bluuebunny/crossref_metadata_2025 huggingface dataset:
A krónikus vesebetegséggel élők betegségismerete és a Kidney Disease Knowledge Survey magyar nyelvű validálása
Authors: Papp-Zipernovszky Orsolya , Varga Alexandra , Ondrik Zoltán , Haris Ágnes
Published: May 2023

Magyarországon becslések alapján körülbelül minden tizedik ember szenved krónikus vesebetegségben (CKD). A CKD pontos ismerete kulcsfontosságú a megküzdési stratégiák, az önellátás, valamint a betegség progres - sziójának megelőzése szempontjából. A 28 kérdéses Kidney Disease Knowledge Survey 2011-ben Wright és munkatársai által a krónikus vesebetegség ismeretének mérésére kifejlesztett tudásteszt. Magyar nyelven jelenleg egyetlen validált CKD-tudásteszt sem érhető el, így tanulmányunk célja ezen kérdőív magyar nyelvű validálása, valamint összefüggéseinek vizsgálata szociodemográfiai és betegségváltozókkal. Keresztmetszeti kérdőíves kutatásunkban 149, krónikus vesebetegségben (1–5. stádium) szenvedő, predialízises beteg vett részt (64 férfi, 83 nő, átlagéletkor: 63,83 év). Feltáró faktoranalízis mellett a kérdőív konvergens és divergens validitását ellenőriztük. Eredményeink alapján a teszt belső konzisztenciája 0,641, amely a mérőeszköz elfogadható megbízhatóságát jelzi. A kérdőív helyes válaszainak aránya 56,64% lett. Ez a nemzetközi eredményekhez képest valamennyivel alacsonyabb betegségismeretet mutat. A válaszadók a betegség során kerülendő gyógyszereket, a proteinuria és a rossz vesefunkció közötti kapcsolatot, a GFR jelentését, illetve a CKD tüneteire vonatkozó kérdéseket ismerték a legkevésbé. A szociodemográfiai és betegségváltozókkal való összefüggések vizsgálata során igazoltuk a kérdőív konvergens, illetve divergens érvényességét. Összességében a magyar nyelvű Krónikus vesebetegség tudás kérdőív megbízható és érvényes mérőeszköz, amely jól alkalmazható predialízises krónikus vesebetegséggel élők tudásszintjének felmérésére. Mintánkban a betegségismeret szintje korlátozott lett, amely eredményeink felhívják a figyelmet a betegek magasabb szintű CKD-tudásának szükségességére.
Insights from Long Noncoding RNAs into Cancer-immunity Cycle Regulation
Authors: Liang Ye-Lin , Zhang Yuan , Tan Xi-Rong , Qiao Han , Ma Jun , Li Ying-Qin , Liu Na
Published: May 2023

Accumulating evidence from recent research offers new perspectives on the functions of long non-coding RNAs (lncRNAs) in immunooncology. In addition to modulating the aggressiveness of cancer cells, lncRNAs are essential players in regulating various immune cells and stromal cells, playing a role in reshaping the tumor microenvironment and affecting anti-tumor immunity. The insightful discoveries on the role of lncRNAs in immuno-oncological activities indicate the prognostic value of lncRNA markers. Here, we present an overview of the roles of lncRNAs derived from different cell types in the tumor microenvironment, that is, immune cells, tumor cells, and stromal cells, and summarize their functional characterization and mechanisms in immuno-oncological activities. We also discuss the opportunities and challenges of single-cell-based technologies for analyzing the cellular function of immune-related lncRNAs.
Misdiagnosed myocarditis in arrhythmogenic cardiomyopathy induced by a homozygous variant of DSG2: a case report
Authors: Liu Xuwei , Zhang Yue , Li Wenjuan , Zhang Qian , Zhou Letao , Hua Yimin , Duan Hongyu , Li Yifei
Published: May 2023

Background

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy that is rarely diagnosed in infants or young children. However, some significant homozygous or compound heterozygous variants contribute to more severe clinical manifestations. In addition, inflammation of the myocardium and ventricular arrhythmia might lead to misdiagnosis with myocarditis. Here, we describe an 8-year-old patient who had been misdiagnosed with myocarditis. Timely genetic sequencing helped to identify this case as ACM induced by a homozygous variant of DSG2.

Case presentation

The proband of this case was an 8-year-old boy who initially presented with chest pain with an increased level of cardiac Troponin I. In addition, the electrocardiogram revealed multiple premature ventricular beats. Cardiac magnetic resonance revealed myocardial edema in the lateral ventricular wall and apex, indicating localized injuries of the myocardium. The patient was primarily suspected to have acute coronary syndrome or viral myocarditis. Whole-exome sequencing confirmed that the proband had a homozygous variation, c.1592T > G, of the DSG2 gene. This mutation site was regulated by DNA modification, which induced amino acid sequence changes, protein structure effects, and splice site changes. According to MutationTaster and PolyPhen-2 analyses, the variant was considered a disease-causing mutation. Next, we used SWISS-MODEL to illustrate the mutation site of p.F531C. The ensemble variance of p.F531C indicated the free energy changes after the amino acid change.

Conclusion

In summary, we reported a rare pediatric case initially presenting as myocarditis that transitioned into ACM during follow-up. A homozygous genetic variant of DSG2 was inherited in the proband. This study expanded the clinical feature spectrum of DSG2-associated ACM at an early age. Additionally, the presentation of this case emphasized the difference between homozygous and heterozygous variants of desmosomal genes in disease progression. Genetic sequencing screening could be helpful in distinguishing unexplained myocarditis in children.
Effect of optimized new Shengmai powder on exercise tolerance in rats with heart failure by regulating the ubiquitin-proteasome signaling pathway
Authors: Wang Shuai , Wang Lin , Gu Shaoke , Han Yixiao , Li Linfeng , Jia Zhuangzhuang , Gao Ning , Liu Yu , Lin Shanshan , Hou Yazhu , Wang Xianliang , Mao Jingyuan
Published: May 2023

Introduction

Decreased exercise tolerance is a common symptom in patients with heart failure, which is closely related to protein degradation and apoptosis regulated by the ubiquitin-proteasome signaling (UPS) pathway. In this study, the effect of Chinese medicine, optimized new Shengmai powder, on exercise tolerance in rats with heart failure was investigated via the UPS pathway.

Methods

The heart failure model was prepared by ligating the left anterior descending branch of the coronary artery in rats, in which the sham-operated group was only threaded and not ligated. Rats (left ventricular ejection fraction ≤ 45%) were randomly divided into the following groups: model group, YHXSMS group, Benazepril group, and proteasome inhibitor Oprozomib group, and they were administered the corresponding drugs by gavage for 4 weeks. The cardiac function of rats was evaluated by performing an echocardiography examination and a hemodynamic test and the exercise tolerance was done by conducting an exhaustive swimming test. The mechanism was revealed by TUNEL detection, immunohistochemistry, immunofluorescence analysis, Western blot, and quantitative real-time PCR.

Results

The study showed that there was a decrease in cardiac function and exercise tolerance of rats in the model group and also destruction of cardiac and skeletal muscle fibers, a proliferation of collagen tissue, and an increment of apoptosis. Our study suggested that optimized new Shengmai powder could exert antiapoptotic effects on myocardial and skeletal muscle cells and improve myocardial contractility and exercise tolerance by inhibiting the overactivation of the UPS pathway, downregulating MAFbx, and Murf-1 overexpression, inhibiting the activation of the JNK signaling pathway, upregulating bcl-2 expression, and decreasing bax and caspase-3 levels.

Conclusions

The study showed that the optimized new Shengmai powder could improve cardiac function and exercise tolerance in rats with heart failure through the UPS pathway.
The pathophysiology of cognitive impairment in individuals with heart failure: a systematic review
Authors: Ni Reine Sam Shi , Mohamed Raffi Hanis Qarissa , Dong Yanhong
Published: May 2023

Introduction

Heart Failure and Cognitive Impairment are both on the rise and shown to be interlinked. Despite existing reviews delineating a relationship between heart failure and cognitive impairment, the underlying pathophysiology is not researched in great depth. Current literature proposed varying pathophysiological mechanisms and focused heavily on the prevalence of cognitive impairment and treatment interventions such as cardiac rehabilitation. In view of the limitations of previous reviews, this systematic review summarized the best existing evidence concerning different pathophysiological mechanisms behind cognitive impairment in individuals with heart failure.

Methods

Eight electronic databases including PubMed, Cochrane Library and EMBASE etc., two grey literatures (ProQuest Theses and Dissertations and Mednar) and hand-searching of references were performed using specific criteria regarding population, exposures and outcomes, before duplicate removal and screening using Endnote and Rayyan respectively. JBI critical appraisal tools for non-randomized studies were used for appraisal. Data extraction was performed using two modified forms from JBI Manual for Evidence Synthesis.

Results

Narrative synthesis was performed to summarize the data from 32 studies. There were three main themes—cognitive impairment due to changes in the brain: brain atrophy, alterations in grey matter and white matter, cerebral alterations, pathway or axis changes, neuroinflammation and hippocampal gene changes; cognitive impairment due to changes in the heart or systemic circulation: inflammation, oxidative stress and changes in serum biomarkers or proteins and the riser rhythm; cognitive impairment due to changes in both the brain and the heart, with seven studies obtaining negative results. There are some limitations such as having non-human studies and large numbers of cross-sectional studies etc.

Discussion

Considering the findings, future research should examine the bi-directional relationship between the brain and the heart as most of the existing research is about the effect of the heart on the brain. By understanding the different pathophysiological mechanisms, the management and prognosis of heart failure patients will be ameliorated. Interventions that slow down or even reverse cognitive impairment can be explored so that these two common issues will not add to the already aggravating disease burden.

Systematic Review Registration

This review is registered under PROSPERO. Identifier: CRD42022381359.
The rise and fall of acute rheumatic fever and rheumatic heart disease: a mini review
Authors: Liang Yunmei , Yu Dingle , Lu Qinghua , Zheng Yuejie , Yang Yonghong
Published: May 2023

Introduction

The incidences of acute rheumatic fever (ARF) and rheumatic heart disease (RHD), which were leading causes of death in children in the 1920s, have decreased substantially. Considering the recent resurgence of scarlet fever and increased incidence of streptococcal pharyngitis in children, an investigation of the current status of ARF and RHD may be worthwhile.

Objective

To summarize the prevalence trends, pathogenic factors, and prevention strategies for ARF and RHD in children.

Methods

A selective search of literature published between January 1920 and February 2023 was done in PubMed, using the terms “acute rheumatic fever”, “rheumatic heart disease”, “group A Streptococcus”, “pharyngitis”, “pharyngeal tonsillitis”, “scarlet fever”, “impetigo”, “obstructive sleep apnea syndrome” and “child”.

Results

Overcrowded homes and inadequate sanitation led to recurrent group A streptococcal infection, and the causal relationship between group A streptococcal infection and ARF/RHD was well established. Streptococcal infectious diseases, such as group A streptococcal pharyngeal tonsillitis, SF, impetigo, and obstructive sleep apnea syndrome, were associated with the occurrence of ARF and RHD. ARF and RHD were still prevalent in young people of developing countries and economically poor populations of high-income countries. Universal disease registration systems were critical to locating disease outbreaks, tracking disease transmission, and identifying high-risk populations. Four-level prevention strategies were effective in reducing the incidence and mortality of ARF and RHD.

Conclusions

Registry and preventive measures for ARF and RHD should be strengthened in areas of dense population; poor sanitation; resurgence of SF; and high incidence of streptococcal pharyngitis, impetigo, and obstructive sleep apnea syndrome.
High risk of osteoporosis and fracture following solid organ transplantation: a population-based study
Authors: Chen Hsin , Lai Yung-Rung , Yang Yih , Gau Shuo-Yan , Huang Cheng-Yang , Tsai Tung-Han , Huang Kuang-Hua , Lee Chien-Ying
Published: May 2023

Background

Osteoporosis and fractures increase morbidity and mortality rates after solid organ transplantation (SOT), but few studies have analyzed the risk of osteoporosis and related fractures after SOT. In this retrospective cohort study, we investigated the risk of osteoporosis and fractures in different SOT recipients.

Methods

This study was a retrospective cohort study using a nationally representative database in Taiwan. We collected the data of SOT recipients and used the propensity score matching method to obtain a comparison cohort. To reduce bias, we excluded patients who had been diagnosed with osteoporosis or fracture before inclusion. All participants were followed up until the date of diagnosis as having a pathological fracture, death, or the end of 2018, whichever occurred first. The Cox proportional hazards model was used to investigate the risk of osteoporosis and pathological fracture in SOT recipients.

Results

After adjustment for the aforementioned variables, SOT recipients were observed to have a higher risk of osteoporosis (hazard ratio (HR) = 1.46, 95% confidence interval (CI): 1.29–1.65) and fracture (HR: 1.19, 95% CI: 1.01–1.39) than the general individuals. Among the different SOT recipients, the highest risk of fractures was noted in heart or lung transplant recipients, with a HR of 4.62 (95% CI: 2.05–10.44). Among the age groups, patients aged >61 years had the highest HRs for osteoporosis (HR: 11.51; 95% CI, 9.10–14.56) and fracture (HR: 11.75, 95% CI: 8.97–15.40).

Conclusion

SOT recipients had a higher risk of osteoporosis and related fractures than the general population, with the highest risks observed in patients receiving heart or lung transplants, older patients, and patients with CCI scores of >3.
Nocturnal melatonin increases glucose uptake via insulin-independent action in the goldfish brain
Authors: Watanabe Kazuki , Nakano Masaki , Maruyama Yusuke , Hirayama Jun , Suzuki Nobuo , Hattori Atsuhiko
Published: May 2023

Melatonin, a neurohormone nocturnally produced by the pineal gland, is known to regulate the circadian rhythm. It has been recently reported that variants of melatonin receptors are associated with an increased risk of hyperglycemia and type 2 diabetes, suggesting that melatonin may be involved in the regulation of glucose homeostasis. Insulin is a key hormone that regulates circulating glucose levels and cellular metabolism after food intake in many tissues, including the brain. Although cells actively uptake glucose even during sleep and without food, little is known regarding the physiological effects of nocturnal melatonin on glucose homeostasis. Therefore, we presume the involvement of melatonin in the diurnal rhythm of glucose metabolism, independent of insulin action after food intake. In the present study, goldfish (Carassius auratus) was used as an animal model, since this species has no insulin-dependent glucose transporter type 4 (GLUT4). We found that in fasted individuals, plasma melatonin levels were significantly higher and insulin levels were significantly lower during the night. Furthermore, glucose uptake in the brain, liver, and muscle tissues also significantly increased at night. After intraperitoneal administration of melatonin, glucose uptake by the brain and liver showed significantly greater increases than in the control group. The administration of melatonin also significantly decreased plasma glucose levels in hyperglycemic goldfish, but failed to alter insulin mRNA expression in Brockmann body and plasma insulin levels. Using an insulin-free medium, we demonstrated that melatonin treatment increased glucose uptake in a dose-dependent manner in primary cell cultures of goldfish brain and liver cells. Moreover, the addition of a melatonin receptor antagonist decreased glucose uptake in hepatocytes, but not in brain cells. Next, treatment with N1-acetyl-5-methoxykynuramine (AMK), a melatonin metabolite in the brain, directly increased glucose uptake in cultured brain cells. Taken together, these findings suggest that melatonin is a possible circadian regulator of glucose homeostasis, whereas insulin acquires its effect on glucose metabolism following food intake.
Myostatin: a potential therapeutic target for metabolic syndrome
Authors: Yang Ming , Liu Chongbin , Jiang Na , Liu Yan , Luo Shilu , Li Chenrui , Zhao Hao , Han Yachun , Chen Wei , Li Li , Xiao Li , Sun Lin
Published: May 2023

Metabolic syndrome is a complex metabolic disorder, its main clinical manifestations are obesity, hyperglycemia, hypertension and hyperlipidemia. Although metabolic syndrome has been the focus of research in recent decades, it has been proposed that the occurrence and development of metabolic syndrome is related to pathophysiological processes such as insulin resistance, adipose tissue dysfunction and chronic inflammation, but there is still a lack of favorable clinical prevention and treatment measures for metabolic syndrome. Multiple studies have shown that myostatin (MSTN), a member of the TGF-β family, is involved in the development and development of obesity, hyperlipidemia, diabetes, and hypertension (clinical manifestations of metabolic syndrome), and thus may be a potential therapeutic target for metabolic syndrome. In this review, we describe the transcriptional regulation and receptor binding pathway of MSTN, then introduce the role of MSTN in regulating mitochondrial function and autophagy, review the research progress of MSTN in metabolic syndrome. Finally summarize some MSTN inhibitors under clinical trial and proposed the use of MSTN inhibitor as a potential target for the treatment of metabolic syndrome.
SARS-CoV-2 infection impairs NK cell functions via activation of the LLT1-CD161 axis
Authors: Lenart Marzena , Górecka Magdalena , Bochenek Michal , Barreto-Duran Emilia , Szczepański Artur , Gałuszka-Bulaga Adrianna , Mazur-Panasiuk Natalia , Węglarczyk Kazimierz , Siwiec-Koźlik Andżelika , Korkosz Mariusz , Łabaj Paweł P. , Baj-Krzyworzeka Monika , Siedlar Maciej , Pyrc Krzysztof
Published: May 2023

Introduction

Natural killer (NK) cells plays a pivotal role in the control of viral infections, and their function depend on the balance between their activating and inhibitory receptors. The immune dysregulation observed in COVID-19 patients was previously associated with downregulation of NK cell numbers and function, yet the mechanism of inhibition of NK cell functions and the interplay between infected cells and NK cells remain largely unknown.

Methods

In this study we show that SARS-CoV-2 infection of airway epithelial cells can directly influence NK cell phenotype and functions in the infection microenvironment. NK cells were co-cultured with SARS-CoV-2 infected epithelial cells, in a direct contact with A549ACE2/TMPRSS2 cell line or in a microenvironment of the infection in a 3D ex vivo human airway epithelium (HAE) model and NK cell surface expression of a set of most important receptors (CD16, NKG2D, NKp46, DNAM-1, NKG2C, CD161, NKG2A, TIM-3, TIGIT, and PD-1) was analyzed.

Results

We observed a selective, in both utilized experimental models, significant downregulation the proportion of CD161 (NKR-P1A or KLRB1) expressing NK cells, and its expression level, which was followed by a significant impairment of NK cells cytotoxicity level against K562 cells. What is more, we confirmed that SARS-CoV-2 infection upregulates the expression of the ligand for CD161 receptor, lectin-like transcript 1 (LLT1, CLEC2D or OCIL), on infected epithelial cells. LLT1 protein can be also detected not only in supernatants of SARS-CoV-2 infected A549ACE2/TMPRSS2 cells and HAE basolateral medium, but also in serum of COVID-19 patients. Finally, we proved that soluble LLT1 protein treatment of NK cells significantly reduces i) the proportion of CD161+ NK cells, ii) the ability of NK cells to control SARS-CoV-2 infection in A549ACE2/TMPRSS2 cells and iii) the production of granzyme B by NK cells and their cytotoxicity capacity, yet not degranulation level.

Conclusion

We propose a novel mechanism of SARS-CoV-2 inhibition of NK cell functions via activation of the LLT1-CD161 axis.
Transcriptomic signatures reveal a shift towards an anti-inflammatory gene expression profile but also the induction of type I and type II interferon signaling networks through aryl hydrocarbon receptor activation in murine macrophages
Authors: Schmidt Johannes R. , Haupt Janine , Riemschneider Sina , Kämpf Christoph , Löffler Dennis , Blumert Conny , Reiche Kristin , Koehl Ulrike , Kalkhof Stefan , Lehmann Jörg
Published: May 2023

Introduction

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates a broad range of target genes involved in the xenobiotic response, cell cycle control and circadian rhythm. AhR is constitutively expressed in macrophages (Mϕ), acting as key regulator of cytokine production. While proinflammatory cytokines, i.e., IL-1β, IL-6, IL-12, are suppressed through AhR activation, anti-inflammatory IL-10 is induced. However, the underlying mechanisms of those effects and the importance of the specific ligand structure are not yet completely understood.

Methods

Therefore, we have compared the global gene expression pattern in activated murine bone marrow-derived macrophages (BMMs) subsequently to exposure with either benzo[a]pyrene (BaP) or indole-3-carbinol (I3C), representing high-affinity vs. low-affinity AhR ligands, respectively, by means of mRNA sequencing. AhR dependency of observed effects was proved using BMMs from AhR-knockout (Ahr-/-) mice.

Results and discussion

In total, more than 1,000 differentially expressed genes (DEGs) could be mapped, covering a plethora of AhR-modulated effects on basal cellular processes, i.e., transcription and translation, but also immune functions, i.e., antigen presentation, cytokine production, and phagocytosis. Among DEGs were genes that are already known to be regulated by AhR, i.e., Irf1, Ido2, and Cd84. However, we identified DEGs not yet described to be AhR-regulated in Mϕ so far, i.e., Slpi, Il12rb1, and Il21r. All six genes likely contribute to shifting the Mϕ phenotype from proinflammatory to anti-inflammatory. The majority of DEGs induced through BaP were not affected through I3C exposure, probably due to higher AhR affinity of BaP in comparison to I3C. Mapping of known aryl hydrocarbon response element (AHRE) sequence motifs in identified DEGs revealed more than 200 genes not possessing any AHRE, and therefore being not eligible for canonical regulation. Bioinformatic approaches modeled a central role of type I and type II interferons in the regulation of those genes. Additionally, RT-qPCR and ELISA confirmed a AhR-dependent expressional induction and AhR-dependent secretion of IFN-γ in response to BaP exposure, suggesting an auto- or paracrine activation pathway of Mϕ.
Mitophagy and immune infiltration in vitiligo: evidence from bioinformatics analysis
Authors: Luo Lingling , Zhu Jing , Guo Youming , Li Chengrang
Published: May 2023

Background

Vitiligo is an acquired, autoimmune, depigmented skin disease with unclear pathogenesis. Mitochondrial dysfunction contributes significantly to vitiligo, and mitophagy is vital for removing damaged mitochondria. Herein, using bioinformatic analysis, we sought to determine the possible role of mitophagy-associated genes in vitiligo and immune infiltration.

Methods

Microarrays GSE53146 and GSE75819 were used to identify differentially expressed genes (DEGs) in vitiligo. By crossing vitiligo DEGs with mitophagy-related genes, the mitophagy-related DEGs were identified. Functional enrichment and protein-protein intersection (PPI) analyses were conducted. Then, the hub genes were identified using two machine algorithms, and receiver operating characteristic (ROC) curves were generated. Next, the immune infiltration and its connection with hub genes in vitiligo were investigated. Finally, the Regnetwork database and NetworkAnalyst were used to predict the upstream transcriptional factors (TFs), microRNAs (miRNAs), and the protein-compound network.

Results

A total of 24 mitophagy-related genes were screened. Then, five mitophagy hub genes (GABARAPL2, SP1, USP8, RELA, and TBC1D17) were identified using two machine learning algorithms, and these genes showed high diagnostic specificity for vitiligo. The PPI network showed that hub genes interacted with each other. The mRNA expression levels of five hub genes were validated in vitiligo lesions by qRT-PCR and were compatible with the bioinformatic results. Compared with controls, the abundance of activated CD4+ T cells, CD8+ T cells, immature dendritic cells and B cells, myeloid-derived suppressor cells (MDSCs), gamma delta T cells, mast cells, regulatory T cells (Tregs), and T helper 2 (Th2) cells was higher. However, the abundance of CD56 bright natural killer (NK) cells, monocytes, and NK cells was lower. Correlation analysis revealed a link between hub genes and immune infiltration. Meanwhile, we predicted the upstream TFs and miRNAs and the target compounds of hub genes.

Conclusion

Five hub mitophagy-related genes were identified and correlated with immune infiltration in vitiligo. These findings suggested that mitophagy may promote the development of vitiligo by activating immune infiltration. Our study might enhance our comprehension of the pathogenic mechanism of vitiligo and offer a treatment option for vitiligo.
Identification and validation of a novel cuproptosis-related stemness signature to predict prognosis and immune landscape in lung adenocarcinoma by integrating single-cell and bulk RNA-sequencing
Authors: Yang Jia , Liu Kaile , Yang Lu , Ji Junqing , Qin Jingru , Deng Haibin , Wang Zhongqi
Published: May 2023

Background

Cancer stem cells (CSCs) play vital roles in lung adenocarcinoma (LUAD) recurrence, metastasis, and drug resistance. Cuproptosis has provided a novel insight into the treatment of lung CSCs. However, there is a lack of knowledge regarding the cuproptosis-related genes combined with the stemness signature and their roles in the prognosis and immune landscape of LUAD.

Methods

Cuproptosis-related stemness genes (CRSGs) were identified by integrating single-cell and bulk RNA-sequencing data in LUAD patients. Subsequently, cuproptosis-related stemness subtypes were classified using consensus clustering analysis, and a prognostic signature was constructed by univariate and least absolute shrinkage operator (LASSO) Cox regression. The association between signature with immune infiltration, immunotherapy, and stemness features was also investigated. Finally, the expression of CRSGs and the functional roles of target gene were validated in vitro.

Results

We identified six CRSGs that were mainly expressed in epithelial and myeloid cells. Three distinct cuproptosis-related stemness subtypes were identified and associated with the immune infiltration and immunotherapy response. Furthermore, a prognostic signature was constructed to predict the overall survival (OS) of LUAD patients based on eight differently expressed genes (DEGs) with cuproptosis-related stemness signature (KLF4, SCGB3A1, COL1A1, SPP1, C4BPA, TSPAN7, CAV2, and CTHRC1) and confirmed in validation cohorts. We also developed an accurate nomogram to improve clinical applicability. Patients in the high-risk group showed worse OS with lower levels of immune cell infiltration and higher stemness features. Ultimately, further cellular experiments were performed to verify the expression of CRSGs and prognostic DEGs and demonstrate that SPP1 could affect the proliferation, migration, and stemness of LUAD cells.

Conclusion

This study developed a novel cuproptosis-related stemness signature that can be used to predict the prognosis and immune landscape of LUAD patients, and provided potential therapeutic targets for lung CSCs in the future.
A systems serology approach to the investigation of infection-induced antibody responses and protection in trachoma
Authors: Barton Amber , Rosenkrands Ida , Pickering Harry , Faal Nkoyo , Harte Anna , Joof Hassan , Makalo Pateh , Ragonnet Manon , Olsen Anja Weinreich , Bailey Robin L. , Mabey David C. W. , Follmann Frank , Dietrich Jes , Holland Martin J.
Published: May 2023

Background

Ocular infections with Chlamydia trachomatis serovars A–C cause the neglected tropical disease trachoma. As infection does not confer complete immunity, repeated infections are common, leading to long-term sequelae such as scarring and blindness. Here, we apply a systems serology approach to investigate whether systemic antibody features are associated with susceptibility to infection.

Methods

Sera from children in five trachoma endemic villages in the Gambia were assayed for 23 antibody features: IgG responses towards two C. trachomatis antigens and three serovars [elementary bodies and major outer membrane protein (MOMP), serovars A–C], IgG responses towards five MOMP peptides (serovars A–C), neutralization, and antibody-dependent phagocytosis. Participants were considered resistant if they subsequently developed infection only when over 70% of other children in the same compound were infected.

Results

The antibody features assayed were not associated with resistance to infection (false discovery rate < 0.05). Anti-MOMP SvA IgG and neutralization titer were higher in susceptible individuals (p < 0.05 before multiple testing adjustment). Classification using partial least squares performed only slightly better than chance in distinguishing between susceptible and resistant participants based on systemic antibody profile (specificity 71%, sensitivity 36%).

Conclusions

Systemic infection-induced IgG and functional antibody responses do not appear to be protective against subsequent infection. Ocular responses, IgA, avidity, or cell-mediated responses may play a greater role in protective immunity than systemic IgG.
Patterns of spatial and temporal dynamics of mixed Mytilus edulis and M. trossulus populations in a small subarctic inlet (Tyuva Inlet, Barents Sea)
Authors: Marchenko Julia , Khaitov Vadim , Katolikova Marina , Sabirov Marat , Malavenda Sergey , Gantsevich Michael , Basova Larisa , Genelt-Yanovsky Evgeny , Strelkov Petr
Published: May 2023

Subarctic populations of “cryptic” blue mussel species Mytilus edulis (ME) and M. trossulus (MT) are less studied than Arctic and boreal populations. Ecological features of ME and MT in sympatry are poorly known everywhere. We studied the habitat segregation of ME and MT and the interannual dynamics of their mixed settlements at the Murman coast of the Barents Sea, the northeastern boundary of the Atlantic littoral mussel communities. Previous data on mussels from this area are 50-100 years old. The 3-km-long Tyuva Inlet (Kola Bay) was used as the study site. Mussels were found in the littoral and the sublittoral down to a depth of 4 m. Their characteristic habitats were sandbanks, littoral rocks, sublittoral kelp forests and “the habitat of the mussel bed” in the freshened top of the inlet. The main spatial gradients explaining the variability of demographics of the settlements (abundance, age structure, size) were associated with the depth and the distance from the inlet top. ME and MT were partially segregated by depth: ME dominated in the sublittoral and MT, in the littoral. In addition, ME dominated throughout the mussel bed. The ratio of species in the mixed settlements varied over time: between 2004 and 2010 the proportions of MT decreased everywhere, by 22% on average. The habitat distribution of mussels apparently changed with time: we found that mussels were abundant in kelp forests, where they had rarely been observed in the 20th century. We suggest that the spatial and temporal dynamics of subarctic mussels can be partly explained by the competition between ME and MT and their differing sensitivity to environmental factors.
Monitoring the light pollution changes of China’s mangrove forests from 1992-2020 using nighttime light data
Authors: Zeng Haihang , Jia Mingming , Zhang Rong , Wang Zongming , Mao Dehua , Ren Chunying , Zhao Chuanpeng
Published: May 2023

Mangrove forests are one of the most biologically diverse and productive ecosystems on Earth. They are important breeding and nursing grounds for amphibians, invertebrates, birds, fish, etc. Light pollution may cause serious degradation of biodiversity in the ecosystem. A report of the long-term holistic views of light pollution changes is essential for sustainable management of mangrove ecosystems. However, to date, such studies have rarely been carried out. This study aimed to monitor the long-term light pollution changes of China’s mangrove forests. To achieve this goal, we used time-series nighttime light (NTL) data to build continuous light pollution data. NTL maps made with DMSP-OLS (DNL) or NPP-VIIRS (VNL) are widely utilized in research on human activity. However, DMSP and VIIRS images are different in spatial resolution, radiation resolution, and data saturation. Thus, this study innovatively set an optimal threshold for generating consistent light pollution data in mangrove areas from 1992-2020. The results showed that: (1) the proportion of light-polluted mangrove forests in China increased from 12% in 1992 to 52% in 2020; (2) the largest net increase occurred in Guangxi with an area of 4,086 ha, followed by Guangdong (3,365 ha) and Hainan (2,944 ha); (3) Zhejiang had the largest proportion of net growth (from 0% in 1992 to 99% in 2020), followed by Hainan (66%) and Fujian (59%). Mangrove forests have been protected and restored for decades in China; this study indicates that the establishment of nature reserves is effective in preventing the light pollution of mangroves and provides the first long-term multi-temporal dataset of light pollution in China’s mangrove forests. This comprehensive information could support related studies and facilitate the development of applicable coastal management strategies in China.
Chromosomal abnormalities and structural defects in fetuses with increased nuchal translucency at a Chinese tertiary medical center
Authors: Zhang Huijing , Wang Shuang , Feng Chunli , Zhao Hongyan , Zhang Weiwei , Sun Yu , Yang Huixia
Published: May 2023

Objectives

To explore the pregnancy outcomes of fetuses with increased NT thickness.

Methods

This was a retrospective study of fetuses with increased NT (≥95th centile) at 11–14 weeks of gestation between January 2020 and November 2020.

Results

Among 264 fetuses with increased NT, the median of CRL and NT was 61.2 mm and 2.41 mm. Among them, 132 pregnancy women chose invasive prenatal diagnosis (43 cases of chorionic villus sampling (CVS), 89 cases of amniocentesis). Eventually, 16 cases of chromosomal abnormalities were discovered, including 6 cases (6.4%) of trisomy 21, 4 cases (3%) of trisomy 18, 1 case (0.8%) of 45, XO, 1 case (0.8%) of 47, XXY and 4 cases (3.03%) of CNV abnormalities. The major structural defects included hydrops (6.4%), cardiac defects (3%), and urinary anomalies (2.7%). The incidences of chromosomal abnormalities and structural defects in the NT < 2.5 mm group were 1.3 and 6%, while the incidences were 8.8 and 28.9% in the NT≥2.5 group.

Conclusion

Increased NT was associated with high risk of chromosomal abnormalities and structural anomalies. Chromosomal abnormalities and structural defects could be detected when NT thickness was between 95th centile and 2.5 mm.
Petroleum pollution changes microbial diversity and network complexity of soil profile in an oil refinery
Authors: Zhuang Jugui , Zhang Ruihuan , Zeng Yufei , Dai Tianjiao , Ye Zhencheng , Gao Qun , Yang Yunfeng , Guo Xue , Li Guanghe , Zhou Jizhong
Published: May 2023

Introduction

Petroleum pollution resulting from spills and leakages in oil refinery areas has been a significant environmental concern for decades. Despite this, the effects of petroleum pollutants on soil microbial communities and their potential for pollutant biodegradation still required further investigation.

Methods

In this study, we collected 75 soil samples from 0 to 5 m depths of 15 soil profiles in an abandoned refinery to analyze the effect of petroleum pollution on soil microbial diversity, community structure, and network co-occurrence patterns.

Results

Our results suggested soil microbial a-diversity decreased under high C10–C40 levels, coupled with significant changes in the community structure of soil profiles. However, soil microbial network complexity increased with petroleum pollution levels, suggesting more complex microbial potential interactions. A module specific for methane and methyl oxidation was also found under high C10–C40 levels of the soil profile, indicating stronger methanotrophic and methylotrophic metabolic activities at the heavily polluted soil profile.

Discussion

The increased network complexity observed may be due to more metabolic pathways and processes, as well as increased microbial interactions during these processes. These findings highlight the importance of considering both microbial diversity and network complexity in assessing the effects of petroleum pollution on soil ecosystems.
IgA nephropathy: a review of existing and emerging therapies
Authors: Noor Sahibzadi Mahrukh , Abuazzam Farah , Mathew Roy , Zhang Zhiwei , Abdipour Amir , Norouzi Sayna
Published: May 2023

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. Recently, there have been multiple advances in the understanding of IgAN pathophysiology and therapeutic options. Despite the advent of new treatment options, individual risk stratification of the disease course and choosing the best treatment strategy for the patient remains challenging. A multitude of clinical trials is ongoing, opening multiple opportunities for enrollment. In this brief review we discuss the current approach to the management of IgAN and highlight the ongoing clinical trials.
VTSNN: a virtual temporal spiking neural network
Authors: Qiu Xue-Rui , Wang Zhao-Rui , Luan Zheng , Zhu Rui-Jie , Wu Xiao , Zhang Ma-Lu , Deng Liang-Jian
Published: May 2023

Spiking neural networks (SNNs) have recently demonstrated outstanding performance in a variety of high-level tasks, such as image classification. However, advancements in the field of low-level assignments, such as image reconstruction, are rare. This may be due to the lack of promising image encoding techniques and corresponding neuromorphic devices designed specifically for SNN-based low-level vision problems. This paper begins by proposing a simple yet effective undistorted weighted-encoding-decoding technique, which primarily consists of an Undistorted Weighted-Encoding (UWE) and an Undistorted Weighted-Decoding (UWD). The former aims to convert a gray image into spike sequences for effective SNN learning, while the latter converts spike sequences back into images. Then, we design a new SNN training strategy, known as Independent-Temporal Backpropagation (ITBP) to avoid complex loss propagation in spatial and temporal dimensions, and experiments show that ITBP is superior to Spatio-Temporal Backpropagation (STBP). Finally, a so-called Virtual Temporal SNN (VTSNN) is formulated by incorporating the above-mentioned approaches into U-net network architecture, fully utilizing the potent multiscale representation capability. Experimental results on several commonly used datasets such as MNIST, F-MNIST, and CIFAR10 demonstrate that the proposed method produces competitive noise-removal performance extremely which is superior to the existing work. Compared to ANN with the same architecture, VTSNN has a greater chance of achieving superiority while consuming ~1/274 of the energy. Specifically, using the given encoding-decoding strategy, a simple neuromorphic circuit could be easily constructed to maximize this low-carbon strategy.
Mechanical digit sensory stimulation: a randomized control trial on neurological and motor recovery in acute stroke
Authors: Zhang Shuting , Yu Yang , Xu Panpan , Shen Xianshan , Fang Chuanqin , Wu Xiaosan , Qu Ping , Wu Tingting , Wang Qing Mei , Luo Xun , Hong Yongfeng
Published: May 2023

Background

Mechanical digit sensory stimulation (MDSS) is a novel therapy designed to accelerate the recovery of upper limb (including hand) function in patients with hemiplegia following a stroke. The primary goal of this study was to investigate the effect of MDSS on patients with acute ischemic stroke (AIS).

Methods

Sixty-one inpatients with AIS were randomly divided into conventional rehabilitation group (RG) and stimulation group (SG), and the latter group received MDSS therapy. A healthy group consisting of 30 healthy adults was also included. The interleukin-17A (IL-17A), vascular endothelial growth factor A (VEGF-A), and tumor necrosis factor-alpha (TNF-α) plasma levels were measured in all subjects. The neurological and motor functions of patients were evaluated using the National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE), Fugel-Meyer Assessment (FMA), and Modified Barthel Index (MBI).

Results

After 12 days of intervention, the IL-17A, TNF-α, and NIHSS levels were significantly decreased, while the VEGF-A, MMSE, FMA, and MBI levels were significantly increased in both disease groups. No significant difference was observed between both disease groups after intervention. The levels of IL-17A and TNF-α were positively correlated with NIHSS but negatively correlated with MMSE, FMA, and MBI. The VEGF-A levels were negatively correlated with NIHSS but positively correlated with MMSE, FMA, and MBI.

Conclusion

Both MDSS and conventional rehabilitation significantly reduce the production of IL-17A and TNF-α, increase the VEGF-A levels, and effectively improve cognition and motor function of hemiplegic patients with AIS, and the effects of MDSS and conventional rehabilitation are comparable.
Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile
Authors: Gonzalez-Bosquet Jesus , Weroha S. John , Bakkum-Gamez Jamie N. , Weaver Amy L. , McGree Michaela E. , Dowdy Sean C. , Famuyide Abimbola O. , Kipp Benjamin R. , Halling Kevin C. , Yadav Siddhartha , Couch Fergus J. , Podratz Karl C.
Published: May 2023

Objective

To identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.

Methods

We searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of E2F1 and CCNA2 expression and sequence variations in POLE, PPP2R1A, or FBXW7 (ECPPF) to prognostically stratify MSI-H/NSMP ECs. Clinical outcomes were annotated after integrating ECPPF and sequence variations in homologous recombination (HR) genes.

Results

Data were available for 239 patients with EC, which included 58 MSI-H and 89 NSMP cases. ECPPF effectively stratified MSI-H/NSMP EC into distinct molecular groups with prognostic implications: molecular low risk (MLR), with low CCNA2 and E2F1 expression, and molecular high risk (MHR), with high CCNA2 and E2F1 expression and/or PPP2R1A and/or FBXW7 variants. The 3-year disease-free survival (DFS) rate was 43.8% in the MHR group with clinicopathologic low-risk indicators and 93.9% in the MLR group (P<.001). In the MHR group, wild-type HR genes were present in 28% of cases but in 81% of documented recurrences. The 3-year DFS rate in patients with MSI-H/NSMP EC with clinicopathologic high-risk indicators was significantly higher in the MLR (94.1%) and MHR/HR variant gene (88.9%) groups than in the MHR/HR wild-type gene group (50.3%, P<.001).

Conclusion

ECPPF may resolve prognostic challenges for MSI-H/NSMP EC by identifying occult high-risk disease in EC with clinicopathologic low-risk indicators and therapeutic insensitivity in EC with clinicopathologic high-risk indicators.
ABHD6 and MAGL control 2-AG levels in the PAG and allodynia in a CSD-induced periorbital model of headache
Authors: Liktor-Busa Erika , Levine Aidan A. , Palomino Seph M. , Singh Simar , Wahl Jared , Vanderah Todd W. , Stella Nephi , Largent-Milnes Tally M.
Published: May 2023

Introduction

The high prevalence and severe symptoms of migraines in humans emphasizes the need to identify underlying mechanisms that can be targeted for therapeutic benefit. Clinical Endocannabinoid Deficiency (CED) posits that reduced endocannabinoid tone may contribute to migraine development and other neuropathic pain conditions. While strategies that increase levels of the endocannabinoid n-arachidonoylethanolamide have been tested, few studies have investigated targeting the levels of the more abundant endocannabinoid, 2-arachidonoylgycerol, as an effective migraine intervention.

Methods

Cortical spreading depression was induced in female Sprague Dawley rats via KCl (potassium chloride) administration, followed by measures of endocannabinoid levels, enzyme activity, and neuroinflammatory markers. Efficacy of inhibiting 2-arachidonoylglycerol hydrolysis to mitigate periorbital allodynia was then tested using reversal and prevention paradigms.

Results

We discovered reduced 2-arachidonoylglycerol levels in the periaqueductal grey associated with increased hydrolysis following headache induction. Pharmacological inhibition of the 2-arachidonoylglycerol hydrolyzing enzymes, α/β-hydrolase domain-containing 6 and monoacylglycerol lipase reversed and prevented induced periorbital allodynia in a cannabinoid receptor-dependent manner.

Discussion

Our study unravels a mechanistic link between 2-arachidonoylglycerol hydrolysis activity in the periaqueductal grey in a preclinical, rat model of migraine. Thus, 2-arachidonoylglycerol hydrolysis inhibitors represent a potential new therapeutic avenue for the treatment of headache.
Case report: The CT features of pediatric retroperitoneal extrarenal Wilms tumor: a report of two cases and literature review
Authors: Li Ting , Wang Haoru , Chen Xin , He Ling
Published: May 2023

Retroperitoneal extrarenal Wilms tumor is a rare condition in children that can be easily misdiagnosed as other retroperitoneal malignancies unrelated to the renal origin. Computerized tomography scan plays a crucial role in diagnosing and distinguishing retroperitoneal malignancies. In this report, we present two cases of retroperitoneal extrarenal Wilms tumor in children who were admitted due to abdominal mass. Laboratory examination did not reveal any significant abnormality. However, a computerized tomography scan revealed a solid or cystic-solid mass in the retroperitoneum accompanied by a bone spur extending from the anterior edge of the vertebral body to the back of the mass, while the origin of the tumor remained unclear. By analyzing these two cases and reviewing previous studies on retroperitoneal extrarenal Wilms tumor in children, we summarized the clinical and imaging characteristics of this rare condition. We also found that the presence of a spinal deformity adjacent to the mass might indicate the possibility of a retroperitoneal extrarenal Wilms tumor.