bluuebunny/crossref_metadata_2025 huggingface dataset:
17β‐estradiol promotes the progression of temporomandibular joint osteoarthritis by regulating the FTO/IGF2BP1/m6A‐NLRC5 axis
Authors: Xue Xintong , Li Changyi , Chen Shuang , Zheng Yan , Zhang Fan , Xu Yan
Published: August 2024

Background

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative cartilage disease. 17β‐estradiol (E2) aggravates the pathological process of TMJOA; however, the mechanisms of its action have not been elucidated. Thus, we investigate the influence of E2 on the cellular biological behaviors of synoviocytes and the molecular mechanisms.

Methods

Primary fibroblast‐like synoviocytes (FLSs) isolated from rats were treated with TNF‐α to establish cell model, and phenotypes were evaluated using cell counting kit‐8, EdU, Tanswell, enzyme‐linked immunosorbent assay, and quantitative real‐time PCR (qPCR). The underlying mechanism of E2, FTO‐mediated NLRC5 m6A methylation, was assessed using microarray, methylated RNA immunoprecipitation, qPCR, and western blot. Moreover, TMJOA‐like rat model was established by intra‐articular injection of monosodium iodoacetate (MIA), and bone morphology and pathology were assessed using micro‐CT and H&E staining.

Results

The results illustrated that E2 facilitated the proliferation, migration, invasion, and inflammation of TNF‐α‐treated FLSs. FTO expression was downregulated in TMJOA and was reduced by E2 in FLSs. Knockdown of FTO promoted m6A methylation of NLRC5 and enhanced NLRC5 stability by IGF2BP1 recognition. Moreover, E2 promoted TMJ pathology and condyle remodeling, and increased bone mineral density and trabecular bone volume fraction, which was rescued by NLRC5 knockdown.

Conclusion

E2 promoted the progression of TMJOA.
Physiologically Based Pharmacokinetic Modeling of Vancomycin in Critically Ill Neonates: Assessing the Impact of Pathophysiological Changes
Authors: Shuai Weiwei , Cao Jing , Qian Miao , Tang Zhe
Published: August 2024

Dosing vancomycin for critically ill neonates is challenging owing to substantial alterations in pharmacokinetics (PKs) caused by variability in physiology, disease, and clinical interventions. Therefore, an adequate PK model is needed to characterize these pathophysiological changes. The intent of this study was to develop a physiologically based pharmacokinetic (PBPK) model that reflects vancomycin PK and pathophysiological changes in neonates under intensive care. PK‐sim software was used for PBPK modeling. An adult model (model 0) was established and verified using PK profiles from previous studies. A neonatal model (model 1) was then extrapolated from model 0 by scaling age‐dependent parameters. Another neonatal model (model 2) was developed based not only on scaled age‐dependent parameters but also on quantitative information on pathophysiological changes obtained via a comprehensive literature search. The predictive performances of models 1 and 2 were evaluated using a retrospectively collected dataset from neonates under intensive care (chictr.org.cn, ChiCTR1900027919), comprising 65 neonates and 92 vancomycin serum concentrations. Integrating literature‐based parameter changes related to hypoalbuminemia, small‐for‐gestational‐age, and co‐medication, model 2 offered more optimized precision than model 1, as shown by a decrease in the overall mean absolute percentage error (50.6% for model 1; 37.8% for model 2). In conclusion, incorporating literature‐based pathophysiological changes effectively improved PBPK modeling for critically ill neonates. Furthermore, this model allows for dosing optimization before serum concentration measurements can be obtained in clinical practice.
Increased levels of circulating cell‐free double‐stranded nucleic acids in the plasma of glioblastoma patients
Authors: Rackles Elisabeth , Zaccheroni Elena , Lopez Patricia Hernandez , Faletti Stefania , Bene Massimiliano Del , DiMeco Francesco , Pelicci Giuliana , Falcon‐Perez Juan M
Published: August 2024

Circulating cell‐free nucleic acids are considered a promising source of biomarkers for diseases and cancer. Liquid biopsy biomarkers for brain tumours represent a major, still unmet, clinical need. In plasma, nucleic acids can be free or be associated with extracellular vesicles (EVs). Here we report an easy and reproducible method to analyse cell‐free nucleic acids in plasma and EVs by conventional flow cytometry easy to translate into the clinics. Nucleic acids associated with the EVs or present in plasma samples are stained by Pyronin Y, which is a fluorescent dye that is preferably binding double‐stranded nucleic acids. Fluorescent staining of EVs isolated from cell‐conditioned media is suitable for DNA and RNA detection by flow cytometry. The nucleic acids are partially protected from degradation by the EVs’ membrane. Additionally, DNA and RNA can be stained in plasma samples and plasma‐derived EVs. Remarkably, analysis of plasma from patients and healthy individuals reveals a difference in their nucleic acid profiles. Taken together, our results indicate that the proposed methodology, which is based on conventional direct flow cytometry, is a promising easy tool for plasma nucleic acid analysis.
A matter of timing? A systematic review of work scheduling dynamics in work recovery research and applications
Authors: Sloan Molly M. , Busick Cortney , Mitropoulos Tanya , Dosumu Fiyinfunjah , Calderwood Charles
Published: August 2024

Work recovery reflects the replenishment of personal resources depleted by working, which has implications for employee health and wellness. However, work scheduling factors have received very limited attention in the recovery literature, despite that recovery is a dynamic process widely recognized to be influenced by contextual factors that define and influence the work role. After first conducting a narrative review of whether and how work scheduling factors are accounted for in existing theories of work recovery, we conduct a systematic review of existing work recovery research to identify any past empirical consideration of work scheduling factors in the recovery research base. We then harness the results of this systematic review to develop a taxonomy of work scheduling and related contextual factors that may be relevant to the process of recovery from work. We discuss the theoretical, practical, and methodological implications that emerged from our narrative and systematic reviews, providing guidance for how this newly developed taxonomy can be applied to understanding the implications of scheduling dynamics for work recovery across a range of different work contexts.
Pioneering Nit Gene Exploitation to Develop Molecular Diagnostic Assay for Rapid Detection of Cotton Root Rot Incitant, Macrophomina phaseolina (Tassi) Goid, in Field Soil
Authors: Saini Anil Kumar , Kumar Mukesh , Singh Karmal , Bhambhu Mukul Kumar , Nain Rohit , Garima  , Aakash  , Mandhania Shiwani , Saini Shubham
Published: August 2024

Cotton root rot caused by Macrophomina phaseolina pose a significant threat to cotton production, leading to substantial yield and quality losses. Early and accurate diagnosis of this pathogen in soil is crucial for effective disease management. This study presents a pioneering investigation into the utilization of the nit gene encoding nitrilase for the development of a molecular diagnostic assay aimed at the rapid detection of M. phaseolina in field soils. The methodology involved the design and validation of primers targeting the Nit gene sequence, followed by the optimization of PCR conditions for efficient amplification. Leveraging state‐of‐the‐art molecular techniques, the assay offers a novel protocol to accurately identify the presence of M. phaseolina in soil with high sensitivity and specificity. The specificity of the designed primers was confirmed through PCR amplification using DNA from M. phaseolina and other related fungi. Sensitivity tests demonstrated that the PCR assay reliably detected M. phaseolina DNA at concentrations as low as 1 ng. Furthermore, the performance of the diagnostic assay was rigorously evaluated using field soil samples with a known status of M. phaseolina infection, demonstrating its reliability and efficacy in real‐world scenarios. This study introduces a novel molecular marker for the detection of M. phaseolina and offers a rapid and efficient means for screening M. phaseolina in large soil samples with minimal time and manpower.
Seasonally dry tropical forests in the late Pleistocene of Mesopotamia, Argentina and their relationship to environmental changes during the Last Interglacial
Authors: Fernandez Pacella L. , Baez J. , Crisafulli A. , Roig M. , Di Pasquo M. , Luna C.A. , Fagúndez I. , Martinez M. , Cuaranta P.
Published: August 2024

The concept of seasonal forests groups structural types of vegetation that are related to climatic seasonality in the tropics of South America. Consequently, this determines the physiognomy of the vegetation, from semi‐deciduous to strongly deciduous. The strongest link between seasonally dry tropical forests (SDTFs) is their floristic composition, where Leguminosae and Anacardiaceae dominate the woody flora. The fossil records of the Neogene of northwestern Argentina reveal a list of species found in various locations and formations of the Miocene–Lower Pleistocene obtained from studies of pollen, woods (logs), cuticles, impressions of leaves and fruits. The analysis of sediments and woody structures from the Tapebicuá, Toropí/Yupoí and El Palmar Formations (Upper Pleistocene) of the Mesopotamia region allowed us to identify several pollen taxa and silicified wood fragments (mineralized). The woody and shrubby association whose current relatives characterize the SDTF is composed of the 16 fossil species described here belonging to seven families. In our samples, Anadenanthera colubrina and Myracrodruon balansae are the most significant members of the families Leguminosae and Anacardiaceae, which are dominant in the SDTF. The paleobotanical species described in this study confirm the extension of the SDTF to the province of Corrientes, coinciding with various climatic events (dry subtropical, semi‐desert and warm‐humid climate) that would have favored the development of these forests during the Pleistocene in this region. The absolute dates obtained for the Toropí/Yupoí and Tapebicuá Formations confirm their synchronicity and correlation to Marine Isotope Stage 5. The palynological analysis, the presence of Menendoxylon and the sedimentological data allow us to infer the existence of a seasonally dry humid paleoclimate in northeastern Argentina during the Late Pleistocene favorable to the development of the SDTF.
Effect of sorghum bran addition on antioxidant activities, sensory properties, and in vitro starch digestibility of Chinese southern‐style steamed bread
Authors: Zhang Pingping , Awika Joseph M
Published: August 2024

BACKGROUND

Chinese steamed bread (CSB) is one of the most important staple foods in China and is also popular in South‐East Asia. Developing functional CSB could improve people's resistance to inflammatory and non inflammatory diseases. This work investigated the effect of sorghum bran addition on antioxidant activities, sensory properties, and in vitro starch digestibility of Chinese southern‐style steamed bread (CSSB).

RESULTS

In this study, the enhanced CSSB with 0–200 g kg−1 of fine black and tannin (sumac) sorghum bran addition was developed. A small change in phenol content and antioxidant activity was observed at various stages in the processing procedure before steaming. Moreover, a high retention of antioxidant phenolics CSSB with sorghum bran addition was observed. Sorghum bran addition significantly increased the total phenol content and antioxidant activity of CSSB by 4.5–10 times, on average, relative to control. Sorghum bran addition significantly also increased the content of resistant starch, and significantly decreased in vitro starch digestibility in CSSB; these effects were likely due to the joint inhibitory effect of tannins and ferulic acid on starch digestibility. Interestingly, the sorghum bran breads scored higher or similar to control in sensory color preference and overall appearance, but lower on most textural and mouthfeel attributes.

CONCLUSION

Sorghum bran addition significantly increased the antioxidant activity of CSSB and significantly decreased starch digestibility. Moreover, the color and appearance properties were maintained or improved. However, the sensorial textural attributes were negatively impacted by the sorghum bran substitutions. Strategies to improve the texture of bran‐fortified breads would likely enhance their consumer acceptability. © 2024 Society of Chemical Industry.
Unintended consequences of wildlife feeders on spatiotemporal activity of white‐tailed deer, coyotes, and wild pigs
Authors: Saldo Elizabeth A. , Jensen Alex J. , Muthersbaugh Michael S. , Ruth Charles , Cantrell Jay , Butfiloski Joseph W. , Yarrow Greg K. , Kilgo John C. , Jachowski David S.
Published: August 2024

Supplemental feeding of wild ungulates has long been and remains a common practice across Europe and North America. Yet by drawing animals together, supplemental feeding can have unintended, negative effects on individual species and broader ecological processes. These include increased risk of disease transmission, intraspecific and interspecific competition, and predation, which are of management concern for white‐tailed deer (Odocoileus virginianus) in the southeastern United States given the arrival of nonnative wild pigs (Sus scrofa) and coyotes (Canis latrans). We conducted a field experiment between March and July of 2021 to assess the effects of supplemental feeding on spatiotemporal activity patterns of deer and wild pigs at wildlife feeders, and space use of coyotes in the Piedmont region of South Carolina, USA. We observed support for our hypothesis that interspecific competition through increased visitation by larger groups of competitor species reduces use of foraging sites by other subordinate ungulates, where feeders highly visited by wild pigs were rarely visited by deer. While adult deer and wild pigs generally did not shift their temporal activity patterns at feeders, juvenile temporal activity shifted to more frequent visits of feeders during the night, supporting our hypothesis that supplemental feed could increase risk to predator exposure, as coyotes tend to be active during crepuscular hours. Our findings suggest that supplemental feed put out to encourage deer activity could actually deter deer if wild pigs occupy that area, and has potential negative demographic effects if juveniles are at increased risk of predation. Collectively, based on our data, we do not recommend supplemental feeding in the southeastern United States where white‐tailed deer, coyotes, and wild pigs co‐occur. More broadly, given how widespread the legal use of supplemental feed remains across the United States, we encourage landowners and policymakers to consider the full suite of potential direct and indirect, short‐term and long‐term negative impacts supplemental feeding can have on both target and nontarget wildlife populations.
Surgical treatment for medium‐sized cystic osteochondral lesions of the talus: Autologous osteoperiosteal transplantation provides better clinical outcomes than bone marrow stimulation when cysts are deeper than 6 mm
Authors: Yang Shuai , Shao Qirui , Zhu Yu , Hu Fengyi , Jiang Dong , Jiao Chen , Hu Yuelin , Shi Weili , Guo Qinwei
Published: August 2024

Purpose

To compare clinical outcomes of autologous osteoperiosteal transplantation versus bone marrow stimulation (BMS) for medium‐sized (100–150 mm2) cystic osteochondral lesions of the talus (OLTs) and assess the correlation between patient demographics and outcomes. It was hypothesised that autologous osteoperiosteal transplantation would provide better clinical outcomes than BMS for medium‐sized cystic OLTs.

Methods

Patients who underwent autologous osteoperiosteal transplantation or BMS for medium‐sized cystic OLTs between 2014 and 2019 were retrospectively evaluated. According to their characteristics, a 1:1 propensity‐score matching was performed and 33 pairs of patients were matched. The visual analogue scale, American Orthopaedic Foot and Ankle Society (AOFAS) score, Foot Ankle Outcome Score (FAOS) and Ankle Activity Score were collected preoperatively and at the last follow‐up. In addition, a general linear model analysis was performed between patient demographics and clinical outcomes in two groups separately to detect potential risk factors.

Results

Finally, 28 patients in the grafted group and 27 patients in the BMS group completed the follow‐up and were enrolled with a mean follow‐up period of 63.5 ± 13.9 months. Both groups showed significant improvement in all patient‐reported outcomes (p < 0.01). At the final follow‐up, no significant differences between groups were found in all postoperative scores except FAOS Pain (p = 0.02). Correlation analysis showed a moderate correlation between cyst depth and the postoperative AOFAS score in the BMS group (r = −0.48, p = 0.01). Based on the regression line, the patients in the BMS group with a cyst deeper than 6 mm showed a lower AOFAS score than the mean score (88.7 ± 9.5) of the grafted group.

Conclusion

Autologous osteoperiosteal transplantation and BMS are both safe and effective for medium‐sized cystic OLTs. However, autologous osteoperiosteal transplantation is expected to provide better clinical outcomes than BMS when the cysts are deeper than 6 mm.

Level of Evidence

Level III.
Gradual stabilization and narrowing of bone tunnels following primary anterior cruciate ligament reconstruction
Authors: Liu Di , Lu Wenhao , Vithran Djandan Tadum Arthur , Bi Qing , Hong Zheping , Liu Xu , Yuan Dongliang , Chen Can , Xiao Wenfeng , Li Yusheng
Published: August 2024

Purpose

The purpose of this study is to dynamically assess variations in tunnel diameters following anterior cruciate ligament reconstruction (ACLR) and investigate correlations with patient‐reported outcomes (PROs) and graft maturity based on signal‐to‐noise quotient (SNQ).

Methods

Tunnel diameter and tunnel position were measured using three‐dimensional models derived from computed tomography (CT) data. Postoperative graft maturity and integration were evaluated using magnetic resonance imaging (MRI). Clinical outcomes were assessed through PROs, which included the International Knee Documentation Committee Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Scores and Lysholm scores. The correlation between tunnel enlargement extent, PROs and SNQ values, as well as correlations between confounding factors, tunnel diameter differences and SNQ were analyzed.

Results

A total of 73 participants underwent primary ACLR and scheduled follow‐ups. At the segment of the articular aperture, the femoral tunnel was enlarged by 32.3% to 10.4 ± 1.6 mm (p < 0.05), and the tibial tunnel was widened by 17.2% to 9.6 ± 1.2 mm (p < 0.05) at the 6‐month follow‐up. At 1 year postoperatively, diameters at the articular aperture were not further increased on the femoral (n.s.) and tibial (n.s.) sides. In early postoperative follow‐up, the femoral tunnel was anteriorly and distally shifted, coupled with posterior and lateral deviation involving the tibial side, exhibiting minimal migration at 1‐year follow‐up. The degree of tunnel widening was not correlated with PROs and SNQ values. Age, gender, body mass index (BMI), time from surgery to follow‐up, concomitant injuries and autograft type were not correlated with tunnel diameter differences and SNQ.

Conclusions

The femoral and tibial bone tunnels exhibited eccentrical widening and gradually stabilized at 1 year following ACLR. Furthermore, the enlarged bone tunnels were not correlated with unsatisfied PROs and inferior graft maturity.

Level of evidence

Level IV.
Recruitment responses of shade‐tolerant and heliophilous trees in degraded areas: The necessity of knowing the recruitment autecology of species for effective reforestation decisions
Authors: Croce Johanna , Badano Ernesto I. , Tálamo Andrés
Published: August 2024

Direct seeding is a reforestation technique that allows introducing a great variety of tree species in degraded areas with less logistics, but tree establishment rates are usually low because developing plants do not tolerate the high sun exposure, extreme temperatures, and low soil moisture that prevail in these habitats. This leads to the proposal that seeds should be planted beneath shrubs or herbaceous plants that ameliorate harsh abiotic conditions, although this can also trigger interspecific competition and impair the performance of developing trees. This study aimed to test these proposals in dry forests in northwest Argentina. For this, seeds of two shade‐tolerant trees and a heliophilous tree, native to this region, were sowed beneath the canopy of pioneer shrubs and in open spaces with and without herbaceous plants. After 2 years, our findings indicated that shade‐tolerant trees performed better beneath shrub canopies, while the heliophilous tree achieved higher establishment rates in the open spaces. Nevertheless, it seems that herbaceous plants compete with the tree seedlings and, therefore, they should be removed before conducting reforestation programs. Thus, we propose that direct seeding could be an efficient reforestation strategy, but the regeneration autecology of the tree species selected for this task, as well as their competitive ability in the face of the pioneer vegetation, must be carefully evaluated before seeding.
Soil quality associated with microbial community characteristics and dominant taxa across different tillage practices
Authors: Liu Wen‐Sheng , Zhu Zhang‐Hua , Lu Zhi‐Gang , Oladele Olatunde Pelumi , Dang Yash Pal , Zhao Xin , Zhang Hai‐Lin
Published: August 2024

Despite conservation tillage being a promising strategy to mitigate soil degradation, the intricate role of microbial communities in shaping soil quality over long‐term tillage remains poorly understood. The study aimed to investigate the microbial mechanisms governing the soil quality index (SQI) and maize yield under different tillage practices spanning 13 years, including no‐till without straw retention (NT0), no‐till with straw retention (NTSR), plough tillage with straw retention (PTSR), and rotary tillage with straw retention (RTSR). The findings revealed that NTSR improved the SQI index by 22.4% and 11.3% higher than PTSR and RTSR, respectively, within the 0–10 cm soil layer. This improvement was correlated with an increase in maize yield (R2 = 0.39, p < 0.05). PERMANOVA analysis confirmed that both soil depth and tillage practices significantly impacted the composition of microbial communities (p < 0.05). Furthermore, conservation tillage, compared to PTSR and RTSR, increased the abundance of arbuscular mycorrhizal symbiosis by 78.6%–460.3% but decreased the saprophytic fungal abundance by 27.5%–28.3%. Soil quality was notably influenced by the interaction between bacterial and fungal communities. The presence of bacterial‐dominated Module 2 was associated with decreased soil quality in the 0–10 cm soil depth (r = −0.47, p < 0.01). This study emphasizes the pivotal role of microbial diversity and dominant taxa in driving soil quality after long‐term conservation tillage practices. Understanding these mechanisms is crucial for establishing farmland management to achieve agricultural and ecological sustainability in the face of climate change and soil degradation challenges.
Comparative study on periodic immersion+infrared aging corrosion behavior of Q345qNH steel and Q420qNH steel in simulated industrial atmospheric environment medium
Authors: Guo T. , Yang H. , Wu W. , Liu X. , Nan X. , Hu Y.
Published: August 2024

The corrosion behavior of Q345qNH steel and Q420qNH steel in simulated industrial atmospheric environment medium was studied by periodic immersion+infrared aging corrosion experiment. The results show that the corrosion type of both samples is uneven comprehensive corrosion, and the rust layer formed in the later stage of corrosion is relatively dense. But average corrosion rate of Q345qNH steel is always lower than that of Q420qNH steel, and the ratio of Iα‐FeOOH/Iγ‐FeOOH in rust layer is always higher. Compared with Q420qNH steel, Q345qNH steel has fewer surface pits but deeper local pits. The self‐corrosion potential of Q345qNH steel increases obviously, the resistance of the rust layer is larger, and protection to the matrix is stronger. This is because the formation of a large number of corrosion microcells induced by fine lamellar sorbite tissue that uneven distributed in Q420qNH steel, which increases the corrosion rate and makes corrosion uneven, while the larger pearlitic group in Q345qNH steel increases the local corrosion rate. However, the higher chromium/carbon ratio in Q345qNH steel promotes the conversion of lepidocrocite to goethite and inhibits the cathode reaction in the infrared drying stage, improving the density and stability of the rust layer.
Targeting Hippo/YAP in intrahepatic cholangiocarcinoma: Promising molecules in cancer therapy
Authors: Ma Xing , Zhou Yangyang , Li Ruping , Ding Xianmin , Li Deyu , Pan Tingting , Zhang Fuqiang , Li Wenliang
Published: August 2024

The tumorigenesis of intrahepatic cholangiocarcinoma (ICC) has been identified to be exceptionally involved in dysregulated Hippo/Yes‐associated protein (YAP) signaling pathway (Hippo/YAP). Hippo/YAP functions as a master regulator engaged in a plethora of physiological and oncogenic processes as well. Therefore, the aberrant Hippo/YAP could serve as an Achilles' heel regarding the molecular therapeutic avenues for ICC patients. Herein, we comprehensively review the recent studies about the underlying mechanism of disrupted Hippo/YAP in ICC, how diagnostic values could be utilized upon the critical genes in this pathway, and what opportunities could be given upon this target pathway.
The anthraquinone derivative KA‐4s reduces energy metabolism and enhances the sensitivity of ovarian cancer cells to cisplatin
Authors: Zhao Yingdan , Li Xinxiao , Xu Shumei , Yang Yingying , Chen Qiangjian , Li Junying , Tian Wei , Zhang Qiuping , Hou Huaxin , Li Danrong
Published: August 2024

Ovarian cancer is the leading cause of death from female gynecological cancers. Cisplatin (DDP) is a first‐line drug for ovarian cancer treatment. Due to DDP resistance, there is an urgent need for novel therapeutic drugs with improved antitumor activity. AMPK‐mediated metabolic regulatory pathways are related to tumor drug resistance. Our study aimed to determine the relationship between reversing DDP resistance with the anthraquinone derivative KA‐4s and regulating AMPK energy metabolism in ovarian cancer. The results showed that KA‐4s inhibited the proliferation of ovarian cancer cells. The combination of KA‐4s with DDP effectively promoted drug‐resistant ovarian cancer cell apoptosis and inhibited cell migration and invasion. Moreover, KA‐4s decreased the intracellular ATP level and increased the calcium ion level, leading to AMPK phosphorylation. Further studies suggested that the AMPK signaling pathway may be involved in the mechanism through which KA‐4s reduce drug resistance. KA‐4s inhibited mitochondrial respiration and glycolysis; downregulated the glucose metabolism‐related proteins GLUT1 and GLUT4; the lipid metabolism‐related proteins SREBP1 and SCD1; and the drug resistance‐related proteins P‐gp, MRP1, and LRP. The inhibitory effect of KA‐4s on GLUT1 was confirmed by the application of the GLUT1 inhibitor BAY‐876. KA‐4s combined with DDP significantly increased the expression of p‐AMPK and reduced the expression of P‐gp. In a xenograft model of ovarian cancer, treatment with KA‐4s combined with DDP reduced energy metabolism and drug resistance, inducing tumor apoptosis. Consequently, KA‐4s might be evaluated as a new agent for enhancing the chemotherapeutic efficacy of treatment for ovarian cancer.
Effect of Early Levodopa Treatment on Mortality in People with Parkinson's Disease
Authors: Talebi Amir H. , Darweesh Sirwan K.L. , Bloem Bas R. , Bucur Ioan G. , Heskes Tom
Published: August 2024

Background

The ideal timing for initiating levodopa in newly diagnosed people with Parkinson's disease (PD) is uncertain due to limited data on the long‐term effects of levodopa.

Objective

The aim was to investigate whether early levodopa initiation postpones mortality (primary outcome), the requirement of device‐aided therapies, and the incidence of PD‐related complications, such as fall‐induced injuries.

Methods

Using nationwide claims data from Dutch hospitals (2012–2020), we grouped newly diagnosed PD individuals as “early initiators” (initiating levodopa within 2 years of diagnosis) or “nonearly initiators.” We used the national death registry to assess mortality and health‐care claims to assess PD‐related complications and device‐aided therapies. We used marginal structural models to compare mortality and device‐aided therapy rates between groups, and a Poisson regression model to compare PD‐related complication rates.

Results

Among 29,943 newly diagnosed PD individuals (mean age at diagnosis: 71.6, 38.5% female), there were 24,847 early and 5096 nonearly levodopa initiators. Over a median 4.25 years, 8109 (27.1%) died. The causal risk ratio for mortality was 1.04 (95% confidence interval [CI] 0.92–1.19) for early versus nonearly initiators. The risk ratio of receiving any device‐aided therapy was 3.19 (95% CI 2.56–5.80). No association was observed with incidence of PD‐related complications (incidence rate ratio: 1.00, 95% CI 0.96–1.05).

Conclusions

Early levodopa initiation in PD does neither postpone nor accelerate mortality or PD‐related complications, nor does it precipitate earlier occurrence of PD‐related complications or mortality. However, we cannot exclude that the results were influenced by residual confounding due to unmeasured risk factors of mortality.
Implications of the stigma of mental illness for professional knowledge development and practice: An Interprofessional Health Education framework from structural violence perspectives
Authors: Gyamfi Sebastian , Forchuk Cheryl , Luginaah Isaac
Published: August 2024

Persons with mental illness (PWMI) continue to encounter stigma from the public with negative outcomes. Recent stigma discourse points to power differentials as key in shaping stigma related to mental illness within social settings. The perceived social injustice towards PWMI is known to exist both anecdotally and in documented discourses. Stigma constitutes the product of public attitudes and behaviors that characterize labeling, stereotyping, prejudice, cognitive separation, status loss, and discrimination that lead to responses that may include stress and esteem‐related appraisal of experienced, anticipated, perceived, or personal endorsement of societal actions that are anchored by existing power relational differentials. The potential consequence of such societal injustices (unfair treatments) towards PWMI may result in stigma and its sequels, including low socioeconomic status, stress, low self‐esteem, unemployment, homelessness, exclusion, and human rights abuse. This paper proposes an Interprofessional Health Education framework and discusses the implications of such unfair social treatments for Professional knowledge development and practice among healthcare professionals, with the view to improving collaboration and patient care outcomes. A more collaborative model of care, where service users and clinicians regard each other as knowledgeable with shared power to achieve healthy outcomes, empowers patients even more in areas where they fall short.
Weighted ultrasound entropy imaging for HIFU ablation monitoring with improved sensitivity and contrast
Authors: Zhou Yingying , Yang Kun , Xu Jiahong , Cai Dejia , Zhou Xiaowei
Published: August 2024

Background

Although B‐mode imaging has been widely used in ultrasound‐guided high‐intensity focused ultrasound (HIFU) treatment, challenges remain in improving its quality and sensitivity for monitoring the thermal dose. Recently, quantitative ultrasound (QUS) imaging has been recognized with the potential to better sense the changes in the microstructure of ablated tissues.

Purpose

This study proposed to use a QUS method called weighted ultrasound entropy (WUE) imaging to monitor the HIFU ablation.

Methods

Based on ex‐vivo and in‐vivo experiments, WUE images reflecting tissue changes during HIFU treatment under different acoustic power levels (174–308 W) were reconstructed with a newly established imaging framework. The performance of the proposed WUE imaging in the monitoring of HIFU treatment was compared with the corresponding B‐mode images in terms of their contrast‐to‐noise ratios (CNRs) between the focal region and the background.

Results

It was found that HIFU irradiation with higher power generated larger WUE values in the focal region, and the bright spots grew in size as the acoustic sonication proceeded. Compared with the in‐situ B‐mode images, the WUE images had higher image quality in indicating lesion formation, with a 39.2%–53.4% improvement in the CNR at different stages. Meanwhile, a correlation (R = 0.84) between the damage area estimated in WUE images and that measured from the dissected ex‐vivo tissue samples was found.

Conclusions

WUE imaging is more sensitive and accurate than B‐mode imaging in monitoring HIFU therapy. These findings suggest that WUE imaging could be a promising technique for assisting ultrasound‐guided HIFU ablation.
High‐order in‐cell discontinuous reconstruction path‐conservative methods for nonconservative hyperbolic systems–DR.MOOD method
Authors: Pimentel‐García Ernesto , Castro Manuel J. , Chalons Christophe , Parés Carlos
Published: August 2024

In this work, we develop a new framework to deal numerically with discontinuous solutions in nonconservative hyperbolic systems. First an extension of the MOOD methodology to nonconservative systems based on Taylor expansions is presented. This extension combined with an in‐cell discontinuous reconstruction operator are the key points to develop a new family of high‐order methods that are able to capture exactly isolated shocks. Several test cases are proposed to validate these methods for the Modified Shallow Water equations and the Two‐Layer Shallow Water system.
Zwitterionic ZnO nanoparticles: Novel additives to synthesize high performance and fouling resistance thin‐film nanocomposite forward osmosis membrane
Authors: Shirazi Sadaf , Shakeri Alireza , Bonsale Rozgol , Razavi Reza , Salehi Hasan
Published: August 2024

Meeting the ever‐increasing need for clean water requires developing highly effective thin‐film nanocomposite (TFN) membranes with outstanding water permeability, selectivity, and good fouling resistance. In this work, ZnO nanoparticles were synthesized and coated with zwitterionic lysine amino acid (ZnO‐lysine) and then incorporated into a polyamide layer to improve their performance as well as to alleviate fouling. The organic shell on the ZnO‐lysine surface promoted the PA layer's interaction with ZnO‐lysine nanoparticles. TFN membranes demonstrated hydrophilic and smooth polyamide layers with improved permeability and selectivity. In particular, the TFN membranes' enhanced hydrophilicity and smooth surface synergized fouling reduction. In comparison to the bare TFC membrane (12.2 LMH) using 1 M NaCl as the draw solution, the ZnO‐lysine‐modified TFN‐ZL.400 membrane (21.1 LMH) yields a water flux that is 75% greater. In the polyamide layer, the zwitterionic functional groups of ZnO‐lysine not only improved the nanoparticles' chemical compatibility, preventing the creation of nonselective gaps, but also enhanced water flux and salt rejection. This study provides insight into the creation of zwitterionic‐functionalized nanoparticles that can successfully address fouling issues and trade‐off restrictions between selectivity and permeability in TFN membranes.
Spatial effects of infiltrating T cells on neighbouring cancer cells and prognosis in stage III CRC patients
Authors: Azimi Mohammadreza , Cho Sanghee , Bozkurt Emir , McDonough Elizabeth , Kisakol Batuhan , Matveeva Anna , Salvucci Manuela , Dussmann Heiko , McDade Simon , Firat Canan , Urganci Nil , Shia Jinru , Longley Daniel B , Ginty Fiona , Prehn Jochen HM
Published: August 2024

Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single‐cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5‐fluorouracil (5FU)‐based chemotherapy. Images underwent segmentation for tumour, stroma, and immune cells, and cancer cell ‘state’ protein marker expression was quantified at a cellular level. We developed a Python package for estimation of spatial proximity, nearest neighbour analysis focusing on cancer cell–T‐cell interactions at single‐cell level. In our discovery cohort (Memorial Sloan Kettering samples), we processed 462 core samples (total number of cells: 1,669,228) from 221 adjuvant 5FU‐treated stage III patients. The validation cohort (Huntsville Clearview Cancer Center samples) consisted of 272 samples (total number of cells: 853,398) from 98 stage III CRC patients. While there were trends for an association between the percentage of cytotoxic T cells (across the whole cancer core), it did not reach significance (discovery cohort: p = 0.07; validation cohort: p = 0.19). We next utilised our region‐based nearest neighbour approach to determine the spatial relationships between cytotoxic T cells, helper T cells, and cancer cell clusters. In both cohorts, we found that shorter distance between cytotoxic T cells, T helper cells, and cancer cells was significantly associated with increased disease‐free survival. An unsupervised trained model that clustered patients based on the median distance between immune cells and cancer cells, as well as protein expression profiles, successfully classified patients into low‐risk and high‐risk groups (discovery cohort: p = 0.01; validation cohort: p = 0.003). © 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.
Enhanced mechanical property and flame retardancy of halogen‐free PE/EVA composites through crosslinking and carbon fiber inclusion
Authors: Du Ao , Chen Hongmei , Chen Jie , Wang Bo , Cai Zeyun , Qiu Hua‐Jun , Xie Guoqiang
Published: August 2024

Due to the exceptional flame retardancy, environmental protection, cost‐effectiveness, and ease of processing, halogen‐free flame‐retardant polyethylene (PE) composites are attracting wide attention. However, the addition of halogen‐free flame retardants usually leads to significantly decreased mechanical properties of PE composites, which greatly limits its application. Herein, we report a halogen‐free flame‐retardant PE/ethylene‐vinyl acetate copolymer composite (PE/EVA) with excellent flame retardancy and mechanical properties by combining compatibilizer, crosslinking agent, and carbon fiber. The presence of compatibilizer not only improves the compatibility of halogen‐free flame retardants and matrix, but also interacts with the crosslinking agent to form a cladding structure on the surface of carbon fiber. The enhanced interaction between carbon fiber surface and matrix then results in significantly enhanced flame retardancy and mechanical properties of the composite. Specifically, adding 4 phr compatibilizer, 0.5 phr crosslinking agent, and 10 phr carbon fiber will lead to the halogen‐free flame‐retardant PE/EVA composite with a UL‐94 V‐1 level, limiting oxygen index of 27.1, and an increased tensile strength by 84.02% reaching 19.12 MPa. Moreover, further carbon fiber surface modification can further enhance the flame retardancy of the composite probably due to a synergistic flame‐retardant effect caused by the surface modified nitrogen and silicon elements. As a result, the composite achieves UL‐94 V‐0 level and the limiting oxygen index of 27.7 with well‐retained high tensile strength of 15.19 MPa. This work provides a practical strategy for enhancing the flame retardancy and mechanical property of PE‐based composite simultaneously.

Highlights

Compatibilizer interacts with crosslinking agent to form a cladding structure on the surface of carbon fiber.

Crosslinking agent promotes the formation of chemical bonds between modified carbon fiber, compatibilizer, and matrix.

Carbon fiber surface modification can enhance the flame retardancy of the composite due to the synergistic flame‐retardant effect.
DeoxyriboNucleic acid‐enhanced carbon nanotube dispersed epoxy resin composites: Mechanical and thermal properties study
Authors: Li Qianxi , Peng Xiong , Zhong Xingu , Zhou Yi , Luo Tianye , Zhang Xinke
Published: August 2024

The homogeneous dispersion of multi‐walled carbon nanotubes (MWCNTs) in a polymer matrix significantly affects the overall properties of composites. In this study, MWCNTs/epoxy (EP) composites were prepared using DeoxyriboNucleic acid (DNA) as a dispersant. The MWCNTs were uniformly dispersed in a phenalkamine curing agent and crosslinked with an epoxy resin matrix. The non‐covalent functionalization of DNA‐dispersed MWCNTs was confirmed by characterizing both the pristine and DNA‐modified MWCNTs. Additionally, the dispersion state and stability of MWCNTs in the curing agent solution were evaluated. Tensile strength and single‐lap‐shear (SLS) were employed to assess the mechanical properties of the composites. The results indicated that the DNA‐dispersed MWCNTs composites exhibited superior strength and toughness, with tensile and shear strengths of 46.81 and 19.64 MPa, respectively, at optimal ratios. These values represent increases of 68.38% and 50.96% compared to pure EP. Dynamic mechanical thermal analysis (DMTA) revealed that the energy storage modulus of DNA‐dispersed MWCNTs/EP composites increased to 2722 MPa, a 24.7% enhancement over pure EP. Furthermore, the thermal properties of the composites were thoroughly investigated. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) showed that the initial decomposition temperature of the DNA‐assisted dispersed composites rose to 330°C. The macromolecular relaxation of the EP materials occurred at higher temperatures, leading to an increased glass transition temperature.

Highlights

DNA was used to disperse MWCNTs in phenalkamine curing agent.

MWCNTs/EP composites were made by crosslinking DNA‐dispersed MWCNTs with epoxy resin.

DNA‐dispersed MWCNTs boosted tensile and lap shear strength.

Thermal properties improved due to DNA‐dispersed MWCNTs, and increased the energy storage modulus of the composite.
Mechanical and thermal properties of rice husk/glass fiber/polylactic acid composites
Authors: Sun Yufeng , Zhang Ziheng , Wang Jinwei , Liu Hengyu , Shi Dongming , Liu Mingyang , Ying Jilai , Mu Wenlong , Li Defeng , Wu Song
Published: August 2024

Polylactic acid (PLA) composites reinforced with rice husk and glass fiber can improve the properties in the aera of the material for vehicle application. In this work, the PLA composite was made and its properties were evaluated using scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). SEM observed that the polymer matrix contained a uniform dispersion of 10 wt% rice husks. The tensile strength and bending strength of the composite are 45.8 and 48.2 MPa, respectively, which are 52% and 41% higher than that of the base material PLA. TGA revealed that the thermal stability of the composite deteriorated with increasing rice husk content. The DTG curve indicated that the incorporation of rice husk and glass fiber led to a reduction in the maximum degradation rate of the PLA matrix. As a result, the thermal degradation of the PLA composite exhibited enhanced stability. The average apparent activation energy (Ea) of the composite, determined using the Friedman (FD), Flynn Wall Ozawa (FWO), Starink (ST), and Kissinger (KS) models, falls within the range of 90 to 120 kJ mol−1.

Highlights

Silane coupling agent was used to improve the interfacial compatibility of fillers.

The synergistic action of rice husk and glass fiber fillers enhances the mechanical properties of polylactic acid composites.

The mean apparent activation energy (Ea) of the composite was calculated using four models, with values in the range of 90 to 120 kJ mol−1.

The Flynn Wall Ozawa and Starink models showed better stability against temperature changes compared to the Friedman model.
Effective recovery of limonene‐rich concentrate from lemon residues using terpene‐based deep eutectic solvents based on statistical experimental design
Authors: Horuzoğlu Melike Meryem , Satılmış Sefanur , Kurtulbaş Ebru , Şahin Selin
Published: August 2024

Introduction

Waste by‐products of the juice industry appear valuable for the circular economy concept, considering that the peel accounts for almost half of the total fruit weight. Therefore, the recovery of these highly valuable components from relevant biowaste has become a very interesting research topic.

Objective

The current study aims to develop an extraction process integrated with hydrophobic deep eutectic solvent (DES) based on statistical experimental design approach.

Material and methods

Homogenizer‐assissted extraction (HAE) was used to recover the citrus extract rich in limonene (the main component of the volatile mixture) from lemon peels. Menthol‐based deep eutectic mixtures were accompanied by carboxylic acids (formic, acetic, and propionic acids). Optimization continued on the combination that gave the highest efficiency (in terms of limonene content) among the solvents prepared at different molar ratios (1/1, 1/2, and 2/1). Process parameters were analyzed to optimize the process through central composite design with response surface method (RSM). D‐Limonene yield was quantified with gas chromatography–mass spectrometry (GC‐MS) with solid‐phase microextraction (SPME) technique. The quality of the lemon peel extracts was also evaluated with respect to in vitro bioactivity assays (phenolic content and 2,2‐diphenyl‐1‐picrylhydrazyl [DPPH] free radical scavenging activity).

Results

The maximum yield (3.80 mg‐limonene per g fresh sample) was achieved by 2 mg solid/30 mL DES, ~53 sec, and ~8500 rpm. Statistically most effective variable was identified as solid mass, followed by second powers of mixing speed and extraction time at p < 0.0001.