bluuebunny/crossref_metadata_2025 huggingface dataset:
How mixed messages may be better than silence in climate change education
Authors: Stevenson Kathryn , Busch K. C. , Peterson M. Nils , Lawson Danielle F. , Chavez Regina Ayala
Published: July 2023

Polarization around climate change viewpoints – including climate change concern and commitment to action – continues to be a persistent challenge to collective action in the United States, and across the globe. Multiple studies have found that K-12 science teacher perceptions of climate change reflect that of the general population, raising concerns that education may be replicating among students the polarization found among adults. However, few have examined how approaches to teaching climate change may be linked to climate change concern and behavior among students. We began to address this gap with a pre/post survey of 354 middle school students from eight science classrooms across North Carolina and their teachers. We measured changes in climate change concern and behavior among students, student-reported frequency of discussing climate change in class, and teacher-reported approach to teaching climate change as consistent with the scientific consensus (climate change is attributed to human activity; 13.2% of students in these classes), mixed messages (climate change is attributed to both human and natural causes; 53.2% of students), denial (climate change is attributed to natural causes; none of students) and avoidance (not discussing climate change; 33.5% of students). We also controlled for socioeconomic status (Title I) and location (rural versus urban) of the school. We detected gains in both concern and behavior across all teaching approaches. We also found frequency of school-based discussion about climate change was the most predictive of gains in concern, but no measured factors predicted gains in behavior. Baseline concern and behavior levels did vary across the different treatment approaches, with lower baselines concern and levels found among teachers who take an avoidance and mixed messages approaches. Together, these results suggest that cultural contexts may be the drivers of both teaching approaches and student climate change concern and behavior, but variations in teaching approaches are not polarizing forces themselves. Instead, encouraging classroom-based conservations about climate may boost concern levels, even in cultural contexts that do not prioritize scientific consensus about climate change drivers. These findings may provide guidance for teaching climate change as well as other politically fraught topics.
Molecular characterization of head and neck infection causing bacterial communities using 16S rRNA in eastern Indian population
Authors: Lenka Smarita , Swain Subrat , Sahu Basanta , Lenka Rajesh , Sahu Kundan , Sahu Mahesh , Swain Santosh , Dubey Debasmita
Published: July 2023

Head and neck infections (HNI) are dangerous illnesses caused by a variety of bacterial species. Due to either incorrect diagnosis or excessive antibiotic usage, multidrug resistance (MDR) poses a problem on a global scale. We aimed this study to identify and compare their relationship with eastern Indian MDR bacteria.We collected 264 HNI clinical samples (2020–2022) from the eastern Indian state of Odisha to investigate the bacterial isolates associated with HNI, as well as the characterization was performed with their drug susceptibility and assessment of their diversity by comparison with worldwide bacterial isolates. There are 218 positive bacterial samples. Using the 16S rRNA gene, we performed molecular characterization and phylogenetic analysis on 25 multidrug-resistant bacteria. According to population genetic factors, the haplotype (Hd) and nucleotide diversity (π) ranged from 0.558 to 0.828 and 0.03236 to 0.28428.The prevalence of these neglected pathogens within this rarely focused geographical area and the transboundary potential to find better therapeutic approaches can be possible through this study.
Decorated graphene oxide with gold nanoparticles as a sensitive modified carbon paste electrode for simultaneous determination of tyrosine and uric acid
Authors: Bojdi Majid Kalate , Behbahani Mohammad , Garazhian Elahe
Published: July 2023

It is presented here as a simple and selective method to simultaneously determine tyrosine and uric acid using a modified carbon paste electrode decorated with graphene oxide and gold nanoparticles (GO/AuNPs/MCPE). In order to characterize and evaluate the morphology and constituents of the nanostructures, X-ray diffraction spectroscopy, Transmission electron microscopes, Dynamic light scattering, Zeta potential, electrochemical impedance spectroscopy, and Voltammetry were employed. The current response on the surface of the modified electrode had a dynamic linear range (DLR) relationship in the concentrations of 0.14-340.00 µmol L-1 and 0.06-141.00 µmol L-1 for tyrosine and uric acid, respectively, and the method detection limit (MDL) was 0.0060 µmol L-1 and 0.0037 µmol L-1, respectively. This modified electrode provided high stability, sensitivity, and acceptable reproducibility for voltammetric measurements of tyrosine and uric acid simultaneously in a biological matrix.
Free-moving-state microscopic imaging of cerebral oxygenation and hemodynamics with a photoacoustic fiberscope
Authors: Jin Long , Zhong Xiaoxuan , liang yizhi , Wang Xiaoyu , Lan Haoying , Bai Xue , Guan Bai-Ou
Published: July 2023

We report the development of a head-mounted photoacoustic fiberscope for cerebral imaging in a freely behaving mouse. The 4.5-gram imaging probe has a 9-µm lateral resolution and 0.2-Hz frame rate over a 1.2-mm wide area. The probe can continuously monitor cerebral oxygenation and hemodynamic responses at single-vessel resolution, showing significantly different cerebrovascular responses to external stimuli under anesthesia and in the freely moving state. For example, when subjected to high-concentration CO2 respiration, enhanced oxygenation to compensate for hypercapnia can be visualized due to cerebral regulation in the freely moving state. Comparative studies exhibit significantly weakened compensation capabilities in obese rodents. This new imaging modality can be used to study normal and diseased-state cerebrovascular functions and shows promise in neuroscience and microcirculation studies.
Enhanced Performance Triboelectric Nanogenerator Based on Polydimethylsiloxane (PDMS)/ Barium Titanite (BTO) / Graphene Quantum Dot (GQD) Nanocomposites for Energy Harvesting
Authors: Hatta Faizatul Farah , Shazni Muhammad Aniq , Mohamed Mohd Ambri
Published: July 2023

Triboelectric nanogenerators (TENGs) have been developed as promising energy-harvesting devices to effectively convert mechanical energy into electricity. A TENGs is using either organic or inorganic materials to initiate the triboelectrification process, followed by charge separation. In this study, a high-performance composite based triboelectric nanogenerators (CTENGs) device, based on PDMS as a polymeric matrix with BTO nano-powders (NPs) as dielectric fillers and graphene as conductive media was fabricated. The PDMS/BTO/GQD composite film was prepared with the GQD doped into the mixture of PDMS/BTO and mechanically stirred. The composition of GQD varied from 0 to 40 wt%. The composite was spin coated onto flexible ITO on PET sheet and dried in the oven at 80°C for 24 hours. The output performance of TENGs is enhanced by the increased concentration of 30 wt% GQD which is two times higher than nanocomposite films without GQD. The PDMS/BTO/G30 TENGs film showed an increase open-circuit voltage output (VOC), short-circuit current output (ISC) and power density reaching ~ 310.0 V, ~ 23.0 mA and 1.6 W/m2 respectively. The simple and scalable process for the PDMS/BTO/GQD TENGs would benefit as a sustainable energy harvesting system in small electronic devices.
Behavioral fluctuation reflecting theta-rhythmic activation of sequential working memory
Authors: Ushiyama Junichi , Ideriha Takuya
Published: July 2023

Sequential working memory, the ability to actively maintain sequential information, is essential for our cognition and has been considered to be represented rhythmically within the theta (3–7 Hz) range. In the current study, we predicted that if the sequential information is truly activated rhythmically, there should be periodic fluctuation in our behavior where the easiness/quickness to recall the information rises and falls according to the theta rhythm. We conducted detailed analyses on reaction times (RT) for retrieving sequential and non-sequential information in six experiments (total n = 110). The results revealed that the RT for recalling the sequential information showed fluctuation in the theta range and was significantly stronger than that observed when sequential order was not necessary to remember. Taken together, we revealed that our behavior displayed theta-rhythmic fluctuation when recalling sequential information in a relatively large sample, supporting theta phase-dependent coding of sequential working memory.
Identification and validation of ferroptosis-Related genes in sarcopenia
Authors: Chen Yanzhong , Zhang Yaonan , Zhang Sihan , Ren Hong
Published: July 2023

Background:Ferroptosis, characterized by iron accumulation and lipid peroxidation, leads to cell death. Growing evidence suggests the involvement of ferroptosis in sarcopenia. However, the fundamental ferroptosis-related genes (FRGs) for sarcopenia diagnosis, prognosis, and therapy remain elusive. This study aimed to identify molecular biomarkers of ferroptosis in sarcopenia patients.Methods:Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between normal and sarcopenia samples were identified using the "limma" package in R software. FRGs were extracted from GeneCards and FerrDB databases. Functional enrichment analysis determined the roles of DEGs using the "clusterProfiler" package. A protein-protein network was constructed using Cytoscape software. Immune infiltration analysis and receiver operating characteristic (ROC) analysis were performed. mRNA-miRNA, mRNA-TF, and mRNA-drug interactions were predicted using ENCORI, hTFtarget, and CHIPBase databases. The network was visualized using Cytoscape.Results:We identified 46 FRGs in sarcopenia. Functional enrichment analysis revealed their involvement in critical biological processes, including responses to steroid hormones and glucocorticoids. KEGG enrichment analysis implicated pathways such as carbon metabolism, ferroptosis, and glyoxylate in sarcopenia. Totally, 11 hub genes were identified, and ROC analysis demonstrated their potential as sensitive and specific markers for sarcopenia in both datasets. Additionally, differences in immune cell infiltration were observed between normal and sarcopenia samples.Conclusion:The hub genes identified in this study are closely associated with ferroptosis in sarcopenia and can effectively differentiate sarcopenia from controls. CDKN1A, CS, DLD, FOXO1, HSPB1, LDHA, MDH2, and YWHAZ show high sensitivity and specificity for sarcopenia diagnosis.
Analyzing Concentration in the Greek Public Procurement Market: A Network Theory Approach
Authors: Pliatsidis Andreas Christos
Published: July 2023

This study uses network theory to analyze the structure and concentration of the Greek public procurement market, focusing on the relationships between Contracting Authorities (CAs) and Economic Operators (EOs) within different Common Procurement Vocabulary (CPV) groups. By examining degree distribution curves and identifying dominant economic operators, we gain valuable insights into market dynamics and competition in Greece. The findings reveal the presence of market concentration, where a few EOs receive a disproportionate share of contracts within certain CPV groups which suggests potential market dominance and lack of competition. In contrast, some CPV groups demonstrate a more balanced distribution of contracts among EOs, suggesting a healthier competitive environment. The analysis of degree distributions between sub-networks based on CPV groups indicates variations in market structures between sectors. These differences highlight the heterogeneity in the Greek public procurement market, as well as the need for sector-specific policy interventions. Given that the concentration of contract awards raises competition, fairness and transparency concerns, the implications of the findings are important for policymakers, regulators and stakeholders involved in the Greek public procurement market. While this study provides valuable information, limitations including variations in data availability and potential inaccuracies in recorded information exist. Future research should address these limitations and explore the effects of market concentration on CPV codes in greater depth. This study contributes to the public procurement literature and serves as a basis for further research and policy making in the Greek procurement sector.
Prevalence and Effects of Late Cardiotoxicity induced by Anthracyclines and/or Anti- HER2 Antibodies in Patients with Breast Cancer: a real world study
Authors: Oliveira Cátia , Flores Rui , Azevedo Raquel , Fontes Raquel , Pereira Vitor Hugo
Published: July 2023

Introduction: Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-related mortality in women. Advances in screening and treatment have improved survival but have also increased morbidity and mortality due to treatment side effects, particularly cardiotoxicity. Late cardiotoxicity generally develops several years after treatment. The risk of cardiotoxicity post BC treatment is increased by cardiovascular (CV) risk factors and previous cardiac disease. Nevertheless, limited data is available about the long-term effects of cardiotoxic treatment in women without CV risk factors before BC diagnosis.
Aims: To assess prevalence and long-term effects of late cardiotoxicity in a low-risk group of BC survivors.
Methods: This prospective study evaluated women aged between 18–65 years, diagnosed with non-metastatic BC and treated between 2011–2016 at a single institution The echocardiographic parameters were compared to an age-matched control group of women recently diagnosed with BC who have not been submitted to anticancer therapy.
Results: Among the 40 recruited women, 32.5% displayed left ventricular systolic dysfunction (LVSD) and 10% fulfilled criteria for late cardiotoxicity based on their previously recorded imaging parameters. There was a significant difference in left ventricular ejection fraction (LVEF) between time points (p < .001). The study group had significant lower LVEF compared to the control group, (p < .001). Additionally, there was a significant reduction in Global Longitudinal Strain in the study group when compared to controls, (p < .001).
Conclusions: In conclusion, this study demonstrated that cancer therapy related cardiac disease is a common side effect in BC survivors. Given this finding, even women without previous CV risk factors should be carefully monitored years after the end of treatment.
Impact of D2 total gastrectomy including splenectomy for scirrhous gastric cancer in the era of effective adjuvant chemotherapy
Authors: Yamagata Yukinori , Yoshikawa Takaki , Sakon Ryota , Ishizu Kenichi , Wada Takeyuki , Hayashi Tsutomu
Published: July 2023

Background
Total gastrectomy with D2 dissection including splenectomy (TGS) is usually selected for locally resectable scirrhous gastric cancer (SGC), which was established in the era of surgery alone. However, it remains unclear whether TGS for SGC is justified in the era of effective adjuvant chemotherapy.
Methods
This study included 120 SGC patients, consisting of 63 cases treated between January 2000 and December 2006 (Former group), and 57 cases treated between January 2007 and December 2016 (Latter group). We collected clinicopathological data, then examined survival and the therapeutic value index.
Results
The background characteristics were well-balanced, except for age and sex. The Latter group might be characterized by older population (P = 0.051) and frequent female (P = 0.067). Adjuvant chemotherapy was administered to 82.5% of the Latter group and was 15.9% in the Former group (P < 0.001). The 5-year overall survival rate of the Latter group was 57.9% (95% confidence interval: 43.2–70.0), seems better than that of the Former group (44.0%, 95% confidence interval: 31.5–55.8) (hazard ratio = 0.735, P = 0.221). Improvement of the index from the Former group was observed in the Latter group at almost all stations. The ratio of the index between these two groups was 1.38 at the D1 station and 1.60 at the D2 station. Index of splenic hilar node ranked similarly high in the both groups.
Conclusion
The therapeutic value index was improved in almost all nodal stations by S-1 adjuvant chemotherapy, especially in D2 nodes. TGS would be more important for locally resectable SGC in the era of effective adjuvant chemotherapy.
Serum glypican-4 and clusterin are increased and associated with insulin resistance in patients with polycystic ovary syndrome
Authors: Chen Zheng , Zeng Haixia , Huang Qiulan , Lin Cuiping , Li Xuan , Sun Shaohua , Liu Jianping
Published: July 2023

Objective:
To investigate the changes in serum glypican-4 (GPC4) and clusterin (CLU) levels in patients with polycystic ovary syndrome (PCOS) as well as their correlation with sex hormones and metabolic parameters.
Method:
A total of 40 PCOS patients and 40 age-matched healthy women during the same period were selected. To detect and compare serum GPC4 and CLU levels between the two groups, binary logistic regression was used to analyze the relative risk of PCOS at different levels of serum GPC4 and CLU. Stepwise linear regression was used to analyze the influential factors of serum GPC4 and CLU in PCOS patients.
Results:
Serum GPC4 (1.82 ± 0.49 vs. 1.30 ± 0.61 ng/ml, P < 0.001) and CLU (468.79 ± 92.85 vs. 228.59 ± 82.42 µg/ml, P < 0.001) in PCOS patients were significantly higher than those in healthy women. In the PCOS group, serum GPC4 was positively correlated with FSH, FPG, FINS, HOMA-IR, TG, and CLU (P < 0.05), whereas serum CLU was positively correlated with BMI, FPG, FINS, and HOMA-IR (P < 0.05), multiple stepwise linear regression analysis showed that HOMA-IR was independently associated with serum GPC4, and it showed that BMI and HOMA-IR were independently associated with CLU (P < 0.05).
Conclusion:
Serum GPC4 and CLU levels in PCOS patients were significantly higher than those in healthy women, suggesting that GPC4 and CLU may be markers associated with insulin resistance in women with PCOS.
Treatment outcomes for idiopathic sudden sensorineural hearing loss in dialysis patients
Authors: Kim Seonju , Lee Dong Kyu , Kim Hae-rim , Park Jung Mee , Kim Soon Bae , Yu Hoon
Published: July 2023

Idiopathic sudden sensorineural hearing loss (ISSNHL) poses a significant challenge for nephrologists in the treatment of dialysis patients. Due to limited studies comparing the treatment response between dialysis and non-dialysis patients, physicians face difficulties in managing this patient population. Therefore, this study aimed to investigate the treatment outcomes of dialysis patients with ISSNHL. This single-center, retrospective, observational study enrolled 700 patients diagnosed with ISSNHL between January 2005 and December 2021 at Asan Medical Center, Korea. Among them, 47 were dialysis patients, while 653 were non-dialysis patients. To balance pre-existing clinical characteristics, a 1:5 propensity score matching analysis was performed on the non-dialysis patients. The standard protocol involved administering high-dose systemic steroid therapy or intra-tympanic steroid injections. The pure tone average of the two groups was compared before initiating treatment, after 2 weeks, and after 2 months of treatment. The degree of improvement in the hearing was evaluated using Siegel's criteria. Before propensity score matching, the age, prevalence of diabetes or hypertension, initial hearing threshold at each frequency level (0.5, 1, 2, and 4 kHz), and treatment strategies exhibited statistically significant differences between the two groups. However, in the propensity score-matched cohort, none of the measured confounding variables showed statistically significant differences between the groups. Two months after steroid treatment, the non-dialysis patient group demonstrated a significantly higher average improvement in pure tone audiometry (P = 0.017) and a greater percentage of complete response according to Siegel's criteria compared to the dialysis patient group (26.8% vs. 6.4%). This study suggests that dialysis patients exhibit significantly poorer treatment outcomes for ISSNHL compared to non-dialysis patients.
Corrosion in reinforced concrete: Diagnostics through Potential Corrosion Technique
Authors: Reginato Lucas Alexandre , Lorenzi Alexandre , de Oliveira Leonardo Covatti , Lorenzi Luciani Somensi , Filho Luiz Carlos Pinto da Silva
Published: July 2023

Among the processes that accelerate the loss of performance of reinforced concrete structures, considering their frequent occurrence and severity, corrosion of reinforcement can be seen as one of the most important. A worrying factor is that most buildings in the main Brazilian urban centers are between 40 and 50 years old, a time when repairs and maintenance become more routine. Therefore, the problems related to the corrosion of the reinforcements tend to accentuate in the coming years and the identification of corrosion will play an important role. Thus, this research has the purpose of analyzing the application of the diagnosis through potential corrosion techniques. For this, full-scale reinforced concrete beams were analyzed. Corrosion was stimulated by the Modified Immersion Accelerated Corrosion - CAIM method, at three levels of mass loss: 5%, 10%, and 15%. The diagnostic technique through the corrosion potential was applied, in which it was observed that there is uncertainty in the corrosion evaluation for the mass loss levels of 5 and 10%, resulting in a corrosion uncertainty interval, but at 15%, the potential technique proved to be satisfactory.
Cytisine–N-methylene-(5,7,4’-trihydroxy)- isoflavone ameliorates ischemic stroke-induced brain injury in mouse by regulating the oxidative stress and BDNF-Trkb/Akt pathway
Authors: Li yongbiao li , fan fangcheng , Liu Qingshan
Published: July 2023

Background
A novel compound Cytisine–N-methylene-(5,7,4’-trihydroxy)- isoflavone (LY01) found in the Sophora alopecuroides L is a neuroprotective agent. However, the effect and potential mechanism of LY01 treatment for ischemic stroke (IS) have not been fully elucidated.
Aim of the study
The aim of this study is to demonstrate whether LY01 LY01 can rescue ischemic stroke-induced brain injury and oxygen–glucose deprivation/reperfusion (OGD/R).
Results
Our results show that intragastric administration of LY01 improves ischemic stroke behaviors in mice, as demonstrated by neurological score, infarct volume, cerebral water content, rotarod test for activity. Compared with the model group, the EGb and LY01 reversed the neurological score, infarct volume, cerebral water content, rotarod test in model mice. Further analysis showed that the LY01 rescued oxidative stress in the model mice, which was reflected in the increased levels of catalase, superoxide dismutase, total antioxidant capacity and decreased levels of malondialdehyde in the serum of the model mice. Moreover, the expression of the brain-derived neurotrophic factor BDNF, p-Akt, Bax, Bcl-2, p-Trkb was restored and the expression of Bax, GFAP in the brains of the model mice was inhibited through LY01 treatment. In the polymerase chain reaction (PCR) data, after giving LY01, the expression in the brains of model mice was that, IL-10 increased and IL-1β, Bax, Bcl-2 decreased. Furthermore, our results indicated that LY01 improved cell viability, reactive oxygen species content, and mitochondrial membrane potential dissipation induced by OGD/R in primary culture of rat cortical neurons. Bax and caspase-3 activity was upregulated compared to the before after treatment with LY01.
Conclusions
Our study suggests that LY01 reversed ischemic stroke by reducing oxidative stress and activating the BDNF-TrkB/Akt pathway and exerted a neuroprotective action against OGD/R injury via attenuation, a novel approach was suggested to treat ischemic stroke.
Comparison of laparoscopic lateral lymph node dissection for rectal cancer with and without routine resection of the visceral branches of internal iliac artery
Authors:   511521199710222718 Xiao, Zhang Xubing , Gu Chaoyang , Deng Xiangbing , Meng Wenjian , Wei Mingtian , Wang Ziqiang
Published: July 2023

Background:The lateral-pelvic recurrence after lateral lymph node (LLN) dissection (LLND) in patients with lateral lymph node metastasis (LLNM) remained high, especially in the absence of neoadjuvant chemoradiotherapy. Incomplete resection of lymphatic tissue in the lateral compartment, given the complex anatomy and variation of the internal iliac vessels, might contribute to the local failure. This study aimed to explore the safety and feasibility of the modified LLND with routine resection of the visceral branches of internal iliac vessels (IIVs) for mid-low-lying rectal cancer.
Materials and method: Consecutive patients undergoing LLND for rectal cancer were divided into the RVR group (routine visceral branches of the IIVs resection group) and the NRVR group (without routine resection). The main outcomes were postoperative complications and the number of LLN harvested.
Results: From 2012 to 2021, a total of 75 and 57 patients were included in the RVR and NRVR group, respectively. The operative time was reduced in the RVR group (P=0.020). No significant difference was observed between the two groups for the incidence of total, major, or minor postoperative complications. Pathologically confirmed LLNM were 24 (32%) patients in the RVR group and 12 (21.1%) in the NRVR group (P=0.162). The number of LLN harvested had no significant difference between two groups (11 vs 12, P=0.329).
Conclusion: LLND with routine resection of visceral branches of IIVs is safe and feasible, which is promising to improve LLN clearance and the detection rate of LLNM without bringing additional major complications or harm to long-term urinary function.
The Impact of governance on agricultural value-added inequality nexus in Pakistan
Authors: Khan Ziaullah , Chiu Yi-Bin
Published: July 2023

This study empirically investigates the intricate relationship between governance (GOV), agricultural value-added (AVA), and income inequality in Pakistan from 1984 to 2018. The study employed a time series threshold regression estimates technique to investigate non-linear dynamics among the variables. The results indicate that the relationship between GOV and income inequality is not linear and dependent on the level of GOV. The empirical results show that GOV improvements reduce income inequality at lower threshold levels. However, at a higher threshold level, GOV improvements can lead to an increase in income inequality. These findings suggest that policy efforts to decrease income disparity in Pakistan should consider both the state of GOV and supplemental measures to reduce inequality successfully. The study further employed the Atkinson and Palam ratio other than the Gini coefficient for reliability. The diagnostic tests show that the model is well-specified and robust. The results further provide some crucial guidelines for reducing income inequality in Pakistan.
The SOX4/EZH2/SLC7A11 signaling axis mediates ferroptosis in calcium oxalate crystal deposition-induced kidney injury.
Authors: Yan Xinzhou , Cheng Fan , Xia Yuqi , Li Bojun , Ye Zehua , Li Lei , Yuan Tianhui , Song Baofeng , Yu Weimin , Rao Ting , Ning Jinzhuo , Lin Fangyou , Mei shuqin , Mao Zhiguo , Zhou Xiangjun , Li Wei
Published: July 2023

Epigenetic regulation is reported to play a significant role in the pathogenesis of various kidney diseases, including renal cell carcinoma, acute kidney injury, renal fibrosis, diabetic nephropathy, and lupus nephritis. However, the role of epigenetic regulation in calcium oxalate (CaOx) crystal deposition-induced kidney injury remains unclear. Our study demonstrated that the upregulation of enhancer of zeste homolog 2 (EZH2)-mediated ferroptosis facilitates CaOx-induced kidney injury. CaOx crystal deposition promoted ferroptosis in vivo and in vitro. Usage of liproxstatin-1 (Lip-1), a ferroptosis inhibitor, mitigated CaOx-induced kidney damage. Single-nucleus RNA-sequencing, RNA-sequencing, immunohistochemical and western blotting analyses revealed that EZH2 was upregulated in kidney stone patients, kidney stone mice, and oxalate-stimulated HK-2 cells. Experiments involving in vivo EZH2 knockout, in vitro EZH2 knockdown, and in vivo GSK-126 (an EZH2 inhibitor) treatment confirmed the protective effects of EZH2 inhibition on kidney injury and ferroptosis. Mechanistically, the results of RNA-sequencing and chromatin immunoprecipitation assays demonstrated that EZH2 regulates ferroptosis by suppressing solute carrier family 7, member 11 (SLC7A11) expression through trimethylation of histone H3 lysine 27 (H3K27me3) modification. Additionally, SOX4 regulated ferroptosis by directly modulating EZH2 expression. Thus, this study demonstrated that SOX4 facilitates ferroptosis in CaOx-induced kidney injury through EZH2/H3K27me3-mediated suppression of SLC7A11.
Hepatitis B virus gene integration affects the efficacy of systemic drug therapy after radical resection of liver cancer: A prospective cohort study
Authors: Li Zixiong , Chen Chao , Si Anfeng , Qu Wenshu , Zhang Jue , Li Huiyu , Xia Zhaojun , Luo Linhua , Zhang Yuanjing , Liu Xiufeng
Published: July 2023

Objective
Hepatitis B virus (HBV) gene integration is an important factor in the occurrence and development of HBV-hepatocellular carcinoma (HBV-HCC); however, its role in the clinical treatment of liver cancer is still unclear. This study aimed to investigate the effect of HBV integration on the prognosis of patients.
Method
Twenty patients with HBV-HCC were included based on strict inclusion criteria. Whole genome sequencing of HBV-HCC surgical specimens was performed to identify HBV gene integration events. After systemic drug treatment (tyrosine kinase inhibitors alone or in combination with immune checkpoint inhibitors), the therapeutic efficacy was evaluated based on RECIST 1.1 criteria. COX regression model was used to identify factors affecting progression-free survival (PFS) and overall survival (OS).
Result
HCC tissue samples from 20 HBV-HCC patients were sequenced and matched with standard sequence. HBV integration was found in 10 out of the 20 patients. The highest frequency of HBV integration occurred on chromosome 5. Survival analysis showed that HBV integration was a risk factor for HCC recurrence (hazard ratio [HR]: 3.366, P = 0.019). However, there was no significant effect of HBV integration on the PFS after first-line systemic drug treatment (P = 0.313). The overall survival of HCC patients with HBV integration was significantly shorter than their counterparts without HBV integration (HR [95% CI]: 6.335 [1.237–32.446]; P = 0.027).
Conclusion
HBV integration event was found to be a risk factor for HCC recurrence in HBV-HCC patients after radical surgery. Patients with HBV integration are potential candidates for active intervention in the early postoperative period.
Effect of Phosphodiesterase Type 5 Inhibitors in the Active Phase of Peyronie’s Disease: A Retrospective Cohort Study
Authors: Durukan Emil , Kraglund Rune , Rashid Shad , Thorkilgaard Tine , Jensen Christian , Fode Mikkel
Published: July 2023

Objectives
Experimental models and preliminary human trials have implied that continuous treatment with Phosphodiesterase Type 5 inhibitors (PDE5is) may be a viable treatment of Peyronie’s disease (PD) in the active phase. The purpose of this study is to assess the effect of PDE5is on penile curvature in the management of PD in the active phase.
Subjects and Methods
We performed a retrospective cohort study of patients with PD in the active phase seen between 2017 and 2021. Patient age, comorbidities, BMI, erectile function, and PD characteristics including pain, treatment, and curvatures at each visit were registered. The primary outcome was the change in penile curvature between visits in patients receiving daily PDE5i treatment compared to patients receiving no treatment.
Results
133 patients were identified, with 101 (75.9%) receiving treatment with daily PDE5is (Group 1) and 32 (24.1%) receiving no treatment (Group 2). The mean age was 58.5 (SD 10) years in group 1 and 59 (SD 13.7) years in group 2. The mean time between the onset of symptoms and the first clinical visit was 10.6 (SD 7.3) months in group 1 and 13.4 (SD 19) months in group 2. The mean change in penile curvature between the first and last observations in group 1 and group 2 was + 0.87° (CI: -1.8, 3.5) and + 5.72° (95% CI: 1.4, 10), respectively (p = 0.07). A multivariate analysis controlling for baseline curvature and time between the onset of symptoms and the first clinical visit showed no significant differences in penile curvature changes between the groups (-4.7, 95% CI: -10, 0.6) (p = 0.08).
Conclusions
Continuous PDE5i treatment appeared to have no influence on the progression of PD in the active phase. The main limitation of the study is its retrospective nature. Randomized controlled trials are needed to draw a definitive conclusion.
Inhibition of sepsis-induced pancreatic injury by leukotriene receptor antagonism via modulation of oxidative injury, and downregulation of inflammatory markers in experimental rats
Authors: Hagar Hanan H. , Alhazmi Shaima M. , Arafa Maha
Published: July 2023

Purpose
The purpose of this study is to investigate the effect of montelukast on lipopolysaccharide (LPS)-induced pancreatitis.
Methods
Acute pancreatitis was induced by a single dose of LPS (6 mg/kg, i.p.) while montelukast was given in two different doses (10 and 20 mg/kg/day) for three consecutive days prior to injection of LPS.
Results
Acute pancreatitis was demonstrated by significant increases in serum levels of pancreatic enzymes lipase and amylase and lactate dehydrogenase (LDH). Proinflammatory response activation was evident by elevated serum levels of nitric oxide (NO) and increased pancreatic concentrations of tumor necrosis factor- α (TNF-α), interleukin-1 (IL-1β) and intercellular adhesion molecule-1 (ICAM-1). The activity of myeloperoxidase (MPO), a neutrophil infiltration marker, has also been increased. Oxidative stress was confirmed by significant increases in the concentrations of lipid peroxides measured as thiobarbituric acid reactive substances (TBARS) and decreases in the concentrations of reduced glutathione (GSH) in the pancreatic tissues of animals treated with LPS. Histological examination confirmed the biochemical alterations. Montelukast treatment reversed all these biochemical indices and histopathological changes that were induced by LPS. Montelukast reduced the increase in serum levels of lipase, amylase, LDH, total nitrite/nitrate, TNF-α, IL-1β and ICAM-1. MPO activities and TBARS concentrations were also suppressed while GSH content was increased in pancreatic tissues.
Conclusion
These results show that montelukast may be a useful pharmacological agent in protection against LPS-induced oxidative pancreatic injury by inhibiting neutrophil infiltration, counteracting oxidative stress, and suppressing inflammatory mediators.
Multi Population's Killer Whales Optimizer: A New Optimization Approach Based On Fixed Primary Objective
Authors: Moosavi Seyyed Hamid samareh , khaliji seyed mostafa moosavi , Bardsiri Vahid Khatibi
Published: July 2023

This paper has presented a new algorithm called Multi Population's Killer Whales Optimizer (MPKWO). This algorithm is inspired by hunting of a group of Southern Hemisphere Killer Whales. In MPKWO algorithm, a fixed primary objective is used for optimization and search of the main target. In MPKWO algorithm, two populations of the Killer Whales, those waves-generating and the spy Killer Whales, have been used to simulate the hunting process. The spy Killer Whales have a fixed position (fixed primary objective) and wave-generating Killer Whales move closer to the target by moving in each iteration of the algorithm. In fact, in MPKWO algorithm, initially, an initial value is considered as the target, and the position of the main objective is searched for around that point. The proposed algorithm has been evaluated by 18 functions of the standard test. The results obtained from the proposed algorithm are compared with several known and new algorithms. In other words, compared to other algorithms, the proposed algorithm has successfully obtained the optimal values in 71.4% of the cases for Unimodal functions, 66.64% for Multi-modal functions and 80% for fixed-dimension multimodal functions. In addition, three classic engineering problems are solved by MPKWO algorithm. For a more accurate evaluation, the MPKWO algorithm was ultimately used to estimate the software effort and optimize the ABE method. Simulation results show that the proposed algorithm has been more effective than the compared algorithms.
The fluorescent ligand bTVBT2 reveals increased p-tau uptake by retinal microglia in Alzheimer’s disease patients and AppNL-F/NL-F mice
Authors: Nuñez-Diaz Cristina , Andersson Emelie , Schultz Nina , Pocevičiūtė Dovilė , Hansson Oskar , Bank The Netherlands Brain , Nilsson K Peter R , Wennström Malin
Published: July 2023

Background: Amyloid beta (Ab) deposits and hyperphosphorylated tau (p-tau) accumulation have been identified in the retina of Alzheimer’s disease (AD) patients and transgenic AD mice. Previous studies have shown that retinal microglia engulf Ab, but this property decrease in AD patients. Whether retinal microglia also take up p-tau and if this event is affected in AD is yet not described. In the current study, we use the p-tau specific thiophene-based ligand bTVBT2 to investigate the relationship between disease progression and microglia p-tau uptake in the retina of AD patients and AppNL-F/NL-F knock-in mice, an AD mouse model known to demonstrate extracellular Ab plaques and dystrophic neurites in the brain from at 6 months of age.
Methods: Evaluation of bTVBT2 specificity and presence of bTVBT2 inside microglia was performed by immunoflourescently stain hippocampi sections and whole mount samples of retina from non-demented controls (NC), AD patients, 3-, 9- and 12-months-old AppNL-F/NL-F knock-in mice and 12-month-old wild type (WT) mice. The amount of bTVBT2 inside Iba-1-positive microglia was analyzed using ImageJ and co-localization between the ligand and p-tau variant Ser396/Ser404 (PHF-1), Ab, phosphorylated TAR DNA binding protein 43 (pTDP-43) and islet amyloid polypeptide (IAPP) in brain and retina was analyzed using confocal imaging.
Results: Confocal imaging analysis showed that bTVBT2 binds to PHF-1-positive aggregates inside retinal microglia, and not to Ab, pTDP-43 or IAPP. The density of bTVBT2 positive microglia was higher in cases with high Ab load patients compared to cases with low Ab load and correlated with neurofibrillary tangle load in brain, but not with retinal levels of high molecular weight (aggregates) Ab40 or Ab42. Analysis of AppNL-F/NL-F knock-in mouse retina further showed that 50% of microglia in 3-months-old AppNL-F/NL-F knock-in mice contained bTVBT2, and that the percentage was significantly increased in 9- and 12-months-old mice.
Conclusion: Our study suggests that microglial capability to take up p-tau in retina remains and enhances along with AD progression. These results also highlight bTVBT2 as a ligand of interest in future monitoring of retinal AD pathology.
Exploring the potential mechanisms of action of Gentiana veitchiorum Hemsl. extract in the treatment of cholestasis using UPLC-MS/MS, systematic network pharmacology, and molecular docking
Authors: Wang Yue , Tan Nixia , Su Rong , Liu Zhenhua , Hu Na , dong Qi
Published: July 2023

Ethnopharmacological relevance
Gentiana veitchiorum Hemsl. (GV) has a long history in Tibetan medicine for the treatment of the hepatobiliary disease, cholestasis. However, the mechanisms mediating its efficacy in the treatment of cholestasis have not been determined.
Purpose
To elucidate the mechanisms of action of GV in the treatment of cholestasis, an integrated approach combining ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis with network pharmacology and molecular docking was established.
Materials and methods
A comprehensive analysis of the chemical composition of GV was achieved by UPLC-MS/MS. Subsequently, a network pharmacology method that integrated target prediction, a protein-protein interaction (PPI) network, gene set enrichment analysis and component-target-pathway network was established. The network pharmacological results were validated through molecular docking analysis.
Results
The UPLC-MS/MS analysis identified twenty compounds in GV. Network pharmacology identified 299 targets for the components of GV and 2999 targets for cholestatic diseases, from which 103 intersectional targets were obtained by Venn diagram. A PPI network was constructed to screen the following core proteins: AKT1, GAPDH, TNF, IL6, VEGFA, and CASP3. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses results suggested that GV may treat cholestatic disease through biological pathways related to proteolysis, cytosol, caspase complex, enzyme binding, and pathways in cancer, lipid and atherosclerosis, HIF-1, TNF, IL-17 and other key signaling pathways. The results were validated by molecular docking studies, which indicated good binding affinities between core compounds and targets, with similar binding energies to those of the positive control drugs.
Conclusions
In this study, UPLC-MS/MS analysis and network pharmacology were used in conjunction to provide potential mechanisms of action of GV in the treatment of cholestasis.
Correlation between paraspinal muscle changes and lumbar lordosis, intervertebral disc degeneration in young adults with low back pain: a retrospective cohort study
Authors: Tang Liang , Liu Xiaoming , Zhang Yangyang , Zhao Jian , Ye Xiaojian , Yu Jiangming
Published: July 2023

Background:
Previous studies have showed that intervertebral disc degeneration was significantly associated with low back pain, and there was a significantly greater proportion of chronic low back pain patients with lower lumbar lordosis. Paraspinal muscles have gained more attention because of their relationship with the spinal degenerative disease in elder patients. The objective of this study was to investigate the correlation between the degree of paraspinal muscle degeneration and decreased lumbar lordosis and lumbar intervertebral disc degeneration in younger patients with low back pain.
Methods:
Seventy patients with chronic low back pain (39 males, 31 females) and seventy-five healthy controls (36 males, 39 females) were enrolled. The correlation of the degree of multifidus muscle degeneration with lumbar intervertebral disc degeneration and lumbar lordosis was analyzed.
Results:
Disc degeneration at L3-4 showed no significant difference between the low back pain group and the control group (p > 0.05). However, there was a significant difference between the two groups at both L4-5 and L5-S1 (P < 0.05). At L4-5, the degree of fat infiltration showed significantly greater in the low back pain group (0.23 ± 0.035) than that in the control group (0.18 ± 0.037) (p < 0.05). At L5-S1, both relative multifidus muscle cross-sectional area and the degree of fat infiltration demonstrated significant differences between the two groups (p < 0.05). A significant correlation was observed between lumbar intervertebral disc degeneration and the degree of fat infiltration at L4-5 (r = 0.405, p < 0.05) and L5-S1 (r = 0.397, p < 0.05), respectively. Additionally, lumbar lordosis was found significantly decreased in the low back pain group (18.5°±4.3) compared with that in the control group (37.4 ± 8.5) (p < 0.05) and also significantly correlated with the degree of fat infiltration at L5-S1 (r= -0.422, P < 0.05).
Conclusions:
Multifidus atrophy and fatty infiltration showed significantly correlated with lumbar lordosis and lumbar intervertebral disc degeneration in younger populations. Enhanced function in paraspinal muscles might contribute to improving the symptoms of low back pain and spinal degeneration.
m6A-Related lncRNAs as Novel Biomarkers in Triple-Negative Breast Cancer with Prognostic and Therapeutic Implication
Authors: Luo Jiayue , Yang Weibang , Liu Qing , Cai Gengxi
Published: July 2023

Purpose：Triple negative breast cancer (TNBC) is highly heterogeneous and lacks effective targeted therapy. N6-methyladenosine (m6A) modification of long noncoding RNAs (lncRNAs) may contribute significantly to the prognostic predictions of TNBC.Methods：Based on 223 m6A-related lncRNAs (MRLs) and 134 TNBC samples from the TCGA database, we comprehensively investigated an MRL-based nomogram to separate TNBC patients into different risk groups. The clinical features, immune infiltration, functional status, chemotherapy responses, the prognosis of different risk groups were further investigated.Results:Three MRLs were selected to construct an MRL-based nomogram and separated patients into high- and low-risk groups by the cut-off point. Compared to low-risk group patients, high-risk group patients had advanced stage and poorer survival outcome. The functional analysis illustrated that the oxidative phosphorylation pathway was enriched in the high-risk group and its inhibitor combined with chemotherapy might be beneficial for these patients. Moreover, we found that the estimated IC50 values of paclitaxel were significantly reduced in the high-risk group, indicating that paclitaxel was the preferred chemotherapy agent for the high-risk group.Conclusion:This study demonstrated that an MRL-based nomogram can serve as an effective prognostic model and predictive indicator for therapeutic responses in TNBC patients.
Modeling, Hardware Architecture, and Performance Analyses of an AEAD-based Lightweight Cipher
Authors: Jhawar Kartik , Gandhi Jugal , Shekhawat Diksha , Upadhyay Aniket , Harkishanka Avadh , Chaturvedi Nitin , Santosh M. , Pandey Jai Gopal
Published: July 2023

Ensuring data security and integrity is crucial for achieving the highest level of protection and performance in modern cyber-physical systems (CPS). Authenticated encryption with associated data (AEAD) is an efficient and secure way to encrypt data that ensures confidentiality and authenticity. In this study, we focus on image encryption using the TinyJAMBU cipher within the AEAD scheme. In this paper, image encryption using the TinyJAMBU cipher with software and hardware modeling has been proposed, and image encryption evaluation over standard matrices has been performed. The hardware architecture for TinyJAMBU has been implemented on the Xilinx Virtex-7 FPGA device. The implementation results are compared with the realization of other contemporary ciphers that bring TinyJAMBU-128's implementation better in terms of look-up tables (LUTs), slice utilization, and power consumption. In the experimentation phase, the results of TinyJAMBU-128/192/256 for image encryption have been compared with existing image encryption techniques. It has been observed that, compared to other implementations, the proposed image encryption application using TinyJAMBU provides better results for PSNR, MSE, RMSE, and UACI.