bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary Electrophoretograms Performed by Capillary Electrophoresis: Comparison between Dogs and Cats
Authors: Gil Laura , Wsol Martyna , Fernández-Barredo Salceda , Navarro Paula Fátima
Published: July 2023

Electrophoresis of urine to evaluate different urinary proteins has been used in recent years in veterinary medicine, as it can be a useful laboratory tool in the early detection of kidney damage. However, urinary capillary electrophoresis (UCE) has not been reported in healthy cats. In healthy dogs, reference intervals have been established and can be compared with pathological samples as these provide an easily interpretable pattern. The electrophoretogram in this study is divided into five fractions (F1–F5) by serum (albumin; alpha1-globulin; alpha2-globulin; beta-globulin; and gamma-globulin). Urine samples from 14 healthy cats were obtained by eco-guided cystocentesis. UCE was run in all samples and compared to 123 dog electrophoretograms from a previously published study. Fraction 2 (alpha1-globulin) was statistically decreased in cats (G1) compared to dogs (G2). Fraction 4 (beta-globulin) was statistically augmented in cats compared to the canine population (G2). Fraction 5 (gamma-globulin) was statistically decreased in cats (G1) compared to dogs (G2). No statistical correlation was found between each cat’s serum and urinary fractions. The results of the present study suggest that UCE patterns in cats are similar to the ones described in dogs. UCE can be a non-invasive new diagnostic tool in cats as pathological patterns can be compared to normal ones.
Latent Subtype of Cognitive Frailty among Multimorbidity Older Adults and Their Association with Social Relationships
Authors: Jiao Dandan , Li Xiang , Zhu Zhu , Zhang Jinrui , Liu Yang , Cui Mingyu , Matsumoto Munenori , Banu Alpona Afsari , Sawada Yuko , Watanabe Taeko , Tanaka Emiko , Anme Tokie
Published: July 2023

This study aimed to explore all the relevant subtypes of cognitive frailty among Japanese community-dwelling older adults with multimorbidity. Moreover, it examined the associations between these potential subtypes of cognitive frailty and social relationships. This study targeted relevant cross-sectional data regarding community-based older adults with multimorbidity. It employed a person-centered method to perform a latent class analysis and explore the subtypes of cognitive frailty among older adults. Moreover, a multinominal logistic regression analysis was employed to examine the association between potential subtypes of cognitive frailty and social relationships. Data for 396 participants (mean age, 75.8 [SD, 7.3] years; 51.3% females) were analyzed. Three cognitive frailty subtypes were subsequently revealed: the robust group (42.0%), the group with partial cognitive frailty (38.6%), and the group with cognitive frailty (19.4%). People with high levels of social relationships were more likely to be in the robust and the partial cognitive frailty groups. This study identified different subtypes of cognitive frailty among multimorbid older adults and highlighted the significance of social relationships. These findings could serve as a reference for conceptualizing cognitive frailty through the person-centered method. Promoting a high level of social relationships could be useful to prevent the cognitive frailty among older adults with multimorbidity.
Plant Growth Promoting and Colonization of Endophytic Streptomyces albus CINv1 against Strawberry Anthracnose
Authors: Pupakdeepan Waraporn , Termsung Natthida , Ruangwong On-Uma , Kunasakdakul Kaewalin
Published: July 2023

Strawberry anthracnose is a serious disease, and fungicides are currently widely used by farmers. Thus, biological control is a good alternative. This study aims to identify the species of endophytic Streptomyces CINv1 that was previously isolated from Cinnamomum verum J. Presl. and to evaluate its properties as a biocontrol agent, plant growth promoter, and plant colonizing endophyte. This strain was identified by analysis of its 16S rRNA gene sequences, and the result shows 100% similarity to Streptomyces albus CINv1. The CINv1 strain displayed high resistance (81.83%) against Colletotrichum sp. isolate CA0110, as tested by the dual culture technique. Additionally, inhibited pathogen growth on IMA-2 agar was observed under a compound microscope. The results demonstrated swelling, bulbousness, and cytoplasmic aggregation of abnormal hyphal, which were confirmed by SEM as well. Furthermore, the functional media used to evaluate plant growth-promoting properties, including nitrogen fixation, phosphate solubilization, and siderophore production, yielded positive results. Analyses of plant hormones by HPLC found their ability to produce indole-3-acetic acid (IAA). Thus, a biological control trial in greenhouse conditions was conducted by spraying a spore suspension of the strain onto strawberry seedlings once a week, which showed a significant reduction in disease severity. After the seventh spraying, the assessment of the number of leaves and canopy height of the seedling showed significant promotion. In addition, the CINv1 strain established a mutualistic interaction with the plant cells through colonization inter-and intracellularly in strawberry roots, leaves, and petioles. Moreover, using LC-MS/MS to analyze the secondary metabolites of this strain, various groups of compounds were found that could potentially benefit pharmaceutical and agricultural uses.
Estimating Nitrogen Release from Organic Fertilizers for Soilless Production by Analysis of C and N Pools
Authors: Lohr Dieter , Gruda Nazim S. , Meinken Elke
Published: July 2023

The use of organic fertilizers in soilless pot plant production has sharply increased in recent years. However, there is still a lack of methods for characterizing the N release from organic fertilizers. This bears the risk of an inadequate nutrient supply and, thus, a waste of resources. Therefore, the current research analyzed fourteen commercial organic fertilizers for various C and N pools by extraction in cold and hot water, acid hydrolysis, and thermal fractionation. Furthermore, we conducted an incubation test using a growing medium (80 vol% peat plus 20 vol% green waste compost) and fitted the nitrogen release to different kinetic models. Finally, we calculated the correlations among the best-suited kinetic model parameters and the C and N pools. The C and N pools soluble in water and weak hydrochloride acid varied significantly among the fourteen fertilizers but were closely correlated with each other. The N release from most organic fertilizers could be described very well using the Gompertz function (R² > 0.9), and the parameters of the Gompertz function showed significant correlations with the C and N pools. Hydrolyzable C and N pools provided valuable information about the N release characteristics of organic fertilizers.
Access to Healthcare Services among Thai Immigrants in Japan: A Study of the Areas Surrounding Tokyo
Authors: Supakul Sopak , Jaroongjittanusonti Pichaya , Jiaranaisilawong Prangkhwan , Phisalaphong Romruedee , Tanimoto Tetsuya , Ozaki Akihiko
Published: July 2023

Numerous undocumented and uninsured foreigners living in Japan have faced barriers when trying to obtain appropriate healthcare services, which have occasionally led to issues with unpaid medical bills to medical institutions. Although information on health and socioeconomic status is essential to tackle such issues, relevant data has been unavailable due to difficulties in contacting this population. This study involved a cross-sectional survey using questionnaires concerning the general demographic characteristics, socioeconomic status, health profiles, information access, and knowledge/attitude/practice of health insurance of Thai nationals living in Japan. The study participants included Thai nationals who lived in Tokyo and the surrounding prefectures. The survey was conducted mainly at public religious events from September 2022 to December 2022. Overall, the questionnaires were obtained from 84 participants, though 67 participants were included in the final analysis after excluding missing variables. There were participants with unspecified visa status (32.8%) and uninsured status (40.3%). Among them, 86.4% expressed positive attitudes towards health insurance. However, multivariate multivariable regression analyses revealed the low insurance practice status among the unspecified visa group (aOR, 0.02; 95% CI, 0.00–0.13). Overall, the results reveal limited access to healthcare services in subgroups of Thai immigrants in Japan.
Patient-Reported Outcome Measures in Liver and Gastrointestinal Cancer Randomized Controlled Trials
Authors: Winkelmann Carolin , Mezentseva Anna , Vogt Bodo , Neumann Thomas
Published: July 2023

Objective: For many years, outcomes such as mortality and morbidity were the standard for evaluating oncological treatment effectiveness. With the introduction of patient-reported outcome measures (PROMs), the focus shifted from a mere extension of a patient’s life or release from disease to the improvement of a multilayered concept of health, decisively affecting life satisfaction. In this study, we deal with the topic of PROMs in liver and gastrointestinal randomized controlled trials. Results: The final database included 43 papers reporting results of randomized controlled trials (RCTs) for liver or gastrointestinal cancer interventions where one of the primary or secondary outcomes was a health-related quality of life measure. The most often used PROM was the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) for both liver cancer and gastrointestinal cancer (in 62% of gastrointestinal cancer studies and 57% of liver cancer studies). For the gastrointestinal cancer group, the QLQ-STO22, a cancer-specific extension of the QLQ-C30, was the second most commonly used PROM. In liver cancer, the generic PROM Short Form 36 and the EORTC QLQ-HCC18, a cancer-specific extension of the QLQ-C30, were the second most commonly used PROMs. Conclusion: We found that RCTs often do not include comprehensive quality-of-life measures. When quality of life is part of an RCT, it is often only a secondary outcome. For a holistic view of the patient, a stronger integration and weighting of patient-reported outcomes in RCTs would be desirable.
The Effect of an Electronic Passive Prompt Intervention on Prolonged Occupational Sitting and Light-Intensity Physical Activity in Desk-Based Adults Working from Home during COVID-19 in Ireland
Authors: Buffey Aidan J. , Hayes Gráinne , Carson Brian P. , Donnelly Alan E.
Published: July 2023

This study aimed to assess the effect of passive prompts on occupational physical behaviours (PBs) and bouts of prolonged sitting among desk-based workers in Ireland who were working from home during the COVID-19 pandemic. Electronic passive prompts were delivered every 45 min, asking participants to walk for five minutes, during working hours. Twenty-eight participants (aged 30–67 years) completed the six-week intervention between October 2020 and April 2021. PBs were measured using an activPAL3TM accelerometer, following a 24 h wear protocol, worn for the duration of the study. Participants were highly sedentary at both baseline (77.71% of work hours) and during the intervention (75.81% of work hours). However, the number of prolonged occupational sedentary bouts > 90 min was reduced compared to baseline (0.56 ± 0.08 vs. 0.77 ± 0.11, p = 0.009). Similar reductions were observed in the time spent in sustained sitting > 60 and >90 min when compared to baseline sedentary patterns (60 min: −31.27 ± 11.91 min, p = 0.014; 90 min: −27.97 ± 9.39 min, p = 0.006). Light-intensity physical activity (LIPA) significantly increased during the intervention (+14.29%, p = 0.001). This study demonstrates that passive prompts, delivered remotely, can both reduce the number and overall time spent in prolonged bouts of occupational sedentary behaviour and increase occupational LIPA.
Examining the Effects of Gestational Physical Activity and Hofbauer Cell Polarization on Angiogenic Factors
Authors: Goudreau Alexandra D. , Tanara Layli , Tzaneva Velislava , Adamo Kristi B.
Published: July 2023

While gestational physical activity (PA) has demonstrated health benefits for both birthing parent and fetus, the mechanisms still need to be fully understood. Placental macrophages, or Hofbauer cells (HBCs), comprise a heterogenous population containing inflammatory (CD206-) and anti-inflammatory (CD206+) phenotypes. Similar to other tissue-resident macrophages (TRMs), HBCs are potential mediators of angiogenesis due to their secretion of both pro- and anti-angiogenic factors, including FGF2, VEGF, and SPRY2. While PA is associated with an increase in the proportion of VEGF- and FGF2-producing CD206+ macrophages in other tissues, the phenotypes producing FGF2, VEGF, and SPRY2 in the placenta and the associated relationships with gestational PA have not been studied. Using accelerometry, pregnant participants were classified as physically active or inactive in mid- and late-gestation. Term placenta tissue was collected at delivery and used for Western blotting and immunofluorescence to examine the protein expression of FGF2 and SPRY2, and to localize FGF2 in histological samples, respectively. Primary cultures of HBCs were used to examine the phenotypic differences in FGF2, SPRY2, and VEGF production. While no differences in the placental expression of SPRY2, total FGF2, or high-molecular-weight FGF2 were observed based on PA status, active individuals had significantly reduced levels of low-molecular-weight FGF2. Additionally, HBCs of all polarizations produce VEGF, FGF2, and SPRY2, and can form intercellular junctions and multinucleated giant cells. These findings suggest a possible relationship between PA and HBC-driven angiogenesis, providing an avenue for future exploration.
Preventing Loneliness and Reducing Dropout: Results from the COMPLETE Intervention Study in Upper Secondary Schools in Norway
Authors: Urke Helga Bjørnøy , Larsen Torill Bogsnes , Kristensen Sara Madeleine Eriksen
Published: July 2023

This study examines the impact of interventions aimed at improving psychosocial health on students’ perception of a caring school climate, their feelings of loneliness, and school completion in Norwegian upper secondary education. Two intervention conditions were tested: a universal single-tier intervention focused on improving the psychosocial school climate: the Dream School Program, and a multi-tier intervention combining the Dream School Program with a targeted measure, the Mental Health Support Team. The direct and indirect effects of these interventions on school completion were analyzed using structural equation models (SEM), with data from 1508 students (mean age at Time 1: 17.02 (SD = 0.92); 60.7% girls; 72.1% Norwegian-born). The results indicated that loneliness levels did not differ significantly between the intervention conditions. However, students in the multi-tier intervention group reported a significantly higher perception of a caring school climate compared to those in the single-tier intervention group. The multi-tier intervention group had a lower rate of school completion compared to the control group and the single-tier intervention group. The SEM analysis revealed that the multi-tier intervention reduced loneliness in the second year of upper secondary school by promoting a caring school climate in the first school year. In contrast, the single-tier intervention was associated with increased loneliness due to a decrease in the perception of a caring school climate. The implications of these findings are discussed.
Characterization of Glutathione Dithiophosphates as Long-Acting H2S Donors
Authors: Ishkaeva Rezeda A. , Khaertdinov Nail N. , Yakovlev Aleksey V. , Esmeteva Marina V. , Salakhieva Diana V. , Nizamov Ilyas S. , Sitdikova Guzel F. , Abdullin Timur I.
Published: July 2023

Considering the important cytoprotective and signaling roles but relatively narrow therapeutic index of hydrogen sulfide (H2S), advanced H2S donors are required to achieve a therapeutic effect. In this study, we proposed glutathione dithiophosphates as new combination donors of H2S and glutathione. The kinetics of H2S formation in dithiophosphate solutions suggested a continuous H2S release by the donors, which was higher for the dithiophosphate of reduced glutathione than oxidized glutathione. The compounds, unlike NaHS, inhibited the proliferation of C2C12 myoblasts at submillimolar concentrations due to an efficient increase in intracellular H2S. The H2S donors more profoundly affected reactive oxygen species and reduced glutathione levels in C2C12 myocytes, in which these parameters were elevated compared to myoblasts. Oxidized glutathione dithiophosphate as well as control donors exerted antioxidant action toward myocytes, whereas the effect of reduced glutathione dithiophosphate at (sub-)micromolar concentrations was rather modulating. This dithiophosphate showed an enhanced negative inotropic effect mediated by H2S upon contraction of the atrial myocardium, furthermore, its activity was prolonged and reluctant for washing. These findings identify glutathione dithiophosphates as redox-modulating H2S donors with long-acting profile, which are of interest for further pharmacological investigation.
MetaSpot: A General Approach for Recognizing the Reactive Atoms Undergoing Metabolic Reactions Based on the MetaQSAR Database
Authors: Mazzolari Angelica , Perazzoni Pietro , Sabato Emanuela , Lunghini Filippo , Beccari Andrea R. , Vistoli Giulio , Pedretti Alessandro
Published: July 2023

The prediction of drug metabolism is attracting great interest for the possibility of discarding molecules with unfavorable ADME/Tox profile at the early stage of the drug discovery process. In this context, artificial intelligence methods can generate highly performing predictive models if they are trained by accurate metabolic data. MetaQSAR-based datasets were collected to predict the sites of metabolism for most metabolic reactions. The models were based on a set of structural, physicochemical, and stereo-electronic descriptors and were generated by the random forest algorithm. For each considered biotransformation, two types of models were developed: the first type involved all non-reactive atoms and included atom types among the descriptors, while the second type involved only non-reactive centers having the same atom type(s) of the reactive atoms. All the models of the first type revealed very high performances; the models of the second type show on average worst performances while being almost always able to recognize the reactive centers; only conjugations with glucuronic acid are unsatisfactorily predicted by the models of the second type. Feature evaluation confirms the major role of lipophilicity, self-polarizability, and H-bonding for almost all considered reactions. The obtained results emphasize the possibility of recognizing the sites of metabolism by classification models trained on MetaQSAR database. The two types of models can be synergistically combined since the first models identify which atoms can undergo a given metabolic reactions, while the second models detect the truly reactive centers. The generated models are available as scripts for the VEGA program.
microRNA Expression of Renal Proximal Tubular Epithelial Cells and Their Extracellular Vesicles in an Inflammatory Microenvironment In Vitro
Authors: Baer Patrick C. , Neuhoff Ann-Kathrin , Schubert Ralf
Published: July 2023

Renal proximal tubular epithelial cells (PTCs) are central players during renal inflammation. In response to inflammatory signals, PTCs not only self-express altered mRNAs, microRNAs (miRNAs), proteins, and lipids, but also release altered extracellular vesicles (EVs). These EVs also carry inflammation-specific cargo molecules and are key players in cell–cell-communication. Understanding the precise molecular and cellular mechanisms that lead to inflammation in the kidney is the most important way to identify early targets for the prevention or treatment of acute kidney injury. Therefore, highly purified human PTCs were used as an in vitro model to study the cellular response to an inflammatory microenvironment. A cytokine-induced inflammatory system was established to analyze different miRNA expression in cells and their EVs. In detail, we characterized the altered miR expression of PTCs and their released EVs during induced inflammation and showed that 12 miRNAs were significantly regulated in PTCs (6 upregulated and 6 downregulated) and 9 miRNAs in EVs (8 upregulated and 1 downregulated). We also showed that only three of the miRNAs were found to overlap between cells and EVs. As shown by the KEGG pathway analysis, these three miRNAs (miR-146a-5p, miR-147b, and miR-155-5p) are functionally involved in the regulation of the Toll-like receptor signaling pathway and significantly correlated with the inflammatory mediators IL6 and ICAM1 released by stimulated PTCs. Especially with regard to a possible clinical use of miRs as new biomarkers, an accurate characterization of the miR expression altered during inflammatory processes is of enormous importance.
Molecular Characterization and Marker Development of the HMW-GS Gene from Thinopyrum elongatum for Improving Wheat Quality
Authors: Dai Yi , Li Jinfeng , Shi Juntao , Gao Yujiao , Ma Haigang , Wang Yonggang , Ma Hongxiang
Published: July 2023

The quality of wheat primarily depends on its storage protein quality, especially in regards to gluten content and high-molecular-weight glutenin subunits (HMW-GS). The number of HMW-GS alleles is limited in bread wheat (Triticum aestivum L.), whereas it is abundant in wheat relatives. Therefore, HMW-GS alleles from wheat relatives could provide a potential for improving quality in wheat breeding. Thinopyrum elongatum (EE) is one of the relatives of wheat. The E genome is closely related to the ABD genome in wheat; therefore, Th. elongatum is often used as an excellent exogenous gene donor for wheat genetic improvement. In this study, the high-molecular glutenin subunit gene was cloned and sequenced from Th. elongatum. A specific molecular marker for identifying the Glu-1Ey subunit gene was developed and applied to detected wheat-Th. elongatum alien introgression lines. Quality analysis indicated that the substitution and addition lines containing Th. elongatum alleles significantly (p < 0.05) increased grain protein content by 3.76% to 5.11%, wet-gluten content by 6.55% to 8.73%, flour 8-MW by 0.25% to 6.35%, and bread volume value by 33.77 mL to 246.50 mL, in comparing it with Chinese Spring. The GMP content and lactic acid SRC showed significant positive correlations with flour processing quality and might be used as indicators for wheat quality. The results were expected to provide a novel route for improving processing quality in wheat quality breeding.
Assessment of Different Circulating Tumor Cell Platforms for Uveal Melanoma: Potential Impact for Future Routine Clinical Practice
Authors: Martel Arnaud , Mograbi Baharia , Romeo Barnabe , Gastaud Lauris , Lalvee Salome , Zahaf Katia , Fayada Julien , Nahon-Esteve Sacha , Bonnetaud Christelle , Salah Myriam , Tanga Virginie , Baillif Stéphanie , Bertolotto Corine , Lassalle Sandra , Hofman Paul
Published: July 2023

Liquid biopsy and circulating tumor cell (CTC) screening has gained interest over the last two decades for detecting almost all solid malignancies. To date, the major limitation in terms of the applicability of CTC screening in daily clinical practice is the lack of reproducibility due to the high number of platforms available that use various technologies (e.g., label-dependent versus label-free detection). Only a few studies have compared different CTC platforms. The aim of this study was to compare the efficiency of four commercially available CTC platforms (Vortex (VTX-1), ClearCell FX, ISET, and Cellsearch) for the detection and identification of uveal melanoma cells (OMM 2.3 cell line). Tumor cells were seeded in RPMI medium and venous blood from healthy donors, and then processed similarly using these four platforms. Melan-A immunochemistry was performed to identify tumor cells, except when the Cellsearch device was used (automated identification). The mean overall recovery rates (with mean recovered cells) were 39.2% (19.92), 22.2% (11.31), 8.9% (4.85), and 1.1% (0.20) for the ISET, Vortex (VTX-1), ClearCell FX, and CellSearch platforms, respectively. Although paramount, the recovery rate is not sufficient to assess a CTC platform. Other parameters, such as the purpose for using a platform (diagnosis, genetics, drug sensitivity, or patient-derived xenograft models), reproducibility, purity, user-friendliness, cost-effectiveness, and ergonomics, should also be considered before they can be used in daily clinical practice and are discussed in this article.
Genome-Wide Analysis and Expression Profiling of the Glutathione Peroxidase-like Enzyme Gene Family in Solanum tuberosum
Authors: Wang Shenglan , Sun Xinxin , Miao Xinyue , Mo Fangyu , Liu Tong , Chen Yue
Published: July 2023

Glutathione peroxidase-like enzyme is an important enzymatic antioxidant in plants. It is involved in scavenging reactive oxygen species, which can effectively prevent oxidative damage and improve resistance. GPXL has been studied in many plants but has not been reported in potatoes, the world’s fourth-largest food crop. This study identified eight StGPXL genes in potatoes for the first time through genome-wide bioinformatics analysis and further studied the expression patterns of these genes using qRT-PCR. The results showed that the expression of StGPXL1 was significantly upregulated under high-temperature stress, indicating its involvement in potato defense against high-temperature stress, while the expression levels of StGPXL4 and StGPXL5 were significantly downregulated. The expression of StGPXL1, StGPXL2, StGPXL3, and StGPXL6 was significantly upregulated under drought stress, indicating their involvement in potato defense against drought stress. After MeJA hormone treatment, the expression level of StGPXL6 was significantly upregulated, indicating its involvement in the chemical defense mechanism of potatoes. The expression of all StGPXL genes is inhibited under biotic stress, which indicates that GPXL is a multifunctional gene family, which may endow plants with resistance to various stresses. This study will help deepen the understanding of the function of the potato GPXL gene family, provide comprehensive information for the further analysis of the molecular function of the potato GPXL gene family as well as a theoretical basis for potato molecular breeding.
Tumor-TME Bipartite Landscape of PD-1/PD-L1 in Endometrial Cancers
Authors: Sulaiman Raed , De Pradip , Aske Jennifer C. , Lin Xiaoqian , Dale Adam , Koirala Nischal , Gaster Kris , Espaillat Luis Rojas , Starks David , Dey Nandini
Published: July 2023

The bipartite landscape of tumor cells and stromal cells determines a tumor’s response to treatment during disease management. In endometrial cancers (ECs), the mechanistic contribution of PD-L1/L2 and PD-1 signaling of the host’s tumor microenvironment (TME) (CAF and immune cells) in the context of the tumor cells is elusive. To understand the tumor–stroma-immune crosstalk, we studied the compartmental pattern of PD-L1/L2 and PD-1 expression in EC tissues and their matched CAFs. Over 116 surgically resected tumors (T) and the tumor-adjacent normal tissues (N) were obtained from consented unselected consecutive patients. IHC was performed in T, N-epi-thelium, and the stromal mesenchymal environment (SME; mesenchyme) in the T and N tissues. The staining intensity and distribution patterns of PD-L1/L2 and PD-1 in the FFPE sections of T and N were evaluated by a pathologist using a standard scoring system of TPS and CPS. We tested the PD-L1/L2 and PD-1 immune landscape of tumor-TME pair and normal epithelial-stromal mesenchyme pairs from patients with different grades of disease vis-à-vis their CAF PD-L1 levels. We used qRT-PCR to determine the expressions of mRNAs, while the flow cytometry and ICC determined the level of expression of proteins. We observed higher levels of PD-L1 mRNA and protein expression in primary CAFs from the resected tumor tissue compared to the tumor-adjacent normal tissues. We also determined the expression of patients’ soluble PD-L1/L2 as peripheral readouts of PD-L1/L2 and PD-1. As we evaluated the results in the context of their pathological parameters, such as grades, stages, lymphovascular invasion, percentage of myometrial invasion, and dMMR in patients, the dominance of PD-L1 expression in TME was positively correlated to the higher pathological grades of tumors, and its relationship with the dMMR. Since the neutralization of CD8-positive cytotoxic T-cells is PD-L1-dependent, our data indicate that irrespective of the PD-L1 positivity of tumor cells, the PD-L1-positive CAFs can play a critical role in bringing out an additional load of PD-L1 for an effective engagement of PD-1 within a tumor mass.
Dihydroisotanshinone I and BMAL-SIRT1 Pathway in an In Vitro 6-OHDA-Induced Model of Parkinson’s Disease
Authors: Su Hui-Chen , Sun Yuan-Ting , Yang Ming-Yu , Wu Ching-Yuan , Hsu Cheng-Ming
Published: July 2023

Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson’s disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of BMAL1 and SIRT1 in the 6-OHDA-treated SH-SY5Y cells. Additionally, the SIRT1 inhibitor attenuated the effect of DT on BMAL1 and reduced the cell viability. The DT and SIRT1 activators activated SIRT1 and BMAL1, and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed.
Overexpression of TaMYB4 Confers Freezing Tolerance in Arabidopsis thaliana
Authors: Tian Yu , Peng Kankan , Ma Xuan , Ren Zhipeng , Lou Guicheng , Jiang Yunshuang , Xia Jingqiu , Wang Duojia , Yu Jing , Cang Jing
Published: July 2023

Freezing stress is one of the main factors limiting the growth and yield of wheat. In this study, we found that TaMYB4 expression was significantly upregulated in the tillering nodes of the strong cold-resistant winter wheat variety Dongnongdongmai1 (Dn1) under freezing stress. Weighted gene co-expression network analysis, qRT-PCR and protein–DNA interaction experiments demonstrated that monodehydroascorbate reductase (TaMDHAR) is a direct target of TaMYB4. The results showed that overexpression of TaMYB4 enhanced the freezing tolerance of transgenic Arabidopsis. In TaMYB4 overexpression lines (OE-TaMYB4), AtMDHAR2 expression was upregulated and ascorbate-glutathione (AsA–GSH) cycle operation was enhanced. In addition, the expression of cold stress marker genes such as AtCBF1, AtCBF2, AtCBF3, AtCOR15A, AtCOR47, AtKIN1 and AtRD29A in OE-TaMYB4 lines was significantly upregulated. Therefore, TaMYB4 may increase freezing tolerance as a transcription factor (TF) in Arabidopsis through the AsA–GSH cycle and DREB/CBF signaling pathway. This study provides a potential gene for molecular breeding against freezing stress.
Clinical and Biological Predictors of Cancer Incidence and Mortality in Patients with Stable Coronary Artery Disease
Authors: Campolo Jonica , Borghini Andrea , Parolini Marina , Mercuri Antonella , Turchi Stefano , Andreassi Maria Grazia
Published: July 2023

Clinical and epidemiological evidence has recently revealed a link between coronary artery disease (CAD) and cancer. Shared risk factors and common biological pathways are probably involved in both pathological conditions. The aim of this paper was to evaluate whether and which conventional risk factors and novel circulating biomarkers could predict cancer incidence and death in patients with CAD. The study included 750 CAD patients, who underwent blood sampling for the evaluation of systemic inflammatory indexes (NLR and SII) and specific biomarkers of oxidative damage (leukocyte telomere length (LTL), mitochondrial DNA copy number (mtDNAcn)). Study participants were followed up for a mean of 5.4 ± 1.2 years. Sixty-seven patients (8.9%) developed cancer during the follow-up time, and nineteen (2.5%) died of cancer. Cox multivariable analysis revealed that age (HR = 1.071; 95% CI: 1.034–1.109; p < 0.001), smoking habit (HR = 1.994; 95% CI: 1.140–3.488; p = 0.016), obesity (HR = 1.708; 95% CI: 1.022–2.854; p = 0.041) and SII (HR = 1.002; 95% CI: 1.001–1.003; p = 0.045) were associated with cancer incidence, while only age (HR = 1.132; 95% CI: 1.052–1.219; p = 0.001) was a predictor of cancer death. Patients with lung and gastrointestinal cancers had significantly higher median mtDNAcn levels than those without cancer. Our study suggests that aggressive risk factor modification and suppression of chronic inflammation may be essential to preventing cancer in CAD patients.
Toll-like Receptors and Cytokine Modulation by Goat Milk Extracellular Vesicles in a Model of Intestinal Inflammation
Authors: De Ciucis Chiara Grazia , Fruscione Floriana , De Paolis Livia , Mecocci Samanta , Zinellu Susanna , Guardone Lisa , Franzoni Giulia , Cappelli Katia , Razzuoli Elisabetta
Published: July 2023

Extracellular vesicles (EVs) are nanometric spherical structures, enclosed in a lipid bilayer membrane and secreted by multiple cell types under specific physiologic and pathologic conditions. Their complex cargo modulates immune cells within an inflammatory microenvironment. Milk is one of the most promising sources of EVs in terms of massive recovery, and milk extracellular vesicles (mEVs) have immunomodulatory and anti-inflammatory effects. The aim of this study was to characterize goat mEVs’ immunomodulating activities on Toll-like receptors (TLRs) and related immune genes, including cytokines, using a porcine intestinal epithelial cell line (IPEC-J2) after the establishment of a pro-inflammatory environment. IPEC-J2 was exposed for 2 h to pro-inflammatory stimuli as a model of inflammatory bowel disease (IBD), namely LPS for Crohn’s disease (CD) and H2O2 for ulcerative colitis (UC); then, cells were treated with goat mEVs for 48 h. RT-qPCR and ELISA data showed that cell exposure to LPS or H2O2 caused a pro-inflammatory response, with increased gene expression of CXCL8, TNFA, NOS2 and the release of pro-inflammatory cytokines. In the LPS model, the treatment with mEVs after LPS determined the down-regulation of NOS2, MMP9, TLR5, TGFB1, IFNB, IL18 and IL12A gene expressions, as well as lower release of IL-18 in culture supernatants. At the same time, we observed the increased expression of TLR1, TLR2, TLR8 and EBI3. On the contrary, the treatment with mEVs after H2O2 exposure, the model of UC, determined the increased expression of MMP9 alongside the decrease in TGFB1, TLR8 and DEFB1, with a lower release of IL-1Ra in culture supernatants. Overall, our data showed that a 48 h treatment with mEVs after a pro-inflammatory stimulus significantly modulated the expression of several TLRs and cytokines in swine intestinal cells, in association with a decreased inflammation. These results further highlight the immunomodulatory potential of these nanosized structures and suggest their potential application in vivo.
Exploring Factors and Challenges Influencing Nursing Interns’ Training Experiences in Emergency Departments in Saudi Arabia
Authors: Alotaibi Reem Mutlaq , Alkhaldi Rawan Maqbool , Turkistani Abeer Adel , Alfaqih Manar Musallam , Alzaidi Lena Saeed , Alosaimi Zainab Shabab , Almutairi Manar Hamed , Al Thobaity Abdulellah
Published: July 2023

This study aims to investigate nursing interns’ training experiences in emergency departments (EDs) in Saudi Arabia and explore the factors influencing their experiences. A descriptive research design was employed utilizing a survey distributed to nursing interns who completed their ED rotation within the last three months. The data were analyzed using SPSS version 27, and principal component analysis (PCA) was conducted to identify the challenges encountered by the interns. This study analyzed the responses of 126 nursing internship students in various regions of Saudi Arabia to assess their training experiences in emergency departments. The principal component analysis revealed two significant factors: (1) “Emergency Department Training and Skill Development”, which focused on challenges faced during training, and (2) “Integrated Emergency Department Training and Competence Development”, which provided a holistic view of nursing internship students’ experiences and preparedness for their careers. The results indicated moderately below-average challenges and a moderately positive overall training experience. The findings suggest a need to address these challenges to improve the training experience and better prepare nursing internship students for careers in emergency departments. This study recommends enhancing the nursing curricula alignment with practical training objectives, focusing on technical and interpersonal skills development. A supportive learning environment in emergency departments is crucial, including effective communication and collaboration. Diverse clinical experiences and reflection on training can guide students in exploring potential career paths in emergency departments or other specialized nursing areas.
Description of Calling, Courtship and Mating Behaviour of Six Species of the Genus Zyginidia (Auchenorrhyncha: Cicadellidae)
Authors: Mazzoglio Peter John , Mozaffarian Fariba , Alma Alberto
Published: July 2023

The vibrational communication and mating behaviour of the graminicolous leafhoppers Zyginidia pullula, Z. ribauti, Z. scutellaris, Z. serpentina, Z. sohrab, and Z. biroi were investigated to explain why the first five species hybridize. Z. biroi was used as a control species. All species behaved in the same way and no significant statistical differences were detected with regard to male calls, while female calls and the male courtship song differed in Z. biroi, thus showing that a specific pre-mating isolation mechanism was used by the latter species and the first five ones lacked such a mechanism. In addition, Z. sohrab is missing in Italy, while the other species live allopatrically in Italy, with the only exceptions being Z. serpentina and Z. biroi, which live in Sicily and are often found in sympatry, and Z. scutellaris and Z. biroi, which live in Sardinia. All these species can be distinguished by means of male genital appendages; however, Z. biroi is longer and has a different body colour. The existence of natural hybrids of Z. pullula, Z. ribauti, and Z. scutellaris in the Italian peninsula and their hybridization in the laboratory with Z. serpentina and Z. sohrab require the investigation of possible post-mating reproductive barriers before re-considering their systematic validity.
A Revision of Empirical Models of Stirling Engine Performance Using Simple Artificial Neural Networks
Authors: González-Plaza Enrique , García David , Prieto Jesús-Ignacio
Published: July 2023

Stirling engines are currently of interest due to their adaptability to a wide range of energy sources. Since simple tools are needed to guide the sizing of prototypes in preliminary studies, this paper proposes two groups of simple models to estimate the maximum power in Stirling engines with a kinematic drive mechanism. The models are based on regression or ANN techniques, using data from 34 engines over a wide range of operating conditions. To facilitate the generalisation and interpretation of results, all models are expressed by dimensionless variables. The first group models use three input variables and 23 data points for correlation construction or training purposes, while another 66 data points are used for testing. Models in the second group use eight inputs and 18 data points for correlation construction or training, while another 36 data points are used for testing. The three-input models provide estimations of the maximum brake power with an acceptable accuracy for feasibility studies. Using eight-input models, the predictions of the maximum indicated power are very accurate, while those of the maximum brake power are less accurate, but acceptable for the preliminary design stage. In general, the best results are achieved with ANN models, although they only employ one hidden layer.
Hemoadsorption in LVAD Surgery: Suitable in Theory?
Authors: Ozturk Mahmut , Popov Aron Frederik
Published: July 2023

The incidence of patients with heart failure is growing steadily, particularly due to advancements in medical therapy [...]
AMH in Males: Effects of Body Size and Composition on Serum AMH Levels
Authors: Tandl Veronika , Haudum Christoph , Eberhard Katharina , Hutz Barbara , Foessl Ines , Kolesnik Ewald , Zirlik Andreas , von Lewinski Dirk , Scherr Daniel , Verheyen Nicolas , Pieber Thomas , Obermayer-Pietsch Barbara
Published: July 2023

Serum concentrations of anti-Müllerian hormone (AMH) have been found to decrease with increasing body mass index (BMI) in many studies. It is not yet clear whether this stems from an adverse effect of adiposity on AMH production, or from dilution due to the greater blood volume that accompanies a larger body size. To investigate a possible hemodilution effect, we explored the relationships between serum AMH levels and different parameters of body composition using linear regression models in a cohort of adult males. Body weight, lean mass (LM), and body surface area (BSA) were found to be better predictors of AMH than measures of adiposity, such as BMI or fat mass. Since both LM and BSA correlate with plasma volume better than adipose tissue, we conclude that hemodilution of AMH does occur in adult males and should be considered for normalization in future studies.
Exercise and Weight Management: The Role of Leptin—A Systematic Review and Update of Clinical Data from 2000–2022
Authors: de Assis Gilmara Gomes , Murawska-Ciałowicz Eugenia
Published: July 2023

A well-balanced metabolism means a lower risk for metabolism-related neuropsychiatric disorders. Leptin is a secretory adipokine involved in the central control of appetite that appears to play a role in the etiology of feeding-related disorders. Additionally, the influence of exercise on feeding behaviors potentially modulates the circulation of metabolites that signal through the central nervous system. In this systematic review, we collected the recent clinical evidence on the effect of exercise on leptin concentrations in health individuals published from 2000 to 20 September 2022, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA 2020 statement). Six hundred and thirty-eight papers were retrieved and forty-eight papers were included in the qualitative synthesis. Data supports that exercise positively influences appetite via enhancing peripheral and central leptin signaling (reuptake), especially during weight loss. Exercise modulation of leptin signaling through leptin receptors helps to stabilize increases in food intake during periods of negative energy balance, prior to a decrease in the body fat tissue content. At a high intensity, exercise appears to counteract leptin resistance.
Study of Radiation Damage Kinetics in Dispersed Nuclear Fuel on Zirconium Dioxide Doped with Cerium Dioxide
Authors: Kozlovskiy Artem L. , Borgekov Daryn B. , Zdorovets Maxim V. , Kenzhina Inesh E. , Shlimas Dmitriy I.
Published: July 2023

One area that holds promise for nuclear energy advancement, which is the most attractive industry for eliminating the imbalance in the energy sector and reducing the world’s energy shortage for the long term, is the replacement of traditional uranium fuel with plutonium fuel. The focus on this research area is due to the growing concern of the world community about the problem of handling spent nuclear fuel, including its further use or storage and disposal. The main aims of this paper are to study the resistance of composite ceramics based on zirconium and cerium dioxide to the hydrogenation processes and subsequent destructive embrittlement, and to identify patterns of growth stability attributable to the occurrence of interfacial boundaries and changes in the phase composition of ceramics. Studies have shown that the main effects of the structural distortion of the crystalline structure of ceramics are caused primarily by tensile deformation distortions, resulting in the accumulation of radiation-induced damage. The formation of Zr0.85Ce0.15O2 tetragonal phase of replacement in the structure of ceramics results in a more than two-fold reduction in the deformation distortion degree in cases of high-dose radiation with protons. The evaluation of the alteration in the strength properties of ceramics revealed that the variation in the phase composition due to polymorphic transformation of the monoclinic Zr0.98Ce0.02O2 → tetragonal Zr0.85Ce0.15O2 type results in the strengthening of the damaged layers and the improvement of the resistance to radiation-induced embrittlement and softening.
Revolutionizing the Use of Honeybee Products in Healthcare: A Focused Review on Using Bee Pollen as a Potential Adjunct Material for Biomaterial Functionalization
Authors: Sanyal Arka , Ghosh Anushikha , Roy Chandrashish , Mazumder Ishanee , Marrazzo Pasquale
Published: July 2023

The field of biomedical engineering highly demands technological improvements to allow the successful engraftment of biomaterials requested for healing damaged host tissues, tissue regeneration, and drug delivery. Polymeric materials, particularly natural polymers, are one of the primary suitable materials employed and functionalized to enhance their biocompatibility and thus confer advantageous features after graft implantation. Incorporating bioactive substances from nature is a good technique for expanding or increasing the functionality of biomaterial scaffolds, which may additionally encourage tissue healing. Our ecosystem provides natural resources, like honeybee products, comprising a rich blend of phytochemicals with interesting bioactive properties, which, when functionally coupled with biomedical biomaterials, result in the biomaterial exhibiting anti-inflammatory, antimicrobial, and antioxidant effects. Bee pollen is a sustainable product recently discovered as a new functionalizing agent for biomaterials. This review aims to articulate the general idea of using honeybee products for biomaterial engineering, mainly focusing on describing recent literature on experimental studies on biomaterials functionalized with bee pollen. We have also described the underlying mechanism of the bioactive attributes of bee pollen and shared our perspective on how future biomedical research will benefit from the fabrication of such functionalized biomaterials.