bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of prognostic risk model based on plasma cell markers in hepatocellular carcinoma through single-cell sequencing analysis
Authors: Li Yuanqi , Huang Hao , Wang Qi , Zheng Xiao , Zhou Yi , Kong Xiangyin , Huang Tao , Zhang Jinping , Zhou You
Published: May 2024

Hepatocellular carcinoma (HCC) represents a substantial global health burden. Tumorinfiltrating B lymphocytes (TIL-Bs) contribute to tumor progression and significantly impact the efficacy of tumor therapy. However, the characteristics of TIL-Bs in HCC and their effect on HCC therapy remain elusive. Single-cell RNA sequencing (scRNAseq) was applied to investigate the heterogeneity, cellular differentiation and cell-cell communication of TIL-Bs in HCC. Further, the Cancer Genome Atlas-liver hepatocellular carcinoma (TCGA-LIHC) and liver cancer institutes (LCI) cohorts were applied to construct and validate the plasma cell marker-based prognostic risk model. The relationship between the prognostic risk model and the responsiveness of immunotherapy and chemotherapy in patients with HCC were estimated by OncoPredict and tumor immune dysfunction and exclusion (TIDE) algorithm. Finally, we established nomogram and calibration curves to evaluate the precision of the risk score in predicating survival probability. Our data identified five subtypes of TIL-Bs in HCC, each exhibiting varying levels of infiltration in tumor tissues. The interactions between TIL-Bs and other cell types contributed to shaping distinct tumor microenvironments (TME). Moreover, we found that TIL-Bs subtypes had disparate prognostic values in HCC patients. The prognostic risk model demonstrated exceptional predictive accuracy for overall survival and exhibited varying sensitivities to immunotherapy and chemotherapy among patients with HCC. Our data demonstrated that the risk score stood as an independent prognostic predictor and the nomogram results further affirmed its strong prognostic capability. This study reveals the heterogeneity of TIL-Bs and provides a prognostic risk model based on plasma cell markers in HCC, which could prove valuable in predicting prognosis and guiding the choice of suitable therapies for patients with HCC.
Genetically predicted associations between circulating cytokines and autoimmune diseases: a bidirectional two-sample Mendelian randomization
Authors: Jie Jie , Gong Yonglu , Luo Songquan , Yang Xing , Guo Kaiyun
Published: May 2024

Objectives

Previous studies have indicated a correlation between cytokines and autoimmune diseases. yet the causality remains uncertain. Through Mendelian Randomization (MR) analysis, we aimed to investigate the causal relationships between genetically predicted levels of 91 cytokines and three autoimmune diseases: Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE), and Hashimoto’s Thyroiditis (HT).

Methods

A bidirectional two-sample MR approach was utilized to assess the causal relationships between cytokines and MS, SLE, and HT. The datasets included 47,429 MS cases and 68,374 controls, 5,201 SLE cases and 9,066 controls, and 16,191 HT cases with 210,612 controls. Data on 91 cytokines comprised 14,824 participants. Causal analyses primarily employed inverse variance weighted, weighted median, and MR-Egger methods, with sensitivity analyses including heterogeneity and pleiotropy assessment.

Results

Genetically predicted levels of IL-18 (OR = 0.706; 95% C.I. 0.538–0.925), ADA (OR = 0.808; 95% C.I. 0.673–0.970), and SCF (OR = 0.898; 95% C.I. 0.816–0.987) were associated with a decreased risk of MS. IL-4 (OR = 1.384; 95% C.I. 1.081–1.771), IL-7 (OR = 1.401; 95% C.I. 1.010–1.943), IL-10RA (OR = 1.266; 95% C.I. 1.004–1.596), CXCL5 (OR = 1.170; 95% C.I. 1.021–1.341), NTN (OR = 1.225; 95% C.I. 1.004–1.496), FGF23 (OR = 0.644; 95% C.I. 0.460–0.902), and MCP4 (OR = 0.665; 95% C.I. 0.476–0.929) were associated with SLE risk. CDCP1 (OR = 1.127; 95% C.I. 1.008–1.261), IL-33 (OR = 0.852; 95% C.I. 0.727–0.999), and TRAIL (OR = 0.884; 95% C.I. 0.799–0.979) were associated with HT risk. Bidirectional MR results suggest the involvement of CCL19, IL-13, SLAM, ARTN, Eotaxin, IL-22RA1, ADA, and MMP10 in the downstream development of these diseases.

Conclusions

Our findings support causal relationships between certain cytokines and the risks of MS, SLE, and HT, identifying potential biomarkers for diagnosis and prevention. Additionally, several cytokines previously unexplored in these autoimmune disease contexts were discovered, laying new groundwork for the study of disease mechanisms and therapeutic potentials.
Do children with developmental dyslexia have syntactic awareness problems once phonological processing and memory are controlled?
Authors: Robertson Erin K. , Mimeau Catherine , Deacon S. Hélène
Published: May 2024

Introduction

Syntactic awareness is the ability to monitor and manipulate word order within sentences. It is unclear whether children with dyslexia have syntactic awareness problems, as there are mixed results in the literature. Dyslexia is typically classified with very poor word and nonword reading and phonological processing problems are often observed in this population. It is conceivable that a phonological deficit could strain memory when performing oral syntactic awareness tasks. Here we examine if syntactic awareness problems are observed in children with dyslexia once phonological processing and memory skills are controlled.

Methods

Real and nonword reading efficiency tests determined reading level. Children with dyslexia (n = 25) were compared to typically developing children (n = 24) matched for age (M = 8;8) and nonverbal abilities. Syntactic awareness was measured with an oral word order correction task (e.g., Is baking Lisa and her son in his room sleeps). Tests of phonological awareness, phonological memory, and verbal working memory were also administered and served as controls.

Results

The dyslexic group performed worse than typically developing readers on syntactic awareness and this group difference persisted once phonological memory and verbal working memory were controlled. However, after controlling for phonological awareness skills, there were no group differences on the syntactic awareness test.

Discussion:

The results suggest that phonological awareness problems in particular might be responsible for syntactic awareness difficulties in dyslexia and future studies should control for this. The results are discussed within theoretical frameworks on the nature of oral language deficits in dyslexia.
The association between circulating leukocytes and inflammatory bowel disease: a two-sample Mendelian randomization study
Authors: Tian Li , Yang Xiaobin , Zheng Yansen , Peng Chaosheng
Published: May 2024

Background

Inflammatory bowel disease (IBD) is a highly prevalent, recurrent, chronic intestinal inflammatory disease. Several observational studies have shown that circulating leukocytes are strongly associated with IBD. However, whether alterations in leukocytes are causally related to IBD remains uncertain. The present study explores this issue with the Mendelian randomization (MR) analysis method.

Methods

The Genome wide association study (GWAS) statistical data related to circulating leukocytes and IBD were obtained from the Blood Cell Consortium and the IEU Qpen GWAS project, respectively. Inverse variance weighting (IVW) was used as the main MR analytical method, coupled with a series of sensitivity analyses to ensure the reliability of the results.

Results

The results of IVW showed that increased monocyte count (especially CD14- CD16+ monocyte absolute counts) was negatively correlated with the risk of IBD and its main subtypes. Increased neutrophil count was positively associated with the risk of IBD and ulcerative colitis. Meanwhile, there was no causal relationship between basophil, eosinophil, lymphocyte counts and IBD risk.

Conclusion

These results indicate that a causal relationship exists between circulating leukocytes and the risk of IBD and its subtypes, which confirms the important role that the leukocyte immune system plays in IBD. Our findings provide additional research directions for the clinical prevention and treatment of IBD.
Causal relationships of gut microbiota, plasma metabolites, and metabolite ratios with diffuse large B-cell lymphoma: a Mendelian randomization study
Authors: Qian Jingrong , Zheng Wen , Fang Jun , Cheng Shiliang , Zhang Yanli , Zhuang Xuewei , Song Chao
Published: May 2024

Background

Recent studies have revealed changes in microbiota constitution and metabolites associated with tumor progression, however, no causal relation between microbiota or metabolites and diffuse large B-cell lymphoma (DLBCL) has yet been reported.

Methods

We download a microbiota dataset from the MiBioGen study, a metabolites dataset from the Canadian Longitudinal Study on Aging (CLSA) study, and a DLBCL dataset from Integrative Epidemiology Unit Open genome-wide association study (GWAS) project. Mendelian randomization (MR) analysis was conducted using the R packages, TwoSampleMR and MR-PRESSO. Five MR methods were used: MR-Egger, inverse variance weighting (IVW), weighted median, simple mode, and weighted mode. Reverse MR analyses were also conducted to explore the causal effects of DLBCL on the microbiome, metabolites, and metabolite ratios. Pleiotropy was evaluated by MR Egger regression and MR-PRESSO global analyses, heterogeneity was assessed by Cochran’s Q-test, and stability analyzed using the leave-one-out method.

Results

119 microorganisms, 1,091 plasma metabolite, and 309 metabolite ratios were analyzed. According to IVW analysis, five microorganisms were associated with risk of DLBCL. The genera Terrisporobacter (OR: 3.431, p = 0.049) andgenera Oscillibacter (OR: 2.406, p = 0.029) were associated with higher risk of DLBCL. Further, 27 plasma metabolites were identified as having a significant causal relationships with DLBCL, among which citrate levels had the most significant protective causal effect against DLBCL (p = 0.006), while glycosyl-N-tricosanoyl-sphingadienine levels was related to higher risk of DLBCL (p = 0.003). In addition, we identified 19 metabolite ratios with significant causal relationships to DLBCL, of which taurine/glutamate ratio had the most significant protective causal effect (p = 0.005), while the phosphoethanolamine/choline ratio was related to higher risk of DLBCL (p = 0.009). Reverse MR analysis did not reveal any significant causal influence of DLBCL on the above microbiota, metabolites, and metabolite ratios (p > 0.05). Sensitivity analyses revealed no significant heterogeneity or pleiotropy (p > 0.05).

Conclusion

We present the first elucidation of the causal influence of microbiota and metabolites on DLBCL using MR methods, providing novel insights for potential targeting of specific microbiota or metabolites to prevent, assist in diagnosis, and treat DLBCL.
Sheng-Jiang powder ameliorates NAFLD via regulating intestinal microbiota in mice
Authors: Zhang Pengcheng , Li Juan , Miao Yifan , Zhao Xianlin , Zhu Lv , Yao Jiaqi , Wan Meihua , Tang Wenfu
Published: May 2024

Background

Intestinal microbiota have been demonstrated to be involved in the development of NAFLD, while the relationship between the severity of NAFLD and intestinal microbiota is still not fully elucidated. Sheng-Jiang Powder (SJP) showed exact efficacy in treating SFL and great potential in regulating intestinal microbiota, but the effects need to be further addressed in NASH and liver fibrosis.

Objectives

To investigate the differences in intestinal microbiota of NAFLD with different severity and the effect of SJP on liver damage and intestinal microbiota.

Design

NAFLD mice models with different severity were induced by high-fat diet (HFD) or choline-deficient, L-amino acid-defined high-fat diet (CDAHFD) feeding and then treated with SJP/normal saline.

Methods

Biochemical blood tests, H&E/Masson/Oil Red O/IHC staining, Western blot, and 16SrDNA sequencing were performed to explore intestinal microbiota alteration in different NAFLD models and the effect of SJP on liver damage and intestinal microbiota.

Results

Intestinal microbiota alteration was detected in all NAFLD mice. SJP induced increased expression of Pparγ and alleviated liver lipid deposition in all NAFLD mice. Microbiome analysis revealed obvious changes in intestinal microbiota composition, while SJP significantly elevated the relative abundance of Roseburia and Akkermansia, which were demonstrated to be beneficial for improving inflammation and intestinal barrier function.

Conclusion

Our results demonstrated that SJP was effective in improving lipid metabolism in NAFLD mice, especially in mice with SFL. The potential mechanism may be associated with the regulation of intestinal microbiota.
Antagonistic activity of two Bacillus strains against Fusarium oxysporum f. sp. capsici (FOC-1) causing Fusarium wilt and growth promotion activity of chili plant
Authors: Iqbal Owais , Syed Rehana Naz , Rajput Nasir Ahmed , Wang Yi , Lodhi Abdul Mubeen , Khan Rizwan , Jibril Sauban Musa , Atiq Muhammad , Li Chengyun
Published: May 2024

Fusarium oxysporum f. sp. capsici (Foc) poses a significant position in agriculture that has a negative impact on chili plant in terms of growth, fruit quality, and yield. Biological control is one of the promising strategies to control this pathogen in crops. Chili is considered as one of the most important crops in the Hyderabad region that is affected by Fusarium wilt disease. The pathogen was isolated from the infected samples in the region and was confirmed by morphological characteristics and PCR with a band of 488 bp. The bacterial strains were isolated from the rhizosphere soil of healthy plant and also confirmed by PCR with a band of 1,542 bp.The molecular characterization of the fungal and bacterial strain has shown 99.9% homology with the retrieved sequences of Fusarium oxysporum f. sp. capsici and Bacillus subtilis from NCBI. The 1-month-old Ghotki chili plants were inoculated with 1×105 cfu spore/ml−1 suspension and confirmed that the FOC-1 is responsible for chili Fusarium wilt disease. Subsequently, among the 33 screened Bacillus strains, only 11 showed antagonistic activity against F. oxysporum. Out of these, only two strains (AM13 and AM21) have shown maximum antagonistic activity against the pathogen by reducing the infection and promoting growth parameters of chili plants under both in vitro and greenhouse conditions. The study suggested that biological control is the most promising control strategy for the management of Fusarium wilt of chili in the field.
Taxonomic identification and antagonistic activity of Streptomyces luomodiensis sp. nov. against phytopathogenic fungi
Authors: Qi Dengfeng , Liu Qiao , Zou Liangping , Zhang Miaoyi , Li Kai , Zhao Yankun , Chen Yufeng , Feng Junting , Zhou Dengbo , Wei Yongzan , Wang Wei , Zhang Lu , Xie Jianghui
Published: May 2024

Banana wilt caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) is a devastating fungal disease. Biocontrol strategies hold immense potential for inhibiting the spread of Foc TR4. Here, 30 actinobacteria were isolated from soils and screened for their antagonistic activity against Foc TR4. Strain SCA4-21T was selected due to its strongest antagonistic activity against Foc TR4. Strain SCA4-21T also exhibited strong antagonistic activity against the other eight phytopathogenic fungi. The strain was identified as the genus Streptomyces according to its physiological, biochemical, and phenotypic characteristics. The phylogenetic trees of 16S rRNA sequences demonstrated that strain SCA4-21T formed a subclade with S. iranensis HM 35T and/or S. rapamycinicus NRRL B-5491T with low bootstrap values. Considering that 16S rRNAs did not provide sufficient resolution for species-level identification, the whole genome of strain SCA4-21T was sequenced. Multilocus sequence analysis (MLSA) based on five housekeeping gene alleles (atpD, gyrB, recA, rpoB, and trpB) revealed that strain SCA4-21T clustered into S. hygroscopicus subsp. hygroscopicus NBRC 13472T with 100% of bootstrap value. The analysis of the genome-based phylogeny also approved the results. Average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) were 91.26 and 44.30%, respectively, with values below the respective species level threshold of 95 and 70%. Hence, strain SCA 4–21T represented a novel species within the genus Streptomyces, named Streptomyces luomodiensis sp. nov. The type strain is SCA4-21T (=GDMCC4.340T = JCM36555T). By the CAZymes analysis, 348 carbohydrate-active enzymes (CAZymes) were detected, including 15 chitinases and eight β-1,3-glucanases. The fermentation broth of strain SCA4-21T, exhibiting strong antagonistic activity against Foc TR4, demonstrated high activities of chitinase and β-1,3-glucanase, which might be involved in antifungal activity. Our results showed an innovative potential biocontrol agent for managing plant fungal diseases, specifically banana fusarium wilt.
Structure and function of type IV IRES in picornaviruses: a systematic review
Authors: Li Yan , Zhang Lei , Wang Ling , Li Jing , Zhao Yanwei , Liu Fuxiao , Wang Qianqian
Published: May 2024

The Picornaviridae is a family of icosahedral viruses with single-stranded, highly diverse positive-sense RNA genomes. Virions consist of a capsid, without envelope, surrounding a core of RNA genome. A typical genome of picornavirus harbors a well-conserved and highly structured RNA element known as the internal ribosome entry site (IRES), functionally essential for viral replication and protein translation. Based on differences in their structures and mechanisms of action, picornaviral IRESs have been categorized into five types: type I, II, III, IV, and V. Compared with the type IV IRES, the others not only are structurally complicated, but also involve multiple initiation factors for triggering protein translation. The type IV IRES, often referred to as hepatitis C virus (HCV)-like IRES due to its structural resemblance to the HCV IRES, exhibits a simpler and more compact structure than those of the other four. The increasing identification of picornaviruses with the type IV IRES suggests that this IRES type seems to reveal strong retention and adaptation in terms of viral evolution. Here, we systematically reviewed structural features and biological functions of the type IV IRES in picornaviruses. A comprehensive understanding of the roles of type IV IRESs will contribute to elucidating the replication mechanism and pathogenesis of picornaviruses.
Implications of helplessness in depression: diagnosing mild cognitive impairment and analyzing its effects on cognitive decline in older adults
Authors: Lee Boung Chul , Choe Young Min , Suh Guk-Hee , Keum Musung , Kim Shin Gyeom , Kim Hyun Soo , Hwang Jaeuk , Yi Dahyun , Kim Jee Wook
Published: May 2024

Background

This study focuses on how elements of depression correlate with mild cognitive impairment (MCI) in older adults and the diagnostic efficacy of combining these components with the Mini-Mental State Examination (MMSE). The study also investigated the connection between individual depression components and overall cognitive function, as measured by the total score (TS) of the consortium to establish a registry for Alzheimer’s disease (AD) assessment battery.

Methods

The study included 196 nondemented adults aged 65 to 90 years at a university hospital and community. Comprehensive clinical assessments including the 30-item Geriatric Depression Scale (GDS) to measure components of depressive symptoms, TS, and blood nutritional biomarkers.

Results

Our stepwise logistic regression analysis highlighted the ‘helplessness item’ (odds ratio = 4.531, 95% CI = 2.218 to 9.258, p < 0.001) as a significant predictor for MCI diagnosis. Further, models incorporating ‘helplessness item + MMSE’ demonstrated markedly enhanced accuracy in diagnosing MCI, surpassing the performance of the MMSE used independently. Notably, the group characterized by helplessness showed a significant reduction in TS (B = −5.300, SE = 1.899, β = −0.162, p = 0.006), with this trend being particularly pronounced in individuals exhibiting lower levels of physical activity. Interestingly, this correlation did not manifest in participants with higher physical activity levels.

Conclusion

Our findings suggest that helplessness is highly effective in diagnosing MCI and is linked to a decrease in cognitive function. Therefore, when addressing MCI and AD-related cognitive decline, clinicians should consider helplessness.
Shaping the olfactory map: cell type-specific activity patterns guide circuit formation
Authors: Nakashima Ai , Takeuchi Haruki
Published: May 2024

The brain constructs spatially organized sensory maps to represent sensory information. The formation of sensory maps has traditionally been thought to depend on synchronous neuronal activity. However, recent evidence from the olfactory system suggests that cell type-specific temporal patterns of spontaneous activity play an instructive role in shaping the olfactory glomerular map. These findings challenge traditional views and highlight the importance of investigating the spatiotemporal dynamics of neural activity to understand the development of complex neural circuits. This review discusses the implications of new findings in the olfactory system and outlines future research directions.
The potassium puzzle: exploring the intriguing connection to albuminuria
Authors: Yuan Weihua , Wang Tiancheng , Yue Wei
Published: May 2024

Background

Studies have revealed a relationship between dietary potassium intake and albuminuria, despite the fact that the human body needs a lot of potassium. Our study concentrated on the link between dietary potassium intake and albuminuria.

Methods

This study used subgroup analysis and weighted multivariate regression analysis. Data from the National Health and Nutrition Examination Survey (NHANES) were examined to determine the urinary albumin-to-creatinine ratio (ACR) and participant age (20 years or older). ACR >30 mg/g was the threshold for albuminuria.

Results

7,564 individuals in all were included in the study. The link between the two was significant in both our original model (OR = 0.99; 95% CI, 0.98–0.99, p < 0.0001) and the minimum adjusted model (OR = 0.99; 95% CI, 0.98–0.99, p < 0.0001). A fully adjusted model did not change the significance of the negative correlation between potassium consumption and albuminuria (OR = 0.99; 95% CI, 0.98–1.00, p = 0.0005), indicating that each unit increase in potassium intake was related with a 1% decrease in the chance of developing albuminuria. The negative correlation between potassium intake and albuminuria was not significantly influenced by sex, age, BMI, hypertension, diabetes, or smoking, according to interaction tests (p for interaction >0.05).

Conclusion

Reduced risk of albuminuria was linked to higher dietary potassium intake. The particular mechanism linking the two still has to be explained by several inventive and prospective studies.
Comparison of the safety profiles for pirfenidone and nintedanib: a disproportionality analysis of the US food and drug administration adverse event reporting system
Authors: Sun Xiangyu , Wang Huaguang , Zhan Xi , Yan Yuanyuan , Chen Kun , An Zhuoling , Zhou Hong
Published: May 2024

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown etiology. Pirfenidone (PFD) and nintedanib (NDN) were both conditionally recommended in the clinical practice guideline published in 2015. Safety and tolerability are related to the risk of treatment discontinuation. Therefore, this study evaluated and compared the adverse events (AEs) of PFD and NDN in a large real-world population by analyzing data from the FDA Adverse Event Reporting System (FAERS) to provide a reference for their rational and safe use.

Methods

The AEs of PFD and NDN were extracted from the FAERS database. The pharmacovigilance online analysis tool OpenVigil 2.1 was used to retrieve data from the FAERS database from the first quarter of 2012 to the second quarter of 2022. The reporting odds ratio (ROR) and proportional reporting ratio were used to detect the risk signals.

Results

The database included 26,728 and 11,720 reports for PFD and NDN, respectively. The most frequent AEs of PFD and NDN were gastrointestinal disorders. The RORs for these drugs were 5.874 and 5.899, respectively. “Cardiac disorders” was the most statistically significant system order class for NDN with an ROR of 9.382 (95% confidence interval = 8.308–10.594). Furthermore, the numbers of designated medical events of PFD and NDN were 552 and 656, respectively. Notably, liver injury was reported more frequently for NDN (11.096%) than for PFD (6.076%).

Conclusion

This study revealed differences in the reporting of AEs between PFD and NDN. The findings provide reference for physicians in clinical practice. Attention should be paid to the risks of cardiac disorders and liver injury associated with NDN.
Advancements and prospects of novel biologicals for myasthenia gravis: toward personalized treatment based on autoantibody specificities
Authors: Ma Chi , Liu Dan , Wang Benqiao , Yang Yingying , Zhu Ruixia
Published: May 2024

Myasthenia gravis (MG) is an antibody-mediated autoimmune disease with a prevalence of 150–250 cases per million individuals. Autoantibodies include long-lived antibodies against the acetylcholine receptor (AChR), mainly of the IgG1 subclass, and IgG4, produced almost exclusively by short-lived plasmablasts, which are prevalent in muscle-specific tyrosine kinase (MuSK) myasthenia gravis. Numerous investigations have demonstrated that MG patients receiving conventional medication today still do not possess satisfactory symptom control, indicating a substantial disease burden. Subsequently, based on the type of the autoantibody and the pathogenesis, we synthesized the published material to date and reached a conclusion regarding the literature related to personalized targeted therapy for MG. Novel agents for AChR MG have shown their efficacy in clinical research, such as complement inhibitors, FcRn receptor antagonists, and B-cell activating factor (BAFF) inhibitors. Rituximab, a representative drug of anti-CD20 therapy, has demonstrated benefits in treatment of MuSK MG patients. Due to the existence of low-affinity antibodies or unidentified antibodies that are inaccessible by existing methods, the treatment for seronegative MG remains complicated; thus, special testing and therapy considerations are necessary. It may be advantageous to initiate the application of novel biologicals at an early stage of the disease. Currently, therapies can also be combined and individualized according to different types of antibodies. With such a wide range of drugs, how to tailor treatment strategies to patients with various conditions and find the most suitable solution for each MG profile are our necessary and urgent aims.
Functionalized nanoparticles to deliver nucleic acids to the brain for the treatment of Alzheimer’s disease
Authors: Muolokwu Chinenye Edith , Chaulagain Bivek , Gothwal Avinash , Mahanta Arun Kumar , Tagoe Benjamin , Lamsal Babita , Singh Jagdish
Published: May 2024

Brain-targeted gene delivery across the blood-brain barrier (BBB) is a significant challenge in the 21st century for the healthcare sector, particularly in developing an effective treatment strategy against Alzheimer’s disease (AD). The Internal architecture of the brain capillary endothelium restricts bio-actives entry into the brain. Additionally, therapy with nucleic acids faces challenges like vulnerability to degradation by nucleases and potential immune responses. Functionalized nanocarrier-based gene delivery approaches have resulted in safe and effective platforms. These nanoparticles (NPs) have demonstrated efficacy in protecting nucleic acids from degradation, enhancing transport across the BBB, increasing bioavailability, prolonging circulation time, and regulating gene expression of key proteins involved in AD pathology. We provided a detailed review of several nanocarriers and targeting ligands such as cell-penetrating peptides (CPPs), endogenous proteins, and antibodies. The utilization of functionalized NPs extends beyond a singular system, serving as a versatile platform for customization in related neurodegenerative diseases. Only a few numbers of bioactive regimens can go through the BBB. Thus, exploring functionalized NPs for brain-targeted gene delivery is of utmost necessity. Currently, genes are considered high therapeutic potential molecules for altering any disease-causing gene. Through surface modification, nanoparticulate systems can be tailored to address various diseases by replacing the target-specific molecule on their surface. This review article presents several nanoparticulate delivery systems, such as lipid NPs, polymeric micelles, exosomes, and polymeric NPs, for nucleic acids delivery to the brain and the functionalization strategies explored in AD research.
Retinal vascular changes and arterial stiffness during 8-month isolation and confinement: the SIRIUS-21 space analog mission
Authors: Elmoselhi Adel B. , Shankhwar Vishwajeet , Qaisar Rizwan , Hamoudi Rifat , Brix Bianca , Salon Adam , Goswami Nandu
Published: May 2024

Introduction

Isolation and confinement are significant stressors during space travel that can impact crewmembers’ physical and mental health. Space travel has been shown to accelerate vascular aging and increase the risk of cardiovascular and cerebrovascular disorders. However, the effect of prolonged isolation and confinement on microvascular function has not yet been thoroughly investigated.

Methods

Retinal vascular imaging was conducted on four crewmembers during- and post-8-month SIRIUS-21 space analog mission. Central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriovenous ratio (AVR) were measured. Pulse wave velocity (PWV), an indicator of arterial stiffness, was also measured.

Results

Data from 4 participants was analyzed. These participants had a mean age of 34.75 ± 5.44 years, height of 170.00 ± 2.00 cm, weight of 74.50 ± 12.53 kg, and average BMI of 25.47 ± 3.94 kg/m2. During- and post-isolation, average CRVE showed an upward trend (Pearson’s r 0.784, R-square 0.62), suggesting a dilation of retinal venules, while AVR showed a downward trend (Pearson’s r −0.238, R-square 0.057), which is suggestive of a higher risk of cardiovascular and cerebrovascular dysfunctions. But neither of these trends were statistically significant. Additionally, the average PWV showed an upward trend during- and after-isolation across all crew members.

Conclusion

Isolation and confinement appear to contribute towards retinal vascular damage and arterial stiffness. This cautiously suggests an increased risk of cardiovascular and cerebrovascular disorders due to the contribution of the isolation in space flight. Further studies are needed to confirm and expand on these results as we prepare for future manned missions to the Moon and Mars.
Not only phosphorus: dauciform roots can also influence aboveground biomass through root morphological traits and metal cation concentrations
Authors: Huang Yulin , Fan Rong , Wang Xiaoqi , Jiang Songlin , Liu Wanting , Ji Wenli , Li Weizhong
Published: May 2024

Background

Phosphorus in the soil is mostly too insoluble for plants to utilize, resulting in inhibited aboveground biomass, while Carex can maintain their aboveground biomass through the presence of dauciform roots. However, dauciform roots lead to both morphological and physiological changes in the root system, making their primary mechanism unclear.

Methods

A greenhouse experiment was conducted on three Carex species, in which Al-P, Ca-P, Fe-P, and K-P were employed as sole phosphorus sources. The plants were harvested and assessed after 30, 60 and 90 days.

Results

(1) The density of dauciform roots was positively correlated with root length and specific root length, positively influencing aboveground biomass at all three stages. (2) The aboveground phosphorus concentration showed a negative correlation with both dauciform root density and aboveground biomass in the first two stages, which became positive in the third stage. (3) Aboveground biomass correlated negatively with the aboveground Al concentration, and positively with Ca and Fe concentration (except Al-P). (4) Root morphological traits emerged as critical factors in dauciform roots’ promotion of aboveground biomass accumulation.

Conclusion

Despite the difference among insoluble phosphorus, dauciform roots have a contributing effect on aboveground growth status over time, mainly by regulating root morphological traits. This study contributes to our understanding of short-term variation in dauciform roots and their regulatory mechanisms that enhance Carex aboveground biomass under low available phosphorus conditions.
Transcriptome analysis of Phytophthora cactorum infecting strawberry identified RXLR effectors that induce cell death when transiently expressed in Nicotiana benthamiana
Authors: Ghimire Bikal , Gogoi Anupam , Poudel Mandeep , Stensvand Arne , Brurberg May Bente
Published: May 2024

Phytophthora cactorum is a plant pathogenic oomycete that causes crown rot in strawberry leading to significant economic losses every year. To invade the host, P. cactorum secretes an arsenal of effectors that can manipulate host physiology and impair its defense system promoting infection. A transcriptome analysis was conducted on a susceptible wild strawberry genotype (Fragaria vesca) 48 hours post inoculation with P. cactorum to identify effectors expressed during the early infection stage. The analysis revealed 4,668 P. cactorum genes expressed during infection of F. vesca. A total of 539 secreted proteins encoded by transcripts were identified, including 120 carbohydrate-active enzymes, 40 RXLRs, 23 proteolytic enzymes, nine elicitins, seven cysteine rich proteins, seven necrosis inducing proteins and 216 hypothetical proteins with unknown function. Twenty of the 40 RXLR effector candidates were transiently expressed in Nicotiana benthamiana using agroinfiltration and five previously unreported RXLR effector genes (Pc741, Pc8318, Pc10890, Pc20813, and Pc22290) triggered cell death when transiently expressed. The identified cell death inducing RXLR effectors showed 31–66% identity to known RXLR effectors in different Phytophthora species having roles in pathogenicity including both activation and suppression of defense response in the host. Furthermore, homology analysis revealed that these cell death inducing RXLR effectors were highly conserved (82 - 100% identity) across 23 different strains of P. cactorum originating from apple or strawberry.
Inequivalent and uncorrelated response priming in motor imagery and execution
Authors: Tien Hsin-Ping , Chang Erik C.
Published: May 2024

Introduction

Theoretical considerations on motor imagery and motor execution have long been dominated by the functional equivalence view. Previous empirical works comparing these two modes of actions, however, have largely relied on subjective judgments on the imagery process, which may be exposed to various biases. The current study aims to re-examine the commonality and distinguishable aspects of motor imagery and execution via a response repetition paradigm. This framework aims to offer an alternative approach devoid of self-reporting, opening the opportunity for less subjective evaluation of the disparities and correlations between motor imagery and motor execution.

Methods

Participants performed manual speeded-choice on prime-probe pairs in each trial under three conditions distinguished by the modes of response on the prime: mere observation (Perceptual), imagining response (Imagery), and actual responses (Execution). Responses to the following probe were all actual execution of button press. While Experiment 1 compared the basic repetition effects in the three prime conditions, Experiment 2 extended the prime duration to enhance the quality of MI and monitored electromyography (EMG) for excluding prime imagery with muscle activities to enhance specificity of the underlying mechanism.

Results

In Experiment 1, there was no significant repetition effect after mere observation. However, significant repetition effects were observed in both imagery and execution conditions, respectively, which were also significantly correlated. In Experiment 2, trials with excessive EMG activities were excluded before further statistical analysis. A consistent repetition effect pattern in both Imagery and Execution but not the Perception condition. Now the correlation between Imagery and Execution conditions were not significant.

Conclusion

Findings from the current study provide a novel application of a classical paradigm, aiming to minimize the subjectivity inherent in imagery assessments while examining the relationship between motor imagery and motor execution. By highlighting differences and the absence of correlation in repetition effects, the study challenges the functional equivalence hypothesis of imagery and execution. Motor representations of imagery and execution, when measured without subjective judgments, appear to be more distinguishable than traditionally thought. Future studies may examine the neural underpinnings of the response repetition paradigm to further elucidating the common and separable aspects of these two modes of action.
Disembedding and re-embedding: the online interaction mechanisms of divorced youth in China
Authors: Wang Junjie , Guo Jialiang
Published: May 2024

Introduction

In recent years, China’s divorce rates have remained high, especially in metropolitan areas such as Beijing and Shanghai, where rates reach up to 40%. Additionally, there has been a notable shift towards younger demographics in divorce cases. In a society that highly values marital harmony, divorce is often seen as a cultural transgression. Anthony Giddens’ theory of disembedding and re-embedding provides a useful framework for understanding these changes. This study addresses a gap in literature by focusing on the online social interactions of divorced Chinese youth, exploring their use of dating apps for emotional support and social reconnections.

Methods

This qualitative study employed semi-structured interviews with 19 divorced young adults in China who engaged with dating apps such as Momo, Tantan, and Soul. Participants were recruited via Douban and Xiaohongshu. The interviews, conducted through WeChat voice calls and Tencent Meetings, lasted 45-70 minutes each. Data was analyzed using Nvivo12 to understand the disembedding and re-embedding processes in their online interactions, exploring themes such as motivations, self-presentation, and the transition from online to offline engagements.

Results and discussion

The findings reveal that these individuals face societal challenges, biases, and the residual effects of past marriages, leading them to seek refuge in online environments to avoid stigmatization. In digital spaces, they cautiously engage, revealing a lack of confidence through selective self-disclosure. Their goals range from forming same-sex and opposite-sex friendships to seeking new romantic relationships, indicating a nuanced approach to remarriage and challenging stereotypes of dating app users. Re-engaging online, they discover social support and a sense of community, which aids in regaining confidence post-divorce, underscoring the complex interplay between societal influences and individual adaptation strategies in the digital age. The study highlights the unique challenges faced by this demographic, including maintaining anonymity and dealing with societal prejudices. Future research should consider a broader age range and gender differences to provide a more comprehensive understanding of the online behaviors and experiences of divorced individuals.
Knowledge and awareness of the Saudi general public toward epistaxis: a cross-sectional study
Authors: Assiri Abdullah M.
Published: May 2024

Background

Epistaxis is one of the most common ear, nose, and throat (ENT) emergencies that present to the emergency or primary care centers.

Study aim

This study aimed to assess the knowledge of the Saudi general public toward epistaxis.

Methods

This study adopted a cross-sectional analytical study design. The questionnaire link was distributed using social media channels. The participants were adult Saudi nationals that live in Saudi Arabia. The data was collected using a self-administered questionnaire that assessed knowledge related to epistaxis. The knowledge score was calculated using the 10 knowledge evaluation questions. Each correct response was assigned a value of “one.” The scores ranged from “zero” to “ten,” with higher scores signifying greater knowledge. A percentage score was computed, and the participants’ knowledge was classified as poor (% score: ≤50%), moderate (% score: 51 to 70%), and good (% score: 71 to 100%). Statistical Package for Social Sciences (SPSS) version 26 was used for statistical analysis.

Results

The study included 452 participants of whom 70.1% were females. Married individuals comprised 60.8% of the sample. The prevalence of self-reported epistaxis was 43.6% in the last 6 months. Among the participants, 42.9%, had “Poor” knowledge score, followed by 39.6% who had “moderate” score, and 17.5% had “Good” score. These results show that most participants had poor to moderate knowledge, with a minority demonstrating a good level of knowledge. All demographic variables have significantly influenced the adequacy of knowledge about epistaxis. Furthermore, participants who believed that the general public has insufficient knowledge on epistaxis had a significantly lower knowledge score (p = 0.001).

Conclusion

The present study found a non-satisfactory, low-to-moderate knowledge level of the Saudi general public toward epistaxis. We propose emphasizing public knowledge and education about first aid for epistaxis because proper first aid can minimize significant complications when done properly.
Influencing factors of home hospice care needs of the older adults with chronic diseases at the end of life in China: a cross-sectional study
Authors: Wang Lei , Li Yaru , Zhao Rui , Li Jiangxu , Gong Xiangru , Li Hongyu , Chi Yuan
Published: May 2024

Introduction

Chronic diseases are becoming a serious threat to the physical and mental health of older people in China as their aging process picks up speed. Home hospice care addresses diverse needs and enhances the quality of life for older adult individuals nearing the end of life. To ensure the well-being of chronically ill older adults at the end of life, it is vital to explore and assess the multidimensional hospice needs of terminally ill older individuals in their homes. The aim of this study was to investigate the current situation of home hospice care needs of Chinese older adults with chronic diseases at the end of life, and to analyze the influencing factors (sociodemographic and disease-related factors).

Methods

In this cross-sectional study, 247 older adult people with chronic diseases at the end of life were selected from the communities of 4 community health service centers in Jinzhou City, Liaoning Province from June to October 2023 by random sampling method. A general information questionnaire and the home hospice care needs questionnaire developed by our research group were used to investigate. Independent samples t-test or one-way ANOVA was used to compare the differences in the scores of different characteristics, and the factors with significant differences were selected for multivariate linear regression analysis to determine the final influencing factors.

Results

The total score of home hospice needs of the dying older adult was 115.70 ± 12, with the mean scores for each dimension in descending order being Information Needs (3.96 ± 0.61), Social Support Needs (3.96 ± 0.44), Spiritual Needs (3.92 ± 0.43), Physical Needs (3.60 ± 0.59), Psychological Needs (3.37 ± 0.65). Status of residence, duration of illness (year), the type of disease, and self-care ability were influential factors in the total score of home hospice needs.

Discussion

The need for hospice care for the terminally ill older adult is high, and healthcare professionals should implement services according to the influencing factors of need to meet their multidimensional needs and improve their quality of life.
Existence of cholera outbreak, challenges, and way forward on public health interventions to control cholera outbreak in Guraghe Zones, southern Ethiopia, 2023
Authors: Berhe Tamirat Melis , Fikadu Yohannes , Sahle Tadesse , Hailegebireal Aklilu Habte , Eanga Shamil , Ketema Temesgen , Wolde Shimelis Getu
Published: May 2024

Introduction

In Ethiopia, despite major improvements seen in health service delivery system, the country continues to be significantly affected by cholera outbreaks. Cholera remains a significant public health problem among the vulnerable populations living in many resource-limited settings with poor access to safe and clean water and hygiene practices. Recurring cholera outbreaks are an indication of deprived water and sanitation conditions as well as weak health systems, contributing to the transmission and spread of the cholera infection.

Objective

To assess the cholera outbreak, its challenges, and the way forward on public health interventions to solve the knowledge and health service delivery gaps related to cholera control in Guraghe Zone, Ethiopia, 2023.

Methods

Active surveillance of the cholera outbreak was conducted in all kebeles and town administrative of Guraghe zone from 7/8/2023 to 30/10/2023. A total of 224 cholera cases were detected during the active surveillance method. Data obtained from Guraghe zone offices were exported to SPSS version 25 for additional analysis. The case fatality rate, incidence of the cases, and other descriptive variables were presented and described using figures and tables.

Result

A total of 224 cholera cases were detected through an active surveillance system. In this study, the case fatality rate of cholera outbreak was 2.6%. To tackle the cholera outbreak, the Guraghe zone health office collaborated with other stakeholders to prepare four cholera treatment centers. The absence of OCV, inaccessible safe water, low latrine coverage, inappropriate utilization of latrines, and absence of cholera laboratory rapid diagnostics test in Guraghe Zone are barriers to tackling the outbreak.

Conclusion

Ethiopia National Cholera Plan targeted eradicating cholera by 2030, 222 cholera outbreak occurred in Guraghe Zone, Ethiopia. To minimize and control cholera mortality rate oral cholera vaccinations should be employed in all areas of the region. Sustainable WASH measures should be guaranteed for the use of safe water and good hygiene practices. Early diagnosis and treatment should be initiated appropriately for those who are infected.