades and Associates with Allergic Asthma
Authors: Sio Yang Yie , Gan Wei Liang , Ng Wing Shan , Matta Sri Anusha , Say Yee-How , Teh Keng Foo , Wong Yi Ru , Rawanan Shah Smyrna Moti , Reginald Kavita , Chew Fook Tim
Published: October 2023

Introduction: Previous studies have indicated the ERBB2 genetic variants in the 17q12 locus might be associated with asthma; however, the functional effects of these variants on asthma risk remain inconclusive. This study aimed to characterize the functional roles of asthma-associated ERBB2 single nucleotide polymorphisms (SNPs) in asthma pathogenesis by performing genetic association and functional analysis studies. Methods: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). Genotype-phenotype associations were assessed by performing a genotyping assay on n = 4,348 ethnic Chinese individuals from the SMCSGES cohort. The phosphorylation levels of receptors and signaling proteins in the MAPK signaling cascades, including ErbB2, EGFR, and ERK1/2, were compared across the genotypes of asthma-associated SNPs through in vitro and ex vivo approaches. Results: The ERBB2 tag-SNP rs1058808 was significantly associated with allergic asthma, with the allele “G” identified as protective against the disease (adjusted logistic p = 6.56 × 10−9, OR = 0.625, 95% CI: 0.544–0.718). The allele “G” of rs1058808 resulted in a Pro1170Ala mutation that results in lower phosphorylation levels of ErbB2 in HaCat cells (p < 0.001), whereas the overall ERBB2 mRNA expression and the phosphorylation levels of EGFR remained unaffected. In the SMCSGES cohort, individuals carrying the genotype “GG” of rs1058808 had lower phosphorylated ERK1/2 proteins in the MAPK signaling cascade. A lower phosphorylation level of ERK1/2 was also associated with reduced asthma risk. Conclusions: The present findings highlighted the involvement of a functional exonic variant of ERBB2 in asthma development via modulating the MAPK signaling cascade.
Disrupted Binding of Cystathionine γ-Lyase to p53 Promotes Endothelial Senescence
Authors: Hu Jiong , Leisegang Matthias S. , Looso Mario , Drekolia Maria-Kyriaki , Wittig Janina , Mettner Janina , Karantanou Christina , Kyselova Anastasia , Dumbović Gabrijela , Li Xiaoming , Li Yuanyuan , Guenther Stefan , John David , Siragusa Mauro , Zukunft Sven , Oo James A. , Wittig Ilka , Hille Susanne , Weigert Andreas , Knapp Stefan , Brandes Ralf P. , Müller Oliver J. , Papapetropoulos Andreas , Sigala Fragiska , Dobreva Gergana , Kojonazarov Baktybek , Fleming Ingrid , Bibli Sofia-Iris
Published: October 2023

BACKGROUND:

Advanced age is unequivocally linked to the development of cardiovascular disease; however, the mechanisms resulting in reduced endothelial cell regeneration remain poorly understood. Here, we investigated novel mechanisms involved in endothelial cell senescence that impact endothelial cell transcription and vascular repair after injury.

METHODS:

Native endothelial cells were isolated from young (20±3.4 years) and aged (80±2.3 years) individuals and subjected to molecular analyses to assess global transcriptional and metabolic changes. In vitro studies were conducted using primary human and murine endothelial cells. A murine aortic re-endothelialization model was used to examine endothelial cell regenerative capacity in vivo.

RESULTS:

RNA sequencing of native endothelial cells revealed that aging resulted in p53-mediated reprogramming to express senescence-associated genes and suppress glycolysis. Reduced glucose uptake and ATP contributed to attenuated assembly of the telomerase complex, which was required for endothelial cell proliferation. Enhanced p53 activity in aging was linked to its acetylation on K120 due to enhanced activity of the acetyltransferase MOZ (monocytic leukemic zinc finger). Mechanistically, p53 acetylation and translocation were, at least partially, attributed to the loss of the vasoprotective enzyme, CSE (cystathionine γ-lyase). CSE physically anchored p53 in the cytosol to prevent its nuclear translocation and CSE absence inhibited AKT (Protein kinase B)-mediated MOZ phosphorylation, which in turn increased MOZ activity and subsequently p53 acetylation. In mice, the endothelial cell–specific deletion of CSE activated p53, induced premature endothelial senescence, and arrested vascular repair after injury. In contrast, the adeno-associated virus 9–mediated re-expression of an active CSE mutant retained p53 in the cytosol, maintained endothelial glucose metabolism and proliferation, and prevented endothelial cell senescence. Adenoviral overexpression of CSE in native endothelial cells from aged individuals maintained low p53 activity and reactivated telomerase to revert endothelial cell senescence.

CONCLUSIONS:

Aging-associated impairment of vascular repair is partly determined by the vasoprotective enzyme CSE.
Resolvin E1/ChemR23 Protects Against Hypertension and Vascular Remodeling in Angiotensin II–Induced Hypertensive Mice
Authors: Zhang Jishou , Yin Zheng , Xu Yao , Wei Cheng , Peng Shanshan , Zhao Mengmeng , Liu Jianfang , Xu Shuwan , Pan Wei , Zheng Zihui , Liu Siqi , Ye Jing , Qin Juan-Juan , Wan Jun , Wang Menglong
Published: October 2023

BACKGROUND:

Inflammation plays a critical role in the development of hypertension and vascular remodeling. Resolvin E1 (RvE1), as one of the specialized proresolving lipid mediators, promotes inflammation resolution by binding with a G protein-coupled receptor, ChemR23 (chemerin receptor 23). However, whether RvE1/ChemR23 regulates hypertension and vascular remodeling is unknown.

METHODS:

Hypertension in mice was induced by Ang II (angiotensin II) infusion (750 ng/kg per minute), and RvE1 (2 µg/kg per day) was administered through intraperitoneal injection. Loss of ChemR23 was achieved by mice receiving intravenous injection of adeno-associated virus 9-encoding shRNA against ChemR23.

RESULTS:

Aortic ChemR23 expression was increased in Ang II-induced hypertensive mice and that ChemR23 was mainly expressed on vascular smooth muscle cells (VSMCs). RvE1 lowered blood pressure, reduced aortic media thickness, attenuated aortic fibrosis, and mitigated VSMC phenotypic transformation and proliferation in hypertensive mice, which were all reversed by the knockdown of ChemR23. Moreover, RvE1 reduced the aortic infiltration of macrophages and T cells, which was also reversed by ChemR23 knockdown. RvE1 inhibited Ccl5 expression in VSMCs via the AMPKα (AMP-activated protein kinase α)/Nrf2 (nuclear factor E2-related factor 2)/canonical NF-κB (nuclear factor κB) pathway, thereby reducing the infiltration of macrophages and T cells. The AMPKα/Nrf2 pathway also mediated the effects of RvE1 on VSMC phenotypic transformation and proliferation. In patients with hypertension, the serum levels of RvE1 and other eicosapentaenoic acid-derived metabolites were significantly decreased.

CONCLUSIONS:

RvE1/ChemR23 ameliorated hypertension and vascular remodeling by activating AMPKα/Nrf2 signaling, which mediated immune cell infiltration by inhibiting the canonical NF-κB/Ccl5 pathway, and regulated VSMC proliferation and phenotypic transformation. RvE1/ChemR23 may be a potential therapeutic target for hypertension.
A Further Note on the Alleged Egyptian Etymology of Sabaoth
Authors: Theis Christoffer
Published: October 2023

This note provides further arguments against a proposed Egyptian etymology of the divine name or title צְבָאוֹת (ṣᵉbāʾōt), as initially proposed by Manfred Görg, and expands a recent article by Giuseppina Lenzo and Christophe Nihan.
“Clitic climbing” in Hittite
Authors: Sideltsev Andrei V.
Published: October 2023

Cross-linguistically, clitic climbing occurs when clitics that belong syntactically and semantically to the subordinate clause (most commonly non-finite, rarely finite) appear in the main clause, i.e., they climb out of the subordinate clause into the main clause. In Hittite, prototypical clitic climbing is attested in two constructions: with non-finite predicates and finite restructuring verbs (Lyutikova & Sideltsev 2021b); and in serial constructions with the finite motion verbs pai- ‘go’ and uwa- ‘come’ co-occurring with another finite verb in the same clause (Koller 2013). In both of these cases, clitics climb out of complements of finite verbs. This paper explores yet another potentially relevant context for clitic climbing, a particular type of complex sentence that may be called ‘mismatch sentences’ (Sideltsev 2023). These involve three structurally distinct types of complex sentences which share one common property: they all have the same surface structure (1a) one word of the main clause (2) subordinate clause (1b) rest of the main clause. The enclitics of the subordinate clause are in (1a), so that they appear to climb out of the subordinate into the main clause. The enclitics of the main clause are consistently in the rest of the main clause (1b), never attached to the first word of the main clause (1a). Structurally, all these subordinate clauses adjoin to the main clause. This distribution of clitics is attested only if there is a one-word constituent in the main clause to the left of the subordinate clause. As movement out of adjoined clauses is held to be illicit in current linguistic theory, it is argued that, differently from prototypical clitic climbing, this is a purely post-syntactic reordering and does not involve any kind of syntactic movement of clitics out of the subordinate into the main clause: the structure one-word constituent of main clause—subordinate clause—main clause is always prosodically realized at the post-syntactic stage as subordinate clause—main clause.
Chronic Rhinosinusitis After Maxillary Advancement Orthognathic Surgery
Authors: Ibrahim Nour , Hwang Peter H. , Jitaroon Kawinyarat , Tyler Matthew A.
Published: October 2023

Introduction:

Maxillomandibular advancement (MMA) remains an effective procedure for the management of obstructive sleep apnea (OSA). Maxillary advancement may lead to anatomical changes that impair paranasal sinus drainage, leading to chronic sinus inflammation. The aim of this study was to describe the clinical features and outcomes of patients suffering from chronic rhinosinusitis (CRS) following MMA.

Methods:

This is a retrospective case series study. Our study included subjects diagnosed with CRS following MMA from January 1992 to October 2018 at Stanford Hospital. We screened 730 patients undergoing MMA and identified a total of 57 with CRS after MMA. A descriptive analysis was performed using clinical data including patient demographics, comorbidities, prior surgical history, physical exam manifestations, CT findings, and quality of life outcomes (SNOT-22).

Results:

Out of 730 patients undergoing MMA, 57(7.8%) were found to have CRS after orthognathic surgery. Presenting symptoms included facial pain (92.5%), nasal drainage (75%), nasal obstruction (67.5%), and hyposmia (20%). Endoscopic examination revealed recirculation (30.5%), purulent discharge (27.7%), polypoid changes (22.2%), and scarring (13.8%). Preoperative CT prior to undergoing endoscopic sinus surgery (ESS) demonstrated mucosal thickening in maxillary (64.2%), anterior ethmoid (39.2%), frontal (14.2%), posterior ethmoid (10.7%), sphenoid sinus (14.2%), and ostiomeatal complex (55.3%). Average Lund-Mackay score was 5.5(±3.8). Additional CT findings included secondary ostium in the inferior meatus (42.8%). Forty patients (70.1%) underwent ESS at a mean of 4.6 years after MMA. Patients undergoing ESS experienced significant improvement in SNOT-22 scores at 12-months post-surgery ( P = .018).

Conclusion:

Patients undergoing maxillary advancement surgery are at risk of developing CRS postoperatively and should be advised of the risk of CRS associated with this procedure. Surgical treatment can be an option for medically refractory CRS related to MMA surgery.
“The girl conductor has come to stay”: Gender and labour on the buses in interwar Australia
Authors: Robertson Emma
Published: October 2023

In the early 1920s, “Lady Bus Conductors” were recruited for the first time in Melbourne, Australia. They were employed by private companies, who entered into competition with the public-funded urban transport sector. Combining labour and cultural history approaches, this article draws on newspapers, photographs and union archives to develop an original gendered analysis of the interwar motorbus industry. It argues that women's labour underpinned the creation of feminised traits of service, safety and aesthetics on this new mode of transport. Such traits were successfully commercialised by private operators at the same time as they benefitted from “traditions” of women's lower wages. When the public sector reasserted control over metropolitan transport, they defined the buses as “men's work”, with long-lasting implications. Yet as this article reveals, some women continued to seek employment on private buses, claiming access to elements of the economic, social and cultural status of uniformed transport work.
Early transthoracic echocardiography and long-term mortality in moderate- to-severe acute respiratory distress syndrome: An analysis of the Medical Information Mart for Intensive Care database
Authors: Liu Qiuyu , Tang Yingkui , Tao Wu , Tang Ze , Wang Hongjin , Nie Shiyu , Wang Nian
Published: October 2023

Background

The clinical use of transthoracic echocardiography (TTE) in patients with acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) has dramatically increased, its impact on long-term prognosis in these patients has not been studied. This study aimed to explore the effect of early-TTE on long-term mortality in patients with moderate-to-severe ARDS in ICU.

Methods

A total of 2833 patients with moderate-to-severe ARDS who had or had not received early-TTE were obtained from the Medical Information Mart for Intensive Care (MIMIC-III) database after imputing missing values by a random forest model, patients were divided into early-TTE group and non-early-TTE group according to whether they received TTE examination in ICU. A variety of statistical methods were used to balance 41 covariates and increase the reliability of this study, including propensity score matching, inverse probability of treatment weight, covariate balancing propensity score, multivariable regression, and doubly robust estimation. Chi-Square test and t-tests were used to examine the differences between groups for categorical and continuous data, respectively.

Results

There was a significant improvement in 90-day mortality in the early-TTE group compared to non-early-TTE group (odds ratio  =  0.79, 95% CI: 0.64–0.98, p-value  =  0.036), revealing a beneficial effect of early-TTE. Net-input was significantly decreased in the early-TTE group on the third day of ICU admission and throughout the ICU stay, compared with non-early-TTE group (838.57 vs. 1181.89 mL, p-value  =  0.014; 4542.54 vs. 8025.25 mL, p-value  =  0.05). There was a significant difference in the reduction of serum lactate between the two groups, revealing the beneficial effect of early-TTE (0.59 vs. 0.83, p-value  =  0.009). Furthermore, the reduction in the proportion of acute kidney injury demonstrated a correlation between early-TTE and kidney protection (33% vs. 40%, p-value < 0.001).

Conclusions

Early application of TTE is beneficial to improve the long-term mortality of patients with moderate-to-severe ARDS.
Eroding Inclusions and Expanding Exclusions: Education During Pandemics
Authors: Purkayastha Bandana
Published: October 2023

The global COVID-related pandemic ushered in high death rates globally, initiated lockdowns of international boundaries and internal borders in countries and regions, and abruptly mandated home-based work for a large swath of professions. This paper focuses on disruptions and dislocations associated with the pandemic to discuss the structures of inequality revealed during this period. I emphasise that the meanings of education, its organisational structures, the tools and sites associated with this work were already changing; the pandemic provided the window to significantly enhance the pace and depth of the shifts.
The Gender Studies Classroom: Its Promise and Discontents
Authors: Sreenivas Deepa
Published: October 2023

This paper explores a unique set of existential and ideological difficulties associated with teaching ‘gender’ in a women’s studies department while drawing on the pedagogic experiences of academics and colleagues teaching gender/feminism in more mainstream departments like sociology. It looks at the gender studies classroom as a transformative space where entrenched systems of beliefs, institutional arrangements and gendered relationships can be contested and rendered unstable. Simultaneously, it remains a space fraught with conflicts, confrontations and vulnerabilities for students and teachers alike. While ‘gender’ as a relational category marks a shift from ‘woman’ as a biological/essentialist/reductionist concept, I argue that the transition from women’s studies to gender studies has not been adequately grappled with. Woman/gender is caught between contending and contingent forces—the legacy of the autonomous women’s movement with its activist thrust, the NGOised/empowerment discourse with a top-down, instrumentalised approach to ‘gender’, and the heterogeneous aspirations and politics of gender transgressive and socially marginalised student constituencies. The gender studies teacher must navigate these complexities which on occasion confront and trouble her/their own gendered sense of self and precarities.
Impact of CEO's Digital Technology Orientation and Board Characteristics on Firm Value: A Signaling Perspective
Authors: Filatotchev Igor , Lanzolla Gianvito , Syrigos Evangelos
Published: October 2023

Integrating signaling research with the institutional perspective on capital markets, we argue that, in conditions of radical technological change, investor perceptions about firm value are enhanced by the CEO's orientation toward digital technologies that exceeds the firm's industry peers. This base relationship is moderated by board characteristics so that the board members’ digital expertise and knowledge diversity enhance the effect of the CEO's relative digital technology orientation on firm value. Furthermore, the monitoring power of independent board members who do not have digital expertise negatively moderates our baseline hypothesis, whereas board monitoring exerted by independent board members with digital expertise has a positive moderating effect. To test our theory, we use advanced natural language processing techniques to develop the CEO's relative digital technology orientation construct combined with a unique, hand-collected set of measures associated with board members’ digital expertise and knowledge diversity in a sample of S&P 500 companies. Our article offers novel insights on how technology-related signals associated with the CEO's communications to shareholders interact with board characteristics in determining investor perceptions of the firm's value in conditions of high technological uncertainty.
Europe in the Indo-Pacific: Economic, security, and normative engagement
Authors: Abbondanza Gabriele , Wilkins Thomas
Published: October 2023

The Indo-Pacific has rapidly become the world’s geopolitical and geo-economic epicentre. Consequently, much scholarly attention has been focused on Sino–United States superpower competition and on the policies of the region’s great and middle powers. However, since Europe has engaged late with the Indo-Pacific, its policies remain under-examined. This Special Issue fills a lacuna in our knowledge through a dedicated appraisal of German, British, Italian, and European Union approaches to the Indo-Pacific. This introductory article provides an analytical survey of the impetus for Europe’s new awareness of the Indo-Pacific’s importance. It then sheds light on the European approach based on a tripartite framework comprising economy, security, and norms, which is adopted by all the articles in this Special Issue to draw out comparative insights. This research thus contributes to the literature on both European and Indo-Pacific strategic landscapes by examining an understudied development under a novel joint assessment.
Toward a dialogical sociology: Presidential address – XX ISA World Congress of Sociology 2023
Authors: Hanafi Sari
Published: October 2023

In the first quarter of the twenty-first century, the entangled pathologies of late modernity are increasingly revealing themselves in a simultaneous: (1) emergence of authoritarianism in the South and Right populism in the North that is gaining momentum year after year; (2) rising trends of inequality, precarity, and exclusion; and (3) hierarchical social polarizations are emerging in more and more societies. How do, and how should, the social sciences, and particularly sociology, react to these pathologies of late modernity? I would argue that the bulk of the responses of the social sciences and/or sociology to these pathologies are defined as being classically liberal but politically illiberal – I call this peculiar combination ‘Symbolic Liberalism’. To address the inherent problems with Symbolic Liberalism and as an alternative to it, I propose Dialogical Sociology as a form of balance between collective and individual political liberal project.
Gentiopicroside ameliorates CCl4-induced liver injury in mice by regulating the PPAR-γ/Nrf2 and NF-κB/IκB signaling pathways
Authors: Zhang Yun , Pan Shiguang , Yi Shiming , Sun Jin , Wang Haitao
Published: October 2023

Objective

This study explored the mechanisms by which gentiopicroside protects against carbon tetrachloride (CCl4)-induced liver injury.

Methods

Male mice were randomly assigned to the control; CCl4; bifendate 100 mg/kg; or gentiopicroside 25, 50, or 100 mg/kg groups. Both vehicle and drugs were administered intragastrically for 7 days. Mice were administered CCl4 intraperitoneally 1 hour after the last drug dose. After 24 hours, we collected blood and liver samples for testing.

Results

Gentiopicroside significantly reduced serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase activities with corresponding reductions in hepatocyte denaturation and necrosis. Gentiopicroside enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and glutathione levels and reduced heme oxygenase 1 (HO-1) activity and malondialdehyde levels in the liver, and these effects were attributed to peroxisome proliferator-activated receptor (PPAR)-γ/nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Meanwhile, gentiopicroside significantly downregulated HO-1 and upregulated SOD and GSH-Px at the mRNA level in the liver. Furthermore, gentiopicroside significantly suppressed serum tumor necrosis factor-α and interleukin-1β secretion, which was associated with the inhibition of nuclear factor-kappa B (NF-κB)/inhibitor of NF-κB (IκB).

Conclusions

Gentiopicroside ameliorated CCl4-induced liver injury in mice via the PPAR-γ/Nrf2 and NF-κB/IκB pathways.
Model for the Evaluation of Urban Transport Policies and Their Interaction with the Housing Market
Authors: Kilani Moez , Zerguini Seghir
Published: October 2023

We analyze several scenarios of transport reforms for the city of Bordeaux (France) using a model that takes into account the interaction between transport and the housing market. We find that road pricing schemes are significantly more effective when they are accompanied by an increase in housing supply in locations where demand increases. This allows households to consider their options for relocation in the medium and long term. Our analysis is based on an aggregate model with a nested decision structure that includes both transport and housing. We provide a full description of the model structure and the calibration steps and make the source code available for those who wish to analyze other cases.