bluuebunny/crossref_metadata_2025 huggingface dataset:
How the corona pandemic affects the global fight against tuberculosis and how to react
Authors: Ulrichs Timo
Published: April 2023

The emergence of the acute pandemic by SARS-CoV-2 is a setback for the fight against chronic pandemics like tuberculosis (TB), malaria, and HIV/AIDS. In fact, after more than a decade of decreasing fatality numbers, 2020 saw a re-increase in the number of people dying from TB. After COVID-19, TB was the infectious disease with the second-highest fatality rate caused by a single pathogen, with 1.6 million deaths in 2021. It is expected by the WHO that the pandemic years to come and even after the pandemic will continue this trend. More efforts are needed to support TB control structures as an integral part of the strengthening measures of the general health care system.
A new permanent, low-cost, low-power SO2 camera for continuous measurement of volcanic emissions
Authors: Wilkes Thomas Charles , Pering Tom David , Aguilera Felipe , Layana Susana , Nadeau Patricia , Kern Christoph , McGonigle Andrew John Samuel , Aguilera Mauricio , Zhu Chengxi
Published: April 2023

Since its introduction to volcanology in the mid-2000 s, the SO2 camera has become an important instrument for the acquisition of accurate and high time-resolution SO2 emission rates, aiding in hazard assessment and volcanological research. However, with the exception of a few locations (Stromboli, Etna, Kīlauea), hitherto the majority of measurements have been made on discrete field campaigns, which provide only brief snapshots into a volcano’s activity. Here, we present the development of a new, low-cost, low-power SO2 camera for permanent deployment on volcanoes, facilitating long-term, quasi-continuous (daylight hours only) measurements. We then discuss preliminary datasets from Lascar and Kīlauea volcanoes, where instruments are now in continuous operation. Further proliferation of such instrumentation has the potential to greatly improve our understanding of the transient nature of volcanic activity, as well as aiding volcano monitoring/eruption forecasting.
Roles of sex hormones in mediating the causal effect of vitamin D on osteoporosis: A two-step Mendelian randomization study
Authors: Du Yongwei , Xie Baohui , Wang Maoyuan , Zhong Yanbiao , Lv Zhimai , Luo Yun , He Qiwei , Liu Zhen
Published: April 2023

Background

Although 25-hydroxyvitamin D [25(OH)D] is a risk factor for osteoporosis, it is not clear whether sex hormones mediate this casual association. We aimed to explore how sex hormones affect the association between 25(OH)D and osteoporosis to provide meaningful insights on the underlying mechanisms from a genetic perspective.

Methods

Genetic variations in 25(OH)D, total testosterone (TT), androstenedione (A4), estradiol (E2), and testosterone/17β-estradiol (T/E2) were determined through summary statistics. Taking osteoporosis as the outcome (FinnGen biobank, 332,020 samples), we conducted a Mendelian randomization (MR) analysis to establish the association between 25(OH)D and these sex hormones. The two-step MR analysis quantified the mediatory effects of sex hormones on osteoporosis. The results were further verified by pleiotropy and heterogeneity analyses.

Results

MR results showed that 25(OH)D (OR= 1.27, p = 0.04) and TT (OR= 1.25, p = 0.04) had a causal effect on osteoporosis. No significant associations were observed between the other sex hormones (A4, E2, and T/E2) and osteoporosis (p>0.05). Sensitivity analysis (p>0.05) confirmed the robustness of the MR results. The two-step MR analysis provided evidence that the mediatory effect of TT was 0.014 (the percentage of TT mediation was 5.91%). Moreover, the direct effect of 25(OH)D on osteoporosis was 0.221. A4, E2, and T/E2 were not considered as potential mediators of the role of 25(OH)D as a risk factor for OP.

Conclusion

This study, through MR analysis, showed that TT mediates the causal effect of 25(OH)D on osteoporosis. Interventions targeting TT, therefore, have the potential to substantially reduce the burden of osteoporosis attributable to high 25(OH)D.
Root-specific flavones and critical enzyme genes involved in their synthesis changes due to drought stress on Scutellaria baicalensis
Authors: Li Ping , Ren Guangxi , Wu Fei , Chen Jiaxin , Jiang Dan , Liu Chunsheng
Published: April 2023

Introduction

Scutellaria baicalensis is rich in bioactive flavonoid, which are widely used in clinical therapy. Many environmental factors, such as water and temperature, affect gene expression and secondary metabolites accumulation in plants.

Methods

In this study, to explore the effect of drought stress on the accumulation of flavonoids and gene expression in S. baicalensis seedlings, 4-week-old Scutellaria baicalensis seedlings were treated with different concentrations of PEG6000 to simulate drought stress. The contents of four root-specific flavones (baicalein, wogonin, baicalin, and wogonoside) in samples under different treatments were quantitatively analyzed by high performance liquid chromatography (HPLC). The expression levels of flavonoid biosynthesis-related genes (PAL1, PAL2, CHS, and UBGAT) were determined by real-time quantitative PCR (qRT-PCR). Also, a correlation analysis between flavonoid contents and gene expression levels was made.

Results

The HPLC results revealed that 5 and 10% PEG6000 treatments significantly increased the content of four flavonoids, with 5% PEG 6000 treatment being the most beneficial to the flavonoids accumulation. The qRT-PCR results showed that PAL2 and CHS gene expressions differed significantly in different organs, while PAL1 and UBGAT had poor organ-specific. For genes in roots, the expression of PAL1 and UBGAT was the highest in 5% PEG6000 treatment, and PAL2 and CHS were the highest in 10% PEG6000 treatment. Compared with other concentrations of PEG6000, 5 and 10% PEG6000 were more advantageous for gene expression. Collectively, PEG6000 at a low concentration promoted the accumulation of flavonoids and the expression of related genes. Additionally, the correlation results demonstrated that PAL1, PAL2, CHS, and UBGAT genes in roots stimulated the formation and accumulation of the four flavonoids to varying degrees, while the exception of PAL2 gene expression in roots was negatively correlated with wogonin content.

Discussion

This study for the first time investigated the effect of drought stress on the downstream gene UBGAT in S.baicalensis seedlings as well as the correlation between gene expression and flavonoid content in S. baicalensis seedlings under drought stress, providing a new sight for studying the effects of drought stress on flavonoid accumulation and related gene expression in S. baicalensis.
Integrating multiple machine learning algorithms for prognostic prediction of gastric cancer based on immune-related lncRNAs
Authors: Li Guoqi , Huo Diwei , Guo Naifu , Li Yi , Ma Hongzhe , Liu Lei , Xie Hongbo , Zhang Denan , Qu Bo , Chen Xiujie
Published: April 2023

Background: Long non-coding RNAs (lncRNAs) play an important role in the immune regulation of gastric cancer (GC). However, the clinical application value of immune-related lncRNAs has not been fully developed. It is of great significance to overcome the challenges of prognostic prediction and classification of gastric cancer patients based on the current study.

Methods: In this study, the R package ImmLnc was used to obtain immune-related lncRNAs of The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) project, and univariate Cox regression analysis was performed to find prognostic immune-related lncRNAs. A total of 117 combinations based on 10 algorithms were integrated to determine the immune-related lncRNA prognostic model (ILPM). According to the ILPM, the least absolute shrinkage and selection operator (LASSO) regression was employed to find the major lncRNAs and develop the risk model. ssGSEA, CIBERSORT algorithm, the R package maftools, pRRophetic, and clusterProfiler were employed for measuring the proportion of immune cells among risk groups, genomic mutation difference, drug sensitivity analysis, and pathway enrichment score.

Results: A total of 321 immune-related lncRNAs were found, and there were 26 prognostic immune-related lncRNAs. According to the ILPM, 18 of 26 lncRNAs were selected and the risk score (RS) developed by the 18-lncRNA signature had good strength in the TCGA training set and Gene Expression Omnibus (GEO) validation datasets. Patients were divided into high- and low-risk groups according to the median RS, and the low-risk group had a better prognosis, tumor immune microenvironment, and tumor signature enrichment score and a higher metabolism, frequency of genomic mutations, proportion of immune cell infiltration, and antitumor drug resistance. Furthermore, 86 differentially expressed genes (DEGs) between high- and low-risk groups were mainly enriched in immune-related pathways.

Conclusion: The ILPM developed based on 26 prognostic immune-related lncRNAs can help in predicting the prognosis of patients suffering from gastric cancer. Precision medicine can be effectively carried out by dividing patients into high- and low-risk groups according to the RS.
Role of GM-CSF in lung balance and disease
Authors: Chen Yingzi , Li Fan , Hua Mengqing , Liang Meng , Song Chuanwang
Published: April 2023

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor originally identified as a stimulus that induces the differentiation of bone marrow progenitor cells into granulocytes and macrophages. GM-CSF is now considered to be a multi-origin and pleiotropic cytokine. GM-CSF receptor signals activate JAK2 and induce nuclear signals through the JAK-STAT, MAPK, PI3K, and other pathways. In addition to promoting the metabolism of pulmonary surfactant and the maturation and differentiation of alveolar macrophages, GM-CSF plays a key role in interstitial lung disease, allergic lung disease, alcoholic lung disease, and pulmonary bacterial, fungal, and viral infections. This article reviews the latest knowledge on the relationship between GM-CSF and lung balance and lung disease, and indicates that there is much more to GM-CSF than its name suggests.
Nutritional and reproductive status affect amino acid appetite in house crickets (Acheta domesticus)
Authors: Tierney Ann Jane , Velazquez Elizabeth , Johnson Lauryn , Hiranandani Sarah , Pauly Meghan , Souvignier Maya
Published: April 2023

We examined amino acid appetite in the omnivorous house cricket (Acheta domesticus), a common model organism for both research and teaching. Our first experiment addressed the hypothesis that house crickets can discriminate between sucrose and essential amino acids (EAA), and that preference for the latter would be affected by prior feeding experience. To test this hypothesis, we compared feeding responses of juvenile and adult crickets following pre-feeding with sucrose or an essential amino acid mixture, predicting that sucrose-only pre-feeding would enhance subsequent intake of amino acids in a two-choice preference test. Based on previous studies, we also predicted that amino acid consumption would be enhanced in females compared to males, and in mated compared to virgin females. Hence we compared responses in male and female last instar nymphs, adult males, virgin females, mated females, and mated females allowed to lay eggs. The second experiment examined how extended periods of essential amino acid deprivation (48 h to 6 days) affected appetite for these nutrients in adult male and female insects. Finally, we examined growth and survival of juvenile and adult crickets fed a holidic diet lacking all amino acids and protein. Our results demonstrated that house crickets can distinguish EAA from sucrose and that consumption of the former is enhanced following sucrose-only pre-feeding. We also found sex and developmental differences, with juvenile and virgin females showing a greater preference for EAA than juvenile or adult males. Contrary to expectation, mated females preferred sucrose over EAA both prior to and after egg laying. We also found that the crickets of both sexes increased their intake of EAA when exposed to longer periods of deprivation, indicating that they engage in compensatory feeding on these nutrients. Finally, as expected we found that growth was severely limited in juveniles fed a diet lacking all amino acids, but adults and many juveniles survived for 30 days on this diet.
Variations on primary metabolites of the carrageenan-producing red algae Sarcopeltis skottsbergii from Chile and Sarcopeltis antarctica from Antarctic Peninsula
Authors: Pasqualetti Cesar B. , Carvalho Maria Angela M. , Mansilla Andres , Avila Marcela , Colepicolo Pio , Yokoya Nair S.
Published: April 2023

Several studies reported that gametophytes and tetrasporophytes of Gigartinaceae produce different carrageenan types, as observed in Sarcopeltis species although they have isomorphic haploid and diploid phases. Cystocarpic and non-fertile plants of Sarcopeltis (ex Gigartina) skottsbergii produced kappa-carrageenans, while tetrasporophytes produced lambda-carrageenans, and yields were higher in cystocarpic and sterile specimens than in tetrasporophytes. However, comparison on the other primary metabolites among different life history phases still needed to be investigated. Then, we tested the hypothesis if the variation on primary metabolites (pigments, proteins and carbohydrates) are related to the life history phases of Sarcopeltis antarctica and Sarcopeltis skottsbergii, and/or are influenced by abiotic factors. Primary metabolites of S. antarctica varied according to the life-history phases: non-fertile specimens presented higher phycobiliprotein concentrations, tetrasporophytes presented higher chlorophyll a concentrations, and cystocarpic specimens presented higher concentrations of proteins, polysaccharides and floridean starch. However, primary metabolites of S. skottsbergii varied in response to some abiotic factors (nutrients, temperature and salinity), since principal component analysis evidenced two groups; one was related by the higher nitrate and phosphate concentrations, and the other was related to the higher temperatures and lower salinities. Concentrations of floridean starch, low molecular weight carbohydrates, and polysaccharides are higher in S. antarctica than in S. skottsbergii, which could be related to the protective role of these compounds against salinity variation and low temperatures faced in the Antarctic extreme environments.
Dipole doping effect in MoS2 field effect transistors based on phase transition of ferroelectric polymer dopant
Authors: Lee Dong Hyun , Park Taehyun , Jeong Taeho , Jung Youngkyun , Park Junghee , Joo Nackyong , Won Uiyeon , Yoo Hocheon
Published: April 2023

Molybdenum disulfide (MoS2) has great potential for next-generation electronic devices. On the other hand, stable doping methods are required to adjust its physical properties so MoS2 can be utilized in practical applications, such as transistors and photodetectors. On the other hand, a conventional doping method based on ion implantation is incompatible with 2D MoS2 because of the damage to the lattice structures of MoS2. This paper presents an n-type doping method for MoS2 field-effect transistors (FETs) using a poly (vinylidene fluoride-co-trifluoroethylene) (P (VDF-TrFE)) and polar polymer. The dipole moment of P (VDF-TrFE) provides n-type doping on MoS2 FETs. The polar phase formation in dopant films enhances the doping effects, and the relationship between phase transition and n-type doping states was investigated using optical and electrical characterization methods. Under the optimal doping conditions, the doped MoS2 FET achieved an improved field effect mobility of 34.4 cm2 V−1s–1, a negative shift in the threshold voltage by −25.6 V, and a high on-current of 21 μA compared to the pristine MoS2 FET.
High intact fibroblast growth factor 23 levels associated with low hemoglobin levels in patients on chronic hemodialysis
Authors: Fang Yu-Wei , Wang Jing-Tong , Lin Tzu Yun , Lee Chung-Jen , Jang Tsrang-Neng , Tsai Ming-Hsien , Liou Hung-Hsiang
Published: April 2023

Introduction

A negative association between C-terminal fibroblast growth factor 23 (cFGF23) and hemoglobin (Hb) levels has been reported in patients with predialysis chronic kidney disease. In dialysis patients, the dominant form of serum FGF23 is intact FGF23 (iFGF23); however, its association with the Hb level remains unclear. Therefore, simultaneously monitoring iFGF23 and cFGF23 levels is crucial. In this study, we investigated the associations between both forms of FGF23 (iFGF23 and cFGF23) and renal anemia in chronic hemodialysis (CHD) patients.

Methods

We included 166 CHD patients from two hospitals in this cross-sectional, observational study. The primary predictors were serum iFGF23, cFGF23, and iFGF23/cFGF23 levels. The main outcome was the Hb level.

Results

Among the CHD patients included, 60.8% were men with a mean age of 59.4 ± 12.7 years. In the crude analysis, iFGF23 and iFGF23/cFGF23 levels showed a significant negative association (−0.27, p = 0.004 and −0.22, p = 0.034, respectively) with the Hb level. Even after adjusting for multiple variables (a parsimonious model), every increment of natural log transformation by 1 for (ln)iFGF23 and ln(iFGF23/cFGF23) levels showed a negative correlation with the Hb level (estimate: −0.27 [95%CI: −0.44, −0.10, p = 0.001]; −0.19 [95%CI: −0.37, −0.01, p = 0.042], respectively), whereas both were positively associated with erythropoietin-stimulating agent (ESA) hyporesponsiveness (odds ratio [OR]: [95%CI: 2.30, 1.26–4.17], p = 0.006; 1.95 [95%CI: 1.08–3.50], p = 0.025). Moreover, these abovementioned associations were more dominant in patients with diabetes who used angiotensin receptor blockers.

Discussion

In conclusion, a negative association between serum iFGF23 or iFGF23/cFGF23 level and the Hb level was observed in our CHD patients. Meanwhile, a higher iFGF23 or iFGF23/cFGF23 level may predispose patients to ESA hyporesponsiveness.
Brain metastases in the elderly – Impact of residual tumor volume on overall survival
Authors: Baumgart Lea , Aftahy Amir Kaywan , Anetsberger Aida , Thunstedt Dennis , Wiestler Benedikt , Bernhardt Denise , Combs Stephanie E. , Meyer Bernhard , Meyer Hanno S. , Gempt Jens
Published: April 2023

Background

Due to demographic changes and an increased incidence of cancer with age, the number of patients with brain metastases (BMs) constantly increases, especially among the elderly. Novel systemic therapies, such as immunotherapy, have led to improved survival in recent years, but intracranial tumor progression may occur independently of a systemically effective therapy. Despite the growing number of geriatric patients, they are often overlooked in clinical trials, and there is no consensus on the impact of BM resection on survival.

Objectives

The aim of this study was to analyze the impact of resection and residual tumor volume on clinical outcome and overall survival (OS) in elderly patients suffering from BM.

Methods

Patients ≥ 75 years who had surgery for BM between April 2007 and January 2020 were retrospectively included. Residual tumor burden (RTB) was determined by segmentation of early postoperative brain MRI (72 h). Contrast-enhancing tumor subvolumes were segmented manually. “Postoperative tumor volume” refers to the targeted BMs. Impact of preoperative Karnofsky performance status scale (KPSS), age, sex and RTB on OS was analyzed. Survival analyses were performed using Kaplan-Meier estimates for the univariate analysis and the Cox regression proportional hazards model for the multivariate analysis.

Results

One hundred and one patients were included. Median age at surgery was 78 years (IQR 76-81). Sixty-two patients (61%) had a single BM; 16 patients (16%) had two BMs; 13 patients (13%) had three BMs; and 10 patients (10%) had more than three BMs. Median preoperative tumor burden was 10.3 cm3 (IQR 5–25 cm3), and postoperative tumor burden was 0 cm3 (IQR 0–1.1 cm3). Complete cytoreduction (RTB = 0) was achieved in 52 patients (52%). Complete resection of the targeted metastases was achieved in 78 patients (78%). Median OS was 7 months (IQR 2–11). In univariate analysis, high preoperative KPSS (HR 0.986, 95% CI 0.973–0.998, p = 0.026) and small postoperative tumor burden (HR 1.025, 95% CI 1.002–1.047, p = 0.029) were significantly associated with prolonged OS. Patients with RTB = 0 survived significantly longer than those with residual tumor did (12 [IQR 5–19] vs. 5 [IQR 3–7] months, p = 0.007). Furthermore, prolongation of survival was significantly associated with surgery in patients with favorable KPSS, with an adjusted HR of 0.986 (p = 0.026). However, there were no significances regarding age.

Conclusions

RTB is a strong predictor for prolonged OS, regardless of age or cancer type. Postoperative MRI should confirm the extent of resection, as intraoperative estimates do not warrant a complete resection. It is crucial to aim for maximal cytoreduction to achieve the best long-term outcomes for these patients, despite the fact the patients are advanced in age.
Appropriateness of frequent use of emergency departments: A retrospective analysis in Rome, Italy
Authors: Furia Giuseppe , Vinci Antonio , Colamesta Vittoria , Papini Paolo , Grossi Adriano , Cammalleri Vittoria , Chierchini Patrizia , Maurici Massimo , Damiani Gianfranco , De Vito Corrado
Published: April 2023

Background

Frequent users (FUs) are patients who repeatedly and inappropriately visit the emergency department (ED) for low-grade symptoms that could be treated outside the hospital setting. This study aimed to investigate the phenomenon of the FU in Rome by profiling such users and analyzing ED attendance by FUs.

Methods

The analysis was carried out for attendance in 2021 at 15 EDs in the Local Health Authority Roma 1 geographical area. A digital app collected data, including information on the following variables: number of attendance, demographic characteristics, emergency medical service (EMS) usage, triage code, and appropriateness of attendance. COVID-19 diagnosis was also studied to analyze any possible influence on ED attendance. Differences between FUs and non-FUs were investigated statistically by t-test and chi-square test. Univariate analysis and multivariable logistic regression were performed to analyze the associated factors.

Results

A total of 122,762 ED attendance and 89,036 users were registered. The FU category represented 2.9% of all users, comprising 11.9% of total ED attendance. There was a three times higher frequency of non-urgent codes in attendance of FU patients (FU: 9.7%; non-FU: 3.2%). FUs were slightly more likely to have used the EMS (13.6% vs. 11.4%) and had a lower frequency of appropriate ED attendance (23.8% vs. 27.0%). Multivariate logistic analysis confirmed a significant effect of triage code, gender, age, EMS usage, and COVID-19 diagnosis for the appropriateness of attendance. The results were statistically significant (p < 0.001).

Conclusion

The FU profile describes mostly non-urgent and inappropriate attendance at the ED, including during the COVID-19 pandemic. This study represents an important tool for strengthening preventive policies outside the hospital setting. The Italian National Recovery and Resilience Plan represents an excellent opportunity for the development of new strategies to mitigate the phenomenon of FUs.
Degradation-Conscious Multiobjective Optimal Control of Reconfigurable Li-Ion Battery Energy Storage Systems
Authors: Karunathilake Dulmini , Vilathgamuwa Mahinda , Mishra Yateendra , Corry Paul , Farrell Troy , Choi San Shing
Published: April 2023

Lithium-ion battery energy storage systems are made from sets of battery packs that are connected in series and parallel combinations depending on the application’s needs for power. To achieve optimal control, advanced battery management systems (ABMSs) with health-conscious optimal control are required for highly dynamic applications where safe operation, extended battery life, and maximum performance are critical requirements. The majority of earlier research assumed that the battery cells in these energy storage systems were identical and would vary uniformly over time in terms of cell characteristics. However, in real-world situations, the battery cells might behave differently for a number of reasons. Overcharging and over-discharging are caused by an electrical imbalance that results from the cells’ differences in properties and capacity. Therefore in this study, a stratified real-time control scheme was developed for the dual purposes of minimizing the capacity fade and the energy losses of a battery pack. Each of the cells in the pack is represented by a degradation-conscious physics-based reduced-order equivalent circuit model. In view of the inconsistencies between cells, the proposed control scheme uses a state estimator such that the parametric values of the circuit elements in the cell model are determined and updated in a decentralized manner. The minimization of the capacity fade and energy losses is then formulated as a multiobjective optimization problem, from which the resulting optimal control strategy is realized through the switching actions of a modular multilevel series-parallel converter which interconnects the battery pack to an external AC system. A centralized controller ensures optimal switching sequence of the converter leading to the maximum utilization of the capacity of the battery pack. Both simulation and experimental results are used to verify the proposed methodologies which aim at minimizing the battery degradation by reconfiguring the battery cells dynamically in accordance with the state of health (SOH) of the pack.
Hepatoprotective and Neuroprotective Effects of Naringenin against Lead-Induced Oxidative Stress, Inflammation, and Apoptosis in Rats
Authors: Mansour Lubna A. H. , Elshopakey Gehad E. , Abdelhamid Fatma M. , Albukhari Talat A. , Almehmadi Samah J. , Refaat Bassem , El-Boshy Mohamed , Risha Engy F.
Published: April 2023

Naringenin (NRG) is one of the most important naturally occurring flavonoids, predominantly found in some edible fruits, such as citrus species and tomatoes. It has several biological activities, such as antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic, and cardioprotective effects. The heavy metal lead is toxic and triggers oxidative stress, which causes toxicity in many organs, including the liver and brain. This study explored the potential protective role of NRG in hepato- and neurotoxicity caused by lead acetate in rats. Four groups of ten male albino rats were included: group 1 was a control, group 2 was orally treated with lead acetate (LA) at a dose of 500 mg/kg BW, group 3 was treated with naringenin (NRG) at a dose of 50 mg/kg BW, and group 4 was treated with 500 mg/kg LA and 50 mg/kg NRG for 4 weeks. Then, blood was taken, the rats were euthanized, and liver and brain tissues were collected. The findings revealed that LA exposure induced hepatotoxicity with a significant increase in liver function markers (p < 0.05). In addition, albumin and total protein (TP) and the albumin/globulin ratio (A/G ratio) (p < 0.05) were markedly lowered, whereas the serum globulin level (p > 0.05) was unaltered. LA also induced oxidative damage, demonstrated by a significant increase in malonaldehyde (MDA) (p < 0.05), together with a pronounced antioxidant system reduction (SOD, CAT, and GSH) (p < 0.05) in both liver and brain tissues. Inflammation of the liver and brain caused by LA was indicated by increased levels of nuclear factor kappa beta (NF-κβ) and caspase-3, (p < 0.05), and the levels of B-cell lymphocyte-2 (BCL-2) and interleukin-10 (IL-10) (p < 0.05) were decreased. Brain tissue damage induced by LA toxicity was demonstrated by the downregulation of the neurotransmitters norepinephrine (NE), dopamine (DA), serotonin (5-HT), and creatine kinase (CK-BB) (p < 0.05). Additionally, the liver and brain of LA-treated rats displayed notable histopathological damage. In conclusion, NRG has potential hepato- and neuroprotective effects against lead acetate toxicity. However, additional research is needed in order to propose naringenin as a potential protective agent against renal and cardiac toxicity mediated by lead acetate.
Temozolomide Resistance in Glioblastoma by NRF2: Protecting the Evil
Authors: Almeida Lima Karoline , Osawa Isabeli Yumi Araújo , Ramalho Maria Carolina Clares , de Souza Izadora , Guedes Camila Banca , Souza Filho Cláudio Henrique Dahne de , Monteiro Linda Karolynne Seregni , Latancia Marcela Teatin , Rocha Clarissa Ribeiro Reily
Published: April 2023

The transcription factor NRF2 is constitutively active in glioblastoma, a highly aggressive brain tumor subtype with poor prognosis. Temozolomide (TMZ) is the primary chemotherapeutic agent for this type of tumor treatment, but resistance to this drug is often observed. This review highlights the research that is demonstrating how NRF2 hyperactivation creates an environment that favors the survival of malignant cells and protects against oxidative stress and TMZ. Mechanistically, NRF2 increases drug detoxification, autophagy, DNA repair, and decreases drug accumulation and apoptotic signaling. Our review also presents potential strategies for targeting NRF2 as an adjuvant therapy to overcome TMZ chemoresistance in glioblastoma. Specific molecular pathways, including MAPKs, GSK3β, βTRCP, PI3K, AKT, and GBP, that modulate NRF2 expression leading to TMZ resistance are discussed, along with the importance of identifying NRF2 modulators to reverse TMZ resistance and develop new therapeutic targets. Despite the significant progress in understanding the role of NRF2 in GBM, there are still unanswered questions regarding its regulation and downstream effects. Future research should focus on elucidating the precise mechanisms by which NRF2 mediates resistance to TMZ, and identifying potential novel targets for therapeutic intervention.
Effects of Melatonin Alone or Associated with Acyclovir on the Suppressive Treatment of Recurrent Genital Herpes: A Prospective, Randomized, and Double-Blind Study
Authors: Roa Cristiane Lima , Cipolla-Neto José , Reiter Russel J. , Linhares Iara Moreno , Lepique Ana Paula , de Aguiar Lana Maria , Seganfredo Isadora Braga , Ferreira-Filho Edson Santos , de Medeiros Sebastião Freitas , Baracat Edmund Chada , Soares-Júnior José Maria
Published: April 2023

Suppressive therapy of recurrent genital herpes is a challenge, and melatonin may be an alternative. Objective: To evaluate the action of melatonin, acyclovir, or the association of melatonin with acyclovir as a suppressive treatment in women with recurrent genital herpes. Design: The study was prospective, double-blind, and randomized, including 56 patients as follows: (a) The melatonin group received 180 placebo capsules in the ‘day’ container and 180 melatonin 3 mg capsules in the ‘night’ container (n = 19); (b) The acyclovir group received 360 capsules of 400 mg acyclovir twice a day (one capsule during the day and another during the night) (n = 15); (c) the melatonin group received 180 placebo capsules in the ‘day’ container and 180 melatonin 3 mg capsules in the ‘night’ container (n = 22). The length of treatment was six months. The follow-up after treatment was six months. Patients were evaluated before, during, and after treatment through clinical visits, laboratory tests, and the application of four questionnaires (QSF-36, Beck, Epworth, VAS, and LANNS). Results: No statistically significant difference was observed for the depression and sleepiness questionnaires. However, in the Lanns scale for pain, all groups decreased the mean and median values in time (p = 0.001), without differentiation among the groups (p = 0.188). The recurrence rates of genital herpes within 60 days after treatment were 15.8%, 33.3%, and 36.4% in the melatonin, acyclovir, and association of melatonin with acyclovir groups, respectively. Conclusion: Our data suggest that melatonin may be an option for the suppressive treatment of recurrent genital herpes.
Correlation between Collagen Type I/III Ratio and Scar Formation in Patients Undergoing Immediate Reconstruction with the Round Block Technique after Breast-Conserving Surgery
Authors: Kim Hyo-young , Im Ho-young , Chang Hee-kyung , Jeong Hwan-do , Park Jin-hyung , Kim Hong-il , Yi Hyung-suk , Kim Yoon-soo
Published: April 2023

The aim of this study was to investigate the relationship between the collagen type I/III ratio and scarring in patients who underwent immediate reconstruction with the round block technique (RBT) after breast conservation surgery. Seventy-eight patients were included, and demographic and clinical characteristics were recorded. The collagen type I/III ratio was measured using immunofluorescence staining and digital imaging, and scarring was assessed using the Vancouver Scar Scale (VSS). The mean VSS scores were 1.92 ± 2.01 and 1.79 ± 1.89, as assessed by two independent plastic surgeons, with good reliability of the scores. A significant positive correlation was found between VSS and the collagen type I/III ratio (r = 0.552, p < 0.01), and a significant negative correlation was found between VSS and the collagen type III content (r = −0.326, p < 0.05). Multiple linear regression analysis showed that the collagen type I/III ratio had a significant positive effect on VSS (β = 0.415, p = 0.028), whereas the collagen type I and collagen type III content had no significant effect on VSS. These findings suggest that the collagen type I/III ratio is associated with scar development in patients undergoing RBT after breast conservation surgery. Further research is needed to develop a patient-specific scar prediction model based on genetic factors affecting the collagen type I/III ratio.
Heated Behaviour in the Classroom for Children with FASD: The Relationship between Characteristics Associated with ADHD, ODD and ASD, Hot Executive Function and Classroom Based Reward Systems
Authors: Carrick Andrea , Hamilton Colin J.
Published: April 2023

Possession of characteristics related to Attention Deficit Hyperactive Disorder, Oppositional Defiance Disorder, and Autism Spectrum Disorder in children prenatally exposed to alcohol contributes to challenges within the diagnostic pathway for Foetal Alcohol Spectrum Disorder (FASD). The presentation of these characteristics, though problematic for the children affected, may not result in referral for diagnosis; focusing on diagnostic thresholds masks the dimensional nature of these characteristics. Children with traits which are undiagnosed may not receive effective support and are often identified as exhibiting challenging behaviour. In the UK, children with undiagnosed Special Educational Needs (SEN) are more likely to experience school exclusion. Common across each condition are challenges to executive function associated with emotional regulation (hot-executive function). This study explored the relationship between characteristics of Attention Deficit Hyperactive Disorder, Oppositional Defiance Disorder, Autistic-Like Traits, and hot executive functions on the helpfulness of reward-based interventions for children with suspected or diagnosed FASD. Data were collected online using caregiver referral questionnaire screeners for each measure (Child Autism Quotient Questionnaire, Vanderbilt ADHD Parental Rating Scale and The Childhood Executive Functioning Inventory) for children aged 6–12 years with suspected or diagnosed FASD (n = 121). Between-group comparisons showed no significant difference in the reporting of Attention Deficit Hyperactive Disorder characteristics, Oppositional Defiance Disorder characteristics, Autistic-Like Traits, and executive function, regardless of diagnostic state. Multiple regression analyses indicated that these personality characteristics and executive functions were associated with the perception of the reward system helpfulness. However, this pattern was qualified by both the type of hot executive function challenged (significant for Regulation not Inhibition) and whether the child had an FASD diagnosis. Thus, a dimensional approach may strengthen our understanding of the child’s classroom experience and help overcome barriers to effective intervention and support.
Morphological and Ultrastructural Collagen Defects: Impact and Implications in Dentinogenesis Imperfecta
Authors: Gadi Lubabah S. A. , Chau David Y. S. , Parekh Susan
Published: April 2023

Collagen is the building block for the extracellular matrix in bone, teeth and other fibrous tissues. Osteogenesis imperfecta (OI), or brittle bone disease, is a heritable disorder that results from defective collagen synthesis or metabolism, resulting in bone fragility. The dental manifestation of OI is dentinogenesis imperfecta (DI), a genetic disorder that affects dentin structure and clinical appearance, with a characteristic feature of greyish-brown discolouration. The aim of this study was to conduct a systematic review to identify and/or define any ultrastructural changes in dentinal collagen in DI. Established databases were searched: Cochrane Library, OVID Embase, OVID Medline and PubMed/Medline. Search strategies included: Collagen Ultrastructure, DI and OI. Inclusion criteria were studies written in English, published after 1990, that examined human dental collagen of teeth affected by DI. A Cochrane data extraction form was modified and used for data collection. The final dataset included seventeen studies published from 1993 to 2021. The most prevalent findings on collagen in DI teeth were increased coarse collagen fibres and decreased fibre quantity. Additional findings included changes to fibre orientation (i.e., random to parallel) and differences to the fibre organisation (i.e., regular to irregular). Ultrastructural defects and anomalies included uncoiled collagen fibres and increased D-banding periodicity. Studies in collagen structure in DI reported changes to the surface topography, quantity, organisation and orientation of the fibres. Moreover, ultrastructural defects such as the packing/coiling and D-banding of the fibrils, as well as differences in the presence of other collagens are also noted. Taken together, this study provides an understanding of the changes in collagen and its impact on clinical translation, paving the way for innovative treatments in dental treatment.
Effects of Non-Enzymatic Browning and Lipid Oxidation on Color of Ready-to-Eat Abalone during Accelerated Storage and Its Control
Authors: Fan Yingchen , Yu Manman , Li Deyang , Zhao Guanhua , Zhang Min , Wang Zonghan , Liu Yuxin , Zhou Dayong
Published: April 2023

The deepening of color of ready-to-eat (RTE) abalone during storage leads to sensory quality degradation, which seriously affects the shelf life of products and consumers’ purchasing desire. The goal of this study is to look into the causes of non-enzymatic browning and lipid oxidation, as well as how to control them, and their effect on the color of RTE abalone during storage. The control, bloodletting and antioxidants groups (lactic acid, citric acid and 4-hexylresorcinol) of RTE abalone were stored for 0, 20 and 40 days at 40 °C, respectively, to explore the rule and mechanism of the color change in RTE abalone. This research shows that RTE abalone undergoes browning during storage. Meanwhile, the content of reducing sugar, phenols and unsaturated fatty acids decreases, while the formation of lipid hydroperoxides and aldehydes increases during storage. In addition, the color change in RTE abalone during storage is mainly related to the Maillard reaction, while the lipid oxidation mainly forms pyrrole and participates in the Strecker degradation process as part of the Maillard reaction. The quality of RTE abalone can be maintained by controlling browning effectively as well as lipid oxidation through bloodletting and the addition of antioxidants to ensure that RTE abalone has high storage stability. According to our research, bloodletting and the addition of antioxidants to RTE abalone have a good application prospect and popularizing value in the storage of RTE abalone.
Identification of Characteristic Peptides of Casein in Cow Milk Based on MALDI-TOF MS for Direct Adulteration Detection of Goat Milk
Authors: Lu Yan , Dai Jinxia , Zhang Sen , Qiao Junqin , Lian Hongzhen , Mao Li
Published: April 2023

It is widely acknowledged that casein is an important allergenic protein in milk which may cause danger to customers. The identification and confirmation of caseins through mass spectrometry requires the selection of suitable characteristic peptides. In this study, by means of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), the three most representative specific peptides of caseins in cow milk were screened out with mass-to-charge ratios (m/z) of 830, 1195, and 1759, respectively. By comparing 2,5-dihydroxybenzoic acid (DHB) and α-cyano-4-hydroxycinnamic acid (CHCA) MALDI matrices, it was found that DHB was more suitable for peptide detection with the limits of detection (LODs) of 0.1 mg/L for α, β-casein. Furthermore, on the basis of verifying the characteristic peptides of casein from cow milk, this protocol was applied to goat milk authentication. Cow milk addition in goat milk was investigated by using the screened specific peptides. The results showed that the adulteration could be identified when the proportion of cow milk was 1% or more. When applied to inspect adulteration in five brands of commercial goat milk, specific peptides of bovine casein were detected in four of them. The method has the advantages of strong reliability, high throughput, simple preprocessing, and fast speed, which can provide powerful help for prewarning dairy allergen.
Evaluating the Chemical Hazards in Wine Production Associated with Climate Change
Authors: Nechita Constantin , Iordache Andreea Maria , Voica Cezara , Costinel Diana , Botoran Oana Romina , Popescu Diana Ionela , Șuvar Niculina Sonia
Published: April 2023

The climate warming trend challenges the chemical risk associated with wine production worldwide. The present study investigated the possible difference between chemical wine profile during the drought year 2012 compared to the post-drought year 2013. Toxic metals (Cd and Pb), microelements (Mn, Ni, Zn, Al, Ba, and Cu), macroelements (Na, Mg, K, Ca, and P), isotopic ratios (87Sr/86Sr and 206Pb/207Pb), stable isotopes (δ18O, δ13C, (D/H)I, and (D/H)II), and climatic data were analyzed. The multivariate technique, correlation analysis, factor analysis, partial least squares–discriminant analysis, and hierarchical cluster analysis were used for data interpretation. The maximum temperature had a maximum difference when comparing data year apart. Indeed, extreme droughts were noted in only the spring and early summer of 2012 and in 2013, which increased the mean value of ground frost days. The microelements, macroelements, and Pb presented extreme effects in 2012, emphasizing more variability in terms of the type of wine. Extremely high Cd values were found in the wine samples analyzed, at up to 10.1 µg/L. The relationship between precipitation and δ18O from wine was complex, indicating grape formation under the systematic influence of the current year precipitation, and differences between years were noted. δ13C had disentangled values, with no differentiation between years, and when coupled with the deuterium–hydrogen ratio, it could sustain the hypothesis of possible adulteration. In the current analysis, the 87Sr/86Sr showed higher values than in other Romanian studies. The temperature had a strong positive correlation with Pb, while the ground frost day frequency correlated with both Pb and Cd toxic elements in the wine. Other significant relationships were disclosed between the chemical properties of wine and climate data. The multivariate statistical analysis indicated that heat stress had significant importance in the chemical profile of the wine, and the ground frost exceeded the influence of water stress, especially in Transylvania.
Protective Effect of Glycomacropeptide on the Inflammatory Response of U937 Macrophages
Authors: Córdova-Dávalos Laura Elena , Cervantes-García Daniel , Ballona-Alba Maria Fernanda , Santos-López Alejandra , Esquivel-Basaldúa Alma Saraí , Gallegos-Alcalá Pamela , Jiménez Mariela , Salinas Eva
Published: April 2023

Macrophages play crucial roles in inflammation and oxidative stress associated with noncommunicable diseases, such as cardiovascular diseases, diabetes, and cancer. Glycomacropeptide (GMP) is a bioactive peptide derived from milk κ-casein that contains abundant sialic acid and has shown anti-inflammatory, antioxidative, anti-obesity, and anti-diabetic properties when is orally administered. The aim of this study was to evaluate the effect of GMP on the regulation of the inflammatory response in human macrophages and the participation of sialic acid in this activity. GMP pretreatment decreased by 35%, 35%, and 49% the production of nitrites, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, respectively, in activated human macrophages U937. The same effect was obtained when cells were pretreated with asialo GMP, and no change on the gene expression of the lectins associated with the recognition of sialic acids, SIGLEC5, 7, and 9, was induced by GMP on macrophages, which suggests that sialic acid might not be involved in this immunoregulatory effect. Interestingly, GMP increased 8.9- and 3.5-fold the gene expression of the canonical anti-inflammatory protein SOCS3 and the antioxidant enzyme HMOX1, respectively, in U937 cells. Thus, GMP exerts anti-inflammatory and antioxidative activities on activated macrophages in a sialic acid-independent manner, which might be related to its in vivo reported bioactivity.
Tough, Injectable Calcium Phosphate Cement Based Composite Hydrogels to Promote Osteogenesis
Authors: Wang Yazhou , Peng Zhiwei , Zhang Dong , Song Dianwen
Published: April 2023

Osteoporosis is one of the most disabling consequences of aging, and osteoporotic fractures and a higher risk of subsequent fractures lead to substantial disability and deaths, indicating that both local fracture healing and early anti-osteoporosis therapy are of great significance. However, combining simple clinically approved materials to achieve good injection and subsequent molding and provide good mechanical support remains a challenge. To meet this challenge, bioinspired by natural bone components, we develop appropriate interactions between inorganic biological scaffolds and organic osteogenic molecules, achieving a tough hydrogel that is both firmly loaded with calcium phosphate cement (CPC) and injectable. Here, the inorganic component CPC composed of biomimetic bone composition and the organic precursor, incorporating gelatin methacryloyl (GelMA) and N-Hydroxyethyl acrylamide (HEAA), endow the system with fast polymerization and crosslinking through ultraviolet (UV) photo-initiation. The GelMA-poly (N-Hydroxyethyl acrylamide) (GelMA-PHEAA) chemical and physical network formed in situ enhances the mechanical performances and maintains the bioactive characteristics of CPC. This tough biomimetic hydrogel combined with bioactive CPC is a new promising candidate for a commercial clinical material to help patients to survive osteoporotic fracture.