bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive analysis of cellular senescence-related genes in the prognosis, tumor microenvironment, and immunotherapy/chemotherapy of clear cell renal cell carcinoma
Authors: Lu Caibao , Wang Yiqin , Nie Ling , Chen Liping , Li Moqi , Qing Huimin , Li Sisi , Wu Shuang , Wang Zhe
Published: September 2022

Background

The transcriptome public database and advances in biological discoveries contributed to significant progresses in identifying the drivers of cancer progression. Cellular senescence (CS) is considered as a leading factor resulting in cancer development. The purpose of this study was to explore the significance of CS-related genes in the molecular classification and survival outcome of clear cell renal cell carcinoma (ccRCC).

Methods

CS-related genes were obtained from the CellAge database, and patients from TCGA-KIRC dataset and ICGC dataset were clustered by ConsesusClusterPlus. The characteristics of overall survival (OS), genomic variation, and tumor microenvironment (TME) of each cluster were analyzed. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was conducted to develop a CS-related risk model to score ccRCC patients and assess the risk scores in predicting patients’ response to immunotherapy and chemotherapy. A nomogram based on the risk model was established to improve the risk stratification of patients.

Results

CcRCC was divided into three molecular subtypes based on CS-related genes. The three molecular phenotypes showed different OS and clinical manifestations, mutation patterns, and TME states. Five genes were obtained from nine differentially expressed CS-related genes in the three molecular subtypes to develop a risk model. Patients with ccRCC were divided into high- and low-risk subgroups. The former showed an unfavorable OS, with a significantly higher genomic variation rate, TME score, and numerous immune checkpoint expressions when compared to the low-risk subgroup. Risk score reflected the response of patients to axitinib, bortezomib, sorafenib, sunitinib, and temsirolimus.

Conclusions

In general, CS-related genes divided ccRCC into three molecular subtypes with distinct OS, mutation patterns, and TME states. The risk model based on the five CS-related genes can predict the prognosis and therapeutic outcome of ccRCC patients, providing a theoretical basis for further study on the molecular mechanism of CS-related ccRCC.
Calcitonin gene-related peptide is a potential autoantigen for CD4 T cells in type 1 diabetes
Authors: Li Wei , Li Ronghui , Wang Yang , Zhang Yan , Tomar Munendra S. , Dai Shaodong
Published: September 2022

The calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide with critical roles in the development of peripheral sensitization and pain. One of the CGRP family peptides, islet amyloid polypeptide (IAPP), is an important autoantigen in type 1 diabetes. Due to the high structural and chemical similarity between CGRP and IAPP, we expected that the CGRP peptide could be recognized by IAPP-specific CD4 T cells. However, there was no cross-reactivity between the CGRP peptide and the diabetogenic IAPP-reactive T cells. A set of CGRP-specific CD4 T cells was isolated from non-obese diabetic (NOD) mice. The T-cell receptor (TCR) variable regions of both α and β chains were highly skewed towards TRAV13 and TRBV13, respectively. The clonal expansion of T cells suggested that the presence of activated T cells responded to CGRP stimulation. None of the CGRP-specific CD4 T cells were able to be activated by the IAPP peptide. This established that CGRP-reactive CD4 T cells are a unique type of autoantigen-specific T cells in NOD mice. Using IAg7-CGRP tetramers, we found that CGRP-specific T cells were present in the pancreas of both prediabetic and diabetic NOD mice. The percentages of CGRP-reactive T cells in the pancreas of NOD mice were correlated to the diabetic progression. We showed that the human CGRP peptide presented by IAg7elicited strong CGRP-specific T-cell responses. These findings suggested that CGRP is a potential autoantigen for CD4 T cells in NOD mice and probably in humans. The CGRP-specific CD4 T cells could be a unique marker for type 1 diabetes. Given the ubiquity of CGRP in nervous systems, it could potentially play an important role in diabetic neuropathy.
Bioinformatics and systems biology approach to identify the pathogenetic link of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Lv Yongbiao , Zhang Tian , Cai Junxiang , Huang Chushuan , Zhan Shaofeng , Liu Jianbo
Published: September 2022

Background

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global crisis. Although many people recover from COVID-19 infection, they are likely to develop persistent symptoms similar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after discharge. Those constellations of symptoms persist for months after infection, called Long COVID, which may lead to considerable financial burden and healthcare challenges. However, the mechanisms underlying Long COVID and ME/CFS remain unclear.

Methods

We collected the genes associated with Long COVID and ME/CFS in databases by restricted screening conditions and clinical sample datasets with limited filters. The common genes for Long COVID and ME/CFS were finally obtained by taking the intersection. We performed several advanced bioinformatics analyses based on common genes, including gene ontology and pathway enrichment analyses, protein–protein interaction (PPI) analysis, transcription factor (TF)–gene interaction network analysis, transcription factor–miRNA co-regulatory network analysis, and candidate drug analysis prediction.

Results

We found nine common genes between Long COVID and ME/CFS and gained a piece of detailed information on their biological functions and signaling pathways through enrichment analysis. Five hub proteins (IL-6, IL-1B, CD8A, TP53, and CXCL8) were collected by the PPI network. The TF–gene and TF–miRNA coregulatory networks were demonstrated by NetworkAnalyst. In the end, 10 potential chemical compounds were predicted.

Conclusion

This study revealed common gene interaction networks of Long COVID and ME/CFS and predicted potential therapeutic drugs for clinical practice. Our findings help to identify the potential biological mechanism between Long COVID and ME/CFS. However, more laboratory and multicenter evidence is required to explore greater mechanistic insight before clinical application in the future.
Peritumoral tertiary lymphoid structure and tumor stroma percentage predict the prognosis of patients with non-metastatic colorectal cancer
Authors: Wang Qianyu , Shen Xiaofei , An Ran , Bai Junchao , Dong Junhua , Cai Huiyun , Zhu Hongyan , Zhong Wentao , Chen Wenliang , Liu Aijun , Du Junfeng
Published: September 2022

Background

Tertiary lymphoid structures (TLSs) are crucial in promoting and maintaining positive anti-tumor immune responses. The tumor stroma has a powerful immunosuppressive function that could exclude tumor-infiltrating lymphocytes from the tumor beds and lead to a “cold” phenotype. TLSs and tumor stroma percentage (TSP) are significantly associated with the prognosis of patients with certain cancers. However, the exact roles of TLSs and TSP and their intrinsic relationship are still largely unknown in colorectal cancer (CRC).

Methods

TLSs and TSP were assessed using hematoxylin-eosin (H&E) and/or immunohistochemistry (IHC) staining from 114 CRC patients in the training set and 60 CRC patients in the external validation set. The correlation between TILs, TLS and clinicopathological characteristics and their prognostic values were assessed. Finally, we plotted a Nomogram including the TLS, TSP and tumor-node-metastasis (TNM) stage to predict the probability of recurrence-free survival (RFS) at 2- and 5-years in non-metastatic colorectal cancer (nmCRC) patients.

Results

Peritumoral TLS (P-TLS), intratumoral TLS (In-TLS) and high TSP (H-TSP, >50%) were present in 99.1%, 26.3% and 41.2% patients, respectively. H-TSP tumor tends to be associated with lower P-TLS density (P =0.0205). The low P-TLS density (< 0.098/mm2) was significantly associated with reduced RFS (HR=6.597 95% CI: 2.882-15.103, P <0.001) and reduced overall survival (OS) (HR=6.628 95% CI: 2.893-15.183, P < 0.001) of nmCRC patients. In-TLS was not of significance in evaluating the clinical outcomes of nmCRC patients. H-TSP was significantly associated with reduced RFS (HR=0.126 95% CI: 0.048-0.333, P <0.001) and reduced OS (HR=0.125 95% CI: 0.047-0.332, P <0.001) of nmCRC patients. The 5-year RFS of the high P-TLS, low-TLS, H-TSP, and L-TSP groups were 89.7%, 47.2%, 53.2%, and 92.5%, respectively. The P-TLS density, TSP and TNM stage were independent prognosis factors of nmCRC patients. The Nomogram, including the P-TLS density, TSP and TNM stage, outperformed the TNM stage.

Conclusions

High P-TLS density and low TSP (L-TSP) were independent and favorable prognostic factors of nmCRC patients, which might provide new directions for targeted therapy in the CRC tumor microenvironment, especially the tumor immune microenvironment.
Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library
Authors: Dormeshkin Dmitri , Shapira Michail , Dubovik Simon , Kavaleuski Anton , Katsin Mikalai , Migas Alexandr , Meleshko Alexander , Semyonov Sergei
Published: September 2022

The COVID−19 pandemic not only resulted in a global crisis, but also accelerated vaccine development and antibody discovery. Herein we report a synthetic humanized VHH library development pipeline for nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) isolation. Trinucleotide-based randomization of CDRs by Kunkel mutagenesis with the subsequent rolling-cycle amplification resulted in more than 1011 diverse phage display library in a manageable for a single person number of electroporation reactions. We identified a number of nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) by screening a novel synthetic humanized antibody library. In order to explore the most robust and fast method for affinity improvement, we performed affinity maturation by CDR1 and CDR2 shuffling and avidity engineering by multivalent trimeric VHH fusion protein construction. As a result, H7-Fc and G12x3-Fc binders were developed with the affinities in nM and pM range respectively. Importantly, these affinities are weakly influenced by most of SARS-CoV-2 VoC mutations and they retain moderate binding to BA.4\5. The plaque reduction neutralization test (PRNT) resulted in IC50 = 100 ng\ml and 9.6 ng\ml for H7-Fc and G12x3-Fc antibodies, respectively, for the emerging Omicron BA.1 variant. Therefore, these VHH could expand the present landscape of SARS-CoV-2 neutralization binders with the therapeutic potential for present and future SARS-CoV-2 variants.
The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung
Authors: Tynecka Marlena , Janucik Adrian , Niemira Magdalena , Zbikowski Arkadiusz , Stocker Nino , Tarasik Agnieszka , Starosz Aleksandra , Grubczak Kamil , Szalkowska Anna , Korotko Urszula , Reszec Joanna , Kwasniewski Miroslaw , Kretowski Adam , Akdis Cezmi , Sokolowska Milena , Moniuszko Marcin , Eljaszewicz Andrzej
Published: September 2022

Mesenchymal stem cells (mesenchymal stromal cells; MSC)-based therapies remain a promising approach to treat degenerative and inflammatory diseases. Their beneficial effects were confirmed in numerous experimental models and clinical trials. However, safety issues concerning MSCs’ stability and their long-term effects limit their implementation in clinical practice, including treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease, and COVID-19. Here, we aimed to investigate the safety of intranasal application of human adipose tissue-derived MSCs in a preclinical experimental mice model and elucidate their effects on the lungs. We assessed short-term (two days) and long-term (nine days) effects of MSCs administration on lung morphology, immune responses, epithelial barrier function, and transcriptomic profiles. We observed an increased frequency of IFNγ- producing T cells and a decrease in occludin and claudin 3 as a long-term effect of MSCs administration. We also found changes in the lung transcriptomic profiles, reflecting redox imbalance and hypoxia signaling pathway. Additionally, we found dysregulation in genes clustered in pattern recognition receptors, macrophage activation, oxidative stress, and phagocytosis. Our results suggest that i.n. MSCs administration to noninflamed healthy lungs induces, in the late stages, low-grade inflammatory responses aiming at the clearance of MSCs graft.
Pyroptosis in development, inflammation and disease
Authors: Pan Yuhong , Cai Wenjun , Huang Juan , Cheng Anchun , Wang Mingshu , Yin Zhongqiong , Jia Renyong
Published: September 2022

In the early 2000s, caspase-1, an important molecule that has been shown to be involved in the regulation of inflammation, cell survival and diseases, was given a new function: regulating a new mode of cell death that was later defined as pyroptosis. Since then, the inflammasome, the inflammatory caspases (caspase-4/5/11) and their substrate gasdermins (gasdermin A, B, C, D, E and DFNB59) has also been reported to be involved in the pyroptotic pathway, and this pathway is closely related to the development of various diseases. In addition, important apoptotic effectors caspase-3/8 and granzymes have also been reported to b involved in the induction of pyroptosis. In our article, we summarize findings that help define the roles of inflammasomes, inflammatory caspases, gasdermins, and other mediators of pyroptosis, and how they determine cell fate and regulate disease progression.
TMBcat: A multi-endpoint p-value criterion on different discrepancy metrics for superiorly inferring tumor mutation burden thresholds
Authors: Wang Yixuan , Lai Xin , Wang Jiayin , Xu Ying , Zhang Xuanping , Zhu Xiaoyan , Liu Yuqian , Shao Yang , Zhang Li , Fang Wenfeng
Published: September 2022

Tumor mutation burden (TMB) is a widely recognized stratification biomarker for predicting the efficacy of immunotherapy; however, the number and universal definition of the categorizing thresholds remain debatable due to the multifaceted nature of efficacy and the imprecision of TMB measurements. We proposed a minimal joint p-value criterion from the perspective of differentiating the comprehensive therapeutic advantages, termed TMBcat, optimized TMB categorization across distinct cancer cohorts and surpassed known benchmarks. The statistical framework applies to multidimensional endpoints and is fault-tolerant to TMB measurement errors. To explore the association between TMB and various immunotherapy outcomes, we performed a retrospective analysis on 78 patients with non-small cell lung cancer and 64 patients with nasopharyngeal carcinomas who underwent anti-PD-(L)1 therapy. The stratification results of TMBcat confirmed that the relationship between TMB and immunotherapy is non-linear, i.e., treatment gains do not inherently increase with higher TMB, and the pattern varies across carcinomas. Thus, multiple TMB classification thresholds could distinguish patient prognosis flexibly. These findings were further validated in an assembled cohort of 943 patients obtained from 11 published studies. In conclusion, our work presents a general criterion and an accessible software package; together, they enable optimal TMB subgrouping. Our study has the potential to yield innovative insights into therapeutic selection and treatment strategies for patients.
Rapid visual detection of Enterocytozoon hepatopenaei by recombinase polymerase amplification combined with lateral flow dipstick
Authors: Pang Jianhu , Zhao Caiyuan , Su Hualong , Liu Zhongcheng , Lu Qiang , He Xinyi , Weng Shaoping , He Jianguo
Published: September 2022

Enterocytozoon hepatopenaei (EHP) is a high-impact pathogen in shrimp farming, causing huge economic losses to the global shrimp farming industry every year. However, current EHP detection methods are primarily based on the development of polymerase chain reaction (PCR) techniques that rely on sophisticated and expensive instruments. Consequently, a rapid, practical, and sensitive protocol for the detection of EHP is necessary. Recombinase polymerase amplification combined with a lateral flow dipstick (LFD-RPA) assay was developed using a pair of primers and nfo-probe targeting the conserved region of the spore wall protein gene. Under optimized reaction conditions, the LFD-RPA assay can detect 10 copies/μL of standard plasmid within 20 min at 40°C. Furthermore, the specificity of the LFD-RPA was also verified with other common pathogens of shrimp. Thirty-nine samples of Litopenaeus vannamei were collected in shrimp farms and detected using LFD-RPA and nested PCR. Thirty-two positive samples were detected by LFD-RPA. Compared with those of nested PCR, the diagnostic sensitivity and specificity of LFD-RPA were 100% and 100%, respectively. These results indicated the great application potential of the newly developed LFD-RPA assay for point-of-care diagnosis, epidemic surveillance, and epidemiological investigation of EHP.
Corneal characteristics in Down syndrome patients with normal and keratoconic cornea
Authors: Hashemi Hassan , Asgari Soheila
Published: September 2022

Purpose

To determine the reference range of corneal indices in Down syndrome patients with normal corneas (DS-N) and to compare it with the corneal indices in Down syndrome patients with keratoconic corneas (DS-KC).

Methods

A study was conducted using the data of 154 eyes of 154 DS-N and 25 eyes of 25 DS-KC patients. Eighteen indices related to thickness, anterior chamber, keratometry, elevation, and aberrations routinely used for KC diagnosis were extracted from the Pentacam.

Results

The mean age of the participants in DS-N and DS-KC groups was 16.73 ± 4.70 and 16.56 ± 4.22 years (P = 0.852). In the DS-N group, 95% CI were 511.65–520.31 for minimum corneal thickness, 2.97–3.07 for anterior chamber depth (ACD), 46.83–47.37 for maximum keratometry (Kmax), 46.13–46.62 for zonal Kmax at 3 mm, 0.35–0.58 for inferior-superior asymmetry (I-S value), 1.56–1.88 for Belin/Ambrósio display-total deviation, 8.65–10.79 for best-fit-sphere posterior elevation at the thinnest point, and 0.18–0.22 for corneal vertical coma. The age-related change in I-S value and corneal spherical aberration (SA) was significant (both P < 0.05). There were significant inter-gender differences in 11 indices; the female DS patients had shallower, steeper, more elevated, and more aberrated corneas (all P < 0.05). There were significant differences in all indices except for ACD (P = 0.372) and corneal SA (P = 0.169) between DS-N and DS-KC groups.

Conclusion

In DS patients aged 10–30 years, the reference ranges of corneal indices are different from the range reported for non-DS subjects and are close to values reported for mild KC non-DS cases. The normal values are different between DS male and female; hence, sex-specific ranges should be considered for diagnosis of corneal abnormality in DS patients.
Highly efficient degradation of cypermethrin by a co-culture of Rhodococcus sp. JQ-L and Comamonas sp. A-3
Authors: He Jian , Zhang Kaiyun , Wang Lin , Du Yingchun , Yang Ying , Yuan Cansheng
Published: September 2022

Cypermethrin is an important synthetic pyrethroid pesticide that widely used to control pests in agriculture. However, extensive use has caused its residue and the metabolite 3-phenoxybenzoic acid (3-PBA) to seriously pollute the environments and agricultural products. In this study, a highly efficient cypermethrin-degrading bacterial consortium was acclimated from long-term pyrethroid-contaminated soil. Two strains, designated JQ-L and A-3, were screened from the consortium, and identified as Rhodococcus sp. and Comamonas sp., respectively. Strain JQ-L transformed 100 mg/L of cypermethrin to 3-PBA within 60 h of incubation; however, 3-PBA could not be further degraded by the strain. Strain A-3 utilized 3-PBA as sole carbon for growth, and completely degraded 100 mg/L of 3-PBA within 15 h of incubation. Co-culture of JQ-L and A-3 completely degraded 100 mg/L of cypermethrin within 24 h of incubation. Furthermore, a complete catabolic pathway of cypermethrin and the metabolite 3-PBA by the co-culture was proposed. This study provided a promising strategy for efficient elimination of cypermethrin residue-contaminated environments and agricultural products.
Recent advances in inhibition of porcine reproductive and respiratory syndrome virus through targeting CD163
Authors: Zhang Xiaoxiao , Guo Chunhe
Published: September 2022

Porcine reproductive and respiratory syndrome virus (PRRSV) has plagued the pig industry for more than 30 years and causes great economic losses. At present different commercial vaccines are available but limited tools. Until now at least six potential host factors are identified as the key receptors for PRRSV infection. Among them, CD163 molecule is the most important and critical in PRRSV life cycle responsible for mediating virus uncoating and genome release. It determines the susceptibility of target cells to the virus. Several PRRSV non-permissive cells (such as PK-15, 3D4/21, and BHK-21) are demonstrated to become completely susceptible to PRRSV infection in the presence of expression of porcine CD163 protein. Therefore, CD163 has become the target for the design of novel antiviral molecules disrupting the interaction between CD163 and viral glycoproteins, or the breeding of gene-modified animals against PRRSV infection. In this review, we comprehensively summarize the recent progress in inhibition of PRRSV replication via targeting CD163 receptor. In addition, whether there are other potential molecules interacting with CD163 in the process of uncoating of virus life cycle is also discussed.
Genomic characterization of a new phage BUCT541 against Klebsiella pneumoniae K1-ST23 and efficacy assessment in mouse and Galleria mellonella larvae
Authors: Pu Mingfang , Li Yahao , Han Pengjun , Lin Wei , Geng Ronghua , Qu Fen , An Xiaoping , Song Lihua , Tong Yigang , Zhang Shuyan , Cai Zhen , Fan Huahao
Published: September 2022

Over the past decades, the spread of multi-drug-resistant Klebsiella pneumoniae (MDR-KP) is becoming a new threat and new effective therapies against this pathogen are needed. Bacteriophage (phage) therapy is considered to be a promising alternative treatment for MDR-KP infections compared with antibacterial drug usage. Here, we reported a new phage BUCT541 which can lyse MDR-KP ST23. The genome of BUCT541 is a double-stranded linear 46,100-bp long DNA molecule with 48% GC content through the Next generation sequencing (NGS) data. A total of 81 open reading frames and no virulence or antimicrobial resistance genes are annotated in the BUCT541 genome. BUCT541 was able to lyse 7 of the 30 tested MDR-KP according to the host range analysis. And the seven sensitive strains belonged to the K. pneumoniae K1-ST23. BUCT541 exhibited high thermal stability (4–70°C) and broad pH tolerance (pH 3-11) in the stability test. The in vivo results showed that BUCT541 (4 × 105 plaque-forming units (PFU)/each) significantly increased the survival rate of K. pneumoniae infected Galleria mellonella from 5.3% to 83.3% within 48 h. Moreover, in the mouse lung infection model, high doses of BUCT541 (2 × 107 PFU/each) cured 100% of BALB/c mice that were infected with K. pneumoniae. After 30 h of treatment with phage BUCT541 of the multiplicity of infection (MOI) = 10, the K. pneumoniae in the lungs of mice was lower than 104 CFU/mL, compared to the control group 109 CFU/mL. Together, these findings indicate that phage BUCT541 holds great promise as an alternative therapy with excellent stability and a wide lysis range for the treatment of MDR-KP ST23 infection.
Association between body weight and distal gut microbes in Hainan black goats at weaning age
Authors: Li Lianbin , Li Kunpeng , Bian Zhengyu , Chen Zeshi , Li Boling , Cui Ke , Wang Fengyang
Published: September 2022

Gut microbiota plays a critical role in the healthy growth and development of young animals. However, there are few studies on the gut microbiota of young Hainan black goats. In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. The results indicated that the HW group exhibited higher community diversity compared with the LW group, based on the Shannon index. The core phyla of the HW and LW groups were both Firmicutes and Bacteroidetes. Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. In addition, genera such as Ruminococcus and Anaerotruncus, which were positively correlated with body weight, were enriched in the HW group; those genera, such as Akkermansia and Christensenellaceae, which were negatively correlated with body weight, were enriched in the LW group. Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth.
Synthetic biology in marine cyanobacteria: Advances and challenges
Authors: Bourgade Barbara , Stensjö Karin
Published: September 2022

The current economic and environmental context requests an accelerating development of sustainable alternatives for the production of various target compounds. Biological processes offer viable solutions and have gained renewed interest in the recent years. For example, photosynthetic chassis organisms are particularly promising for bioprocesses, as they do not require biomass-derived carbon sources and contribute to atmospheric CO2 fixation, therefore supporting climate change mitigation. Marine cyanobacteria are of particular interest for biotechnology applications, thanks to their rich diversity, their robustness to environmental changes, and their metabolic capabilities with potential for therapeutics and chemicals production without requiring freshwater. The additional cyanobacterial properties, such as efficient photosynthesis, are also highly beneficial for biotechnological processes. Due to their capabilities, research efforts have developed several genetic tools for direct metabolic engineering applications. While progress toward a robust genetic toolkit is continuously achieved, further work is still needed to routinely modify these species and unlock their full potential for industrial applications. In contrast to the understudied marine cyanobacteria, genetic engineering and synthetic biology in freshwater cyanobacteria are currently more advanced with a variety of tools already optimized. This mini-review will explore the opportunities provided by marine cyanobacteria for a greener future. A short discussion will cover the advances and challenges regarding genetic engineering and synthetic biology in marine cyanobacteria, followed by a parallel with freshwater cyanobacteria and their current genetic availability to guide the prospect for marine species.
Osteoporosis is associated with elevated baseline cerebrospinal fluid biomarkers and accelerated brain structural atrophy among older people
Authors: Pan Hao , Cao Jiali , Wu Congcong , Huang Furong , Wu Peng , Lang Junzhe , Liu Yangbo
Published: September 2022

Objective

The aim of this study was to examine whether osteoporosis (OP) is associated with Alzheimer’s disease-related cerebrospinal fluid (CSF) biomarkers and brain structures among older people.

Methods

From the Alzheimer’s disease Neuroimaging Initiative database, we grouped participants according to the OP status (OP+/OP−) and compared the Alzheimer’s disease (AD)-related CSF biomarker levels and the regional brain structural volumes between the two groups using multivariable models. These models were adjusted for covariates including age, education, gender, diagnosis of Alzheimer’s disease, and apolipoprotein E4 carrier status.

Results

In the cross-sectional analyses at baseline, OP was related to higher CSF t-tau (total tau) and p-tau181 (tau phosphorylated at threonine-181) but not to CSF amyloid-beta (1–42) or the volumes of entorhinal cortex and hippocampus. In the longitudinal analyses, OP was not associated with the change in the three CSF biomarkers over time but was linked to a faster decline in the size of the entorhinal cortex and hippocampus.

Conclusion

OP was associated with elevated levels of CSF t-tau and p-tau181 at baseline, and accelerated entorhinal cortex and hippocampal atrophies over time among older people.
Cerebellar and basal ganglia motor network predicts trait depression and hyperactivity
Authors: Jackson T. Bryan , Bernard Jessica A.
Published: September 2022

In the human brain, the cerebellum (CB) and basal ganglia (BG) are implicated in cognition-, emotion-, and motor-related cortical processes and are highly interconnected, both to cortical regions via separate, trans-thalamic pathways and to each other via subcortical disynaptic pathways. We previously demonstrated a distinction between cognitive and motor CB-BG networks (CCBN, MCBN, respectively) as it relates to cortical network integration in healthy young adults, suggesting the subcortical networks separately support cortical networks. The CB and BG are also implicated in the pathophysiology of schizophrenia, Parkinson's, and compulsive behavior; thus, integration within subcortical CB-BG networks may be related to transdiagnostic symptomology. Here, we asked whether CCBN or MCBN integration predicted Achenbach Self-Report scores for anxiety, depression, intrusive thoughts, hyperactivity and inactivity, and cognitive performance in a community sample of young adults. We computed global efficiency for each CB-BG network and 7 canonical resting-state networks for all right-handed participants in the Human Connectome Project 1200 release with a complete set of preprocessed resting-state functional MRI data (N = 783). We used multivariate regression to control for substance abuse and age, and permutation testing with exchangeability blocks to control for family relationships. MCBN integration negatively predicted depression and hyperactivity, and positively predicted cortical network integration. CCBN integration predicted cortical network integration (except for the emotional network) and marginally predicted a positive relationship with hyperactivity, indicating a potential dichotomy between cognitive and motor CB-BG networks and hyperactivity. These results highlight the importance of CB-BG interactions as they relate to motivation and symptoms of depression.
Computer vision quantization research on the architectural color of Avenida de Almeida Ribeiro in Macau based on the human eye perspective
Authors: Yan Lina , Li Qian , Zhang Yi , Zhu Chun
Published: September 2022

In this study, a new quantifiable and refined urban street color analysis method was proposed by combining professional color cards and efficient software color recognition, which solved the problems of low efficiency and difficulty in the quantification of urban color research and analysis. The research mainly uses China Building Color Card (CBCC) and Python (use programs for the HSV color segmentation of pictures) and other software to carry out color recognition for a street view. From the aspects of color composition, type, proportion, visual level, and color sequence of the street facade, this article makes a quantitative analysis of the color of Avenida de Almeida Ribeiro in Macao from multiple angles. The method of combining color card colorimetry with computer color recognition, which not only considers the inherent color of the building but also includes the color situation under the influence of the environment, can express the “actual color situation” of the building more completely. This article quantifies, combs, summarizes, and compares architectural color and environmental color completely. This method has good universality and ease of use in practice, and the conclusion of the study can provide a reference for the color planning of Macao, the color selection of urban renewal has reference significance, and provide a new method for the study of urban color.
Opium abuse and stroke in Iran: A systematic review and meta-analysis
Authors: Mardi Parham
Published: September 2022

Introduction

Opium dependence is a significant health concern in low and middle-income countries, leading to a considerable number of deaths annually. Opium has several detrimental effects on its consumers. Data regarding the impact of opium on stroke are controversial. The objective of this study is to evaluate the association between opium dependence and stroke.

Methods

I conducted a systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the association between opium dependence and stroke. Following the extraction of qualitative findings from included studies, a meta-analysis was performed to assess the pooled estimate of odds ratios (ORs).

Results

Eight and four studies were included in qualitative and quantitative synthesis, respectively. Opium dependence increases the hazard of stroke mortality. Also, opium increases the odds of ischemic stroke by 127% (pooled OR = 2.27, 95% CI: 1.47–3.07).

Conclusion

Opium not only merely increases the odds of being diagnosed with ischemic stroke but also leads to a notable increase in the mortality rate following stroke.
Diffusion-weighted imaging hyperintensities during the chronic stage of intracerebral hemorrhage with surgery: A new clinical situation or post-surgery artifact?
Authors: Chen Xiaoyan , Li Ying , Guo Shengli , Han Xun , Liu Ruozhuo , Tian Chenglin , Cui Rongtai , Dong Zhao , Yu Shengyuan
Published: September 2022

Background and objective

Diffusion-weighted imaging (DWI) hyperintensities were occasionally seen at previous hematoma in patients several months after intracerebral hemorrhage with surgery. Whether they are newly occurred clinical situations or post-surgery changes is unknown. This study aims to investigate the prevalence and possible mechanisms for this phenomenon.

Methods

We retrospectively reviewed the MRI database for intracerebral hemorrhage with surgery after 3 months of disease onset in our hospital. We also prospectively performed repeated multimodal MRI scans for two patients at the chronic stage after surgery for intracerebral hemorrhage.

Results

We found that 14 out of 23 patients (60.9%) had DWI hyperintensities at the site of previous hematoma 3 months after intracerebral hemorrhage with surgery. All the DWI lesions were hyperintense on T1- and T2-weighted imaging, most of which appeared long and narrow in shape. The DWI lesions were usually located adjacent to the thin wall of the previous hematoma cavity close to the lateral ventricle. They were more associated with the basal ganglia hemorrhage than with the lobar hemorrhage (P = 0.02) and were more frequently seen for those with intraventricular hemorrhage than without (P = 0.02). Prospectively repeated MRI exams of two patients revealed unchanged DWI hyperintensity during the 18- and 2-month follow-up, respectively.

Conclusion

The DWI lesions at previous hematoma were commonly seen in patients after surgery for intracerebral hemorrhage at the chronic stage which would persist for years. We hypothesized a possible mechanism by which extracellular methemoglobin “islands” are formed with delayed or no absorption by macrophages from adjacent thin residual brain tissue. Unnecessary further examinations and treatment would be avoided by realizing this imaging phenomenon.
Identifying different cognitive phenotypes and their relationship with disability in neuromyelitis optica spectrum disorder
Authors: Kong Lingyao , Lang Yanlin , Wang Xiaofei , Wang Jiancheng , Chen Hongxi , Shi Ziyan , Zhou Hongyu
Published: September 2022

Background

The existence, frequency, and features of cognitive impairment (CI) in patients with neuromyelitis optica spectrum disorder (NMOSD) are still debated. A precise classification and characterization of cognitive phenotypes in patients with NMOSD are lacking.

Methods

A total of 66 patients with NMOSD and 22 healthy controls (HCs) underwent a neuropsychological assessment. Latent profile analysis (LPA) on cognitive test z scores was used to identify cognitive phenotypes, and ANOVA was used to define the clinical features of each phenotype. Univariate and multivariate analyses were used to explore the predictors of severe CI, and a corresponding nomogram was created to visualize the predictive model.

Results

LPA results suggested four distinct meaningful cognitive phenotypes in NMOSD: preserved cognition (n = 20, 30.3%), mild-attention (n = 21, 31.8%), mild-multidomain (n = 18, 27.3%), and severe-multidomain (n = 7, 10.6%). Patients with the last three phenotypes were perceived to have CI, which accounts for 67.6% of patients with NMOSD. Patients with NMOSD and worse cognitive function were older (p < 0.001) and had lower educational levels (p < 0.001), later clinical onset (p = 0.01), worse Expanded Disability Status Scale scores (p = 0.001), and poorer lower-limb motor function (Timed 25-Foot Walk, p = 0.029; 12-item Multiple Sclerosis Walking Scale [MSWS-12], p < 0.001). Deterioration of Nine-Hole Peg Test (odds ratio, OR: 1.115 [1, 1.243], p = 0.05) and MSWS-12 (OR: 1.069 [1.003, 1.139], p = 0.04) were the independent risk factors for severe cognitive dysfunction. Finally, a nomogram was built based on the entire cohort and the above factors to serve as a useful tool for clinicians to evaluate the risk of severe cognitive dysfunction.

Conclusions

We introduced a classification scheme for CI and highlighted that the deterioration of upper- and lower-limb motor disability potentially predicts cognitive phenotypes in NMOSD.
Intracranial pressure, lateral sinus patency, and jugular ultrasound hemodynamics in patients with venous pulsatile tinnitus
Authors: Gao Xiuli , Hsieh Yue-Lin , Wang Shenjiang , Shi Suming , Wang Wuqing
Published: September 2022

The clinical and hemodynamic characteristics of venous pulsatile tinnitus (PT) patients with normal or elevated cerebrospinal fluid pressure (CSFP) have not been clearly differentiated. This study aimed to explore CSFP among patients with PT as the solitary symptom, as well as quantitatively and qualitatively assess the role of the degree of transverse sinus (TS) stenosis and jugular hemodynamics in venous PT patients. A total of 50 subjects with venous PT with or without sigmoid sinus wall anomalies (SSWAs) were enrolled in this study. In addition to radiologic assessments for TS stenosis and invagination of arachnoid granulation (AG) in TS, CSFP and jugular hemodynamics were measured via cerebrospinal fluid (CSF) manometry and Doppler ultrasound. Apart from group comparisons and correlation analyses, multivariate linear regression, and receiver operating characteristic (ROC) models were used to identify the sensitivity and specificity of the index of transverse sinus stenosis (ITSS) and hemodynamic variables with inferential significance. The mean CSFP of all cases was 199.5 ± 52.7 mmH2O, with no statistical difference in CSFP between the diverticulum and dehiscence groups. Multivariate linear regression analysis demonstrated that CSFP was linearly correlated with ITSS and pulsatility index (PI). ROC analysis showed that the area under the ROC curve of PI was 0.693 at 200 mmH2O threshold, and the best PI cut-off value was 0.467, with a sensitivity of 65.7% and specificity of 81.8%. For 250 mmH2O threshold, the area under the ROC curve of PI was 0.718, and the best PI cut-off value was 0.467 with a sensitivity of 68.4% and specificity of 75.0%. Additionally, the area under the ROC curve of ITSS was 0.757, and the best ITSS cutoff value was 8.5 (p = 0.002, 95% CI = 0.616–0.898) with a sensitivity of 72.4% and specificity of 75.0% at 200 mmH2O threshold. In conclusion, patients with venous PT as the only presenting symptom should be suspected of having borderline or increased CSFP when they present with high ITSS, BMI and low PI. Further, AG in TS without encephalocele and empty sellae are not limiting findings for differentiating the level of CSFP in patients with venous PT.
Case report: A novel de novo variant of SCN8A in a child with benign convulsions with mild gastroenteritis
Authors: Chen Hui , Li Xiaoyan , Wu Huaping , Sun Xiaolan , Che Yuanyuan , Zha Jian , Wang Ruiyan , Yu Xiongying , Chen Yong , Zhong Jianmin
Published: September 2022

Benign convulsions with mild gastroenteritis (CwG) is characterized by afebrile convulsions accompanied by mild gastroenteritis, and it can be considered after central nervous system infection, hypoglycemia, electrolyte disturbance, and moderate and severe dehydration are excluded. Previous studies have suggested that genetics may be involved in CWG. Herein, we reported a novel de novo variant of SCN8A in a child with CwG. This is the first report that SCN8A may be associated with CwG. Our report may provides evidence for the genetic etiology of CwG and expands the phenotypic and genetic spectrum of SCN8A-related disorders, which previously included severe developmental and epileptic encephalopathy (DEE) phenotype, benign epilepsy phenotype, spectrum of intermediate epilepsies, and patients with cognitive and/or behavioral disturbances without epilepsy. Phenotype of CwG has a good prognosis, and it does not require long-term antiepileptic therapy. Overtreatment should be avoided clinically. However, the conclusion needs to be further defined by long-term follow-up and similar clinical reports. In spite of this, our clinical observation provides possible evidence for future studies on the relationship between SCN8A and CwG.
Speed up discharge planning at the acute stroke unit: A development and external validation study for the early prediction of discharge home
Authors: Veerbeek Janne Marieke , Ottiger Beatrice , Cazzoli Dario , Vanbellingen Tim , Nyffeler Thomas
Published: September 2022

Background

To reduce healthcare costs, it has become increasingly important to shorten the length of stay in acute stroke units. The goal of this study was to develop and externally validate a decision tree model applicable < 48 h poststroke for discharge home from an acute stroke unit with a short length of stay, and to assess the inappropriate home discharge rate.

Methods

A prospective study including two samples of stroke patients admitted to an acute stroke unit. The outcome was discharge home (yes/no). A classification and regression tree analysis was performed in Sample 1. The model's performance was tested in Sample 2.

Results

In total, 953 patients were included. The final decision tree included the patients' activities of daily living (ADL) performance <48 h poststroke, including motor function, cognition, and communication, and had an area under the curve (AUC) of 0.84 (95% confidence interval 0.76, 0.91). External validation resulted in an AUC of 0.74 (95% confidence interval 0.72, 0.77). None of the patients discharged home were re-admitted < 2 months after discharge to a hospital or admitted to a rehabilitation center for symptoms that had needed inpatient neurorehabilitation.

Conclusions

The developed decision tree shows acceptable external validity in predicting discharge home in a heterogeneous sample of stroke patients, only based on the patient's actual ADL performance <48 h poststroke. Importantly, discharge was safe, i.e., no re-hospitalization was registered. The tree's application to speed up discharge planning should now be further evaluated.
Case report: SGLT2i, transcutaneous vagus nerve stimulation, and their effects on intrarenal venous flow pattern in HFpEF
Authors: Nagai Michiaki , Dote Keigo , Kato Masaya , Sasaki Shota , Oda Noboru , Förster Carola Y.
Published: September 2022

Renal congestion in heart failure (HF) is a predictor of the prognosis of cardiovascular disease. The effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and vagus nerve stimulation (VNS) on renal congestion has not been reported in HF. A 77-year-old man with HF with preserved ejection fraction (HFpEF) was referred to our hospital because of poor response to loop diuretics. Echocardiography showed severe tricuspid regurgitation with dilation of the right atrium. Three months after adding SGLT2i, body weight was lost without worsening of renal function. Left and right doppler-derived intrarenal venous flow (IRVF) has been changed from a monophasic to a discontinuous pattern with a systolic interruption. One month later, he discontinued SGLT2i administration at his own discretion. In order to stabilizing autonomic balance, transcutaneous VNS (tVNS) was performed via left ear tragus. One hour after transcutaneous tVNS, ipsilateral IRVF has been dramatically improved from a fusional biphasic to a discontinuous pattern with a systolic interruption. SGLT2i and tVNS may be associated with renal decongestion in HFpEF.
The balbyter ant Camponotus fulvopilosus combines several navigational strategies to support homing when foraging in the close vicinity of its nest
Authors: Yilmaz Ayse , Gagnon Yakir , Byrne Marcus J. , Foster James J. , Baird Emily , Dacke Marie
Published: September 2022

Many insects rely on path integration to define direct routes back to their nests. When shuttling hundreds of meters back and forth between a profitable foraging site and a nest, navigational errors accumulate unavoidably in this compass- and odometer-based system. In familiar terrain, terrestrial landmarks can be used to compensate for these errors and safely guide the insect back to its nest with pin-point precision. In this study, we investigated the homing strategies employed by Camponotus fulvopilosus ants when repeatedly foraging no more than 1.25 m away from their nest. Our results reveal that the return journeys of the ants, even when setting out from a feeder from which the ants could easily get home using landmark information alone, are initially guided by path integration. After a short run in the direction given by the home vector, the ants then switched strategies and started to steer according to the landmarks surrounding their nest. We conclude that even when foraging in the close vicinity of its nest, an ant still benefits from its path-integrated vector to direct the start of its return journey.