bluuebunny/crossref_metadata_2025 huggingface dataset:
Modern methods and means of technical diagnostics of artillery weapons and prospects for their development
Authors: Shabatura Yurii , Popovchenko Oleksandr
Published: April 2024

The analysis of full-scale military operations in the east of Ukraine indicates an increase in the variety of firing tasks for artillery weapons and the intensity of their execution. This, in turn, requires the maintenance of artillery weapons and systems that ensure their proper operation in a serviceable and ready-to-use condition, as well as the prevention of sudden breakdowns and failures during combat missions.
Taking into account the influence of the technical condition on the effectiveness and safety of the combat use of artillery weapons, there is a need to improve the methods and means of its diagnosis.
This article analyzes the available domestic and foreign studies devoted to the development and improvement of methods for diagnosing the technical condition of artillery weapons. Existing devices for measuring, inspecting, evaluating and controlling the technical condition are considered. The existing systematization was expanded, generalization and addition of known methods and tools was carried out. The main possibilities, advantages and disadvantages of known methods, as well as promising directions for further research are determined.
It has been established that the majority of studies of possible methods of diagnosing the technical condition of artillery weapons are focused mainly on the analysis of the parameters of only the gun barrel and do not consider the ability of the studied methods to assess the technical condition of artillery weapons comprehensively.
The analysis also showed that despite the large number of existing techniques for diagnosing the technical condition (determining the degree of wear), most of them are not suitable for use directly in field conditions, morally outdated or very expensive.
In addition, it was determined that the application of the analysis of acoustic and vibration signals that occur during a shot is a promising direction for diagnosing the technical condition of artillery weapons, which potentially has the ability to detect more malfunctions, breakdowns and deviations of technical parameters.
Modifying the D3 Clinical Applications in Orthodontics Seminar
Authors: Lipp Mitchell
Published: April 2024

Despite obvious challenges, the COVID pandemic has given educators time to pause and consider how to construct remote instruction that is effective — and possibly better than — the use of traditional methods. The purpose of this report is to contrast pre-COVID and COVID-era methods, describe new methods developed, and present early outcomes data. Key points include: 1) Increasing active formative "clinical" experiences 2) Methods to enhance in-class engagement 3) A new case-based competency assessment that evaluates the student's ability to make evidence-based decisions in diagnosis and patient management. Although this report is based on a D3 course, "Clinical Applications in Orthodontics Seminars," these methods can be used in any clinical area that emphasizes critical thinking skills.
The Use of Plastinated Prosections to Teach Anatomy in the Time of COVID-19
Authors: Johnson Joshua , Warshaw Johanna H , Lopez Elizabeth N , Cunningham Elena P , Baker Eric W
Published: April 2024

The shift in 2004 from cadaveric dissection to using plastinated anatomical prosections at NYU Dentistry was made with the knowledge that an extensive, though limited, collection of plastinated teaching specimens would be handled by hundreds of students every year. This shift was followed by curricular changes that called for small, consistent groups, frequent administration of low-impact quizzes, and the addition of computers to guide self-directed study (Baker et al. 2013). In terms of anatomy retention and student satisfaction, we attribute the success of the Head & Neck Anatomy course to the plastinated Anatomical Teaching Collection and principles of small group independent learning (Lopez et al. 2021). We have found that this format of teaching head and neck anatomy proved highly adaptable to the demands of remote learning as a result of the COVID pandemic. This presentation discusses our curricular adaptations to remote learning for Head & Neck Anatomy and our personal observations regarding the impact those changes had on anatomy education and student satisfaction.
Redefining the ICP Experience through Online Learning
Authors: De Bartolo Angela
Published: April 2024

The Integrated Case Presentation (ICP) provides an introduction to the clinical experience and the importance of evidence-based science to the practice of dentistry. The ICP is part of the Comprehensive Care course at NYU College of Dentistry. The collaboration between the D4 and D3 students in presenting a patient to their peers allows them to form collegial relationships and facilitates a team-based learning philosophy. On entering the clinic, dental students can feel anxious about the responsibility they will have delivering patient care. The ICP allows the D3 novice to be exposed to clinical cases and to establish a relationship with the D4 student, who will then mentor, support, and guide them. The Integrated Case Presentation enhances the students' professional growth by emphasizing the dentist's role as a primary health care provider and a member of the health care team. The initial challenge of presenting the ICP seminars via Zoom has successfully been overcome and accepted by students and faculty.
Are Dental Therapists the Answer to Increasing Care for the Underserved? So Far, the Results Fall Short.
Authors: Hill Greg
Published: April 2024

In "Are Dental Therapists the Answer to Increasing Care for the Underserved? So Far, the Results Fall Short," Mr. Hill is critical of dental therapy's track record in improving access to care and suggests alternative models.
COLLABORATIVE GOVERNANCE DALAM PENANGGULANGAN KEMISKINAN DI KABUPATEN BANGKALAN PROVINSI JAWA TIMUR
Authors: Handayani Nur , Risyanti Riza , Suripto Suripto , Simangungsong Fernandes
Published: April 2024

Penelitian ini bertujuan untuk menggambarkan collaborative governance dalam penanggulangan kemiskinan di Kabupaten Bangkalan, pihak-pihak yang bertanggung jawab dan strategi penanggulangan kemiskinan apa yang digunakan di Kabupaten Bangkalan Provinsi Jawa Timur. Metode yang digunakan deskriptif kualitatif dengan pendekatan teori dari Ansell and Gash (2007) sebagai dasar  kajian dalam peneliian ini. Data dikumpulkan dengan teknik wawancara, observasi dan dokumentasi kemudian dianalisis dengan reduksi data, penyajian data, kesimpulan dan verivikasi. Hasil penelitian menunjukkan bahwa coolaborative governance dalam penanggulangan kemiskinan di Kabupaten Bangkalan belum berjalan secara efektif dilihat dari kondisi awal, design institusional, kepemimpinan fasilitatif, dan proses kolaborasi disebabkan belum adanya keseragaman standar dan persepsi mengenai masyarakat miskin. Bupati selaku penanggung jawab dan para pemangku kepentingan yang tergabung dalam  TKPKD  dalam penanggulangan kemiskinan  merujuk pada kerangka kebijakan yang ditetapkan pemerintah dalam penanggulangan kemiskinan.  Dipandang perlu adanya penyamaan persepsi tentang standar masyarakat miskin di tingkat pusat dan daerah serta sinkronisasi data masyarakat miskin secara periodik sehingga terjamin kevalidannya.

Kata kunci : coolaborative governance, kemiskinan, Bangkalan
PENGARUH CORPORATE SOCIAL RESPONSIBILITY (CSR), MANAGERIAL OWNERSHIP DAN INSTITUTIONAL OWNERSHIP TERHADAP TAX AVOIDANCE
Authors: Jenifer  , Yulis Diana Alfia
Published: April 2024

This study aims to examine the effect of Corporate Social Responsibility (CSR), Managerial Ownership and Institutional Ownership on Tax Avoidance in foods and beverages sub-sector companies listed on the Indonesia Stock Exchange for the 2019-2022 period. The selection of this sample used purposive sampling method that has been determined with several criteria. The data collection method uses documentation, using the Company Annual Financaial Report Data obtained from Indonesia Stock Exchange (IDX) website. The data analysis method uses multiple linear regression tests. This study proves that the Institutional Ownership has a significant positive effect on tax avoidance. CSR and Managerial Ownership has no effect on tax avoidance.
Application of exosomes in tumor immunity: recent progresses
Authors: Qiu Haiyan , Liang Junting , Yang Guang , Xie Zhenyu , Wang Zhenpeng , Wang Liyan , Zhang Jingying , Nanda Himansu Sekhar , Zhou Hui , Huang Yong , Peng Xinsheng , Lu Chengyu , Chen Huizhi , Zhou Yubin
Published: April 2024

Exosomes are small extracellular vesicles secreted by cells, ranging in size from 30 to 150 nm. They contain proteins, nucleic acids, lipids, and other bioactive molecules, which play a crucial role in intercellular communication and material transfer. In tumor immunity, exosomes present various functions while the following two are of great importance: regulating the immune response and serving as delivery carriers. This review starts with the introduction of the formation, compositions, functions, isolation, characterization, and applications of exosomes, and subsequently discusses the current status of exosomes in tumor immunotherapy, and the recent applications of exosome-based tumor immunity regulation and antitumor drug delivery. Finally, current challenge and future prospects are proposed and hope to demonstrate inspiration for targeted readers in the field.
Derangements of immunological proteins in HIV-associated diffuse large B-cell lymphoma: the frequency and prognostic impact
Authors: Vaughan Jenifer , Patel Moosa , Suchard Melinda , Gededzha Maemu , Ranchod Heena , Howard Wayne , Snyman Tracy , Wiggill Tracey
Published: April 2024

Introduction

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of B-cells frequently encountered among people living with HIV. Immunological abnormalities are common in immunocompetent individuals with DLBCL, and are often associated with poorer outcomes. Currently, data on derangements of immunological proteins, such as cytokines and acute phase reactants, and their impact on outcomes in HIV-associated DLBCL (HIV-DLBCL) is lacking. This study assessed the levels and prognostic relevance of interleukin (IL)-6, IL-10 and Transforming Growth Factor Beta (TGFβ), the acute phase proteins C-reactive protein (CRP) and ferritin; serum free light chains (SFLC) (elevation of which reflects a prolonged pro-inflammatory state); and the activity of the immunosuppressive enzyme Indoleamine 2,3-dioxygenase (IDO)in South African patients with DLBCL.

Methods

Seventy-six patients with incident DLBCL were enrolled, and peripheral blood IL-6, IL-10, TGFβ, SFLC and IDO-activity measured in selected patients. Additional clinical and laboratory findings (including ferritin and CRP) were recorded from the hospital records.

Results

Sixty-one (80.3%) of the included patients were people living with HIV (median CD4-count = 148 cells/ul), and survival rates were poor (12-month survival rate 30.0%). The majority of the immunological proteins, except for TGFβ and ferritin, were significantly higher among the people living with HIV. Elevation of IL-6, SFLC and IDO-activity were not associated with survival in HIV-DLBCL, while raised IL-10, CRP, ferritin and TGFβ were. On multivariate analysis, immunological proteins associated with survival independently from the International Prognostic Index (IPI) included TGFβ, ferritin and IL-10.

Conclusion

Derangements of immunological proteins are common in HIV-DLBCL, and have a differential association with survival compared to that reported elsewhere. Elevation of TGFβ, IL-10 and ferritin were associated with survival independently from the IPI. In view of the poor survival rates in this cohort, investigation of the directed targeting of these cytokines would be of interest in our setting.
Whole-body water mass and kidney function: a Mendelian randomization study
Authors: Wei Xuejiao , Long Mengtuan , Fan Zhongyu , Hou Yue , Yang Liming , Qu Zhihui , Du Yujun
Published: April 2024

Background

The morbidity and mortality of chronic kidney disease (CKD) are increasing worldwide, making it a serious public health problem. Although a potential correlation between body water content and CKD progression has been suggested, the presence of a causal association remains uncertain. This study aimed to determine the causal effect of body water content on kidney function.

Methods

Genome-wide association study summary data sourced from UK Biobank were used to evaluate single-nucleotide polymorphisms (SNPs) associated with whole-body water mass (BWM). The summary statistics pertaining to kidney function were extracted from the CKDGen consortium. The primary kidney function outcome measures included estimated glomerular filtration rate (eGFR), albuminuria, CKD stages 3–5, and rapid progression to CKD (CKDi25). Two-sample Mendelian randomization (MR) analysis estimated a potential causal relationship between the BWM and kidney function. The inverse variance weighted MR method was used as the primary analysis, accompanied by several sensitive MR analyses.

Results

The increase of BWM exhibited a correlation with a reduction in eGFR (β = −0.02; P = 6.95 × 10−16). Excluding 13 SNPs responsible for pleiotropy (P = 0.05), the increase of BWM was also associated with the decrease of the ratio of urinary albumin to creatinine (β = −0.16; P = 5.91 × 10−36). For each standard deviation increase in BWM, the risk of CKD stages 3–5 increases by 32% (OR, 1.32; 95% CI, 1.19–1.47; P = 1.43 × 10−7), and the risk of CKDi25 increases by 22% (OR, 1.22; 95% CI, 1.07–1.38; P = 0.002).

Conclusion

The increase of BWM is associated with impaired kidney function. Proactively managing body water content is of great significance in preventing the progression of CKD.
The impact of obesity-associated glycine deficiency on the elimination of endogenous and exogenous metabolites via the glycine conjugation pathway
Authors: Tan Hong Chang , Hsu Jean W. , Tai E Shyong , Chacko Shaji , Kovalik Jean-Paul , Jahoor Farook
Published: April 2024

Background

Glycine is an integral component of the human detoxification system as it reacts with potentially toxic exogenous and endogenously produced compounds and metabolites via the glycine conjugation pathway for urinary excretion. Because individuals with obesity have reduced glycine availability, this detoxification pathway may be compromised. However, it should be restored after bariatric surgery because of increased glycine production.

Objective

To examine the impact of obesity-associated glycine deficiency on the glycine conjugation pathway. We hypothesize that the synthesis rates of acylglycines from endogenous and exogenous sources are significantly reduced in individuals with obesity but increase after bariatric surgery.

Methods

We recruited 21 participants with class III obesity and 21 with healthy weight as controls. At baseline, [1,2-13C2] glycine was infused to study the glycine conjugation pathway by quantifying the synthesis rates of several acylglycines. The same measurements were repeated in participants with obesity six months after bariatric surgery. Data are presented as mean ± standard deviation, and p-value< 0.05 is considered statistically significant.

Results

Baseline data of 20 participants with obesity were first compared to controls. Participants with obesity were significantly heavier than controls (mean BMI 40.5 ± 7.1 vs. 20.8 ± 2.1 kg/m2). They had significantly lower plasma glycine concentration (168 ± 30 vs. 209 ± 50 μmol/L) and slower absolute synthesis rates of acetylglycine, isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine. Pre- and post-surgery data were available for 16 participants with obesity. Post-surgery BMI decreased from 40.9 ± 7.3 to 31.6 ± 6.0 kg/m2. Plasma glycine concentration increased from 164 ± 26 to 212 ± 38 μmol/L) and was associated with significantly higher rates of excretion of acetylglycine, isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine. Benzoic acid (a xenobiotic dicarboxylic acid) is excreted as benzoylglycine; its synthesis rate was significantly slower in participants with obesity but increased after bariatric surgery.

Conclusion

Obesity-associated glycine deficiency impairs the human body’s ability to eliminate endogenous and exogenous metabolites/compounds via the glycine conjugation pathway. This impairment is ameliorated when glycine supply is restored after bariatric surgery. These findings imply that dietary glycine supplementation could treat obesity-associated metabolic complications due to the accumulation of intramitochondrial toxic metabolites.

Clinical trial registration

https://clinicaltrials.gov/study/NCT04660513, identifier NCT04660513.
Endothelial dysfunction in vascular complications of diabetes: a comprehensive review of mechanisms and implications
Authors: Yang Dong-Rong , Wang Meng-Yan , Zhang Cheng-Lin , Wang Yu
Published: April 2024

Diabetic vascular complications are prevalent and severe among diabetic patients, profoundly affecting both their quality of life and long-term prospects. These complications can be classified into macrovascular and microvascular complications. Under the impact of risk factors such as elevated blood glucose, blood pressure, and cholesterol lipids, the vascular endothelium undergoes endothelial dysfunction, characterized by increased inflammation and oxidative stress, decreased NO biosynthesis, endothelial-mesenchymal transition, senescence, and even cell death. These processes will ultimately lead to macrovascular and microvascular diseases, with macrovascular diseases mainly characterized by atherosclerosis (AS) and microvascular diseases mainly characterized by thickening of the basement membrane. It further indicates a primary contributor to the elevated morbidity and mortality observed in individuals with diabetes. In this review, we will delve into the intricate mechanisms that drive endothelial dysfunction during diabetes progression and its associated vascular complications. Furthermore, we will outline various pharmacotherapies targeting diabetic endothelial dysfunction in the hope of accelerating effective therapeutic drug discovery for early control of diabetes and its vascular complications.
Optimizing flood disaster management: unraveling the role of social organizations in China’s GBA through social network analysis
Authors: Chen Zhaoxu , Zhang Li , Wang Ningning , Wang Qinsheng , Cao Yi , Chen Haoxuan
Published: April 2024

This study delves into the efficiency and structure of the social organization network involved in flood disaster management in China’s Guangdong-Hong Kong-Macao Greater Bay Area (GBA). Leveraging the global knowledge graph, we analyzed social media data and news reports to identify the pivotal roles and interactions of various social organization types in flood disaster governance. The empirical findings underscore the central role of national public social organizations, evidenced by their high frequency of news coverage and mentions. Meanwhile, International Social Organizations and Local Public Social Organizations exhibit growing influence and participation. As China shifts toward a comprehensive disaster reduction strategy, the study observes increased diversity and decentralization among these organizations, with non-governmental organizations and volunteer groups playing vital roles in resource mobilization, information dissemination, and disaster coordination. Network analysis unveils evolving interaction patterns and co-occurrence frequencies among social organizations, reflecting the evolving roles of different organization types in disaster relief. This research aims to provide actionable insights to enhance the effectiveness of social organizations in disaster management, contributing to the establishment of a more resilient and efficient disaster management framework in the GBA.
Satellite-observed precipitation and total column water vapor
Authors: Johnson Sara E. A. , Ye Hengchun , Fetzer Eric J. , Li Jingjing
Published: April 2024

This study explores the relationship between water vapor and rainfall intensities over three tropical lands (Amazon Basin, Sahel, southern South America) and three tropical ocean regions (Atlantic Ocean, Indian Ocean, Niño 4). We utilized daily total column water vapor (TCWV) data from the Atmospheric Infrared Sounder (AIRS) and daily precipitation records from the Tropical Rainfall Measuring Mission (TRMM) Multi-satellite Precipitation. Over tropical land, precipitation shows higher sensitivity to changes in water vapor, with a well-sorted pattern of an increased occurrence of higher daily precipitation as TCWV increases. Precipitation intensity over the Sahel, in particular, is extremely responsive to TCWV change. Over tropical oceans, the precipitation intensity is less sensitive to water vapor, particularly in the Indian Ocean and Niño 4 where precipitation intensities above the 40th percentile are no longer responding to the increasing TCWV. Quantifying water vapor and precipitation intensity aids in forecasting the occurrence of precipitation between tropical land and oceans.
Analyzing the applicability of wetland ecological modes in the Minjiang Estuary wetland
Authors: Bai Yuntao , Wang Lan
Published: April 2024

Wetlands are badly damaged in many parts of the world. The wetland management of Minjiang Estuary wetland has achieved remarkable results. This provides valuable experience for wetland management in other areas. Minjiang Estuary wetland can achieve the effect, mainly because of the adoption of the water quality management, ecological restoration, and ecological tourism development. However, different management modes have their own scope of application. In order to spread its successes, three differential game modes related to Minjiang Estuary wetland management are constructed, and their equilibrium results are compared and analyzed. Finally, research shows that the amount of water quality control by governments is directly proportional to the resilience of wetlands. The amount of social organization culture is proportional to the degree of better water quality. The amount of development by the government and social organizations is directly proportional to the decrease of investment in the spontaneous tourism industry. When the loss caused by flood or the ecological restoration effect is large, the wetland should adopt the ecological restoration mode. When the increased income or reputation of ecotourism is large, the ecotourism development mode should be adopted. This provides a reference for how to manage wetlands and how to promote the management mode of Minjiang Estuary wetland to other areas more effectively.
Introducing dynamic consent for improved trust and privacy in research involving human biological material and associated data in South Africa
Authors: Prinsen Larisse
Published: April 2024

Biomedical research using human biological material and data is essential for improving human health, but it requires the active participation of many human volunteers in addition to the distribution of data. As a result, it has raised numerous vexing questions related to trust, privacy and consent. Trust is essential in biomedical research as it relates directly to the willingness of participants to continue participating in research. Privacy and the protection of personal information also influence trust. Informed consent has proven to be insufficient as it cannot overcome the informational deficit between primary and unknown future uses of material and data and is therefore not fully informed and invalid. Broad consent is also problematic as it takes full control of samples and data flow from the research participant and inherently requires that a participant must trust that the researcher will use their material or data in a manner that they would find acceptable. This paper attempts to offer some insight into how these related issues can be overcome. It introduces dynamic consent as a consent model in research involving human biological material and its associated data. Dynamic consent is explained, as well as its claims of superiority in instances where future research is possible. It is also shown how dynamic consent contributes to better control of the samples and data by the research participant, and how trust may be improved by using this consent model. Dynamic consent’s co-existence with and support of the South African Protection of Personal Information Act of 2013 is also assessed. The limitations of dynamic consent are also discussed.
Analysis of weighted gene co-expression networks and clinical validation identify hub genes and immune cell infiltration in the endometrial cells of patients with recurrent implantation failure
Authors: Liu Zhenteng , Lai Shoucui , Qu Qinglan , Liu Xuemei , Zhang Wei , Zhao Dongmei , He Shunzhi , Sun Yuxia , Bao Hongchu
Published: April 2024

Background:

About 10% of individuals undergoing in vitro fertilization encounter recurrent implantation failure (RIF), which represents a worldwide social and economic concern. Nevertheless, the critical genes and genetic mechanisms underlying RIF are largely unknown.

Methods:

We first obtained three comprehensive microarray datasets “GSE58144, GSE103465 and GSE111974”. The differentially expressed genes (DEGs) evaluation, enrichment analysis, as well as efficient weighted gene co-expression network analysis (WGCNA), were employed for distinguishing RIF-linked hub genes, which were tested by RT-qPCR in our 30 independent samples. Next, we studied the topography of infiltration of 22 immune cell subpopulations and the association between hub genes and immune cells in RIF using the CIBERSORT algorithm. Finally, a novel ridge plot was utilized to exhibit the potential function of core genes.

Results:

The enrichment of GO/KEGG pathways reveals that Herpes simplex virus 1 infection and Salmonella infection may have an important role in RIF. After WGCNA, the intersected genes with the previous DEGs were obtained using both variance and association. Notably, the subsequent nine hub genes were finally selected: ACTL6A, BECN1, SNRPD1, POLR1B, GSK3B, PPP2CA, RBBP7, PLK4, and RFC4, based on the PPI network and three different algorithms, whose expression patterns were also verified by RT-qPCR. With in-depth analysis, we speculated that key genes mentioned above might be involved in the RIF through disturbing endometrial microflora homeostasis, impairing autophagy, and inhibiting the proliferation of endometrium. Furthermore, the current study revealed the aberrant immune infiltration patterns and emphasized that uterine NK cells (uNK) and CD4+ T cells were substantially altered in RIF endometrium. Finally, the ridge plot displayed a clear and crucial association between hub genes and other genes and key pathways.

Conclusion:

We first utilized WGCNA to identify the most potential nine hub genes which might be associated with RIF. Meanwhile, this study offers insights into the landscape of immune infiltration status to reveal the underlying immune pathogenesis of RIF. This may be a direction for the next study of RIF etiology. Further studies would be required to investigate the involved mechanisms.
Neuronal-specific methylome and hydroxymethylome analysis reveal significant loci associated with alcohol use disorder
Authors: Andrade-Brito Diego E. , Núñez-Ríos Diana L. , Martínez-Magaña José Jaime , Nagamatsu Sheila T. , Rompala Gregory , Zillich Lea , Witt Stephanie H. , Clark Shaunna L. , Lattig Maria C. , Montalvo-Ortiz Janitza L.
Published: April 2024

Background: Alcohol use disorder (AUD) is a complex condition associated with adverse health consequences that affect millions of individuals worldwide. Epigenetic modifications, including DNA methylation (5 mC), have been associated with AUD and other alcohol-related traits. Epigenome-wide association studies (EWAS) have identified differentially methylated genes associated with AUD in human peripheral and brain tissue. More recently, epigenetic studies of AUD have also evaluated DNA hydroxymethylation (5 hmC) in the human brain. However, most of the epigenetic work in postmortem brain tissue has examined bulk tissue. In this study, we investigated neuronal-specific 5 mC and 5 hmC alterations at CpG sites associated with AUD in the human orbitofrontal cortex (OFC).

Methods: Neuronal nuclei from the OFC were evaluated in 34 human postmortem brain samples (10 AUD, 24 non-AUD). Reduced representation oxidative bisulfite sequencing was used to assess 5 mC and 5 hmC at the genome-wide level. Differential 5 mC and 5 hmC were evaluated using the methylKit R package and significance was set at false discovery rate < 0.05 and differential methylation > 2. Functional enrichment analyses were performed, and gene-level convergence was evaluated in an independent dataset that assessed 5 mC and 5 hmC of AUD in bulk cortical tissue.

Results: We identified 417 5 mC and 363 5hmC significant differential CpG sites associated with AUD, with 59% in gene promoters. Some of the identified genes have been previously implicated in alcohol consumption, including SYK, DNMT3A for 5 mC, GAD1, DLX1, DLX2, for 5 hmC and GATA4 in both. Convergence with a previous AUD 5 mC and 5 hmC study was observed for 28 genes. We also identified 5 and 35 differential regions for 5 mC and 5 hmC, respectively. Lastly, GWAS enrichment analysis showed an association with AUD for differential 5 mC genes.

Discussion: This study reveals neuronal-specific methylome and hydroxymethylome dysregulation associated with AUD, identifying both previously reported and potentially novel gene associations with AUD. Our findings provide new insights into the epigenomic dysregulation of AUD in the human brain.
Effects of supplementing coated methionine in a high plant-protein diet on growth, antioxidant capacity, digestive enzymes activity and expression of TOR signaling pathway associated genes in gibel carp, Carassius auratus gibelio
Authors: Du Yingying , Lin Xiaowen , Shao Xianping , Zhao Jianhua , Xu Hong , de Cruz Clement R. , Xu Qiyou
Published: April 2024

This study explored the impacts of supplementation of different levels of coated methionine (Met) in a high-plant protein diet on growth, blood biochemistry, antioxidant capacity, digestive enzymes activity and expression of genes related to TOR signaling pathway in gibel carp (Carassius auratus gibeilo). A high-plant protein diet was formulated and used as a basal diet and supplemented with five different levels of coated Met at 0.15, 0.30, 0.45, 0.60 and 0.75%, corresponding to final analyzed Met levels of 0.34, 0.49, 0.64, 0.76, 0.92 and 1.06%. Three replicate groups of fish (initial mean weight, 11.37 ± 0.02 g) (20 fish per replicate) were fed the test diets over a 10-week feeding period. The results indicated that with the increase of coated Met level, the final weight, weight gain (WG) and specific growth rate initially boosted and then suppressed, peaking at 0.76% Met level (P< 0.05). Increasing dietary Met level led to significantly increased muscle crude protein content (P< 0.05) and reduced serum alanine aminotransferase activity (P< 0.05). Using appropriate dietary Met level led to reduced malondialdehyde concentration in hepatopancreas (P< 0.05), improved superoxide dismutase activity (P< 0.05), and enhanced intestinal amylase and protease activities (P< 0.05). The expression levels of genes associated with muscle protein synthesis such as insulin-like growth factor-1, protein kinase B, target of rapamycin and eukaryotic initiation factor 4E binding protein-1 mRNA were significantly regulated, peaking at Met level of 0.76% (P< 0.05). In conclusion, supplementing optimal level of coated Met improved on fish growth, antioxidant capacity, and the expression of TOR pathway related genes in muscle. The optimal dietary Met level was determined to be 0.71% of the diet based on quadratic regression analysis of WG.
Immune system-related plasma extracellular vesicles in healthy aging
Authors: Zhang Xin , Ma Sisi , Huebner Janet L. , Naz Syeda Iffat , Alnemer Noor , Soderblom Erik J. , Aliferis Constantin , Kraus Virginia Byers
Published: April 2024

Objectives

To identify age-related plasma extracellular vehicle (EVs) phenotypes in healthy adults.

Methods

EV proteomics by high-resolution mass spectrometry to evaluate EV protein stability and discover age-associated EV proteins (n=4 with 4 serial freeze-thaws each); validation by high-resolution flow cytometry and EV cytokine quantification by multiplex ELISA (n=28 healthy donors, aged 18-83 years); quantification of WI-38 fibroblast cell proliferation response to co-culture with PKH67-labeled young and old plasma EVs. The EV samples from these plasma specimens were previously characterized for bilayer structure, intra-vesicle mitochondria and cytokines, and hematopoietic cell-related surface markers.

Results

Compared with matched exo-EVs (EV-depleted supernatants), endo-EVs (EV-associated) had higher mean TNF-α and IL-27, lower mean IL-6, IL-11, IFN-γ, and IL-17A/F, and similar mean IL-1β, IL-21, and IL-22 concentrations. Some endo-EV and exo-EV cytokine concentrations were correlated, including TNF-α, IL-27, IL-6, IL-1β, and IFN-γ, but not IL-11, IL-17A/F, IL-21 or IL-22. Endo-EV IFN-γ and exo-EV IL-17A/F and IL-21 declined with age. By proteomics and confirmed by flow cytometry, we identified age-associated decline of fibrinogen (FGA, FGB and FGG) in EVs. Age-related EV proteins indicated predominant origins in the liver and innate immune system. WI-38 cells (>95%) internalized similar amounts of young and old plasma EVs, but cells that internalized PKH67-EVs, particularly young EVs, underwent significantly greater cell proliferation.

Conclusion

Endo-EV and exo-EV cytokines function as different biomarkers. The observed healthy aging EV phenotype reflected a downregulation of EV fibrinogen subpopulations consistent with the absence of a pro-coagulant and pro-inflammatory condition common with age-related disease.
Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment
Authors: Ugalde-Triviño Lola , Molina-Jiménez Francisca , H-Vázquez Juan , Relaño-Rupérez Carlos , Arias-González Laura , Casabona Sergio , Pérez-Fernández María Teresa , Martín-Domínguez Verónica , Fernández-Pacheco Jennifer , Lucendo Alfredo J. , Bernardo David , Santander Cecilio , Majano Pedro
Published: April 2024

Objectives

The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response.

Methods

PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients.

Results

Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI.

Conclusions

We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.
Identification of Escherichia coli multidrug resistance transporters involved in anthocyanin biosynthesis
Authors: Wu Xia , Chen Rongxia , Liang Ping , Zha Jian
Published: April 2024

The anthocyanin compound cyanidin 3-O-glucoside (C3G) is a natural pigment widely used in food and nutraceutical industries. Its microbial synthesis by E. coli is a promising alternative to the traditional extraction methods. However, part of the synthesized C3G accumulates in the cytoplasm, thus potentially causing growth inhibition and product degradation. Therefore, it is necessary to enhance C3G secretion via exploration of native transporters facilitating C3G export. In this study, we report the screening and verification of native multidrug resistance transporters from 40 candidates in E. coli that can improve the extracellular C3G production when using catechin as the substrate. Overexpression of single transporter genes including fsr, yebQ, ynfM, mdlAB, and emrKY were found to increase C3G production by 0.5- to 4.8-fold. Genetic studies indicated that mdlAB and emrKY are vital transporters in the secretion of C3G. Our study reveals a set of new multidrug resistance transporters for the improvement of microbial biosynthesis of C3G and other anthocyanins.
Impact of Pediococcus acidilactici GLP06 supplementation on gut microbes and metabolites in adult beagles: a comparative analysis
Authors: Zhao Mengdi , Zhang Yuanyuan , Li Yueyao , Liu Keyuan , Bao Kun , Li Guangyu
Published: April 2024

There is growing interest in the potential health benefits of probiotics for both humans and animals. The study aimed to investigate the effects of feeding the canine-derived probiotic Pediococcus acidilactici GLP06 to adult beagles by analysing the microbiome and metabolome. Twenty-four healthy adult beagles were randomly assigned to four groups. The CK group received a standard diet, while the three probiotic groups, the LG group (2 × 108 CFU/day/dog), MG group (2 × 109 CFU/day/dog), and HG group (2 × 1010 CFU/day/dog), received the standard diet supplemented with varying amounts of probiotics. The results show that, compared to the CK group, total antioxidant capacity was significantly increased in the MG and HG groups (p < 0.05), and superoxide dismutase and catalase were significantly increased in the HG group (p < 0.05). Compared to the CK group, malondialdehyde and blood urea nitrogen content were significantly decreased in the MG and HG groups (p < 0.05). Additionally, secretory immunoglobulin A activity was significantly increased in the HG group compared to the CK and LG groups (p < 0.05), and immunoglobulin G activity was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). In addition, compared with the CK group, the abundance of Faecalitalea and Collinsella increased in the LG group, and the relative abundance of Tyzzerella and Parasutterella increased in the MG group. The α diversity and the relative abundances of beneficial bacteria (Faecalibacterium, Lachnospiraceae_NK4A1316, and Ruminococcaceae_UCG-005) were higher in the HG group than in the CK group. Furthermore, acetic acid content was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). Butyric acid, isobutyric acid, and the total SCFA content were significantly increased in the HG group compared to the CK group (p < 0.05). Moreover, metabolome analysis revealed 111 upregulated and 171 downregulated metabolites in the HG group. In conclusion, this study presents evidence that supplementing with P. acidilactici GLP06 can have a positive impact on antioxidant activity, immunoproteins, SCFAs, and gut microbiota in adult beagles. These findings highlight the potential of probiotics as a dietary intervention to enhance gut health and overall wellbeing in companion animals.
Combining data augmentation and deep learning for improved epilepsy detection
Authors: Ru Yandong , Wei Zheng , An Gaoyang , Chen Hongming
Published: April 2024

Introduction

In recent years, the use of EEG signals for seizure detection has gained widespread academic attention. Aiming at the problem of overfitting deep learning models due to the small number of EEG signal data during epilepsy detection, this paper proposes an epilepsy detection method that combines data augmentation and deep learning.

Methods

First, the Adversarial and Mixup Data Augmentation (AMDA) method is used to realize the data augmentation, which effectively enriches the number of training samples. To further improve the classification accuracy and robustness of epilepsy detection, this paper proposes a one-dimensional convolutional neural network and gated recurrent unit (AM-1D CNN-GRU) network model based on attention mechanism for epilepsy detection.

Results and discussion

The experimental results show that the performance of epilepsy detection achieved by using augmented data is significantly improved, and the accuracy, sensitivity, and area under the subject’s working characteristic curve are up to 96.06, 95.48%, and 0.9637, respectively. Compared with the non-augmented data, all indicators are increased by more than 6.2%. Meanwhile, the detection performance was significantly improved compared with other epilepsy detection methods. The results of this research can provide a reference for the clinical application of epilepsy detection.
GKT137831 and hydrogen peroxide increase the release of 6-nitrodopamine from the human umbilical artery, rat-isolated right atrium, and rat-isolated vas deferens
Authors: Britto-Júnior José , Furlaneto Rafael , Lima Antonio Tiago , de Oliveira Mariana Gonçalves , Severino Beatrice , Frecentese Francesco , Fiorino Ferdinando , Caliendo Giuseppe , Muscará Marcelo Nicolás , De Nucci Gilberto
Published: April 2024

Introduction: The human umbilical artery (HUA), rat-isolated right atrium, and rat-isolated vas deferens present a basal release of 6-nitrodopamine (6-ND). The basal release of 6-ND from these tissues was significantly decreased (but not abolished) when the tissues were pre-incubated with Nω-nitro-L-arginine methyl ester (L-NAME).

Methods: In this study, the effect of the pharmacological modulation of the redox environment on the basal release of 6-ND was investigated. The basal release of 6-ND was measured using Liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Results and Discussion: Pre-incubation (30 min) of the tissues with GKT137831 (1 μM) caused a significant increase in the basal release of 6-ND from all tissues. In the HUA, pre-incubation with diphenyleneiodonium (DPI) (100 μM) also caused significant increases in the basal release of 6-ND. Preincubation of the HUA with hydrogen peroxide (H2O2) (100 μM) increased 6-ND basal release, whereas pre-incubation with catalase (1,000 U/mL) significantly decreased it. Pre-incubation of the HUA with superoxide dismutase (SOD) (250 U/mL; 30 min) also significantly increased the basal release of 6-ND. Preincubation of the HUA with either allopurinol (100 μM) or uric acid (1 mM) had no effect on the basal release of 6-ND. Pre-treatment of the HUA with L-NAME (100 μM) prevented the increase in the basal release of 6-ND induced by GKT137831, diphenyleneiodonium, and H2O2. The results obtained indicate a major role of endogenous H2O2 and peroxidases as modulators of 6- ND biosynthesis/release and a lack of peroxynitrite contribution.
Decoding the research landscape of drug resistance and therapeutic approaches in head and neck cancer: a bibliometric analysis from 2000 to 2023
Authors: Han Qi , Shi Junqi , Liu Jiaojiao , Fu Yang , Li Zhongxun , Guo Huina , Guan Xiaoya , Xue Xuting , Liu Hongliang , Zhao Liting , Zhang Chunming
Published: April 2024

Introduction:

Head and neck cancer is one of the most common tumors worldwide. However, drug resistance in its treatment has become a major factor limiting the efficacy. This study aims to comprehensively understand the current status of research in this field.

Methods:

The study analyzes papers related to therapeutic resistance in head and neck cancer published between 2000 and 2023 in the Web of Science Core Collection To achieve the research objectives, we searched the WoSCC for research and review papers on therapeutic resistance in head and neck cancer from 2000 to 2023, screened the English literature, and analyzed the research hotspots, academic collaborations, and trends in detail using tools such as Citespace, SCImago Graphica, and VOS viewer.

Results:

This study summarizes 787 head and neck cancer treatment resistance publications from WoSCC. The analysis showed that China and the United States are the major contributors in this field, and Grandis Jennifer R and Yang Jai-Sing are the key scholars. Keyword analysis showed that “cisplatin resistance” is a continuing focus of attention, while “Metastasis” and “Ferroptosis” may be emerging research hotspots. Literature clustering analysis pointed out that “Ferroptosis”, “Immunotherapy” and “ERK signaling” were the recent hotspots that received extensive attention and citations. Finally, we discuss the current status and challenges in drug-resistant therapies for head and neck cancer.

Conclusion:

This study is the first comprehensive bibliometric analysis of drug resistance in head and neck cancer. Reveals current trends and helps researchers grasp cutting-edge hotspots in the field.
CDK4/6 inhibitors in drug-induced liver injury: a pharmacovigilance study of the FAERS database and analysis of the drug–gene interaction network
Authors: She Youjun , Guo Zihan , Zhai Qing , Liu Jiyong , Du Qiong , Zhang Zhongwei
Published: April 2024

Objective:

The aim of this study was to investigate the potential risk of drug-induced liver injury (DILI) caused by the CDK4/6 inhibitors (CDK4/6is abemaciclib, ribociclib, and palbociclib by comprehensively analyzing the FDA Adverse Event Reporting System (FAERS) database. Moreover, potential toxicological mechanisms of CDK4/6is-related liver injury were explored via drug–gene network analysis.

Methods:

In this retrospective observational study, we collected reports of DILI associated with CDK4/6i use from the FAERS dated January 2014 to March 2023. We conducted disproportionality analyses using the reporting odds ratio (ROR) with a 95% confidence interval (CI). Pathway enrichment analysis and drug-gene network analyses were subsequently performed to determine the potential mechanisms underlying CDK4/6i-induced liver injury.

Results:

We found positive signals for DILI with ribociclib (ROR = 2.60) and abemaciclib (ROR = 2.37). DILIs associated with liver-related investigations, signs, and symptoms were confirmed in all three reports of CDK4/6is. Moreover, ascites was identified as an unlisted hepatic adverse effect of palbociclib. We isolated 189 interactive target genes linking CDK4/6 inhibitors to hepatic injury. Several key genes, such as STAT3, HSP90AA1, and EP300, were revealed via protein-protein analysis, emphasizing their central roles within the network. KEGG pathway enrichment of these genes highlighted multiple pathways.

Conclusion:

Our study revealed variations in hepatobiliary toxicity among the different CDK4/6 inhibitors, with ribociclib showing the highest risk of liver injury, followed by abemaciclib, while palbociclib appeared relatively safe. Our findings emphasize the need for cautious use of CDK4/6 inhibitors, and regular liver function monitoring is recommended for long-term CDK4/6 inhibitor use.