bluuebunny/crossref_metadata_2025 huggingface dataset:
Zn2+@Polyvinylpyrrolidone and Urushiol Preparation of Nanofibrous Membranes and Their Synergistic Effect
Authors: Shiu Bing‐Chiuan , Wulin Shihan , Yuan Qian‐Yu , Zhang Ying , Yu Zhicai
Published: July 2023

In this study, lacquer is gathered from a lacquer tree and rotary evaporation is used to remove impurities to obtain urushiol. Next, 10 mL of anhydrous ethanol serves as the solvent for blending polyvinylpyrrolidone (PVP) at a specified content (0.7 g and 0.2–0.7 g urushiol) to form an electrospinning solution. Electrospinning is carried out with a voltage of 18 kV to prepare PVP/urushiol nanofibrous membranes. At a ratio of 7/4, the PVP/urushiol nanofibrous membranes are not eroded in 98% sulfuric acid and these membranes also demonstrate a 50–60% antibacterial effect against Staphylococcus aureus and Escherichia coli. Moreover, the antibacterial effect can be boosted to 98% with the incorporation of zinc ions. The results indicate that anhydrous ethanol can remove the sensitization of urushiol from PVP/urushiol membranes. Furthermore, animal test results indicate that when rats are in contact with PVP/urushiol anhydrous ethanol for 48 h, their skins are free from dark brown skin allergy. The presence of PVP eliminates the sensitization of urushiol, and the nanofibrous membranes demonstrate low toxicity. Hence, urushiol is the only natural material that enables PVP to withstand 98% sulfuric acid as well as acquire hydrolyzability, thereby qualify PVP as a medical material.
A pilot study of camrelizumab with docetaxel and cisplatin for the first line treatment in recurrent/metastatic oral squamous cell carcinoma
Authors: Ju Houyu , Wei Dongliang , Wu Yunteng , Liu Yang , Ding Qi , Rui Mengyu , Fan Zongyu , Yao Yanli , Hu Jingzhou , Ren Guoxin
Published: July 2023

Pembrolizumab with cisplatin and 5‐fluorouracil showed survival benefit but relatively high occurrence of treatment‐related adverse events (TRAEs) for recurrent/metastatic oral squamous cell carcinoma (R/M OSCC). A more tolerable regime is needed. This trial enrolled 20 R/M OSCC patients with previously untreated and PD‐L1 positive. Patients were administered camrelizumab with docetaxel and cisplatin every 3 weeks for six cycles, followed by camrelizumab monotherapy every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was occurrence of grade ≥ 3 TRAEs, secondary endpoints included overall survival (OS), progression‐free survival (PFS), and overall response rate (ORR). 45% patients experienced grade ≥ 3 TRAEs, which the most common were anemia (15%), stomatitis (15%), and neutropenia (10%). The most common potential immune‐related adverse events were reactive cutaneous capillary endothelial proliferation (RCCEP; 60%), hypothyroidism (35%), and pneumonitis (15%). No treatment‐related deaths occurred. The median OS, PFS, and ORR was 14.4 months, 5.35 months, and 40.0% respectively. The study also found RCCEP occurrence, lower FOXP3+ cells, and higher density of intratumor tertiary lymphoid structure were associated with improved efficacy. Our data suggest that camrelizumab with docetaxel/cisplatin as first‐line therapy was well tolerable and had potentially favorite efficacy in PD‐L1‐positive patients with R/M OSCC.
Regularity criteria for 3D shear‐thinning fluids in terms of two components of vorticity
Authors: Sin Cholmin , Pak Jisong , Baranovskii Evgenii S.
Published: July 2023

In this paper, we show that a weak solution for unsteady flows of 3D shear‐thinning fluids is strong under certain integrability assumptions about two components of the vorticity. In particular, if two components of the vorticity belong to the marginal critical space
, then the solution is strong.
Periodic traveling wave solutions of discrete nonlinear Klein‐Gordon lattices
Authors: Hennig Dirk , Karachalios Nikos I.
Published: July 2023

We prove the existence of periodic traveling wave solutions for general discrete nonlinear Klein‐Gordon systems, considering both cases of hard and soft on‐site potentials. In the case of hard on‐site potentials, we implement a fixed‐point theory approach, combining Schauder's fixed‐point theorem and the contraction mapping principle. This approach enables us to identify a ring in the energy space for nontrivial solutions to exist, energy (norm) thresholds for their existence, and upper bounds on their velocity. In the case of soft on‐site potentials, the proof of existence of periodic traveling wave solutions is facilitated by a variational approach based on the mountain pass theorem. Thresholds on the averaged kinetic energy for these solutions to exist are also derived.
The multi‐purpose K‐drones general routing problem
Authors: Campbell James , Corberán Ángel , Plana Isaac , Sanchis José M. , Segura Paula
Published: July 2023

In this article, we present and solve the multi‐purpose ‐drones general routing problem (MP ‐DGRP). In this optimization problem, a fleet of multi‐purpose drones, aerial vehicles that can both make deliveries and conduct sensing activities (e.g., imaging), have to jointly visit a set of nodes to make deliveries and map one or more continuous areas. This problem is motivated by global healthcare applications that deploy multipurpose drones that combine delivery trips with collection of aerial imaging data for use in emergency preparedness and resilience planning. The continuous areas that have to be mapped may correspond to terrain surfaces (e.g., flooded areas or regions with a disease outbreak) or to infrastructure networks to be inspected. The continuous areas can be modeled as a set of lines so that each area is completely serviced if all the lines covering it are traversed. Thus, given a set of nodes and a set of lines, the problem is to design drone routes of shortest total duration traversing the lines and visiting the nodes, while not exceeding the range limit (flight time) and capacity (loading) of the drones. Unlike ground vehicles in classical routing problems, drones can enter a line through any of its points, service only a part of that line and then exit through another of its points. The possibility of flying directly between any two points of the network offered by drones can lead to reduced costs, but it increases the difficulty of the problem. To deal with this problem, the lines are discretized, allowing drones to enter and exit each line only at a finite set of points, thus obtaining an instance of the ‐vehicles general routing problem (‐GRP). We present in this article an integer programming formulation for the ‐GRP and propose a matheuristic algorithm and a branch‐and‐cut procedure for its solution. Results are provided for problems with up to 20 deliveries and up to 28 continuous areas.
Alzheimer's disease knowledge of nursing staff in East China: A latent profile analysis
Authors: Zuo Shufang , Wang Yueju , Wang Ziyu , Chen Si , Liang Jinghong , Meng Hongyan , Lin Lu
Published: July 2023

Aim

The dementia population is expanding fast globally, posing a huge challenge to the healthcare system. Improving the level of Alzheimer's disease knowledge (ADK) in nursing staff is the key to providing quality dementia care and improving the patients' quality of life. This study aimed to investigate and classify the ADK level of nursing staff in East China and to identify the factors influencing the nursing staff's ADK level.

Design

A cross‐sectional study.

Methods

A cross‐sectional survey was conducted among 1896 nursing staff in East China from September 2022 to December 2022, using a self‐designed general information questionnaire and the Chinese version of the Alzheimer's Disease Knowledge Scale. Latent profile analysis (LPA) was used to classify the nursing staff according to their ADK level, and multinomial logistic regression was used to identify the factors influencing the nursing staff's ADK level.

Results

Nursing staff could be classified into four latent profiles according to their ADK level (p < 0.05), namely, the ‘Low ADK group’, ‘Medium ADK group’, ‘Medium‐high ADK group’, and ‘High ADK group’. Age, education, experience in AD care and training in ADK were the main factors influencing the classification of the nursing staff's ADK level. Therefore, upgrading education, participating in ADK training, and increasing AD care experience will be conducive to improving the ADK of nursing staff.

No Patient or Public Contribution.
The effects of early time restricted eating plus daily caloric restriction compared to daily caloric restriction alone on continuous glucose levels
Authors: Zaman Adnin , Grau Laura , Jeffers Rebecca , Steinke Sheila , Catenacci Victoria A. , Cornier Marc‐Andre , Rynders Corey A. , Thomas Elizabeth A.
Published: July 2023

Background

The median eating duration in the U.S. is 14.75 h, spread throughout the period of wakefulness and ending before sleep. Food intake at an inappropriate circadian time may lead to adverse metabolic outcomes. Emerging literature suggests that time restricted eating (TRE) may improve glucose tolerance and insulin sensitivity. The aim was to compare 24‐h glucose profiles and insulin sensitivity in participants after completing 12 weeks of a behavioral weight loss intervention based on early TRE plus daily caloric restriction (E‐TRE+DCR) or DCR alone.

Methods

Eighty‐one adults with overweight or obesity (age 18–50 years, BMI 25–45 kg/m2) were randomized to either E‐TRE+DCR or DCR alone. Each participant wore a continuous glucose monitor (CGM) for 7 days and insulin sensitivity was estimated using the homeostatic model assessment of insulin resistance (HOMA‐IR) at Baseline and Week 12. Changes in CGM‐derived measures and HOMA‐IR from Baseline to Week 12 were assessed within and between groups using random intercept mixed models.

Results

Forty‐four participants had valid CGM data at both time points, while 38 had valid glucose, insulin, HOMA‐IR, and hemoglobin A1c (A1c) data at both timepoints. There were no significant differences in sex, age, BMI, or the percentage of participants with prediabetes between the groups (28% female, age 39.2 ± 6.9 years, BMI 33.8 ± 5.7 kg/m2, 16% with prediabetes). After adjusting for weight, there were no between‐group differences in changes in overall average sensor glucose, standard deviation of glucose levels, the coefficient of variation of glucose levels, daytime or nighttime average sensor glucose, fasting glucose, insulin, HOMA‐IR, or A1c. However, mean amplitude of glycemic excursions changed differently over time between the two groups, with a greater reduction found in the DCR as compared to E‐TRE+DCR (p = 0.03).

Conclusion

There were no major differences between E‐TRE+DCR and DCR groups in continuous glucose profiles or insulin sensitivity 12 weeks after the intervention. Because the study sample included participants with normal baseline mean glucose profiles and insulin sensitivity, the ability to detect changes in these outcomes may have been limited.
Children's Oncology Group's 2023 blueprint for research: Myeloid neoplasms
Authors: Cooper Todd M. , Alonzo Todd A. , Tasian Sarah K. , Kutny Matthew A. , Hitzler Johann , Pollard Jessica A. , Aplenc Richard , Meshinchi Soheil , Kolb E. Anders
Published: July 2023

During the past decade, the outcomes of pediatric patients with acute myeloid leukemia (AML) have plateaued with 5‐year event‐free survival (EFS) and overall survival (OS) of approximately 46 and 64%, respectively. Outcomes are particularly poor for those children with high‐risk disease, who have 5‐year OS of 46%. Substantial survival improvements have been observed for a subset of patients treated with targeted therapies. Specifically, children with KMT2A‐rearranged AML and/or FLT3 internal tandem duplication (FLT3‐ITD) mutations benefitted from the addition of gemtuzumab ozogamicin, an anti‐CD33 antibody–drug conjugate, in the AAML0531 clinical trial (NCT00372593). Sorafenib also improved response and survival in children with FLT3‐ITD AML in the AAML1031 clinical trial (NCT01371981). Advances in characterization of prognostic cytomolecular events have helped to identify patients at highest risk of relapse and facilitated allocation to consolidative hematopoietic stem cell transplant (HSCT) in first remission. Some patients clearly have improved survival with HSCT, although the benefit is largely unknown for most patients. Finally, data‐driven refinements in supportive care recommendations continue to evolve with meaningful and measurable reductions in toxicity and improvements in EFS and OS. As advances in application of targeted therapies, risk stratification, and improved supportive care measures are incorporated into current trials and become standard‐of‐care, there is every expectation that we will see improved survival with a reduction in toxic morbidity and mortality. The research agenda of the Children's Oncology Group's Myeloid Diseases Committee continues to build upon experience and outcomes with an overarching goal of curing more children with AML.
Appropriateness of 14‐year cutoff in pediatric differentiated thyroid cancer: Comparison of clinical characteristics and long‐term outcomes in 14 years and younger and 15–18 years age groups
Authors: Satapathy Swayamjeet , Majeed Althaf K. , Ballal Sanjana , Bal Chandrasekhar
Published: July 2023

Background

Pediatric differentiated thyroid cancers (DTCs) differ in pathophysiology, presentation, and clinical outcomes from adult DTCs. However, the cutoff age for defining pediatric DTCs remains debatable, with the American Thyroid Association (ATA) and International Incidence of Childhood Cancer (IICC) report recommending different cutoffs of 18 and 14 years, respectively. In this study, we investigated the appropriateness of 14‐year cutoff by comparing the clinical characteristics and long‐term outcomes in the 14 years and younger and 15–18 years age groups.

Methods

Data of DTC patients, aged 18 years and older, from 1981 to 2016, were sequentially extracted and compared between two age groups: ≤14 and 15–18 years.

Results

Total of 176 pediatric DTC patients were included (age group ≤14 years: n = 75; age group 15–18 years: n = 101). None of the baseline clinical characteristics were significantly different between the two age groups. At 2‐year follow‐up, patients in the age group ≤14 years had significantly higher incomplete response rate compared to those in the age group 15–18 years (69% vs. 42%, respectively, p < .001). However, over a median follow‐up of 10.6 years (interquartile range: 7.7–15.5), the 5‐ and 10‐year Disease‐free survival (DFS) probabilities were not significantly different (p = .406). On multivariate analysis, incomplete response at 2‐year follow‐up was the sole independent predictor of poor DFS (hazard ratio: 5.85, 95% confidence interval: 1.69–20.23).

Conclusions

Subdivision of pediatric DTCs into less than or equal to 14 years and 15–18 years age groups did not have any long‐term predictive value. The cutoff of 18 years as recommended by ATA is reasonable and should be uniformly followed to avoid inconsistencies and confusion.
Role and structure of the small subunit forming heterodimers with laccase‐like enzymes
Authors: Aza Pablo , Linde Dolores , Molpeceres Gonzalo , Vind Jesper , Medrano F. Javier , Camarero Susana
Published: July 2023

Unlike laccases sensu stricto, which are usually monomeric enzymes, laccase‐like enzymes recently re‐classified as Novel Laccases (NLACs) are characterized by the formation of heterodimers with small proteins (subunits) of unknown function. Here the NLAC from Pleurotus eryngii (PeNL) and a small protein selected from the fungal genome, that is homologous to reported POXA3 from Pleurotus ostreatus, were produced in Aspergillus oryzae separately or together. The two proteins interacted regardless of whether the small subunit was co‐expressed or exogenously added to the enzyme. The stability and catalytic activity of PeNL was significantly enhanced in the presence of the small subunit. Size exclusion chromatography‐multi angle light scattering (SEC‐MALS) analysis confirmed that the complex PeNL‐ss is a heterodimer of 77.4 kDa. The crystallographic structure of the small protein expressed in Escherichia coli was solved at 1.6 Å resolution. This is the first structure elucidated of a small subunit of a NLAC. The helix bundle structure of the small subunit accommodates well with the enzyme model structure, including interactions with specific regions of NLACs and some amino acid residues of the substrate‐binding loops.
Influence of External Plane Stress on Electric Parameters of AlGaN/GaN HEMT Heterostructures
Authors: Paszkiewicz Bartłomiej Kazimierz , Paszkiewicz Bogdan , Dziedzic Andrzej
Published: July 2023

Herein, the influence of stresses on parameters of 2D electron gas (2DEG) in AlGaN/GaN high‐electron‐mobility transistor‐type heterostructures grown on sapphire substrate by metal–organic vapor‐phase epitaxy technique is presented. The as‐grown heterostructures as well as Schottky diodes fabricated in them are subjected to compressive stress. The custom stressing system induces a homogeneous state of compressive stress in the samples without causing electrical side effects. Time‐dependent heterostructures characteristics of electron concentration, electron mobility, and bandgap width are measured. Additionally, in the case of the Schottky diodes, current–voltage characteristics and charge flow in the contact are measured. The measurements are performed in cycles with and without applied stresses to determine the repeatability of effects and to separate the influence of thermal and electrical factors. Additionally, electrical simulations are performed using APSYS software package. The obtained results lead to conclusions that are different to those reported in existing literature, especially in regard to the time dependence of the measured effects, that is essential to proper explanation. It is also shown that a key role in the change of 2DEG parameters is played by deep surface states and interlayer piezoelectric effects. Finally, the anisotropic character of the derived relations is demonstrated.
Changes of tropical gravity waves and the quasi‐biennial oscillation in storm‐resolving simulations of idealized global warming
Authors: Franke Henning , Preusse Peter , Giorgetta Marco
Published: July 2023

Gravity waves generated by tropical deep convection contribute significantly to driving the downward propagation of the quasi‐biennial oscillation (QBO). However, it is currently uncertain how gravity waves and their interaction with the QBO, and thus the QBO itself, will respond to a warming climate. Previous work showed that this uncertainty is a consequence of the parametrization of gravity waves employed in conventional general circulation models. In this study, we therefore perform short explicit simulations of the QBO for different idealized climate states with the model ICON‐A in a deep convection‐permitting set‐up, which means that neither a parametrization of convection nor a parametrization of gravity waves is employed and that the QBO is entirely driven by explicitly resolved waves. Thereby, our simulations allow us to provide a very first direct estimate of how tropical gravity waves and the QBO may change in a warming climate. We found that the gravity wave momentum flux in the lower stratosphere that is relevant for the QBO increases substantially in the warmer climate states and shifts towards faster zonal phase speeds. As a consequence, the downward propagation of the QBO accelerates and the magnitude of the QBO jets in the upper QBO domain increases in the warmer climate states. Thus, our work builds an important first step towards a more comprehensive assessment of potential QBO changes using global storm‐resolving models.
A Phase II score‐based distribution‐free method for jointly monitoring location and scale
Authors: Ding Dong , Li Jian , Tsung Fugee , Li Yang
Published: July 2023

In recent years, motivated by various applications, the joint monitoring of location and scale parameters have attracted increasing attention from researchers. Although parametric methods are useful and have been extensively studied, their efficiency is highly compromised when the process distribution is non‐normal or unknown. This leads to the study of nonparametric or distribution‐free methods. This article proposes a novel distribution‐free approach for location and scale monitoring, based on the proper transformation of the score test and the incorporation of the exponentially weighted moving average (EWMA) scheme. The proposed method is efficient to detect shifts in location and scale parameters, and is robust under various underlying distributions. Simulation study and a real example from manufacturing industry have guaranteed the usefulness and effectiveness of the proposed method.
Does improved cooking fuel empower women? Evidence from India
Authors: Lee YuJung Julia , Husain Zakir , Dutta Mousumi
Published: July 2023

Reliance on biomass fuel remains high in many developing countries, like India. Shifting to clean fuel has widely recognized benefits for women in saving time, improving health, and creating a better environment. Other benefits to women in the form of increasing empowerment are a relatively under‐researched area. Using data from the nationally representative National Family Health Survey (2019–21) in India, this study uses endogenous treatment effect models to explore the causal effect of shifting to clean fuel on awareness, work, mobility, decision‐making and financial autonomy. Analysis reveals significant gains in all dimensions, particularly in women's mobility and decision‐making. The gains are relatively higher among less educated women, those from poor households, and those belonging to socially advantaged groups. Focusing on gains to empowerment will motivate women to adopt clean fuel and enable a holistic transformation of society through the simultaneous attainment of several Sustainable Development Goals.
High‐Speed Optoelectronic Nonvolatile Memory Based on van der Waals Heterostructures
Authors: Wang Wenxiang , Jin Jiyou , Wang Yanrong , Wei Zheng , Xu Yushi , Peng Zhisheng , Liu Hui , Wang Yu , You Jiawang , Impundu Julienne , Zheng Qiang , Li Yong Jun , Sun Lianfeng
Published: July 2023

High‐performance optoelectronic nonvolatile memory is promising candidate for next‐generation information memory devices. Here, a floating‐gate memory is constructed based on van der Waals heterostructure, which exhibits a large storage window ratio (≈75.5%) and an extremely high on/off ratio (107), as well as an ultrafast electrical writing/erasing speed (40 ns). The enhanced performance enables as‐fabricated devices to present excellent multilevel data storage, robust retention, and endurance performance. Moreover, stable optical erasing operations can be achieved by illuminating the device with a laser pulse, showcasing outstanding optoelectronic storage performance (optical erasing speed ≈ 2.3 ms). The nonvolatile and high‐speed characteristics of these devices hold significant potential for the integration of high‐performance nonvolatile memory.
Interface Wetting and Reaction Behavior between Mold Flux and Submerged Entry Nozzle under an External Electric Field
Authors: Tian Chen , Yuan Lei , Peng Zijun , Liu Xiaoming , Wang Qiang
Published: July 2023

Herein, to provide theoretical foundation and experimental data for using electric field to control the service performance and improve the service life of submerged entry nozzle, the effect of the external electric field on the interfacial reaction and wetting behavior between the mold flux and the slag‐line materials is studied. The results show that the wettability of mold flux on the surface of the slag‐line materials is mainly affected by the dissolution and spreading under normal conditions. However, the electrochemical reaction and electric force generated by the applied electric field are also important factors for driving and changing the wettability between the mold flux and slag‐line materials. Under the positive electric field, the total duration of complete spreading and wetting is 227 s, which is 13 s shorter than that under normal conditions; the contact angle after complete wetting is about 17°, which is 1.5° lower than that under normal conditions. Under the negative electric field, the total duration of complete spreading and wetting is 260 s, which is 20 s longer than that under normal conditions; the contact angle after complete wetting is about 21°, which is 2.5° higher than that under normal conditions.
Numerical evaluation of axial compressive behavior of hollow concrete columns reinforced with GFRP bars and spirals
Authors: Tahir Muhammad , Karam Muhammad Shoaib , Hassam Muhammad , Umer Muhammad , Hameed Rashid
Published: July 2023

With the advancement in the concrete technology, the application of precast concrete elements in the buildings and road infrastructures is increasing very rapidly. One of such applications is the use of precast hollow concrete elements in the bridge construction. As the conventional steel reinforcement is highly susceptible to corrosion, the use of non‐corrosive reinforcement in precast hollow concrete piers and piles of bridges could be a good option for the durability of bridge structures., In this regard, hollow concrete columns reinforced with fiber‐reinforced polymer (FRP) have been considered as a potential solution to overcome the structural deterioration due to corrosion. In the past, limited studies have been carried out on hollow concrete columns reinforced with FRP, consequently, the behavior of such columns is not fully understood. Therefore, to comprehensively evaluate the behavior of hollow concrete columns for various design parameters, a finite element model (FEM) was developed in this study using the commercial tool “Abaqus”. The model was developed and verified based on the experimental results of studies conducted by two independent research groups on circular concrete columns. The proposed model well predicted the peak loads with an error less than 10% and the failure modes of the tested columns. The verified constitutive relation and establishing method were further employed to conduct parametric evaluations to observe the influence of different parameters, such as inner‐to‐outer diameter ratio, longitudinal reinforcement ratio, lateral reinforcement ratio, and concrete strength, on the behavior of hollow concrete columns. Parametric analyses show that reduced inner‐to‐outer diameter ratio and larger longitudinal or lateral reinforcement may lead to higher peak load and confined concrete strength. Finally, based on the experimental and FEM evaluations, the strength prediction equations were developed for the analysis and design of hollow concrete columns reinforced with GFRP bars.
Green and large‐scale production of ammonia: Laser‐driven pyrolysis of nitrogen‐enriched biomass
Authors: Li Yue , Wu Tong , Wang Yujie , Li Jiawei , Yu Wanqiang , Zhang Guixiang , Chang Bin , Zhao Lili , Liu Hong , Zhou Weijia
Published: July 2023

As a vital chemical, ammonia (NH3) plays an irreplaceable role in many fields such as chemical synthesis and energy storage. Green renewable biomass can be converted into biofuels, but its nitrogen resources are underused throughout. Laser‐driven pyrolysis is envisaged to debuts as a bridge to connect them to realize the direct conversion from nitrogen‐rich biomass into ammonia. The pulsed laser‐induced local‐transient thermal effect recognized the biological nitrogen resources conversion, such as cheap and plentiful yeasts, to small gaseous molecules and achieved spectacular ammonia production rate up to 260.4 mg/h, an order of magnitude higher performance than thermochemical ammonia synthesis. Simultaneously, the tiny hot point generated by a low‐energy laser (20 W) guarantees the whole ammonia synthesis reaction system is in a mild environment of low temperature and normal pressure. Additionally, the remaining solid residue after laser‐driven pyrolysis also can be further exploited as a highly active catalyst for electrocatalytic nitrate reduction reaction (NIRR).
Circ_0040994 depletion alleviates lipopolysaccharide‐induced HK2 cell injury through miR‐17‐5p/TRPM7 axis
Authors: Li Yanping , Chai Yanfen
Published: July 2023

Background

Sepsis is a fatal systemic inflammatory disease that causes septic acute kidney injury (AKI). In this work, we explored the roles of circ_0040994 in lipopolysaccharide (LPS)‐induced human kidney‐2 (HK2) cell injury.

Methods

Circ_0040994, miR‐17‐5p and transient receptor potential melastatin 7 (TRPM7) expression were detected by qRT‐PCR. Cell functions were examined by MTT assay, flow cytometry assay, western blot, ELISA assay, and oxidative stress assay. The molecular association was detected by dual‐luciferase reporter assay.

Results

Circ_0040994 was upregulated in the serum of septic AKI patients in comparison with the serum of healthy controls. Silencing circ_0040994 enhanced cell viability but inhibited cell apoptosis, cell inflammation and oxidative stress in LPS‐triggered HK2 cells. Circ_0040994 acted as a miR‐17‐5p sponge to regulate the level of TRPM7. Moreover, miR‐17‐5p could alleviate LPS‐induced HK2 cell injury by suppressing TRPM7.

Conclusion

Circ_0040994 downregulation alleviated LPS‐induced HK2 cell injury through the miR‐17‐5p/TRPM7 axis.
Luteolin/ZnO nanoparticles attenuate neuroinflammation associated with diabetes via regulating MicroRNA‐124 by targeting C/EBPA
Authors: Moustafa Enas M. , Moawed Fatma S. M. , Elmaghraby Dina F.
Published: July 2023

Objective

The most prevalent brain‐specific microRNA, MicroRNA‐124, exhibits anti‐inflammatory properties. Luteolin nano‐formulation with Zn oxide in the form of L/ZnO NPs may boost anti‐diabetic properties; however, its beneficial effect on miRNAs is yet unknown in diabetes. The effectiveness of L/ZnONPs supplements in preventing diabetic neurodegeneration by modulating inflammatory responses in a diabetic model was investigated.

Methods

A diabetic rat model was induced by a high‐fat diet and streptozotocin (30 mg/kg I.P.). Plasma glucose, insulin, and HOMR‐IR levels, as well as cytokines, lipid peroxidation, GSH/GSSG, and glucose transporter 1, were determined along with the tight junction proteins occludin (OCLN) and zona occludens 1 (ZO‐1). Moreover, the expressions of brain CCAAT/enhancer‐binding protein (C/EBPA mRNA), miR‐124, glial fibrillary acidic protein (GFAP), and NF‐kBp65 were measured alongside the histological investigation.

Results

The results revealed that L/ZnO NPs were able to diminish lipid peroxidation, increase the activity of antioxidant enzymes, and reduce inflammation under oxidative stress. Consequently, it was able to reduce hyperglycemia, elevate insulin levels, and improve insulin resistance. Besides, L/ZnO NPs upregulate miR‐124, reduce C/EBPA mRNA, increase BCl‐2, and inhibit apoptosis. The results indicate that diabetes raises BBB permeability via tight junction protein decline, which is restored following L/ZnO NPs treatment. Luteolin/ZnO NPs regulate miR‐124 and microglia polarization by targeting C/EBPA and are expected to alleviate inflammatory injury via modulation of the redox‐sensitive signal transduction pathways. Luteolin/ZnO NPs have a novel target for the protection of the BBB and the prevention of neurological complications in diabetes.
Towards a climate‐smart cultural heritage management
Authors: Fatorić Sandra , Daly Cathy
Published: July 2023

Globally, cultural heritage is on the front line of anthropogenic climate change. Therefore, it could be argued that climate change should now be a primary lens through which cultural heritage conservation and management are viewed. We argue that addressing the growing and compounding risks and impacts of climate change requires a fundamental rethink and transformation of cultural heritage management and policy. In this article, we propose a climate‐smart cultural heritage (CSCH) approach that captures the notion that climate adaptation can be developed and implemented within the heritage sector to simultaneously reduce the impacts of changing climate and variability on tangible and intangible cultural heritage and provide co‐benefits for climate change mitigation while also enhancing human security at different spatial scales. The CSCH is an integrated approach to implementing forward‐looking and transformative cultural heritage management and policy and is not a new set of practices to be advocated to cultural heritage stakeholders and decision‐makers. Findings also demonstrate that institutional mechanisms such as multi‐stakeholder planning, increased awareness of the economic, social, and environmental benefits of diverse cultural heritage, improved cross‐sectoral coordination and communication, strong political will for transformative approaches, and investments in CSCH are necessary for implementation of CSCH.

This article is categorized under:

Climate, History, Society, Culture > Disciplinary Perspectives

The Social Status of Climate Change Knowledge > Climate Science and Decision Making

Integrated Assessment of Climate Change > Assessing Climate Change in the Context of Other Issues
GSK-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo
Authors: Moreno-Jiménez E. P. , Flor-García M. , Hernández-Vivanco A. , Terreros-Roncal J. , Rodríguez-Moreno C. B. , Toni N. , Méndez P. , Llorens-Martín María
Published: July 2023

Adult hippocampal neurogenesis enhances brain plasticity and contributes to the cognitive reserve during aging. Adult hippocampal neurogenesis is impaired in neurological disorders, yet the molecular mechanisms regulating the maturation and synaptic integration of new neurons have not been fully elucidated. GABA is a master regulator of adult and developmental neurogenesis. Here we engineered a novel retrovirus encoding the fusion protein Gephyrin:GFP to longitudinally study the formation and maturation of inhibitory synapses during adult hippocampal neurogenesis in vivo. Our data reveal the early assembly of inhibitory postsynaptic densities at 1 week of cell age. Glycogen synthase kinase 3 Beta (GSK-3β) emerges as a key regulator of inhibitory synapse formation and maturation during adult hippocampal neurogenesis. GSK-3β-overexpressing newborn neurons show an increased number and altered size of Gephyrin+postsynaptic clusters, enhanced miniature inhibitory postsynaptic currents, shorter and distanced axon initial segments, reduced synaptic output at the CA3 and CA2 hippocampal regions, and impaired pattern separation. Moreover, GSK-3β overexpression triggers a depletion of Parvalbumin+interneuron perineuronal nets. These alterations might be relevant in the context of neurological diseases in which the activity of GSK-3β is dysregulated.
Myeloid-derived suppressor cells impair CD4+ T cell responses during chronic Staphylococcus aureus infection via lactate metabolism
Authors: Goldmann Oliver , Medina Eva
Published: July 2023

Staphylococcus aureus is an important cause of chronic infections resulting from the failure of the host to eliminate the pathogen. Effective S. aureus clearance requires CD4+ T cell-mediated immunity. We previously showed that myeloid-derived suppressor cells (MDSC) expand during staphylococcal infections and support infection chronicity by inhibiting CD4+ T cell responses. The aim of this study was to elucidate the mechanisms underlying the suppressive effect exerted by MDSC on CD4+ T cells during chronic S. aureus infection. It is well known that activated CD4+ T cells undergo metabolic reprogramming from oxidative metabolism to aerobic glycolysis to meet their increased bioenergetic requirements. In this process, pyruvate is largely transformed into lactate by lactate dehydrogenase with the concomitant regeneration of NAD+, which is necessary for continued glycolysis. The by-product lactate needs to be excreted to maintain the glycolytic flux. Using SCENITH (single-cell energetic metabolism by profiling translation inhibition), we demonstrated here that MDSC inhibit CD4+ T cell responses by interfering with their metabolic activity. MDSC are highly glycolytic and excrete large amount of lactate in the local environment that alters the transmembrane concentration gradient and prevent removal of lactate by activated CD4+ T. Accumulation of endogenous lactate impedes the regeneration of NAD+, inhibit NAD-dependent glycolytic enzymes and stop glycolysis. Together, the results of this study have uncovered a role for metabolism on MDSC suppression of CD4+ T cell responses. Thus, reestablishment of their metabolic activity may represent a mean to improve the functionality of CD4+ T cells during chronic S. aureus infection.
Measuring perceived empathy in dialogue systems
Authors: Concannon Shauna , Tomalin Marcus
Published: July 2023

Dialogue systems, from Virtual Personal Assistants such as Siri, Cortana, and Alexa to state-of-the-art systems such as BlenderBot3 and ChatGPT, are already widely available, used in a variety of applications, and are increasingly part of many people’s lives. However, the task of enabling them to use empathetic language more convincingly is still an emerging research topic. Such systems generally make use of complex neural networks to learn the patterns of typical human language use, and the interactions in which the systems participate are usually mediated either via interactive text-based or speech-based interfaces. In human–human interaction, empathy has been shown to promote prosocial behaviour and improve interaction. In the context of dialogue systems, to advance the understanding of how perceptions of empathy affect interactions, it is necessary to bring greater clarity to how empathy is measured and assessed. Assessing the way dialogue systems create perceptions of empathy brings together a range of technological, psychological, and ethical considerations that merit greater scrutiny than they have received so far. However, there is currently no widely accepted evaluation method for determining the degree of empathy that any given system possesses (or, at least, appears to possess). Currently, different research teams use a variety of automated metrics, alongside different forms of subjective human assessment such as questionnaires, self-assessment measures and narrative engagement scales. This diversity of evaluation practice means that, given two DSs, it is usually impossible to determine which of them conveys the greater degree of empathy in its dialogic exchanges with human users. Acknowledging this problem, the present article provides an overview of how empathy is measured in human–human interactions and considers some of the ways it is currently measured in human–DS interactions. Finally, it introduces a novel third-person analytical framework, called the Empathy Scale for Human–Computer Communication (ESHCC), to support greater uniformity in how perceived empathy is measured during interactions with state-of-the-art DSs.
Row mixture-based clustering with covariates for ordinal responses
Authors: Preedalikit Kemmawadee , Fernández Daniel , Liu Ivy , McMillan Louise , Nai Ruscone Marta , Costilla Roy
Published: July 2023

Existing methods can perform likelihood-based clustering on a multivariate data matrix of ordinal data, using finite mixtures to cluster the rows (observations) of the matrix. These models can incorporate the main effects of individual rows and columns, as well as cluster effects, to model the matrix of responses. However, many real-world applications also include available covariates, which provide insights into the main characteristics of the clusters and determine clustering structures based on both the individuals’ similar patterns of responses and the effects of the covariates on the individuals' responses. In our research we have extended the mixture-based models to include covariates and test what effect this has on the resulting clustering structures. We focus on clustering the rows of the data matrix, using the proportional odds cumulative logit model for ordinal data. We fit the models using the Expectation-Maximization algorithm and assess performance using a simulation study. We also illustrate an application of the models to the well-known arthritis clinical trial data set.
Oral nicotine pouches with an aftertaste? Part 2: in vitro toxicity in human gingival fibroblasts
Authors: Rinaldi Selina , Pieper Elke , Schulz Thomas , Zimmermann Ralf , Luch Andreas , Laux Peter , Mallock-Ohnesorg Nadja
Published: July 2023

Nicotine pouches contain fewer characteristic toxicants than conventional tobacco products. However, the associated risks in terms of toxicity and addiction potential are still unclear. Therefore, endpoints of toxicity and contents of flavoring substances were investigated in this study. The in vitro toxicity of five different nicotine pouches and the reference snus CRP1.1 were studied in human gingival fibroblasts (HGF-1). Cells were exposed to product extracts (nicotine contents: 0.03–1.34 mg/mL) and sampled at different time points. Cytotoxicity, total cellular reactive oxygen species (ROS) levels, and changes in the expression levels of inflammatory and oxidative stress genes were assessed. Flavor compounds used in the nicotine pouches were identified by GC–MS. Cytotoxicity was observed in two nicotine pouches. Gene expression of interleukin 6 (IL6) and heme oxygenase 1 (HMOX1) was upregulated by one and three pouches, respectively. ROS production was either increased or decreased, by one pouch each. CRP1.1 caused an upregulation of IL6 and elevated ROS production. Toxicity was not directly dependent on nicotine concentration and osmolarity. A total of 56 flavorings were detected in the five nicotine pouches. Seven flavorings were classified according to the harmonized hazard classification system as laid down in the European Classification, Labelling and Packaging regulation. Nine flavorings are known cytotoxins. Cytotoxicity, inflammation, and oxidative stress responses indicate that adverse effects such as local lesions in the buccal mucosa may occur after chronic product use. In conclusion, flavorings used in nicotine pouches likely contribute to the toxicity of nicotine pouches.
Chronic exposure to inorganic arsenic and fluoride induces redox imbalance, inhibits the transsulfuration pathway, and alters glutamate receptor expression in the brain, resulting in memory impairment in adult male mouse offspring
Authors: González-Alfonso Wendy L. , Pavel Petrosyan , Karina Hernández-Mercado , Del Razo Luz M. , Sanchez-Peña Luz C. , Zepeda Angélica , Gonsebatt María E.
Published: July 2023

Exposure to toxic elements in drinking water, such as arsenic (As) and fluoride (F), starts at gestation and has been associated with memory and learning deficits in children. Studies in which rodents underwent mechanistic single exposure to As or F showed that the neurotoxic effects are associated with their capacity to disrupt redox balance, mainly by diminishing glutathione (GSH) levels, altering glutamate disposal, and altering glutamate receptor expression, which disrupts synaptic transmission. Elevated levels of As and F are common in groundwater worldwide. To explore the neurotoxicity of chronic exposure to As and F in drinking water, pregnant CD-1 mice were exposed to 2 mg/L As (sodium arsenite) and 25 mg/L F (sodium fluoride) alone or in combination. The male litter continued to receive exposure up to 30 or 90 days after birth. The effects of chronic exposure on GSH levels, transsulfuration pathway enzymatic activity, expression of cysteine/cystine transporters, glutamate transporters, and ionotropic glutamate receptor subunits as well as behavioral performance in the object recognition memory task were assessed. Combined exposure resulted in a significant reduction in GSH levels in the cortex and hippocampus at different times, decreased transsulfuration pathway enzyme activity, as well as diminished xCT protein expression. Altered glutamate receptor expression in the cortex and hippocampus and decreased transaminase enzyme activity were observed. These molecular alterations were associated with memory impairment in the object recognition task, which relies on these brain regions.
Distal Tibial Bone Properties and Bone Stress Injury Risk in Young Men Undergoing Arduous Physical Training
Authors: Eastman Katharine , O’Leary Thomas J. , Carswell Alexander , Walsh Neil , Izard Rachel , Fraser William , Greeves Julie
Published: July 2023

Trabecular microarchitecture contributes to bone strength, but its role in bone stress injury (BSI) risk in young healthy adults is unclear. Tibial volumetric BMD (vBMD), geometry, and microarchitecture, whole-body areal BMD, lean and fat mass, biochemical markers of bone metabolism, aerobic fitness, and muscle strength and power were measured in 201 British Army male infantry recruits (age 20.7 [4.3] years, BMI 24.0 ± 2.7 kg·m2) in week one of basic training. Tibial scans were performed at the ultra-distal site, 22.5 mm from the distal endplate of the non-dominant leg using High Resolution Peripheral Quantitative Computed Tomography (XtremeCT, Scanco Medical AG, Switzerland). Binary logistic regression analysis was performed to identify associations with lower body BSI confirmed by MRI. 20 recruits (10.0%) were diagnosed with a lower body BSI. Pre-injured participants had lower cortical area, stiffness and estimated failure load (p = 0.029, 0.012 and 0.011 respectively) but tibial vBMD, geometry, and microarchitecture were not associated with BSI incidence when controlling for age, total body mass, lean body mass, height, total 25(OH)D, 2.4-km run time, peak power output and maximum dynamic lift strength. Infantry Regiment (OR 9.3 [95%CI, 2.6, 33.4]) Parachute versus Line Infantry, (p ≤ 0.001) and 2.4-km best effort run time (1.06 [95%CI, 1.02, 1.10], p < 0.033) were significant predictors. Intrinsic risk factors, including ultradistal tibial density, geometry, and microarchitecture, were not associated with lower body BSI during arduous infantry training. The ninefold increased risk of BSI in the Parachute Regiment compared with Line Infantry suggests that injury propensity is primarily a function of training load and risk factors are population-specific.
SLICC-Frailty Index and Its Association with Low Bone Mineral Density and Vertebral Fractures in Women with Systemic Lupus Erythematosus
Authors: Mendoza-Pinto Claudia , Etchegaray-Morales Ivet , Munguía-Realpozo Pamela , Méndez-Martínez Socorro , Ayón-Aguilar Jorge , Arellano-Avendaño Francisco , Montel-Jarquín Álvaro Joaquín , García-Carrasco Mario
Published: July 2023

The Systemic Lupus International Clinics (SLICC)-Frailty Index (FI) is associated with adverse outcomes in systemic lupus erythematosus (SLE). However, to our knowledge, its association with bone mineral density (BMD) and vertebral fractures (VF), has not been investigated using a standardized methods. Our aim was to evaluate the relationship between frailty assessed by SLICC-FI, and BMD and VF in Mestizo women with SLE. Adult women were included in this cross-sectional study. Information concerning the risk factors for VF and BMD in the lumbar spine and total hip was acquired. SLICC-FI was assessed at baseline. A semi-quantitative method was utilized to evaluate the prevalence of VF on lateral thoracolumbar radiographs. Univariate and multivariate regression analyses were performed adjusting for age, body mass index (BMI), SLE duration, cumulative glucocorticoid dose, bisphosphonate use, and BMD measurements. We included 202 women with SLE (mean age [SD] = 43.3 [13.6] years). The mean (SD) SLICC-FI value was 0.14 (0.09). Eleven (5.4%) patients were categorized as robust, 62 (30.7%) as relatively less fit, 84 (41.6%) as least fit, and 45 (22.3%) as frail. Both univariate and multivariate models showed associations between frailty (defined as SLICC-FI > 0.21) and prevalent VF in the entire population (OR 5.76, 95% CI 2.53–13.12; P < 0.001) and in the premenopausal group (OR 4.29, 95% CI; P = 0.047). We also found an association between the SLICC-FI and low BMD. In conclusion, frailty assessed by SLICC-FI might be associated with VF and low BMD in mestizo females with SLE.