bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Correlates of Poor Sleep Quality Among Psychiatry Physicians in Saudi Arabia: A Cross‐Sectional Study
Authors: Alshahrani Najim Z. , Alarifi Abdullah M. , Alotaibi Wejdan Saqer , Alsayed Afnan Abdulrahman , Alwasm Khalid Sultan Latif , Alhunti Alaa Abdulkarim , AlDahleh Lana Alaa , Alshahrani Meaad Mohammed A , Albeshry Abdalrhman M. , Aljunaid Mohammed A.
Published: October 2024

Background and Aims

Sleep issues pose a significant burden to public health and well‐being in Saudi Arabia. However, research evidence on sleep health among psychiatry physicians in this territory is limited. Therefore, to bridge the research gap, this study was designed to assess the prevalence and predictors of poor sleep quality among psychiatry physicians in the country.

Methods

This cross‐sectional study included 554 psychiatry physicians in Saudi Arabia from March to August 2023. Data were collected via online through a structured questionnaire (Google survey form). Sleep quality, the outcome variable of our study, was evaluated with the Pittsburgh Sleep Quality Index (PSQI; 19 items). Independent variables included sociodemographic and behavioral characteristics, sleep habits, major depression (assessed with Patient Health Questionnaire‐9), and anxiety (measured with Generalized Anxiety Disorder‐7) symptoms. Binary logistic regression analysis was performed to identify the correlates of poor sleep quality.

Results

Based on the PSQI, 61.3% of the study participants had poor‐quality sleep (age range: 24–56 years, male: 48.0%). The adjusted model revealed that male participants (AOR = 2.80, 95% CI = 1.70–4.61) and those who had on‐call duties ≥ 2 times per week (for three/four per week: AOR = 3.41, 95% CI = 1.89–6.14) were at higher risk of developing poor sleep quality compared to their respective counterparts. Participants with depressive symptoms (AOR = 3.46, 95% CI = 1.60–7.48) and smoking habits (AOR = 3.47, 95% CI = 1.32–9.08) had higher odds of developing poor sleep quality than their counterparts. Moreover, participants who always used their smartphone/laptop before going to bed were more likely to have poor sleep quality than those who never used such (AOR = 3.15, 95% CI = 1.31–7.60).

Conclusion

Poor sleep quality is extremely prominent among psychiatry physicians in Saudi Arabia. Male sex, higher on‐call duty, smoking habits, depression, and smartphone/laptop use before bedtime were significantly associated with poor sleep quality. These findings emphasize the need for sleep‐health promotion interventions for Saudi psychiatry physicians.
Evaluation of dental students' learning curve in intraligamentary anesthesia using different syringe systems: A prospective crossover study
Authors: Luhrenberg Philipp , Renders Mirjam , Heimes Diana , Hollinderbäumer Anke , Kaya Sebahat , Kyyak Solomiya , Schröger Saskia V. , Thiem Daniel G. E. , Wagner Helen , Kämmerer Peer W.
Published: October 2024

Purpose/objectives

This prospective crossover preclinical trial aimed to evaluate the learning curve of dental students in successfully administering intraligamentary anesthesia (ILA) using three different syringe systems.

Methods

Dental students performed ILA using three devices in two separate sessions, each targeting mandibular and/or maxillary premolars. The devices included two manual systems (pistol‐type and lever‐based) and one computer‐controlled local anesthetic delivery system (CCLAD). The primary research parameter was the success rate of anesthesia, defined as the percentage of successful ILA administrations confirmed by a negative response to a cold test. Secondary parameters included pain experienced during needle penetration and injection, students' self‐reported levels of mental tension and handling of the syringes, and any potential side effects.

Results

A total of 110 students performed ILA on 599 teeth during the study period. When comparing the CCLAD system to the manual syringes, the CCLAD system exhibited a significantly higher overall success rate in the first session (92.5% vs. 77.4%; p < 0.001), potentially due to its precise control of anesthetic flow and pressure, which likely facilitated more effective anesthetic delivery. However, when examining the individual manual techniques, no significant difference was found between the pistol‐type manual and the CCLAD system (p = 0.66). All techniques' success rate increased from the first to the second session (80.4% vs. 86.9%; p = 0.0357). Additionally, penetration pain demonstrated a significant decrease across all techniques (p < 0.01). Notably, students' anxiety levels decreased, and self‐assurance increased significantly over the sessions. Undesired reversible side effects were documented in 10.9% of cases.

Conclusion

These findings suggest that repeated practice of ILA, particularly with different syringe systems, enhances anesthetic success and psychological readiness for patient interaction. Additional training sessions may further improve proficiency.
When does it pay to be green? The strategic benefits of adoption speed
Authors: Su Hung‐Chung , Fu Wayne , Linderman Kevin
Published: October 2024

Does the speed of adopting environmental practices impact financial benefits? The strategy literature discusses the contingencies under which firms can gain an early‐mover advantage or a late‐mover advantage. This research examines the effect of adoption speed on two types of environmental practices: environmental innovation practices (EIP) and environmental management practices (EMP). The results show that early adoption of EIP increases competitive advantage when firms face intense competition. In comparison, we show that early adoption of EMP increases competitive advantage when firms face extremely low competition or have moderate to high levels of slack resources. The study contributes to the literature by revealing the nuances, contingencies, and boundary conditions of when it pays to be green. Prior research shows mixed results when studying firms' decisions to implement environmental practices, which implies that it may not pay to be green. This study shows that firms can get an early mover advantage from environmental practices, but it depends on the type of environmental practices, the firm's internal slack resources, and the firm's external competitive environment.
Synergy Between Woody Peat and Bentonite Alters Stability of Soil Organic Carbon in Coarse Soil by Enhancing Capacity for Soil Aggregation and Hydro‐Physical Properties
Authors: Wang Xi , Fan Jun , Wang Huan , Du Mengge
Published: October 2024

Coarse soil has a poor structure and is susceptible to wind and water erosion, thereby making it difficult to maintain the soil organic carbon (SOC) content. Woody peat (WP) is an organic material that can increase the SOC content of the soil, while clay materials can rapidly enhance the capacity for soil aggregate formation. In order to explore the synergistic effects of WP and clay materials (bentonite and red clay) on the aggregate structure and hydro‐physical properties of coarse soil, as well as the mechanism associated with SOC mineralization (ΔSOC), we conducted an incubation study using lou soil (L0) and loessial soil (H0) with three treatments: addition of WP alone (LW, HW), mixture of WP and bentonite (LWB, HWB), and mixture of WP and red clay (LWR, HWR). The three treatments enhanced the proportion of macroaggregate (> 2 mm) and aggregate stability of the two soils, and optimized the water retention and ventilation performance. The highest aggregate stability of LWB and HWB can be attributed to the positive synergistic effect of WP and bentonite, and bentonite was more effective than red clay due to its crystal structure. The results also showed that the ΔSOC values were significantly lower under LWB and HWB than those under WP addition alone and adding the mixture of WP and red clay (p < 0.05). Moreover, partial least squares path modeling analysis showed that the hydro‐physical properties of the two improved soils inhibited SOC mineralization (p > 0.05), whereas particulate organic carbon (POC) content significantly accelerated SOC mineralization (p < 0.01). The synergistic effect of clay materials increased mineral‐associated organic carbon (MAOC), which was beneficial to maintain the long‐term effectiveness of WP. Overall, our results demonstrated that the synergistic use of WP and bentonite enhanced the aggregate stability and hydro‐physical properties of coarse soil and improved SOC storage capacity. These results provide scientific and theoretical guidance to facilitate the rapid improvement of coarse soil through engineering measures in arid and semi‐arid areas with water and fertilizer limitations.
Effect of different calcium sulfate aspect ratios and chitosan addition methods on the interface properties of calcium sulfate/chitosan composite bone cement
Authors: Jiang Liuyun , Tang Chunyan , Tang Shuo , Wang Yuqing , Ouyang Qi , Hu Xiang
Published: October 2024

It is a great challenge to improve the properties of pure calcium sulfate bone cement. Here, two calcium sulfate hemihydrate powders with different aspect ratios were prepared, and three chitosan addition methods were adopted to investigate the effect on the surface and interface properties of calcium sulfate/chitosan composite bone cement. The results showed that it lacked chemical bond between chitosan and calcium sulfate, and the short rod calcium sulfate displayed better interface adhesion with chitosan owing to its smaller size, so it possessed shorter setting time, better compressive strength and slower degradation than the long rod calcium sulfate, while the biocompatibility had no remarkable difference. Moreover, chitosan solution as liquid phase was a better solidification mode than citric acid, and calcium sulfate/chitosan composite as solid phase was the worst mode because of poor interface compatibility. Conclusively, it was a simple, low‐cost, and effective preparation process to choose short rod calcium sulfate powder as solid phase and 1 wt% chitosan solution as liquid phase, which could achieve calcium sulfate/chitosan composite bone cement with the best properties, including setting time, compressive strength, degradation rate, and biocompatibility, displaying a promising application in bone defect repair.
A prediction model for differential resilience to the effects of combat‐related stressors in US army soldiers
Authors: Kessler Ronald C. , Bossarte Robert M. , Hwang Irving , Luedtke Alex , Naifeh James A. , Nock Matthew K. , Petukhova Maria , Sadikova Ekaterina , Sampson Nancy A. , Sverdrup Erik , Zubizarreta Jose R. , Wager Stefan , Wagner James , Stein Murray B. , Ursano Robert J.
Published: October 2024

Objectives

To develop a composite score for differential resilience to effects of combat‐related stressors (CRS) on persistent DSM‐IV post‐traumatic stress disorder (PTSD) among US Army combat arms soldiers using survey data collected before deployment.

Methods

A sample of n = 2542 US Army combat arms soldiers completed a survey shortly before deployment to Afghanistan and then again two to three and 8–9 months after redeployment. Retrospective self‐reports were obtained about CRS. Precision treatment methods were used to determine whether differential resilience to persistent PTSD in the follow‐up surveys could be developed from pre‐deployment survey data in a 60% training sample and validated in a 40% test sample.

Results

40.8% of respondents experienced high CRS and 5.4% developed persistent PTSD. Significant test sample heterogeneity was found in resilience (t = 2.1, p = 0.032), with average treatment effect (ATE) of high CRS in the 20% least resilient soldiers of 17.1% (SE = 5.5%) compared to ATE = 3.8% (SE = 1.2%) in the remaining 80%. The most important predictors involved recent and lifetime pre‐deployment distress disorders.

Conclusions

A reliable pre‐deployment resilience score can be constructed to predict variation in the effects of high CRS on persistent PTSD among combat arms soldiers. Such a score could be used to target preventive interventions to reduce PTSD or other resilience‐related outcomes.
Inflammatory arthropathies: Perspectives from a Portuguese male individual (1574–1834 CE)
Authors: Antunes‐Ferreira Nathalie , Curate Francisco , Prates Carlos , Marques Carina
Published: October 2024

Arthropathies are common in past populations and can be categorized into two groups: those with predominant bone production (e.g., osteoarthritis) and those with significant bone loss (e.g., erosive arthropathies). The former is frequent in the archaeological record, whereas the latter are uncommon. We present a Post‐Medieval male individual, recovered in the Convent of the Holy Spirit (Loures, Portugal), with multiple articular and entheseal bone changes, particularly extensive periarticular, marginal, and subchondral erosive processes, often exposing trabecular bone. Proliferative lesions and extensive ankylosis are also observed in the synovial joints. These pathological changes affect both the axial and peripheral skeleton in a polyarticular, bilateral, and asymmetric pattern. Given that the appendicular skeleton, particularly the hands and feet, are the most affected areas, the most probable diagnosis is a peripheral spondyloarthropathy such as psoriatic arthritis or reactive arthritis. This case study is the first archaeological instance of psoriatic arthritis or reactive arthritis described in Portugal, highlighting the importance of a differential diagnosis and the need for reflection when pathological changes characteristics overlap, advocating for a broader diagnostic approach.
Guaranteed Cost Control of Impulsive Nonlinear Stochastic Systems With Mixed Time Delays
Authors: Zhao Pengfei , Chen Dongyan , Hu Jun , Zhang Zhiyang , Yang Ning
Published: October 2024

This article mainly addresses the guaranteed cost control (GCC) problem for a class of impulsive nonlinear stochastic systems with mixed time delays, where both distributed time delay as well as discrete time delay are considered. Utilizing the Hamilton–Jacobi inequalities technique, Lyapunov–Krasovskii functional (LKF) and stochastic control theory, a new delay‐dependent sufficient condition is acquired to ensure the asymptotic stability in probability (ASP) of the closed‐loop system (CLS). Moreover, the guaranteed cost controller is designed and the upper bound of cost function is given. At the same time, three corollaries are presented for the special circumstance without impulse, distributed time delays or time‐varying time delay, respectively. Finally, the feasibility of the theoretical results is verified by an example.
Protein Quakes in Redox Metalloenzymes: Clues to Molecular Enzyme Conductivity Triggered by Binding of Small Substrate Molecules
Authors: Bohr Henrik , Shim Irene , Ulstrup Jens , Xiao Xinxin
Published: October 2024

Multicentre redox metalloproteins undergo conformational changes on electrochemical surfaces, or on enzyme substrate binding. The two‐centre copper enzymes, laccase (Type I and TypeII/III Cu) and nitrite reductase (CuNIR) (Type I and Type II Cu) are examples. With some exceptions, these enzymes show no non‐turnover voltammetry on Au(111)‐surfaces modified by thiol based self‐assembled molecular monolayers, but dioxygen or nitrite substrate triggers strong electrocatalytic signals. Scanning tunnelling microscopy also shows high conductivity only when dioxygen or nitrite is present. Atomic force microscopy shows constant CuNIR height but pronounced structural expansion in the electrocatalytic range on nitrite binding. We have recently offered a rationale, based on ab initio quantum chemical studies of water/nitrite substitution in a 740‐atom CuNIR fragment. Presently we provide much more detailed structural assignment mapped to single‐residue resolution. NO2−‐binding induces both a 2 Å Cu−Cu distance increase, and pronounced frontier orbital delocalization strongly facilitating ET between the Cu regions. The conformational changes transmit from the catalytic Type II centre to the electron inlet Type I centre, via the His129‐Cys130 ligands, and via Type I–Cys130 or Type I‐His129 ending at Type II Asp92. The ET patterns are reflected in different atomic Mulliken charges in the water and nitrite CuNIR fragment.
Runt‐related transcription factor 1 (RUNX1) is a mediator of acute kidney injury
Authors: Fontecha‐Barriuso Miguel , Villar‐Gomez Natalia , Guerrero‐Mauvecin Juan , Martinez‐Moreno Julio M , Carrasco Susana , Martin‐Sanchez Diego , Rodríguez‐Laguna María , Gómez Manuel J , Sanchez‐Niño María D , Ruiz‐Ortega Marta , Ortiz Alberto , Sanz Ana B
Published: October 2024

Treatment for acute kidney injury (AKI) is suboptimal. A better understanding of the pathogenesis of AKI may lead to new therapeutic approaches. Kidney transcriptomics of folic acid‐induced AKI (FA‐AKI) in mice identified Runx1 as the most upregulated RUNX family gene. We then examined the expression of RUNX1 in FA‐AKI, in bacterial lipopolysaccharide (LPS)‐induced cytokine storm‐AKI (CS‐AKI), and in human AKI. In cultured mouse tubule cells, we explored the expression and role of RUNX1 in response to the cytokine TWEAK or LPS. A chemical inhibitor of RUNX1 (Ro5‐3335) was used in animal models of AKI to test its potential as a therapeutic target. RUNX1 overexpression in FA‐AKI was validated at the mRNA and protein levels and localized mainly to tubule cell nuclei. CS‐AKI also upregulated kidney RUNX1. Increased tubule and interstitial RUNX1 expression were also observed in human AKI. In cultured mouse tubule cells, the pro‐inflammatory cytokine TWEAK and LPS increased RUNX1 and IL‐6 expression. Mechanistically, RUNX1 bound to the Il6 gene promoter and RUNX1 targeting with the chemical inhibitor Ro5‐3335, or a specific small interfering RNA (siRNA), prevented the TWEAK‐ and LPS‐induced upregulation of IL6 through a RUNX1/NFκB1 p50 pathway. In vivo, preventive Ro5‐3335 improved kidney function and reduced inflammation in FA‐AKI and CS‐AKI. However, Ro5‐3335 administration after the insult only improved kidney function in CS‐AKI. Kidney transcriptomics identified inflammatory genes and transcription factor mRNAs such as Yap1 and Trp53 as key targets of Ro5‐3335 in CS‐AKI. In conclusion, RUNX1 contributes to AKI by driving the expression of genes involved in inflammation and represents a novel therapeutic target in AKI. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Understanding the Morphology and Cross‐Link Density in Silicone Rubber‐Multiwalled Carbon Nanotube Composites via Solvent Transport Studies
Authors: Krishnageham Sidharthan Sisanth , Keloth Paduvilan Jibin , Velayudhan Prajitha , Kaliyathan Abitha Vayyaprontavida , Krishnan Remya , Zapotoczny Szczepan , Thomas Sabu
Published: October 2024

The diffusion characteristics of silicone rubber‐based nanocomposites have not been extensively studied in the literature. This study aims to provide a comprehensive analysis of the solvent transport properties of these materials, incorporating detailed dissolution modeling. This study reported a novel approach to elucidate the morphological and diffusion characteristics of silicone rubber‐MWCNT (multiwalled carbon nanotube) composites. FESEM micrograph analysis reveals structural changes with the lower loadings forming continuous networks and higher loadings leading to agglomeration of the fillers. Diffusion studies highlight reduced solvent uptake over time due to compact physical networks, while Kraus plot analysis confirms MWCNTs' reinforcing ability. Dissolution modeling using Korsmeyer–Peppas and Peppas–Sahlin models indicates the type of solvent release behavior, with the latter offering a superior fit. Mode of transport analysis suggests a less Fickian mode influenced by MWCNT loading, while swelling parameters demonstrate hindered solvent transport with increasing MWCNT content. The molecular mass between successive cross‐links and the cross‐link density decreases with rising MWCNT loading, which is theoretically predicted by the affine model. This study also focused on the complex interplay between filler loading, composite structure, and solvent transport behavior in silicone rubber‐MWCNTs composites, offering valuable insights for their potential applications in various fields.
Enhanced cellular death in liver and breast cancer cells by dual BET/BRPF1 inhibitors
Authors: Cazzanelli Giulia , Dalle Vedove Andrea , Sbardellati Nicolò , Valer Luca , Caflisch Amedeo , Lolli Graziano
Published: October 2024

The acetylpyrrole scaffold is an acetylated lysine mimic that has been previously explored to develop bromodomain inhibitors. When tested on the hepatoma cell line Huh7 and the breast cancer cell line MDA‐MB‐231, a few compounds in our acetylpyrrole‐thiazole library induced peculiar morphological changes, progressively causing cell death at increasing concentrations. Their evaluation on a panel of human bromodomains revealed concurrent inhibition of BRPF1 and BET bromodomains. To dissect the observed cellular effects, the acetylpyrrole derivatives were compared to JQ1 and GSK6853, chemical probes for the bromodomains of BET and BRPF1, respectively. The appearance of neurite‐like extrusions, accompanied by βIII‐tubulin overexpression, is caused by BET inhibition, with limited effect on cellular viability. Conversely, interference with BRPF1 induces cellular death but not phenotypic alterations. Combined treatment with JQ1 and GSK6853 showed additivity in reducing cellular viability, comparably to the acetylpyrrole‐thiazole‐based BET/BRPF1 inhibitors. In addition, we determined the crystallographic structures of the BRD4 and BRPF1 bromodomains in complex with the acetylpyrrole‐thiazole compounds. The binding modes in the two bromodomains show similar interactions for the acetylpyrrole and different orientations of the moiety that point to the rim of the acetyl‐lysine pocket.
Protein degradation of antizyme depends on the N‐terminal degrons
Authors: Hsieh Ju‐Yi , Leong Pui‐Ying , Yang Yi‐Fang , Liu Yi‐Liang , Liu Guang‐Yaw , Hung Hui‐Chih
Published: October 2024

Antizyme (AZ) is a regulatory protein that plays a crucial role in modulating the activity of ornithine decarboxylase (ODC), which is the initial and rate‐limiting enzyme in the complex pathway of polyamine biosynthesis. AZ facilitates the swift degradation of ODC, thereby modulating the levels of cellular polyamines. This study unveils a new ubiquitin‐independent mechanism for AZ degradation, emphasizing the essential role of N‐terminal degrons. Contrary to traditional ubiquitin‐dependent degradation, our findings reveal that AZ degradation is significantly influenced by its N‐terminal region. By conducting a series of experiments, including in vitro degradation assays, cycloheximide chase experiments, differential scanning calorimetry, and measurement of cellular concentrations of polyamines, we demonstrate that N‐terminal truncation significantly enhances AZ's stability and facilitates the reduction of polyamine levels by accelerating ODC degradation. The removal of the N‐terminal portion of AZ results in a reduced degradation rate and enhanced thermal stability of the protein, leading to a more efficient inhibition of polyamine synthesis. These findings are corroborated by the analysis of AZ isoforms, AZ1, AZ2, and AZ3, which display differential degradation patterns based on the specific N‐terminal segments. This substantiates a degradation mechanism driven by an intrinsically disordered N‐terminal region acting as a degron, independent of lysine ubiquitination. These results underscore the significant regulatory function of the N‐terminal domain in the activity of AZ and the maintenance of polyamine homeostasis.
Acaricide resistance mechanisms and host plant responses in the tomato specialist Aculops lycopersici
Authors: Vervaet Lore , Charamis Jason , Vandenhole Marilou , Vontas John , Van Leeuwen Thomas
Published: October 2024

BACKGROUND

The mite Aculops lycopersici is a major tomato pest with extremely reduced gene families involved in chemoreception and detoxification. How this limited detoxification toolbox affects the evolution of resistance to acaricides in tomato russet mite(s) (TRM) remains enigmatic. Moreover, although a tomato specialist, TRM has been observed on other Solanaceae and Convolvulaceae plant species, raising questions about transcriptional plasticity underlying host exchange.

RESULTS

We identified a field strain with strongly decreased susceptibility to both abamectin and spiromesifen. We detected target‐site resistance caused by mutations at conserved positions in two glutamate‐gated chloride channels (GluCl), as well as four overexpressed detoxification genes. We then examined transcriptional responses after host shift from tomato to two Solanaceae (potato and black nightshade) and two Convolvulaceae (sweet potato and hedge bindweed) species, as more challenging host plants. Transcriptional responses varied significantly between host plant families, with key differentially expressed genes (DEGs) related to proteolytic, metabolic and detoxification processes. Last, we also identified DEGs encoding for secreted proteins potentially involved in TRM–host plant interactions.

CONCLUSIONS

Despite a limited detoxification toolbox, A. lycopersici might quickly evolve target‐site resistance, probably facilitated by strong selection pressure on the genetic variation associated with enormous population size in field settings. Responses to host plant changes include plasticity in genes related to digestion and detoxification, while most responsive genes are of unknown function and remain to be investigated. © 2024 Society of Chemical Industry.
miRNAs targeted transcription factors HaGATAa/b to mediate the post‐mating switch in Helicoverpa armigera female reproductive behavior
Authors: Zhang Songdou , Cai Limei , Wang Yilin , Liu Xiaoxia
Published: October 2024

BACKGROUND

The process of mating induces significant shifts in female reproductive behavior across various species, with the postmating behavioral switch playing a crucial role in insect reproduction. Previous studies have demonstrated the regulatory role of GATA transcription factors in vitellogenin transcription and egg formation in insects, while miRNAs have been implicated in modulating GATA expression and insect reproductive processes. Nevertheless, the precise regulatory mechanism underlying the interaction between miRNAs and GATA transcription factors in the postmating behavioral switch remains largely unexplored.

RESULTS

In this study, we identified two key GATA transcription factors, HaGATAa and HaGATAb, as central players in orchestrating the postmating behavior of H. armigera using transcriptomics and RNAi technologies. HaGATAa was found to act upstream of HaGATAb, regulating its expression. Furthermore, we observed a postmating increase in miR‐282 levels in females, targeting HaGATAa to regulate egg‐laying capacity. Conversely, the decreased expression of miR‐2 following mating functioned as a negative feedback regulator, influencing the expression of HaGATAb and thus impacting the postmating behavior of female individuals.

CONCLUSION

Our results revealed a signal‐mediated feedback regulatory mechanism that sustains female postmating behavior in H. armigera. These findings not only establish a strong basis for understanding the postmating behavior mechanisms in female moths, but also offer valuable insights for identifying potential targets for pest control strategies. © 2024 Society of Chemical Industry.
Formononetin Induces Ferroptosis in Activated Hepatic Stellate Cells to Attenuate Liver Fibrosis by Targeting NADPH Oxidase 4
Authors: Liu Ming‐xuan , Gu Ying‐ying , Nie Wen‐yuan , Zhu Xiao‐ming , Qi Meng‐jing , Zhao Rui‐min , Zhu Wei‐zhong , Zhang Xiao‐ling
Published: October 2024

Ferroptosis is a newly discovered type of cell death that exerts a crucial role in hepatic fibrosis. Formononetin (FMN), a natural isoflavone compound mainly isolated from Spatholobus suberectus Dunn, shows multiple biological activities, including antioxidant, anti‐inflammatory, and hepatoprotection. This research aims to explore the regulatory mechanism of FMN in liver fibrosis and the relationship between NADPH oxidase 4 (NOX4) and ferroptosis. The effects of FMN on HSC ferroptosis were evaluated in rat model of CCl4‐induced hepatic fibrosis. In vitro, N‐acetyl‐L‐cysteine (NAC) and deferoxamine (DFO) were used to block ferroptosis and then explored the anti‐fibrotic effect of FMN. The target protein of FMN was identified by bio‐orthogonal click chemistry reaction as well as drug affinity responsive target stability (DARTS), cellular thermal shift (CETSA), surface plasmon resonance (SPR) assays, and isothermal titration calorimetry (ITC) analysis. Here, we found that FMN exerted anti‐fibrotic effects via inducing ferroptosis in activated HSCs. NAC and DFO prevented FMN‐induced ferroptotic cell death and collagen reduction. Furthermore, FMN bound directly to NOX4 through possible active amino acid residues sites, and increased NOX4‐based NADPH oxidase activity to enhance levels of NADP+/NADPH, thus promoting ferroptosis of activated HSCs and relieving liver fibrosis. These results demonstrate that the direct target and mechanism by which FMN improves liver fibrosis, suggesting that FMN may be a natural candidate for further development of liver fibrosis therapy.
Co‐Micronized Palmitoylethanolamide and Rutin Associated With Hydroxytyrosol Recover Diabesity‐Induced Hepatic Dysfunction in Mice: In Vitro Insights Into the Synergistic Effect
Authors: Melini S. , Pirozzi C. , Lama A. , Comella F. , Opallo N. , Del Piano F. , Di Napoli E. , Mollica M. P. , Paciello O. , Ferrante M. C. , Mattace Raso G. , Meli R.
Published: October 2024

Metabolic dysfunction‐associated fatty liver disease (MAFLD) and diabesity (diabetes related to obesity) are interrelated since glucose and lipid alterations play a vital role in the development of both disorders. Due to their multi‐variant metabolic features, more than one drug or natural product may be required to achieve proper therapeutic effects. This study aimed to evaluate the effectiveness of a formulation containing co‐micronized palmitoylethanolamide and rutin (PEA‐Rut) associated with hydroxytyrosol (HT), namely NORM3, against hepatic damage and metabolic alterations in high‐fat diet (HFD)‐induced diabesity in mice. NORM3 decreased the body weight and fat mass of obese mice. The formulation improved HFD‐altered insulin sensitivity and hepatic glucose production and metabolism, as shown by glucose, insulin, pyruvate tolerance tests, Western blot, and real‐time PCR. In the liver, NORM3 limited macro‐ and micro‐vacuolar steatosis, as revealed by morphological analysis, and reduced the associated hepatic inflammation. NORM3 counteracted lipid dysfunctions of HFD animals, activating AMPK, a key cellular energy sensor, and normalizing the expression of carnitine palmitoyl‐transferase (CPT)1, a rate‐limiting enzyme of fatty acid β‐oxidation, and other genes involved in lipid homeostasis. Relevantly, the hepatic antioxidant activity of NORM3 was proved (reduced ROS and increased detoxifying factors and enzymes). Finally, in vitro synergistic protective effects of the components (PEA‐Rut and HT) on H2O2‐induced oxidative challenge in HepG2 were determined (ROS production, inflammation, and antioxidant defense). Our results show the beneficial effect of NORM3 and its potential as an innovative phytotherapeutic combination in limiting hepatic damage progression and counteracting glucose and lipid dysmetabolism associated with diabesity.
Are holograms sculpture, or is that pile of Cola cans really art?
Authors: Wu Yingjie , Rich Paul
Published: October 2024

This article delves into the question of what constitutes art in public and discusses the changes in the art world. Although realism has gained popularity in public spaces for a long time, critics are emerging regarding the subject of art figures. Given the rapid technological advancement, various forms of art, including AI‐programmed ones, are coming into being. The example of holography is achieving what is beyond the limits of realism. Artists have been using AI to program public installations, and the trend of using data to create sculptures has been growing, particularly among younger artists. Still, one basic question is whether the new techniques, if that is the applicable term, deserve to be included in the art panoply. The other question concerns the subjects. Using examples of artworks by famous figures including Refik Anadol, Andrew Lacey, Simon Verity, Liza Lou, Kara Walker, and Scott Burton, this discussion paper contributes to the debate on the expression of diverse art forms and how public perceptions change over time.
The four strands: A simplified approach to SLA for CLIL
Authors: Yeo Marie Alina , Newton Jonathan Mark
Published: October 2024

While it is widely accepted that language teachers require knowledge of second language acquisition (SLA) (Richards, 2010), what about content teachers, who are increasingly required to help develop their learners' academic language proficiency? How much do they need to know about SLA theories and how can they acquire such knowledge and expertise? This article proposes P. Nation's (2007) four strands framework as a straightforward and accessible model for content and language integrated learning (CLIL) teachers to address the challenge of balancing content and language instruction, a common concern within CLIL programs. The article begins by looking at two well‐known CLIL teacher competence frameworks. It then raises questions about the extent to which CLIL teachers need to master aspects of pedagogical content knowledge about SLA. The authors argue that while CLIL teachers do indeed need knowledge of how languages are learned and of SLA‐informed approaches to developing learners' second language (L2) proficiency, questions about just how much SLA knowledge CLIL teachers need and how they can be equipped with this knowledge remain unanswered. By delineating language learning opportunities into the four strands framework—meaning‐focused input, meaning‐focused output, language‐focused learning, and fluency development—the authors illustrate how this framework offers a practical guide for integrating language and content education effectively in CLIL and bilingual education contexts. The article ends with a presentation of three principles to help CLIL teachers achieve both the content and language teaching objectives of CLIL.
Variation in the detection of lymphovascular invasion in T1 colorectal cancer and its impact on treatment: A nationwide Dutch study
Authors: van der Schee Lisa , Verbeeck Annabelle , Deckers Ivette A. G. , Kuijpers Chantal C. H. J. , Offerhaus G. Johan A. , Seerden Tom C. J. , Vleggaar Frank P. , Brosens Lodewijk A. A. , Moons Leon M. G. , Snaebjornsson Petur , Laclé Miangela M. ,   the Dutch T1 CRC Working Group
Published: October 2024

Background

Lymphovascular invasion (LVI) plays an important role in determining the risk of lymph node metastasis (LNM) in T1 colorectal cancer (CRC) patients and influencing treatment decisions and patient outcomes.

Objective

This study evaluated how the detection of LVI varies between Dutch laboratories and investigated its impact on the treatment and oncological outcomes of T1 CRC patients.

Methods

Pathology reports and clinical data of T1 CRC patients who underwent local resection between 2015 and 2019 were obtained from the Dutch nationwide pathology databank (Palga cohort, n = 5513). Data on the standard of LVI diagnosis (H&E/Immunohistochemistry) were not available. We categorized laboratories as low, average, or high detectors and evaluated the impact of LVI detection practice on the surgical resection rate and the proportion of LNM‐negative (LNM‐) surgeries. In the second part of the study, we used the Dutch T1 CRC Working Group cohort (n = 1268) to evaluate the impact of LVI detection practice on cancer recurrences during follow‐up. Multivariable logistic regression analyses and Cox proportional hazard regression were used to study the association between LVI detection practice and the outcomes.

Results

In the PALGA cohort, the proportion of surgical resections after local resection of a T1 CRC was significantly higher among patients diagnosed by laboratories with a high LVI detection rate (high vs. low: adjusted OR [aOR] 1.87; 95% confidence interval [CI] 1.52–2.31) as was the proportion of LNM‐surgeries (aOR 1.73; 95% CI 1.39–2.15). In the second cohort, no significant difference was observed in cancer recurrences among patients diagnosed in laboratories with high detection rates compared with low detection rates (aHR 2.23; 95% CI 0.94–5.23).

Conclusion

These findings suggest that a high detection rate of LVI does not improve oncological outcomes and may expose more patients to unnecessary oncological surgery, emphasizing the need for standardization of LVI diagnosis.
Solid‐phase synthesis of grafted carbon black for superior aging resistance in biodegradable poly(butylene adipate‐co‐butylene terephthalate) composite films
Authors: Wang Ke , Sun Xiaoyan , Li Fayong , Xie Dong
Published: October 2024

Biodegradable films mitigate plastic pollution but often lack UV‐aging resistance, shortening their lifespan. While anti‐aging additives can boost the films' durability, small molecule migration constrains the extension of their service life. This study introduces a straightforward solid‐phase reaction for producing carbon black (CB) grafted with the UV absorber UV531, termed CB‐UV531. This material was then blended with the biodegradable polymer PBAT and transformed into a film via blow molding, yielding a durable UV‐resistant biodegradable film (PBAT/CB‐UV531). This solid‐phase grafting reaction does not require any solvents, thereby reducing solvent contamination and waste, and it is simple to operate, allowing for scalable production. Compared to the unmodified CB, the obtained CB‐UV531 exhibits significantly improved thermal stability, which can effectively reduce the loss of UV531 during the subsequent high‐temperature film‐blowing process. Furthermore, the chemically bonded UV absorber on the surface of CB‐UV531, coupled with its reduced particle size, promotes enhanced dispersibility and consistent stability within the PBAT/CB‐UV531 film, markedly improving its long‐term resistance to UV aging. This method is expected to enhance the anti‐aging effects of various commercial light stabilizer additives and can be used to extend the lifespan of different biodegradable materials.

Highlights

A simple solid‐phase reaction method was developed to prepare CB‐UV531.

CB‐UV531 reveals smaller size and superior dispersibility.

Biodegradable PBAT/CB‐UV531 film was prepared via a blowing process.

UV531 migration loss in PBAT/CB‐UV531 film is significantly reduced.

PBAT/CB‐UV531 film shows enhanced thermal stability and aging resistance.
Effect of intumescent flame retardants on the properties of poly(ethylene‐co‐vinyl acetate)/high‐density polyethylene blends
Authors: Kang Kyu‐Hyun , Kim Hyun‐Rae , Park Sangwon , Park Jong‐Seok , Hwang Daeyoung , Lee Byoung‐Min , Choi Jae‐Hak
Published: October 2024

This study investigates the innovative use of intumescent flame retardants (IFRs), specifically ammonium polyphosphate (APP), dipentaerythritol (DPER), and melamine cyanurate (MC), to enhance the flame retardancy and thermal stability of poly(ethylene‐co‐vinyl acetate)/high‐density polyethylene (EVA/HDPE) blends. The blends were prepared through a melt mixing process, followed by compression molding, allowing for a thorough integration of the IFRs into the polymer matrix. Comprehensive characterization techniques, including limiting oxygen index (LOI) measurements, UL‐94 vertical combustion tests, and cone calorimeter tests, were employed to evaluate the flame retardant performance of the blends. The findings reveal that the incorporation of IFRs significantly improves the flame retardant properties of the EVA/HDPE blends, achieving LOI values of 30.0% and UL‐94 ratings of V‐0 at higher IFR concentrations. This work contributes to the field by demonstrating the effectiveness of IFRs in forming a protective char layer that enhances thermal stability and reduces heat release during combustion. The study not only provides insights into the optimal formulation of EVA/HDPE blends for improved fire safety but also paves the way for the development of advanced materials suitable for applications in wire and cable insulation, where enhanced flame resistance is paramount.

Highlights

Intumescent flame retardants (IFRs) were incorporated to improve flame retardancy.

The effect of IFRs content was investigated.

EVA/HDPE/IFRs blends exhibited high thermal stability and flame retardancy.
Applying minirhizotrons to observe spatiotemporal variations in rooting depth and distribution in agroecosystems to improve the performance of hydrological models
Authors: Böske Lennart N. , Falge Eva , Liedtke Marco , Böttcher Christopher , Iwers‐Braden Dorothea , Meisner Heike , Herbst Mathias
Published: October 2024

To understand and explain soil moisture dynamics, the role of the vegetation is crucial. Hydrological processes in agricultural soils are strongly affected by rooting depth and root distribution. We present a new approach to monitor and model root dynamics and its influence on soil moisture using minirhizotrons combined with phenological observations. Field setups consist of a portable root scanner and acrylic glass tubes installed in the soil at the start of the growing season. 360° scans of soil and roots are taken regularly at different depths in the tubes. Root traits are identified automatically for each soil layer and complemented by observations of aboveground plant phenology. Results from minirhizotron data collected at an agrometeorological observatory in Germany show for both cereal and rapeseed (Brassica napus L.) crops a higher root density in deeper soil layers and a lower density near the soil surface when compared to literature data. An opposite picture emerged for maize (Zea mays L.) and potato (Solanum tuberosum L.), whereas vertical root distribution in sugar beet (Beta vulgaris subsp. vulgaris) had a different seasonal course than expected from literature. Applying the new root distribution data in calculations of the soil water balance resulted in differences of more than 3% in absolute volumetric soil water content. A comparison with in situ measurements of volumetric soil moisture at 20‐ and 50‐cm depth revealed a significant improvement of the model results due to the new parameterization. Thus, we argue that minirhizotrons constitute a useful supplement to hydrological observatories and can help understand and predict soil moisture dynamics in the critical zone.
Balancing Transparency and Risk: An Overview of the Security and Privacy Risks of Open-Source Machine Learning Models
Authors: Hintersdorf Dominik , Struppek Lukas , Kersting Kristian
Published: October 2024

The field of artificial intelligence (AI) has experienced remarkable progress in recent years, driven by the widespread adoption of open-source machine learning models in both research and industry. Considering the resource-intensive nature of training on vast datasets, many applications opt for models that have already been trained. Hence, a small number of key players undertake the responsibility of training and publicly releasing large pre-trained models, providing a crucial foundation for a wide range of applications. However, the adoption of these open-source models carries inherent privacy and security risks that are often overlooked. To provide a concrete example, an inconspicuous model may conceal hidden functionalities that, when triggered by specific input patterns, can manipulate the behavior of the system, such as instructing self-driving cars to ignore the presence of other vehicles. The implications of successful privacy and security attacks encompass a broad spectrum, ranging from relatively minor damage like service interruptions to highly alarming scenarios, including physical harm or the exposure of sensitive user data. In this work, we present a comprehensive overview of common privacy and security threats associated with the use of open-source models. By raising awareness of these dangers, we strive to promote the responsible and secure use of AI systems.
Thinking Outside the Box?
Authors: Ruschemeier Hannah
Published: October 2024

This legal article deals with the concept of regulatory sandboxes as part of experimental regulation to meet the challenges of digitalisation for legal regimes. It focuses on a critical analysis of the new provisions of the AI Act and their weaknesses in relation to the objectives of regulatory sandboxes to promote innovation and regulatory learning. Finally, suggestions for improvement and future areas of application are outlined.
Safer Than Perception: Increasing Resilience of Automated Vehicles Against Misperception
Authors: Fränzle Martin , Hein Andreas
Published: October 2024

Autonomous vehicles (AV) rely on environmental perception to take manoeuvre decisions. Safety assurance for AV thus hinges on achieving confidence in all percepts that are safe-guarding critical manoeuvres. As the safety targets for such critical manoeuvres are considerably higher than the statistical figures for the reliability of at least current learning-enabled classification algorithms within the environmental perception, we need means for assuring that the overall system is “safer than perception” in that the frequency of erratically adopting a critical manoeuvre is considerably lower than the frequency of individual misclassifications. We present a methodology for constructively generating reformulations of guard conditions that are more resilient to misperception than the original condition. The synthesized, rephrased guard conditions reconcile a given safety target, i.e. a given a societally accepted upper bound on erratically activating a critical manoeuvre due to a false positive in guard evaluation, with maximal availability, i.e. maximal true positive rate. By synthesizing a resilient rephrasing of the guard condition, the constructive setting presented herein complements the analytical setting from a previous companion paper [6], which merely analysed a given condition for its safety under uncertain perception.
Explanation of the excesses in associated di-photon production at 152 GeV in 2HDM
Authors: Banik Sumit , Crivellin Andreas
Published: October 2024

Abstract

Statistically significant excesses exist at around 152 GeV in associated di-photon production (γγ + X) in the sidebands of SM Higgs analyses of ATLAS (using the full run-2 dataset). They are most pronounced in the single-τ, missing-transverse-energy, four-jet and ⩾ 1ℓ+ ⩾ 1b-jet channels (≈ 3σ) and can be explained by the Drell-Yan production of new Higgs bosons, i.e. pp → W*→ H±H0. We first examine the excesses in a simplified model approach, considering that H± decays to τν, WZ or tb. Both the τν and tb decay modes individually lead to a significance of ⪅ 4σ while for WZ one can obtain at most 3.5σ. This is because the decays of WZ lead to multiple leptons contributing to the two-lepton channel which does not show an excess at 152 GeV. Next, we consider two-Higgs-doublet models where the charged Higgs does not decay to WZ at tree-level, finding a significance of ⪆ 4σ for a branching ratio of the new neutral Higgs to photons of ≈2%. Even though this branching fraction is quite sizable, it can be obtained in composite models or via the Lagrangian term $${\lambda }_{6}{H}_{1}^{†}{H}_{1}{H}_{2}^{†}{H}_{1}$$ + h.c. breaking the commonly imposed Z2 symmetry.