bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple methods of diet assessment reveal differences in Atlantic puffin diet between ages, breeding stages, and years
Authors: Kennerley William L. , Clucas Gemma V. , Lyons Donald E.
Published: June 2024

Introduction

Atlantic puffin (Fratercula arctica, hereafter “puffin”) reproductive success in the Gulf of Maine (GoM) has declined following a recent oceanographic regime shift that has led to rapid warming and increasingly frequent marine heatwaves. Concurrent changes in both the regional forage fish community and puffin chick diets and provisioning rates suggest that inadequate prey resources may be driving this decline. Traditional, noninvasive methods of diet assessment, however, are unable to determine seabird diet at many age classes and breeding stages.

Methods

To determine what prey GoM puffins were feeding on during two years of marine heatwave conditions, we assessed puffin diet using two complementary methods: traditional, observational methods that utilize bill-load photography and emerging methods employing fecal DNA metabarcoding. We then examined the effect of methodology, age, breeding stage, and year on puffin diet composition.

Results

We identified a strong correlation between the composition of chick diet as estimated through traditional and emerging methods, supporting the interpretation of DNA relative read abundance as a quantitative metric of diet composition. Both methods identified the same dominant prey groups yet metabarcoding identified a greater number of species and offered higher taxonomic resolution. Additionally, metabarcoding revealed adult puffin diet during the incubation period for the first time. Although puffin adults and chicks fed on many of the same prey types, adults consumed a greater variety of taxa and consumed more low quality prey types than they provisioned chicks.

Discussion

For both age classes, diet varied both between and within years, likely reflecting changes in the local forage fish community in response to environmental variability. Puffins exploited unusual abundances of typically-uncommon prey during these two years of marine heatwave conditions, yet low puffin productivity suggests the observed dietary plasticity was not fully able to compensate for apparent prey shortages. Continued refinement of molecular methods and the interpretation of the data they provide will enable better assessments of how seabirds of diverse ages and breeding stages are adapting to changing prey communities.
Characterizing pearlite transformation in an API X60 pipeline steel through phase-field modeling and experimental validation
Authors: Araghi Mohammad Y. , Parsa M. H. , Ghane Ezabadi Mostafa , Roumina Reza , Mirzadeh Hamed , Xu Shuozhi
Published: June 2024

This study explores the microstructural characterization of pearlite phase transformation in high-strength low-alloy API X60 steel, which is used in pipelines. Understanding the formation, phase percentages, and morphology of the pearlitic phase is crucial since it affects the mechanical properties of the considered steel. In this research, a phase-field model, particularly the Cahn–Hilliard approach, was used in order to simulate the formation and morphology of the pearlite phase in response to different heat treatments. Both double- and triple-well potentials were considered for comprehensively studying pearlite’s morphology in the simulations. The simulation results were then compared with experimental outcomes obtained by metallography and field-emission scanning electron microscopy analyses. Considering the double-well potential can help simulate only two phases, ferrite and cementite, which is less compatible with the experiment results than the triple-well potential, which gives the possibility of simulating a three-phase microstructure, ferrite, cementite, and austenite, and a better match with experimental data. The study revealed that as the cooling rate increases, the interlamellar spacing and layer thickness decrease. Additionally, the difference between experimental and simulation results using triple-well potential was approximately ∼10%. Therefore, triple-well potential formulation predictions have better agreements with experimental results for the development circumstance of pearlitic structures.
A dicoumarol-graphene oxide quantum dot polymer inhibits porcine reproductive and respiratory syndrome virus through the JAK-STAT signaling pathway
Authors: Li Zhuowei , Wang Junjun , Wang Siyu , Zhao Wei , Hou Xiaolin , Wang Jianfang , Dong Hong , Zhou Shuanghai , Gao Yuan , Yao Wei , Li Huanrong , Liu Xuewei
Published: June 2024

Introduction

Porcine reproductive and respiratory syndrome virus (PRRSV) causes substantial economic losses in the global swine industry. The current vaccine options offer limited protection against PRRSV transmission, and there are no effective commercial antivirals available. Therefore, there is an urgent need to develop new antiviral strategies that slow global PRRSV transmission.

Methods

In this study, we synthesized a dicoumarol-graphene oxide quantum dot (DIC-GQD) polymer with excellent biocompatibility. This polymer was synthesized via an electrostatic adsorption method using the natural drug DIC and GQDs as raw materials.

Results

Our findings demonstrated that DIC exhibits high anti-PRRSV activity by inhibiting the PRRSV replication stage. The transcriptome sequencing analysis revealed that DIC treatment stimulates genes associated with the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway. In porcine alveolar macrophages (PAMs), DIC-GQDs induce TYK2, JAK1, STAT1, and STAT2 phosphorylation, leading to the upregulation of JAK1, STAT1, STAT2, interferon-β (IFN-β) and interferon-stimulated genes (ISGs). Animal challenge experiments further confirmed that DIC-GQDs effectively alleviated clinical symptoms and pathological reactions in the lungs, spleen, and lymph nodes of PRRSV-infected pigs.

Discussion

These findings suggest that DIC-GQDs significantly inhibits PRRSV proliferation by activating the JAK/STAT signalling pathway. Therefore, DIC-GQDs hold promise as an alternative treatment for PRRSV infection.
Cervical HPV infection and related diseases among 149,559 women in Fujian: an epidemiological study from 2018 to 2023
Authors: Lin Kun , Hong Qiyang , Fu Ya , Tu Haijian , Lin Hua , Huang Jiexiang , Hu Yajing , Huang Minjun , Chen Mingqiao
Published: June 2024

Objectives

To comprehensively analyze the epidemiological features of human papillomavirus (HPV) and HPV-related cervical diseases in females aged 35–64 years.

Methods

A total of 149,559 samples of exfoliated cervical cells screened for HPV and related cervical lesions from January 2018 to December 2023 were enrolled. The prevalence of 15 high-risk and 6 low-risk HPV genotypes were detected, and the cervical cytology were analyzed. The impact of single and multiple HPV infections was characterized, and the effect of age was studied.

Results

The cervix cytology was normal in 86.60% of the females, while 7.13% of the females were diagnosed with cervix inflammation, 0.60% with ASC-US, 0.22% with ASC-H, 0.72% with LSIL, 0.49% with HSIL, 0.03% with ICC. The highest median age was observed in ASC-H group with 54 years old. Females with primary school education or lower have the highest positive rates. The overall HPV prevalence was 8.60%. The relatively prevalent HPV types were HPV52, 58, 16, 39, 51. HPV16, HPV18, HPV58, HPV33 and HPV52 were the top5 predominant types in ICC patients. 17.41% females suffered from multiple HPV infection with the most frequently co-infection subtypes being HPV52, HPV58 and HPV16. The prevalence of all HPV subtypes increased with age. Multiple HPV infections accounted for a larger proportion in those aged above 55 years. The peak HPV16 prevalence was observed in ICC group in cases aged 45–49 and 55–59. The peak HPV33 prevalence was observed in younger individuals aged 40–44 who developed ICC.

Conclusion

More action should be taken against HPV33 infection.
Development of a colloidal gold immunochromatographic strip for the simultaneous detection of porcine epidemic diarrhea virus and transmissible gastroenteritis virus
Authors: Zhou Jinzhu , Wu Wei , Wang Dandan , Wang Wei , Chang Xinjian , Li Yunchuan , Li Jizong , Fan Baochao , Zhou Junming , Guo Rongli , Zhu Xuejiao , Li Bin
Published: June 2024

In recent years, porcine diarrhea-associated viruses have caused significant economic losses globally. These viruses present similar clinical symptoms, such as watery diarrhea, dehydration, and vomiting. Co-infections with porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are common. For the rapid and on-site preliminary diagnosis on the pig farms, this study aimed to develop a colloidal gold immunochromatography assay (GICA) strip for the detection of PEDV and TGEV simultaneously. The GICA kit showed that there was no cross-reactivity with the other five common porcine viruses. With visual observation, the lower limits were approximately 104 TCID50/mL and 104 TCID50/mL for PEDV and TGEV, respectively. The GICA strip could be stored at 4°C or 25°C for 12 months without affecting its efficacy. To validate the GICA strip, 121 clinical samples were tested. The positive rates of PEDV and TGEV were 42.9 and 9.9%, respectively, and the co-infection rate of the two viruses was 5.8% based on the duplex GICA strip. Thus, the established GICA strip is a rapid, specific, and stable tool for on-site preliminary diagnosis of PEDV- and TGEV-associated diarrhea.
Development of a top-down MS assay for specific identification of human periostin isoforms
Authors: Rusbjerg-Weberskov Christian E. , Gant Megan S. , Chamot-Rooke Julia , Nielsen Nadia Sukusu , Enghild Jan J.
Published: June 2024

Periostin is a matricellular protein encoded by the POSTN gene that is alternatively spliced to produce ten different periostin isoforms with molecular weights ranging from 78 to 91 kDa. It is known to promote fibrillogenesis, organize the extracellular matrix, and bind integrin-receptors to induce cell signaling. As well as being a key component of the wound healing process, it is also known to participate in the pathogenesis of different diseases including atopic dermatitis, asthma, and cancer. In both health and disease, the functions of the different periostin isoforms are largely unknown. The ability to precisely determine the isoform profile of a given human sample is fundamental for characterizing their functional significance. Identification of periostin isoforms is most often carried out at the transcriptional level using RT-PCR based approaches, but due to high sequence homogeneity, identification on the protein level has always been challenging. Top-down proteomics, where whole proteins are measured by mass spectrometry, offers a fast and reliable method for isoform identification. Here we present a fully developed top-down mass spectrometry assay for the characterization of periostin splice isoforms at the protein level.
In-vivo neuronal dysfunction by Aβ and tau overlaps with brain-wide inflammatory mechanisms in Alzheimer’s disease
Authors: Sanchez-Rodriguez Lazaro M. , Khan Ahmed F. , Adewale Quadri , Bezgin Gleb , Therriault Joseph , Fernandez-Arias Jaime , Servaes Stijn , Rahmouni Nesrine , Tissot Cécile , Stevenson Jenna , Jiang Hongxiu , Chai Xiaoqian , Carbonell Felix , Rosa-Neto Pedro , Iturria-Medina Yasser
Published: June 2024

The molecular mechanisms underlying neuronal dysfunction in Alzheimer’s disease (AD) remain uncharacterized. Here, we identify genes, molecular pathways and cellular components associated with whole-brain dysregulation caused by amyloid-beta (Aβ) and tau deposits in the living human brain. We obtained in-vivo resting-state functional MRI (rs-fMRI), Aβ- and tau-PET for 47 cognitively unimpaired and 16 AD participants from the Translational Biomarkers in Aging and Dementia cohort. Adverse neuronal activity impacts by Aβ and tau were quantified with personalized dynamical models by fitting pathology-mediated computational signals to the participant’s real rs-fMRIs. Then, we detected robust brain-wide associations between the spatial profiles of Aβ-tau impacts and gene expression in the neurotypical transcriptome (Allen Human Brain Atlas). Within the obtained distinctive signature of in-vivo neuronal dysfunction, several genes have prominent roles in microglial activation and in interactions with Aβ and tau. Moreover, cellular vulnerability estimations revealed strong association of microglial expression patterns with Aβ and tau’s synergistic impact on neuronal activity (q < 0.001). These results further support the central role of the immune system and neuroinflammatory pathways in AD pathogenesis. Neuronal dysregulation by AD pathologies also associated with neurotypical synaptic and developmental processes. In addition, we identified drug candidates from the vast LINCS library to halt or reduce the observed Aβ-tau effects on neuronal activity. Top-ranked pharmacological interventions target inflammatory, cancer and cardiovascular pathways, including specific medications undergoing clinical evaluation in AD. Our findings, based on the examination of molecular-pathological-functional interactions in humans, may accelerate the process of bringing effective therapies into clinical practice.
Implementation of a virtual, shared medical appointment program that focuses on food as medicine principles in a population with obesity: the SLIM program
Authors: Kirbach Kyleigh , Marshall-Moreno Imani , Shen Alice , Cullen Curtis , Sanigepalli Shravya , Bobadilla Alejandra , MacElhern Lauray , Grunvald Eduardo , Kallenberg Gene , Tristão Parra Maíra , Sannidhi Deepa
Published: June 2024

Background

Multimodal lifestyle interventions, employing food as medicine, stand as the recommended first-line treatment for obesity. The Shared Medical Appointment (SMA) model, where a physician conducts educational sessions with a group of patients sharing a common diagnosis, offers an avenue for delivery of comprehensive obesity care within clinical settings. SMAs, however, are not without implementation challenges. We aim to detail our experience with three implementation models in launching a virtual integrative health SMA for weight management.

Methods

Eligible patients included individuals 18 years of age or older, having a body mass index (BMI) of 30 kg/m2 or 27 kg/m2 or greater with at least one weight related comorbidity. The Practical, Robust Implementation and Sustainability Model (PRISM), Plan, Do, Study, Act (PDSA), and the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME) models were applied to guide the implementation of the Supervised Lifestyle Integrative Medicine (SLIM) program, a virtually delivered, lifestyle medicine focused SMA program, in a weight management clinic within a major health system. We describe how these models, along with attendance for the initial cohorts, were used for decision-making in the process of optimizing the program.

Results

172 patients completed the SLIM program over two years. Attendance was lowest for sessions held at 8:00 AM and 4:00 PM compared to sessions at 10:00 AM, 1:00 PM, and 3:00 PM, leading to only offering midday sessions (p = 0.032). Attendance data along with feedback from patients, facilitators, and administrative partners led to changes in the curriculum, session number and frequency, session reminder format, and intake visit number.

Conclusion

The use of implementation and quality improvement models provided crucial insight for deployment and optimization of a virtual, lifestyle medicine focused SMA program for weight management within a large healthcare system.
Effects of different preparation and cooking processes on the bioactive molecules of Allium vegetables
Authors: Katırcıoğlu Beyza , Navruz-Varlı Semra
Published: June 2024

Allium species are among the most widely cultivated vegetables for centuries for their positive effects on human health and their variety of uses in food preparation and cooking. Preparation and cooking processes create chemical changes that can affect the concentration and bioavailability of bioactive molecules. Understanding the changes in bioactive compounds and bioactive activities in Allium vegetables resulting from preparation and cooking processes is essential for better retention of these compounds and better utilization of their health benefits. This study aimed to investigate the effects of different preparation and cooking processes on the bioactive molecules of Allium vegetables. This review concludes that bioactive compounds in Allium vegetables are affected by each preparation and cooking process depending on variables including method, time, temperature. Owing to differences in the matrix and structure of the plant, preparation and cooking processes show different results on bioactive compounds and bioactive activities for different vegetables. Continued research is needed to help fill gaps in current knowledge, such as the optimal preparation and cooking processes for each Allium vegetable.
Risk factors and prognostic analysis of right ventricular dysfunction after lung resection for NSCLC
Authors: Tan Xilun , Tao Jing , Zhang Qin , Li Xiang , Wang Jia , Song Hao , Zhou Yanni , Wang Sihan , Cheng Jun , Wang Ming
Published: June 2024

Objectives

Lung cancer is the leading cause of cancer death, and 80–85% of all lung cancer cases are non-small cell lung cancer (NSCLC). Surgical resection is the standard treatment for early-stage NSCLC. However, lung resection, a surgical procedure, can result in complications and increased mortality. Recent studies have shown a significant correlation between complications after lung resection and right ventricular dysfunction.

Methods

Transthoracic echocardiography-derived right ventricular-pulmonary artery coupling (RV-PAC) was utilized to assess right ventricular function in these patients. Multivariate logistic regression analysis was also conducted to assess risk factors independently associated with RV-PA uncoupling. The 3- and 5-year cumulative survival rates were estimated with Kaplan-Meier curves, and differences between groups were analyzed using the Mantel-Cox log-rank test.

Results

RV-PA uncoupling was defined as a TAPSE/PASP value < 0.67 mm/mm Hg according to spline analysis. The results of multivariable logistic regression analysis indicated that diabetes is an independent risk factor for right ventricular dysfunction after lung resection in patients with NSCLC. Kaplan-Meier analysis revealed a significant decrease in the survival rate of patients with RV-PA uncoupling at both the 3-year follow-up (73% vs 40%, p < 0.001) and 5-year follow-up (64% vs 37%, p < 0.001).

Conclusions

After lung resection for NSCLC, the patient’s right ventricular function predicts prognosis. Patients with right ventricular dysfunction, particularly those with diabetes mellitus, have a worse prognosis. It is crucial to actively prevent and correct risk factors to reduce the mortality rate in these patients.
Hepatitis B virus X protein and TGF-β: partners in the carcinogenic journey of hepatocellular carcinoma
Authors: Yan Wei , Rao Dean , Fan Feimu , Liang Huifang , Zhang Zunyi , Dong Hanhua
Published: June 2024

Hepatitis B infection is substantially associated with the development of liver cancer globally, with the prevalence of hepatocellular carcinoma (HCC) cases exceeding 50%. Hepatitis B virus (HBV) encodes the Hepatitis B virus X (HBx) protein, a pleiotropic regulatory protein necessary for the transcription of the HBV covalently closed circular DNA (cccDNA) microchromosome. In previous studies, HBV-associated HCC was revealed to be affected by HBx in multiple signaling pathways, resulting in genetic mutations and epigenetic modifications in proto-oncogenes and tumor suppressor genes. In addition, transforming growth factor-β (TGF-β) has dichotomous potentials at various phases of malignancy as it is a crucial signaling pathway that regulates multiple cellular and physiological processes. In early HCC, TGF-β has a significant antitumor effect, whereas in advanced HCC, it promotes malignant progression. TGF-β interacts with the HBx protein in HCC, regulating the pathogenesis of HCC. This review summarizes the respective and combined functions of HBx and TGB-β in HCC occurrence and development.
Case Report: Scalp pityriasis versicolor may be a neglected problem
Authors: Zhou Ya Bin , Chao Jin Jing , Ma Lin , Xiao Yuan Yuan
Published: June 2024

Pityriasis versicolor, a common skin fungal infection, is typically observed on trunk and limb skin. Here, we highlight an unusual presentation: scalp involvement, often overlooked due to its asymptomatic, mildly scaly patches. We report four pediatric cases, emphasizing the potential underestimation of this scalp variant. This case series underscores the importance of considering this diagnosis in patients with unexplained scalp hypopigmentation, especially in males with short hair who may readily notice these subtle changes. The report contributes to the understanding of this variant's clinical presentation and emphasizes the need for awareness among clinicians to ensure accurate diagnosis and appropriate management.
Implementation of risk-based lipid-lowering therapies in older (age ≥ 65 years) and very-old adults (age ≥ 75 years) with ischemic heart disease in the greater Salzburg region
Authors: Kopp Kristen , Motloch Lukas J. , Wernly Bernhard , Berezin Alexander E. , Maringgele Victoria , Dieplinger Anna , Hoppe Uta C. , Lichtenauer Michael
Published: June 2024

Introduction: European guidelines recommend the implementation of lipid-lowering therapies (LLTs) in adults (≥ 65 years) with established atherosclerotic cardiovascular disease (ASCVD) and for risk-based primary prevention in older adults (≤ 75 years), yet their use in very-old adults (> 75 years) is controversial, discretionary, and oriented on the presence of risk factors. The aim of this retrospective study is to assess guideline-directed LLT implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in high-/very-high-risk older/very-old adults (65–74 and ≥ 75 years) at presentation for ST-segment elevation myocardial infarction (STEMI) and also to assess evidence-based care delivery to older adults in our region.

Methods: All STEMI patients with available LDL-C and total cholesterol presenting for treatment at a large tertiary center in Salzburg, Austria, 2018–2020, were screened (n = 910). High-risk/very-high-risk patients (n = 369) were classified according to European guidelines criteria and divided into cohorts by age: < 65 years (n = 152), 65–74 years (n = 104), and ≥ 75 years (n = 113).

Results: Despite being at high-/very-high-risk, prior LLT use was < 40% in the total cohort, with no significant difference by age. Statin monotherapy predominated; 20%–23% of older/very-old adults in the entire cohort were using low-/moderate-intensity stains, 11%–13% were using high-intensity statins, 4% were on ezetimibe therapy, and none were taking proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In the secondary prevention cohort, 53% of older/very-old patients used prior LLTs. Significantly higher percentages of older/oldest ASCVD patients (43% and 49%) met LDL-C targets < 70 mg/dL compared to patients < 65 years (29%; p = 0.033), although just 22% and 30% of these older groups attained stricter LDL-C targets of < 55 mg/dL. Low LLT uptake (16%) among older adults aged 64–74 years for primary prevention resulted in 17% and 10% attainment of risk-based LDL-C targets < 70 mg/dL and < 55 mg/dL, respectively. Oldest adults (≥ 75 years) in both primary and secondary prevention groups more often met risk-based targets than older and younger adults, despite predominantly receiving low-/moderate-intensity statin monotherapy.

Conclusion: Secondary prevention was sub-optimal in our region. Less than half of older/very-old adults with established ASCVD met LDL-C targets at the time of STEMI, suggesting severe care-delivery deficits in LLT implementation. Shortcomings in initiation of risk-based LLTs were also observed among high-/very-high-risk primary prevention patients < 75 years, with the achievement of risk-based LDL-C targets in 10%–48% of these patients.
Assessment of the safety of Roxadustat for cardiovascular events in chronic kidney disease-related anemia using meta-analysis and bioinformatics
Authors: Li Xiangmeng , Jiang Shimin , Gu Xia , Liu Xiaojing , Shang Shunlai , Zhang Jiao , Pang Keying , Li Wenge
Published: June 2024

Objective

This study compares the cardiovascular risk in anemic chronic kidney disease patients treated with Roxadustat versus erythropoietin stimulating agents (ESAs). It also explores the cardiovascular impact of Roxadustat.

Methods

We searched PubMed, EMBASE, Cochrane, Scopus, and Web of Science databases up to 13 August 2023, using terms such as “ESA,” “Roxadustat,” “MACE,” “stroke,” “death,” “myocardial infarction,” and “heart failure.” Two researchers independently selected and extracted data based on predefined criteria. We assessed the risk of bias with the Cochrane tool and analyzed statistical heterogeneity using the Q and I2 tests. We conducted subgroup analyses by geographical region and performed data analysis with Stata 14.0 and RevMan 5.4 software. Data were sourced from the NCBI database by filtering for “Roxadustat” and “human,” and differentially expressed genes were identified using R software, setting the significance at p < 0.01 and a 2-fold logFC, followed by GO enrichment analysis, KEGG pathway analysis, and protein interaction network analysis.

Results

A total of 15 articles encompassing 1,43,065 patients were analyzed, including 1,38,739 patients treated with ESA and 4,326 patients treated with Roxadustat. In the overall population meta-analysis, the incidences of Major Adverse Cardiovascular Events (MACE), death, and heart failure (HF) were 13%, 8%, and 4% in the Roxadustat group, compared to 17%, 12%, and 6% in the ESA group, respectively, with P-values greater than 0.05. In the subgroup analysis, the incidences were 13%, 11%, and 4% for the Roxadustat group versus 17%, 15%, and 5% for the ESA group, also with p-values greater than 0.05. Bioinformatics analysis identified 59 differentially expressed genes, mainly involved in the inflammatory response. GO enrichment analysis revealed that these genes are primarily related to integrin binding. The main pathways identified were the TNF signaling pathway, NF-κB signaling pathway, and lipid metabolism related to atherosclerosis. The protein interaction network highlighted IL1B, CXCL8, ICAM1, CCL2, and CCL5 as the top five significantly different genes, all involved in the inflammatory response and downregulated by Roxadustat, suggesting a potential role in reducing inflammation.

Conclusion

The meta-analysis suggests that the use of Roxadustat and ESA in treating anemia associated with chronic kidney disease does not significantly alter the likelihood of cardiovascular events in the overall and American populations. However, Roxadustat exhibited a safer profile with respect to MACE, death, and heart failure. The bioinformatics findings suggest that Roxadustat may influence integrin adhesion and affect the TNF and NF-κB signaling pathways, along with lipid and atherosclerosis pathways, potentially reducing inflammation.
Development of radioiodine-labeled mequitazine for evaluation of hepatic CYP2D activity
Authors: Mizutani Asuka , Kobayashi Masato , Nishi Kodai , Fujita Ken-ichi , Takahashi Kotaro , Muranaka Yuka , Sato Kakeru , Kitamura Masanori , Suzuki Chie , Nishii Ryuichi , Shikano Naoto , Magata Yasuhiro , Ishida Yasushi , Kunishima Munetaka , Fukuchi Kazuki , Kawai Keiichi
Published: June 2024

Background: As drug-metabolizing enzyme activities are affected by a variety of factors, such as drug-drug interactions, a method to evaluate drug-metabolizing enzyme activities in real time is needed. In this study, we developed a novel SPECT imaging probe for evaluation of hepatic CYP2D activity.

Methods: Iodine-123- and 125-labeled 4-iodobenzylmequitazine (123/125I-BMQ) was synthesized with high labeling and purity. CYP isozymes involved in the metabolism of 125I-BMQ in mouse liver microsomes were evaluated, and the utility of 123/125I-was assessed from biological distribution and SPECT imaging evaluation in normal and CYP2D-inhibited mice.

Results:In vitro metabolite analysis using mouse liver microsomes showed that 125I-BMQ is specifically metabolized by CYP2D. Biological distribution and SPECT imaging of 123/125I-BMQ in normal mice showed that injection 123/125I-BMQ accumulated early in the liver and was excreted into the gallbladder and intestines. In CYP2D-inhibited mice, accumulation in the liver was increased, but accumulation in the gallbladder and intestines, the excretory organ, was delayed. Since only metabolites of 125I-BMQ are detected in bile, visualization and measuring of the accumulation of metabolites over time in the intestine, where bile is excreted, could predict the amount of metabolites produced in the body and evaluate CYP2D activity, which would be useful in determining the dosage of various drugs metabolized by CYP2D.

Conclusion:123/125I-BMQ is useful as a SPECT imaging probe for comprehensive and direct assessment of hepatic CYP2D activity in a minimally invasive and simple approach.
Insights into the role of mitophagy in lung cancer: current evidence and perspectives
Authors: Zhang Xin , Yu Dongzhi , Tang Peng , Chen Fengshou
Published: June 2024

Lung cancer, recognized globally as a leading cause of malignancy-associated morbidity and mortality, is marked by its high prevalence and lethality, garnering extensive attention within the medical community. Mitophagy is a critical cellular process that plays a crucial role in regulating metabolism and ensuring quality control within cells. Its relevance to lung cancer has garnered significant attention among researchers and scientists. Mitophagy’s involvement in lung cancer encompasses its initiation, progression, metastatic dissemination and treatment. The regulatory landscape of mitophagy is complex, involving numerous signaling proteins and pathways that may exhibit aberrant alterations or mutations within the tumor environment. In the field of treatment, the regulation of mitophagy is considered key to determining cancer chemotherapy, radiation therapy, other treatment options, and drug resistance. Contemporary investigations are directed towards harnessing mitophagy modulators, both inhibitors and activators, in therapeutic strategies, with an emphasis on achieving specificity to minimize collateral damage to healthy cellular populations. Furthermore, molecular constituents and pathways affiliated with mitophagy, serving as potential biomarkers, offer promising avenues for enhancing diagnostic accuracy, prognostic assessment, and prediction of therapeutic responses in lung cancer. Future endeavors will also involve investigating the impact of mitophagy on the composition and function of immune cells within the tumor microenvironment, aiming to enhance our understanding of how mitophagy modulates the immune response to lung cancer. This review aims to comprehensively overview recent advancements about the role of mitophagy in the tumor genesis, progenesis and metastasis, and the impact of mitophagy on the treatment of lung cancer. We also discussed the future research direction of mitophagy in the field of lung cancer.
Next-generation risk assessment read-across case study: application of a 10-step framework to derive a safe concentration of daidzein in a body lotion
Authors: Najjar Abdulkarim , Kühnl Jochen , Lange Daniela , Géniès Camille , Jacques Carine , Fabian Eric , Zifle Anne , Hewitt Nicola J. , Schepky Andreas
Published: June 2024

Introduction:We performed an exposure-based Next Generation Risk Assessment case read-across study using New Approach Methodologies (NAMs) to determine the highest safe concentration of daidzein in a body lotion, based on its similarities with its structural analogue, genistein. Two assumptions were: (1) daidzein is a new chemical and its dietary intake omitted; (2) onlyin vitrodata were used for daidzein, whilein vitroand legacyin vivodata for genistein were considered.

Methods:The 10-step tiered approach evaluating systemic toxicity included toxicokinetics NAMs: PBPK models andin vitrobiokinetics measurements in cells used for toxicogenomics and toxicodynamic NAMs: pharmacology profiling (i.e., interaction with molecular targets), toxicogenomics and EATS assays (endocrine disruption endpoints). Whole body rat and human PBPK models were used to convert external doses of genistein to plasma concentrations andin vitroPoints of Departure (PoD) to external doses. The PBPK human dermal module was refined usingin vitrohuman skin metabolism and penetration data.

Results:The most relevant endpoint for daidzein was from the ERα assay (Lowest Observed Effective Concentration was 100 ± 0.0 nM), which was converted to anin vitroPoD of 33 nM. After application of a safety factor of 3.3 for intra-individual variability, the safe concentration of daidzein was estimated to be 10 nM. This was extrapolated to an external dose of 0.5 μg/cm2 for a body lotion and face cream, equating to a concentration of 0.1%.

Discussion:Whenin vitroPoD of 33 nM for daidzein was converted to an external oral dose in rats, the value correlated with thein vivoNOAEL. This increased confidence that the rat oral PBPK model provided accurate estimates of internal and external exposure and that thein vitroPoD was relevant in the safety assessment of both chemicals. When plasma concentrations estimated from applications of 0.1% and 0.02% daidzein were used to calculate bioactivity exposure ratios, values were >1, indicating a good margin between exposure and concentrations causing adverse effects. In conclusion, this case study highlights the use of NAMs in a 10-step tiered workflow to conclude that the highest safe concentration of daidzein in a body lotion is 0.1%.
Bifurcation analysis of a Leslie-type predator–prey system with prey harvesting and group defense
Authors: Zhang Yongxin , Luo Jianfeng
Published: June 2024

In this paper, we investigate a Leslie-type predator–prey model that incorporates prey harvesting and group defense, leading to a modified functional response. Our analysis focuses on the existence and stability of the system’s equilibria, which are essential for the coexistence of predator and prey populations and the maintenance of ecological balance. We identify the maximum sustainable yield, a critical factor for achieving this balance. Through a thorough examination of positive equilibrium stability, we determine the conditions and initial values that promote the survival of both species. We delve into the system’s dynamics by analyzing saddle-node and Hopf bifurcations, which are crucial for understanding the system transitions between various states. To evaluate the stability of the Hopf bifurcation, we calculate the first Lyapunov exponent and offer a quantitative assessment of the system’s stability. Furthermore, we explore the Bogdanov–Takens (BT) bifurcation, a co-dimension 2 scenario, by employing a universal unfolding technique near the cusp point. This method simplifies the complex dynamics and reveals the conditions that trigger such bifurcations. To substantiate our theoretical findings, we conduct numerical simulations, which serve as a practical validation of the model predictions. These simulations not only confirm the theoretical results but also showcase the potential of the model for predicting real-world ecological scenarios. This in-depth analysis contributes to a nuanced understanding of the dynamics within predator–prey interactions and advances the field of ecological modeling.
Optimizing agricultural sustainability: enriched organic formulations for growth, yield, and soil quality in a multi-crop system
Authors: Garg Kamal , Dhar Shiva , Sharma Vinod Kumar , Azman Elisa Azura , Meena Rajendra Prasad , Hashim Mohammad , Kumar Dileep , Ali Ghous , Karunakaran Vetrivel , Kumar Yogesh , Athnere Sonal , Kumar Sourabh , Om Hari , Tuti Mangal Deep , Meena Babu Lal , Kumar Birendra , Meena Vijendra Kumar , Kumar Sanjeev
Published: June 2024

Utilizing agricultural and industrial wastes, potent reservoirs of nutrients, for nourishing the soil and crops through composting embodies a sustainable approach to waste management and organic agriculture. To investigate this, a 2-year field experiment was conducted at ICAR-IARI, New Delhi, focusing on a pigeon pea–vegetable mustard–okra cropping system. Seven nutrient sources were tested, including a control (T1), 100% recommended dose of nitrogen (RDN) through farmyard manure (T2), 100% RDN through improved rice residue compost (T3), 100% RDN through a paddy husk ash (PHA)–based formulation (T4), 75% RDN through PHA-based formulation (T5), 100% RDN through a potato peel compost (PPC)–based formulation (T6), and 75% RDN through PPC-based formulation (T7). Employing a randomized block design with three replications, the results revealed that treatment T4 exhibited the significantly highest seed (1.89 ± 0.09 and 1.97 ± 0.12 t ha−1) and stover (7.83 ± 0.41 and 8.03 ± 0.58 t ha−1) yield of pigeon pea, leaf yield (81.57 ± 4.69 and 82.97 ± 4.17 t ha−1) of vegetable mustard, and fruit (13.54 ± 0.82 and 13.78 ± 0.81 t ha−1) and stover (21.64 ± 1.31 and 22.03 ± 1.30 t ha−1) yield of okra during both study years compared to the control (T1). Treatment T4 was on par with T2 and T6 for seed and stover yield in pigeon pea, as well as okra, and leaf yield in vegetable mustard over both years. Moreover, T4 demonstrated notable increase of 124.1% and 158.2% in NH4-N and NO3-N levels in the soil, respectively, over the control. The enhanced status of available nitrogen (N) and phosphorus (P) in the soil, coupled with increased soil organic carbon (0.41%), total bacteria population (21.1%), fungi (37.2%), actinomycetes (44.6%), and microbial biomass carbon (28.5%), further emphasized the positive impact of T4 compared to the control. Treatments T2 and T6 exhibited comparable outcomes to T4 concerning changes in available N, P, soil organic carbon, total bacteria population, fungi, actinomycetes, and microbial biomass carbon. In conclusion, treatments T4 and T6 emerge as viable sources of organic fertilizer, particularly in regions confronting farmyard manure shortages. These formulations offer substantial advantages, including enhanced yield, soil quality improvement, and efficient fertilizer utilization, thus contributing significantly to sustainable agricultural practices.
Case study: Evaluating deep-water start techniques and training demands in seated slalom waterskiing for an athlete with paraplegia
Authors: Suárez-Iglesias David , Ayán Carlos , García-Fresneda Adrián , Villa-Vicente José Gerardo , Rodríguez-Medina Juan , Rodríguez-Marroyo Jose A.
Published: June 2024

Purpose

Recreational and competitive slalom waterskiing is increasingly popular among individuals with spinal cord injuries (SCI), particularly for those with paraplegia using sit-skis. A key component of slalom skiing is the deep-water start (DWS), yet little is known about the physiological and physical demands of this activity when the athlete is seated. This study aims to fill this gap by focusing on the training requirements for a seated slalom athlete.

Materials and methods

Focusing on a young male athlete with paraplegia, this case study evaluates the effectiveness and efficiency of traditional (TDWS) and alternative (ADWS) DWS techniques during seated slalom waterskiing sessions. It assesses internal training load (TL) through heart rate (HR) zones and session rating of perceived exertion (sRPE), alongside pre- and post-session handgrip strength measurements to gauge peripheral muscle fatigue.

Results and conclusions

Performing the ADWS, achieving a full success rate, proved more effective but slightly more time-consuming than TDWS, which had limited success. HR during DWS maneuvers ranged from 63.2 to 81.3% of maximal HR, with most sessions occurring below the ventilatory threshold, thus perceived as hard effort. A moderate yet non-significant correlation was found between HR and sRPE-based TL. A significant reduction in handgrip strength post-session underscores the activity’s demands. These insights illuminate the technical, physiological, and physical challenges in mastering DWS for seated slalom athletes with SCI, providing valuable guidance for the development of tailored training programs and techniques in this sport.
Regulation of emotions in project-based collaborative learning: an empirical study in academic English classrooms
Authors: Huang Lu , Wang Ruiying , Han Jinlong
Published: June 2024

In spite of the increasing popularity of project-based collaborative learning (PBCL) as a pedagogy, real successful collaboration cannot always be achieved due to the cognitive, motivational and social emotional challenges students encounter during collaboration. Recognizing the challenges and developing regulation strategies to cope with the challenges at both individual and group level is essential for successful collaboration. In the last decades, a growing interest has been developed around socially shared regulation of emotions and how it is interwoven with self-regulation and co-regulation. However, capturing the process of students’ emotional challenges and regulations in a long and dynamic project proves difficult and there remains a paucity of evidence on how co-regulation and socially-shared regulation co-occur with learners’ cognitive and emotional progress in project-based collaborative learning. The purpose of the present study is to investigate and identify what kind of social emotional challenges students encountered during PBCL and how they regulate themselves and the groups in order to finish the projects. A quasi-experimental research design was adopted in an academic English classroom, with thirty-eight students self-reporting their challenges and regulations three times after finishing each of the projects. The results of qualitative analysis plus a case study of two groups indicate that students encounter a variety of social emotional challenges and employed different levels of co-regulation and socially shared regulation in addition to self-regulation, leading to varying collaboration results and experiences. The findings of the study offer insights into the emotional regulation in PBCL and shed light for future design of pedagogical interventions aiming at supporting socially shared regulation.
Basic moral sensitivity, moral disengagement, and defender self-efficacy as predictors of students’ self-reported bystander behaviors over a school year: a growth curve analysis
Authors: Sjögren Björn , Thornberg Robert , Kim Jingu , Hong Jun Sung , Kloo Mattias
Published: June 2024

Though school children tend to view peer victimization as morally wrong most do not to intervene on the victim’s behalf and some instead choose to aid the victimizer. The aim of this longitudinal study was to investigate how students’ defending and pro-aggressive bystander behaviors evolved over the course of one school year and their association to basic moral sensitivity, moral disengagement, and defender self-efficacy. Three-hundred-fifty-three upper elementary school students (55% girls; 9.9–12.9 years of age) each completed self-report surveys at three points during one school year. Results from latent growth curve models showed that pro-aggressive bystander behavior remained stable over the year, whereas defending behavior decreased. Moreover, students who exhibited greater basic moral sensitivity were both less likely to be pro-aggressive and simultaneously more likely to defend. Students with defender self-efficacy were not only associated with more defending behavior at baseline but also were also less likely to decrease in defender behavior over time. Conversely, students reporting a higher degree of moral disengagement were linked to more pro-aggressive behavior, particularly when also reporting lower basic moral sensitivity. These short-term longitudinal results add important insight into the change in bystander behavior over time and how it relates to students’ sense of morality. The results also highlight the practical necessity for schools to nurture students’ sense of morality and prosocial behavior in their efforts to curb peer victimization.
Public hospital reform, family health consumption and health inequality: evidence from China Family Panel Studies
Authors: Jiang Lan , He Yiqing , Hu Chunqi
Published: June 2024

Background

In 2017, China launched a comprehensive reform of public hospitals and eliminated drug markups, aiming to solve the problem of expensive medical treatment and allow poor and low-income people to enjoy basic health opportunities. This study attempts to evaluate the policy impact of public hospital reform on the health inequality of Chinese residents and analyze its micro-level mechanism from the perspective of household consumption structure. Studying the inherent causal connection between public hospital reform and health inequality is of paramount significance for strengthening China’s healthcare policies, system design, raising the average health level of Chinese residents, and achieving the goal of ensuring a healthy life for individuals of all age groups.

Methods

Based on the five waves of data from the China Family Panel Studies (CFPS) conducted in 2012–2020, We incorporates macro-level statistical indicators such as the time of public hospital reforms, health insurance surplus, and aging, generating 121,447 unbalanced panel data covering 27 provinces in China for five periods. This data was used to explore the impact of public hospital reform on health inequality. Logical and empirical tests were conducted to determine whether the reform, by altering family medical care and healthy leisure consumption expenditures, affects the micro-pathways of health inequality improvement. We constructed a two-way fixed model based on the re-centralized influence function (RIF_CI_OLS) and a chained mediation effects model to verify the hypotheses mentioned above.

Results

Public hospital reform can effectively improve the health inequality situation among Chinese residents. The reform significantly reduces household medical expenses, increases healthy leisure consumption, promotes the upgrading of family health consumption structure, and lowers the health inequality index. In terms of indirect effects, the contribution of the increase in healthy leisure consumption is relatively greater.

Conclusion

Public hospital reform significantly alleviates health inequality in China, with household health consumption serving as an effective intermediary pathway in the aforementioned impact. In the dual context of global digitization and exacerbated population aging, enhancing higher education levels and vigorously developing the health industry may be two key factors contributing to this effect.