bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic model constructed by nine inflammation-related genes for diagnosing ischemic stroke and reflecting the condition of immune-related cells
Authors: Ren Peng , Wang Jing-Ya , Chen Hong-Lei , Lin Xiao-Wan , Zhao Yong-Qi , Guo Wen-Zhi , Zeng Zhi-Rui , Li Yun-Feng
Published: December 2022

Background

Ischemic cerebral infarction is the most common type of stroke with high rates of mortality, disability, and recurrence. However, the known diagnostic biomarkers and therapeutic targets for ischemic stroke (IS) are limited. In the current study, we aimed to identify novel inflammation-related biomarkers for IS using machine learning analysis and to explore their relationship with the levels of immune-related cells in whole blood samples.

Methods

Gene expression profiles of healthy controls and patients with IS were download from the Gene Expression Omnibus. Analysis of differentially expressed genes (DEGs) was performed in healthy controls and patients with IS. Single-sample gene set enrichment analysis was performed to calculate inflammation scores, and weighted gene co-expression network analysis was used to analyze genes in significant modules associated with inflammation scores. Key DEGs in significant modules were then analyzed using LASSO regression analysis for constructing a diagnostic model. The effectiveness and specificity of the diagnostic model was verified in healthy controls and patients with IS and with cerebral hemorrhage (CH) using qRT-PCR. The relationship between diagnostic score and the levels of immune-related cells in whole blood were analyzed using Pearson correlations.

Results

A total of 831 DEGs were identified. Both chronic and acute inflammation scores were higher in patients with IS, while 54 DEGs were also clustered in the gene modules associated with chronic and acute inflammation scores. Among them, a total of 9 genes were selected to construct a diagnostic model. Interestingly, RT-qPCR showed that the diagnostic model had better diagnostic value for IS but not for CH. The levels of lymphocytes were lower in blood of patients with IS, while the levels of monocytes and neutrophils were increased. The diagnostic score of the model was negatively associated with the levels of lymphocytes and positively associated with levels of monocytes and neutrophils.

Conclusions

Taken together, the diagnostic model constructed using the inflammation-related genes TNFSF10, ID1, PAQR8, OSR2, PDK4, PEX11B, TNIP1, FFAR2, and JUN exhibited high and specific diagnostic value for IS and reflected the condition of lymphocytes, monocytes, and neutrophils in the blood. The diagnostic model may contribute to the diagnosis of IS.
Comprehensive analysis of the amino acid metabolism-related gene signature for prognosis, tumor immune microenvironment, and candidate drugs in hepatocellular carcinoma
Authors: Li Yue , Mo Huanye , Jia Siying , Wang Jun , Ma Ying , Liu Xin , Tu Kangsheng
Published: December 2022

Introduction

Metabolic rewiring satisfies increased nutritional demands and modulates many oncogenic processes in tumors. Amino acid metabolism is abnormal in many malignancies. Metabolic reprogramming of amino acids not only plays a crucial role in sustaining tumor cell proliferation but also influences the tumor immune microenvironment. Herein, the aim of our study was to elucidate the metabolic signature of amino acids in hepatocellular carcinoma (HCC).

Methods

Transcriptome profiles of HCC were obtained from the TCGA and ICGC databases. Based on the expression of amino acid metabolism-related genes (AAMRGs), we clustered the HCC samples into two molecular subtypes using the non-negative matrix factorization algorithm. Then, we constructed the amino acid metabolism-related gene signature (AAMRGS) by Cox regression and LASSO regression. Afterward, the clinical significance of the AAMRGS was evaluated. Additionally, we comprehensively analyzed the differences in mutational profiles, immune cell infiltration, immune checkpoint expression, and drug sensitivity between different risk subgroups. Furthermore, we examined three key gene expressions in liver cancer cells by quantitative real-time PCR and conducted the CCK8 assay to evaluate the influence of two chemotherapy drugs on different liver cancer cells.

Results

A total of 81 differentially expressed AAMRGs were screened between the two molecular subtypes, and these AAMRGs were involved in regulating amino acid metabolism. The AAMRGS containing GLS, IYD, and NQO1 had a high value for prognosis prediction in HCC patients. Besides this, the two AAMRGS subgroups had different genetic mutation probabilities. More importantly, the immunosuppressive cells were more enriched in the AAMRGS-high group. The expression level of inhibitory immune checkpoints was also higher in patients with high AAMRGS scores. Additionally, the two AAMRGS subgroups showed different susceptibility to chemotherapeutic and targeted drugs. In vitro experiments showed that gemcitabine significantly reduced the proliferative capacity of SNU449 cells, and rapamycin remarkedly inhibited Huh7 proliferation. The five HCC cells displayed different mRNA expression levels of GLS, IYD, and NQO1.

Conclusions

Our study explored the features of amino acid metabolism in HCC and identified the novel AAMRGS to predict the prognosis, immune microenvironment, and drug sensitivity of HCC patients. These findings might help to guide personalized treatment and improve the clinical outcomes of HCC.
A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients – indications for their potential involvement in the development of Long COVID?
Authors: Haunhorst Simon , Bloch Wilhelm , Javelle Florian , Krüger Karsten , Baumgart Sabine , Drube Sebastian , Lemhöfer Christina , Reuken Philipp , Stallmach Andreas , Müller Michael , Zielinski Christina E. , Pletz Mathias W. , Gabriel Holger H. W. , Puta Christian
Published: December 2022

Background

Recovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms.

Objective

The objective of this scoping review was to summarize the existing literature regarding the frequency and functionality of Tregs in convalescent COVID-19 patients and to explore indications for their potential involvement in the development of Long COVID

Design

A systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE (via Pubmed) and Web of Science.

Results

The literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndrome’s etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population.

Conclusions

Persistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies.
Steroid receptor coactivators – their role in immunity
Authors: Gilad Yosi , Lonard David M. , O’Malley Bert W.
Published: December 2022

Steroid Receptor Coactivators (SRCs) are essential regulators of transcription with a wide range of impact on human physiology and pathology. In immunology, SRCs play multiple roles; they are involved in the regulation of nuclear factor-κB (NF-κB), macrophage (MΦ) activity, lymphoid cells proliferation, development and function, to name just a few. The three SRC family members, SRC-1, SRC-2 and SRC-3, can exert their immunological function either in an independent manner or act in synergy with each other. In certain biological contexts, one SRC family member can compensate for lack of activity of another member, while in other cases one SRC can exert a biological function that competes against the function of another family counterpart. In this review we illustrate the diverse biological functionality of the SRCs with regard to their role in immunity. In the light of recent development of SRC small molecule inhibitors and stimulators, we discuss their potential relevance as modulators of the immunological activity of the SRCs for therapeutic purposes.
Thrombotic microangiopathy mediates poor prognosis among lupus nephritis via complement lectin and alternative pathway activation
Authors: Zhang Binshan , Xing Guolan
Published: December 2022

Objective

The pathogenesis of thrombotic microangiopathy (TMA) in lupus nephritis (LN) remains complicated. This study aimed to detect the deposition of complement lectin pathway (LP) and alternative pathway (AP) components in renal tissues, then evaluate the clinicopathological characteristics and risk factors for renal survival between patients with or without TMA in LN cohorts.

Methods

We included 79 patients with biopsy-proven LN-associated TMA and matched the same number of LN patients without TMA as the control group. The deposition of mannose binding lectin (MBL), MBL-associated serine proteases 1/3 (MASP1/3), complement factor B (CFB), complement factor D (CFD), C4d, and von Willebrand factor (VWF) in renal tissue was assessed by immunohistochemistry and immunofluorescence. Besides, co-localization of C5b-9 and CD34 was detected by confocal microscopy.

Results

In our retrospective cohort, the incidence of acute kidney injury (30% vs. 14%, p = 0.013), acute hemodialysis (35% vs. 5%, p < 0.001), and interstitial fibrosis (43% vs. 13%, p < 0.001) is higher in the TMA, compared with the control group. Despite aggressive steroids pulse, plasma exchange, and immunosuppressive therapy among TMA group, they still had significantly inferior 3-year renal survival rates (68% vs. 89%, p = 0.002) than those in the non-TMA group. COX regression analysis identified that TMA (HR 4.807, 95% CI [2.052, 11.263], p < 0.001) is a risk factor in LN. MBL, MASP1/3, CFB, CFD, C4d, and VWF deposited along the glomerulus among LN, while TMA had stronger staining intensity and deposition. The co-localized expression of CD34 and C5b-9 in the endothelial cells was also observed in the renal tissues.

Conclusions

TMA is an independent risk factor for renal survival in LN patients. Moreover, LP and AP activation are involved in the pathogenesis of LN-associated TMA.
Novel clinical presentation and PAX6 mutation in families with congenital aniridia
Authors: Guo Ruru , Zhang Xiaotian , Liu Aihua , Ji Jian , Liu Wei
Published: December 2022

Purpose

To explore the clinical phenotype and genetic defects of families with congenital aniridia.

Methods

Four Chinese families with aniridia were enrolled in this study. The detailed ocular presentations of the patients were recorded. Whole exome sequencing (BGI MGIEasy V4 chip) was used to detect the gene mutation. Sanger sequencing was performed to validate the potential pathogenic variants, and segregation analysis was performed on all available family members.

Results

By whole exome sequencing and Sanger sequencing, three recurrent mutations (c.112del, p.Arg38Glyfs*16; c.299G > A, p.Trp100* and c.718C > T, p.Arg240*) and one novel mutation (c.278_281del, p.Glu93Alafs*30) of PAX6 were identified. All the mutations were co-segregated with the phenotype in the families. We also observed spontaneous anterior lens capsule rupture in aniridia for the first time.

Conclusion

We report spontaneous anterior lens capsule rupture as a novel phenotype of aniridia and three recurrent mutations and one novel mutation of PAX6 in families with aniridia. Our results expanded the phenotype and genotype spectra of aniridia and can help us better understand the disease.
Current developments in the diagnosis and treatment of giant cell arteritis
Authors: Szekeres Denes , Al Othman Bayan
Published: December 2022

Giant cell arteritis is the most common vasculitis in adults above 50 years old. The disease is characterized by granulomatous inflammation of medium and large arteries, particularly the temporal artery, and is associated acutely with headache, claudication, and visual disturbances. Diagnosis of the disease is often complicated by its protean presentation and lack of consistently reliable testing. The utility of color doppler ultrasound at the point-of-care and FDG-PET in longitudinal evaluation remain under continued investigation. Novel techniques for risk assessment with Halo scoring and stratification through axillary vessel ultrasound are becoming commonplace. Moreover, the recent introduction of the biologic tocilizumab marks a paradigm shift toward using glucocorticoid-sparing strategies as the primary treatment modality. Notwithstanding these developments, patients continue to have substantial rates of relapse and biologic agents have their own side effect profile. Trials are underway to answer questions about optimal diagnostic modality, regiment choice, and duration.
Plant-growth promotion by proteobacterial strains depends on the availability of phosphorus and iron in Arabidopsis thaliana plants
Authors: Orellana Daniela , Machuca Daniel , Ibeas Miguel Angel , Estevez José Manuel , Poupin María Josefina
Published: December 2022

Phosphorus (as phosphate, Pi) and iron (Fe) are critical nutrients in plants that are often poorly available in the soil and can be microbially affected. This work aimed to evaluate how plant-rhizobacteria interaction changes due to different Pi or Fe nutritional scenarios and to study the underlying molecular mechanisms of the microbial modulation of these nutrients in plants. Thus, three proteobacteria (Paraburkholderia phytofirmans PsJN, Azospirillum brasilense Sp7, and Pseudomonas putida KT2440) were used to inoculate Arabidopsis seeds. Additionally, the seeds were exposed to a nutritional factor with the following levels for each nutrient: sufficient (control) or low concentrations of a highly soluble source or sufficient concentrations of a low solubility source. Then, the effects of the combinatorial factors were assessed in plant growth, nutrition, and genetic regulation. Interestingly, some bacterial effects in plants depended on the nutrient source (e.g., increased aerial zones induced by the strains), and others (e.g., decreased primary roots induced by Sp7 or KT2440) occurred regardless of the nutritional treatment. In the short-term, PsJN had detrimental effects on plant growth in the presence of the low-solubility Fe compound, but this was not observed in later stages of plant development. A thorough regulation of the phosphorus content was detected in plants independent of the nutritional treatment. Nevertheless, inoculation with KT2440 increased P content by 29% Pi-deficiency exposed plants. Conversely, the inoculation tended to decrease the Fe content in plants, suggesting a competition for this nutrient in the rhizosphere. The P-source also affected the effects of the PsJN strain in a double mutant of the phosphate starvation response (PSR). Furthermore, depending on the nutrient source, PsJN and Sp7 strains differentially regulated PSR and IAA- associated genes, indicating a role of these pathways in the observed differential phenotypical responses. In the case of iron, PsJN and SP7 regulated iron uptake-related genes regardless of the iron source, which may explain the lower Fe content in inoculated plants. Overall, the plant responses to these proteobacteria were not only influenced by the nutrient concentrations but also by their availabilities, the elapsed time of the interaction, and the specific identities of the beneficial bacteria.

Graphical Abstract

The effects of the different nutritional and inoculation treatments are indicated for plant growth parameters (A), gene regulation (B) and phosphorus and iron content (C). Figures created with BioRender.com with an academic license.
Climate-smart agricultural practices influence the fungal communities and soil properties under major agri-food systems
Authors: Choudhary Madhu , Jat Hanuman S. , Jat Mangi L. , Sharma Parbodh C.
Published: December 2022

Fungal communities in agricultural soils are assumed to be affected by climate, weather, and anthropogenic activities, and magnitude of their effect depends on the agricultural activities. Therefore, a study was conducted to investigate the impact of the portfolio of management practices on fungal communities and soil physical–chemical properties. The study comprised different climate-smart agriculture (CSA)-based management scenarios (Sc) established on the principles of conservation agriculture (CA), namely, ScI is conventional tillage-based rice–wheat rotation, ScII is partial CA-based rice–wheat–mungbean, ScIII is partial CSA-based rice–wheat–mungbean, ScIV is partial CSA-based maize–wheat–mungbean, and ScV and ScVI are CSA-based scenarios and similar to ScIII and ScIV, respectively, except for fertigation method. All the scenarios were flood irrigated except the ScV and ScVI where water and nitrogen were given through subsurface drip irrigation. Soils of these scenarios were collected from 0 to 15 cm depth and analyzed by Illumina paired-end sequencing of Internal Transcribed Spacer regions (ITS1 and ITS2) for the study of fungal community composition. Analysis of 5 million processed sequences showed a higher Shannon diversity index of 1.47 times and a Simpson index of 1.12 times in maize-based CSA scenarios (ScIV and ScVI) compared with rice-based CSA scenarios (ScIII and ScV). Seven phyla were present in all the scenarios, where Ascomycota was the most abundant phyla and it was followed by Basidiomycota and Zygomycota. Ascomycota was found more abundant in rice-based CSA scenarios as compared to maize-based CSA scenarios. Soil organic carbon and nitrogen were found to be 1.62 and 1.25 times higher in CSA scenarios compared with other scenarios. Bulk density was found highest in farmers' practice (Sc1); however, mean weight diameter and water-stable aggregates were found lowest in ScI. Soil physical, chemical, and biological properties were found better under CSA-based practices, which also increased the wheat grain yield by 12.5% and system yield by 18.8%. These results indicate that bundling/layering of smart agricultural practices over farmers' practices has tremendous effects on soil properties, and hence play an important role in sustaining soil quality/health.
Diversity and adaptation properties of actinobacteria associated with Tunisian stone ruins
Authors: Saadouli Ilhem , Marasco Ramona , Mejri Lassaad , Hamden Haytham , Guerfali Meriem M’saad , Stathopoulou Panagiota , Daffonchio Daniele , Cherif Ameur , Ouzari Hadda-Imene , Tsiamis George , Mosbah Amor
Published: December 2022

Stone surface is a unique biological niche that may host a rich microbial diversity. The exploration of the biodiversity of the stone microbiome represents a major challenge and an opportunity to characterize new strains equipped with valuable biological activity. Here, we explored the diversity and adaptation strategies of total bacterial communities associated with Roman stone ruins in Tunisia by considering the effects of geo-climatic regions and stone geochemistry. Environmental 16S rRNA gene amplicon was performed on DNA extracted from stones samples collected in three different sampling sites in Tunisia, along an almost 400km aridity transect, encompassing Mediterranean, semiarid and arid climates. The library was sequenced on an Illumina MiSeq sequencing platform. The cultivable Actinobacteria were isolated from stones samples using the dilution plate technique. A total of 71 strains were isolated and identified based on 16S rRNA gene sequences. Cultivable actinobacteria were further investigated to evaluate the adaptative strategies adopted to survive in/on stones. Amplicon sequencing showed that stone ruins bacterial communities were consistently dominated by Cyanobacteria, followed by Proteobacteria and Actinobacteria along the aridity gradient. However, the relative abundance of the bacterial community components changed according to the geo-climatic origin. Stone geochemistry, particularly the availability of magnesium, chromium, and copper, also influenced the bacterial communities’ diversity. Cultivable actinobacteria were further investigated to evaluate the adaptative strategies adopted to survive in/on stones. All the cultivated bacteria belonged to the Actinobacteria class, and the most abundant genera were Streptomyces, Kocuria and Arthrobacter. They were able to tolerate high temperatures (up to 45°C) and salt accumulation, and they produced enzymes involved in nutrients’ solubilization, such as phosphatase, amylase, protease, chitinase, and cellulase. Actinobacteria members also had an important role in the co-occurrence interactions among bacteria, favoring the community interactome and stabilization. Our findings provide new insights into actinobacteria’s diversity, adaptation, and role within the microbiome associated with stone ruins.
Small-molecule compound from AlphaScreen disrupts tau-glycan interface
Authors: Faris Shannon , Jin Weihua , Gibson James , Murray Anqesha , Smith Nathan , He Peng , Zhang Fuming , Linhardt Robert , Wang Chunyu
Published: December 2022

Tauopathies are neurodegenerative diseases characterized by intracellular abnormal tau deposits in the brain. Tau aggregates can propagate from one neuron to another in a prion-like manner, mediated by the interaction between tau and cell surface heparan sulfate proteoglycans. We developed an AlphaScreen assay, with His-tagged tau and biotinylated heparin, to represent the tau-HS interface to target the tau-glycan interface. Using our AlphaScreen assay, with a Z-factor of 0.65, we screened ∼300 compounds and discovered a small-molecule compound (herein referred to as A9), which can disrupt the tau-heparin interaction with micromolar efficacy. A9 also effectively inhibited heparin-induced tau aggregation in Thioflavin T fluorescence assays and attenuated tau internalization by H4 neuroglioma cells. These results strongly suggest that A9 can disrupt the tau-glycan interface in both in vitro molecular and cellular environments. We further determined that A9 interacts with heparin rather than tau and does so with micromolar binding affinity as shown by nuclear magnetic resonance and surface plasmon resonance experiments. A9 binds to heparin in a manner that blocks the sites where tau binds to heparin on the cell surface. These results demonstrate our AlphaScreen method as an effective method for targeting the tau-glycan interface in drug discovery and A9 as a promising lead compound for tauopathies, including Alzheimer’s disease.
Why people keep watching: neurophysiologic immersion during video consumption increases viewing time and influences behavior
Authors: Lin Li-Hsin , Narender Rainita , Zak Paul J.
Published: December 2022

Streaming services provide people with a seemingly infinite set of entertainment choices. This large set of options makes the decision to view alternative content or stop consuming content altogether compelling. Yet, nearly all experimental studies of the attributes of video content and their ability to influence behavior require that participants view stimuli in their entirety. The present study measured neurophysiologic responses while participants viewed videos with the option to stop viewing without penalty in order to identify signals that capture the neural value of content. A post-video behavioral choice was included to reduce the likelihood that measured neurophysiologic responses were noise rather than signal. We found that a measure derived from neurophysiologic Immersion predicted how long participants would watch a video. Further, the time spent watching a video increased the likelihood that it influenced behavior. The analysis indicates that the neurologic value one receives helps explain why people continue to watch videos and why they are influenced by them.
Spatiotemporal scaling changes in gait in a progressive model of Parkinson's disease
Authors: Doyle Alex M. , Bauer Devyn , Hendrix Claudia , Yu Ying , Nebeck Shane D. , Fergus Sinta , Krieg Jordan , Wilmerding Lucius K. , Blumenfeld Madeline , Lecy Emily , Spencer Chelsea , Luo Ziling , Sullivan Disa , Brackman Krista , Ross Dylan , Best Sendréa , Verma Ajay , Havel Tyler , Wang Jing , Johnson Luke , Vitek Jerrold L. , Johnson Matthew D.
Published: December 2022

Objective

Gait dysfunction is one of the most difficult motor signs to treat in patients with Parkinson's disease (PD). Understanding its pathophysiology and developing more effective therapies for parkinsonian gait dysfunction will require preclinical studies that can quantitatively and objectively assess the spatial and temporal features of gait.

Design

We developed a novel system for measuring volitional, naturalistic gait patterns in non-human primates, and then applied the approach to characterize the progression of parkinsonian gait dysfunction across a sequence of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatments that allowed for intrasubject comparisons across mild, moderate, and severe stages.

Results

Parkinsonian gait dysfunction was characterized across treatment levels by a slower stride speed, increased time in both the stance and swing phase of the stride cycle, and decreased cadence that progressively worsened with overall parkinsonian severity. In contrast, decreased stride length occurred most notably in the moderate to severe parkinsonian state.

Conclusion

The results suggest that mild parkinsonism in the primate model of PD starts with temporal gait deficits, whereas spatial gait deficits manifest after reaching a more severe parkinsonian state overall. This study provides important context for preclinical studies in non-human primates studying the neurophysiology of and treatments for parkinsonian gait.
Tandem mass tag-based quantitative proteomic analysis of effects of multiple sevoflurane exposures on the cerebral cortex of neonatal and adult mice
Authors: Feng Jingyu , Lin Hua , Zhao Yue , Yang Yongyan , Zhuang Xiaoli , Yu Yang , Yu Yonghao
Published: December 2022

Introduction

Sevoflurane is the most commonly used general anesthetic in pediatric surgery, but it has the potential to be neurotoxic. Previous research found that long-term or multiple sevoflurane exposures could cause cognitive deficits in newborn mice but not adult mice, whereas short-term or single inhalations had little effect on cognitive function at both ages. The mechanisms behind these effects, however, are unclear.

Methods

In the current study, 6- and 60-day-old C57bl mice in the sevoflurane groups were given 3% sevoflurane plus 60% oxygen for three consecutive days, each lasting 2 hours, while those in the control group only got 60% oxygen. The cortex tissues were harvested on the 8th or 62nd day. The tandem mass tags (TMT)pro-based quantitative proteomics combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, Golgi staining, and western blotting analysis were applied to analyze the influences of multiple sevoflurane anesthesia on the cerebral cortex in mice with various ages. The Morris water maze (MWM) test was performed from postnatal day (P)30 to P36 or P84 to P90 after control or multiple sevoflurane treatment. Sevoflurane anesthesia affected spatial learning and memory and diminished dendritic spines primarily in newborn mice, whereas mature animals exhibited no significant alterations.

Results

A total of 6247 proteins were measured using the combined quantitative proteomics methods of TMTpro-labeled and LC-MS/MS, 443 of which were associated to the age-dependent neurotoxic mechanism of repeated sevoflurane anesthesia. Furthermore, western blotting research revealed that sevoflurane-induced brain damage in newborn mice may be mediated by increasing the levels of protein expression of CHGB, PTEN, MAP2c, or decreasing the level of SOD2 protein expression.

Conclusion

Our findings would help to further the mechanistic study of age-dependent anesthetic neurotoxicity and contribute to seek for effective protection in the developing brain under general anesthesia.
Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points
Authors: Cohen Laurie D. , Ziv Tamar , Ziv Noam E.
Published: December 2022

Synaptic integrity and function depend on myriad proteins - labile molecules with finite lifetimes that need to be continually replaced with freshly synthesized copies. Here we describe experiments designed to expose synaptic (and neuronal) properties and functions that are particularly sensitive to disruptions in protein supply, identify proteins lost early upon such disruptions, and uncover potential, yet currently underappreciated failure points. We report here that acute suppressions of protein synthesis are followed within hours by reductions in spontaneous network activity levels, impaired oxidative phosphorylation and mitochondrial function, and, importantly, destabilization and loss of both excitatory and inhibitory postsynaptic specializations. Conversely, gross impairments in presynaptic vesicle recycling occur over longer time scales (days), as does overt cell death. Proteomic analysis identified groups of potentially essential ‘early-lost’ proteins including regulators of synapse stability, proteins related to bioenergetics, fatty acid and lipid metabolism, and, unexpectedly, numerous proteins involved in Alzheimer’s disease pathology and amyloid beta processing. Collectively, these findings point to neuronal excitability, energy supply and synaptic stability as early-occurring failure points under conditions of compromised supply of newly synthesized protein copies.
Characterization of starch structures isolated from the grains of waxy, sweet, and hybrid sorghum (Sorghum bicolor L. Moench)
Authors: Kang Xuemin , Zhu Wentao , Xu Tongcheng , Sui Jie , Gao Wei , Liu Zhiquan , Jing Haichun , Cui Bo , Qiao Xuguang , Abd El-Aty A. M.
Published: December 2022

In this study, starches were isolated from inbred (sweet and waxy) and hybrid (sweet and waxy) sorghum grains. Structural and property differences between (inbred and hybrid) sweet and waxy sorghum starches were evaluated and discussed. The intermediate fraction and amylose content present in hybrid sweet starch were lower than those in inbred sweet starch, while the opposite trend occurred with waxy starch. Furthermore, there was a higher A chain (30.93–35.73% waxy, 13.73–31.81% sweet) and lower B2 + B3 chain (18.04–16.56% waxy, 24.07–17.43% sweet) of amylopectin in hybrid sorghum starch. X-ray diffraction (XRD) and Fourier transform infrared reflection measurements affirm the relative crystalline and ordered structures of both varieties as follows: inbred waxy > hybrid waxy > hybrid sweet > inbred sweet. Small angle X-ray scattering and 13C CP/MAS nuclear magnetic resonance proved that the amylopectin content of waxy starch was positively correlated with lamellar ordering. In contrast, an opposite trend was observed in sweet sorghum starch due to its long B2 + B3 chain content. Furthermore, the relationship between starch granule structure and function was also concluded. These findings could provide a basic theory for the accurate application of existing sorghum varieties precisely.
The correlation between serum 25-hydroxy-vitamin D levels and anti-SARS-CoV-2 S-RBD IgG and neutralizing antibody levels among cancer patients receiving COVID-19 vaccines
Authors: Rachman Andhika , Iriani Anggraini , Priantono Dimas , Rumondor Bayu Bijaksana , Betsy Rachelle , Juanputra Samuel
Published: December 2022

Introduction

During the coronavirus disease 2019 (COVID-19) pandemic, vitamin D has been established as an immune-modulator that reduces pro-inflammatory damage which effectively diminish the severity of COVID-19. Vitamin D also has a significant effect against influenza and dengue and increase the seroconversion following influenza vaccination. To date, the role of vitamin D in optimizing the efficacy of COVID-19 vaccines remains unclear. This study aimed to analyze the correlation between serum 25-hydroxy-cholecalciferol or 25(OH)D levels and anti-SARS-CoV-2 S-RBD IgG and neutralizing antibody levels among cancer patients.

Methodology

A multicenter cross-sectional study was conducted among solid and hematologic cancer patients who were vaccinated with two doses of the same types of COVID-19 vaccines (either mRNA, non-replicating viral vector, or inactivated) within 6 months.

Result

The median serum 25(OH)D level in 119 cancer patients was 36.36 [IQR = 30.30] ng/mL. The seropositivity of S-RBD IgG and NAb reached 93.3 and 94.1%, respectively. The S-RBD IgG level was significantly higher in the sufficient group (median = 414.07 [1,441.83] AU/mL) than in the deficient group (median = 91.56 [652.00] AU/mL) (p-value = 0.049). Among non-chemotherapy subjects, the anti-SARS-CoV-2 S-RBD IgG levels had a significant positive correlation with 25(OH)D levels (p-value = 0.03; R = 0.588). The NAb levels also showed significantly positive correlation with 25(OH)D level (p-value = 0.005; R = 0.561). The 25(OH)D levels were positively correlated with S-RBD IgG levels among subjects younger than 60 years old (p-value = 0.047; R = 0.136). However, serum 25 (OH)D levels showed no such correlation with S-RBD IgG levels among subjects older than 60 years old (p-value = 0.933; R = 0.136).

Conclusion

Both anti-SARS-CoV-2 S-RBD IgG and NAb levels developed moderate correlation with 25(OH)D levels among subjects treated without chemotherapy. The S-RBD IgG levels also had positive correlation with 25(OH)D levels among subjects younger than 60 years old. Thus, we recommended cancer patients to maintain serum 25(OH)D levels above 30 ng/mL (75 nmol/L) to enhance the efficacy of COVID-19 vaccines.
Low carbohydrate ketogenic diets reduce cardiovascular risk factor levels in obese or overweight patients with T2DM: A meta-analysis of randomized controlled trials
Authors: Luo Wei , Zhang Jin , Xu Dan , Zhou Yao , Qu Zhen , Yang Qin , Lv Qiujv
Published: December 2022

Background

The purpose of this meta-analysis was to explore the effects of low-carbohydrate ketogenic diets on cardiovascular risk factors in overweight or obese patients. However, there are limited literature data about effects of low-carbohydrate ketogenic diets on cardiovascular risk factors in obese or overweight patients.

Methods

We systematically searched PubMed, EMBASE, Web of Science, OVID, and Cochrane Library databases (last updated in September 2022) for randomized controlled trials (RCTs) which recruited overweight or obesity patients on ketogenic diets in order to control cardiovascular risk factors (blood glucose, weight, and lipids). The overall effect size for continuous variables was expressed as a weighted standardized mean difference (SMD) with a confidence interval of 95%. Considering type 2 diabetes mellitus (T2DM) status at baseline, subgroup analyses were performed when appropriate, based on T2DM comorbidity among patients. The effect model was selected according to heterogeneity.

Results

We finally selected 21 studies. Low carbohydrate ketogenic diets exerted a greater impact on cardiovascular risk factors in obese/ overweight patients with T2DM when compared with those on non-ketogenic diets, with lower fasting plasma glucose (FPG) (SMD, −0.75; P < 0.001) and hemoglobin A1c (HbA1c) (SMD, −0.53; P < 0.001) levels identified. Low-carbohydrate ketogenic diets significantly reduced body mass index (BMI) (SMD, −2.27; P = 0.032), weight (SMD, −6.72; P < 0.001), and waist circumference (SMD, −4.45; P = 0.003) in obese/ overweight patients with T2DM. Also, ketogenic diets improved lipid profiles in these patients; triglyceride (TG) (SMD, −0.32; P = 0.013) levels were lowered and high density lipoprotein (HDL) showed an upward trend with the P-value close to statistically significant level (SMD, −0.32; P = 0.052). In general, irrespective of diabetic status at baseline, ketogenic diets were more effective in reducing TG (SMD, −0.2; P = 0.02) and increasing HDL (SMD, 0.11; P = 0.03) levels when compared with non-ketogenic diets.

Conclusions

Low-carbohydrate ketogenic diets effectively improved cardiovascular risk factors (blood glucose, weight, and lipids) in obese/ overweight patients, especially those with T2DM when compared with non-ketogenic diets.
Palliative care for patients with glioma: A recent scientometric analysis of the Web of Science in 2022
Authors: Xiao Zhiyuan , Chen Wenlin , Zhao Haiyan , Wang Hai , Zhao Binghao , Liu Delin , Yang Tianrui , Liang Tingyu , Xing Hao , Wang Yaning , Wang Yuekun , Guo Xiaopeng , Zhang Yi , Wang Yu , Ma Wenbin
Published: December 2022

Background

Patients with glioma present with complex palliative care needs throughout their disease trajectory. A scientometric analysis is effective and widely used to summarize the most influential studies within a certain field. We present the first scientometric analysis of palliative care for patients with glioma.

Methods

Based on a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) principle, we conducted a generalized search for articles on palliative care for glioma in the Web of Science database and evaluated the top 100 most frequently cited articles among 2,542 articles.

Results

The number of citations for the top 100 cited articles on palliative care for glioma ranged from 10 to 223. We have a narrative conclusion, as follows: most of these articles were published in oncology-specific journals (n = 53) and palliative-specific journals (n = 22). The United States, Australia, and the Netherlands were the top three countries contributing most of the articles (n = 59). Most of the research methods were quantitative analyses, qualitative analyses, and systematic reviews and meta-analyses (n = 70). In quantitative studies, 66 scales were used, and the top three scales used included the following: the Distress Thermometer, Functional Assessment of Cancer Therapy-Brain Index (FACT-Br), and Karnofsky Performance Scale (KPS). The articles were classified into six major categories based on research subjects, including patients (n = 44), caregivers (n = 16), patients and caregivers (n = 20), literature (n = 19), and healthcare providers (n = 1). Articles were classified into seven major categories based on research themes: quality of life (n = 11); end-of-life symptoms and care (n = 16); palliative and supportive care needs (n = 35); advance care planning and decision making (n = 4); psychological, social, and spiritual needs (n = 12); hospice utilization and referral (n = 3); and others (n = 19). The studies of the primary topic are correlated with the number of citations.

Conclusions

The results of the analysis indicated that patients diagnosed with glioma present a high variety of palliative care needs, including physical, psychological, social, and spiritual needs. The caregiver’s burden and needs are important as well. The proportion of quantitative analyses, qualitative analyses, and systematic reviews and meta-analyses is relatively high, but the number of randomized controlled trials (RCTs) was low. End-of-life care and supportive care needs appeared frequently. Thus, palliative care is an urgent need to be addressed in glioma management. The appropriate scales should be selected for patients with glioma and meet their palliative needs.
A mechanistic understanding of the relationship between skin innervation and chemotherapy-induced neuropathic pain
Authors: Meregalli Cristina , Monza Laura , Jongen Joost L. M.
Published: December 2022

Neuropathic pain is a frequent complication of chemotherapy-induced peripheral neurotoxicity (CIPN). Chemotherapy-induced peripheral neuropathies may serve as a model to study mechanisms of neuropathic pain, since several other common causes of peripheral neuropathy like painful diabetic neuropathy may be due to both neuropathic and non-neuropathic pain mechanisms like ischemia and inflammation. Experimental studies are ideally suited to study changes in morphology, phenotype and electrophysiologic characteristics of primary afferent neurons that are affected by chemotherapy and to correlate these changes to behaviors reflective of evoked pain, mainly hyperalgesia and allodynia. However, hyperalgesia and allodynia may only represent one aspect of human pain, i.e., the sensory-discriminative component, while patients with CIPN often describe their pain using words like annoying, tiring and dreadful, which are affective-emotional descriptors that cannot be tested in experimental animals. To understand why some patients with CIPN develop neuropathic pain and others not, and which are the components of neuropathic pain that they are experiencing, experimental and clinical pain research should be combined. Emerging evidence suggests that changes in subsets of primary afferent nerve fibers may contribute to specific aspects of neuropathic pain in both preclinical models and in patients with CIPN. In addition, the role of cutaneous neuroimmune interactions is considered. Since obtaining dorsal root ganglia and peripheral nerves in patients is problematic, analyses performed on skin biopsies from preclinical models as well as patients provide an opportunity to study changes in primary afferent nerve fibers and to associate these changes to human pain. In addition, other biomarkers of small fiber damage in CIPN, like corneal confocal microscope and quantitative sensory testing, may be considered.
Evaluation of tunica vaginalis flap-covering combined with modified Glenn–Anderson in one-stage repair of proximal hypospadias with incomplete penoscrotal transposition
Authors: Wang Xin , Guan Yong , Wu Yong , Wang Cong , Ma Xiong , Zhang Zhenhua , Zhang Dongzheng
Published: December 2022

Objective

To explore a novel repair method for proximal hypospadias with incomplete penoscrotal transposition in children and evaluate its safety and outcomes.

Methods

A retrospective analysis of clinical data was conducted for 86 children with severe proximal hypospadias with incomplete penoscrotal transposition who were hospitalized in our department between June 2018 and February 2021. In total, 42 patients (Group A) underwent repair following a one-stage method in which tunica vaginalis flap-covering was combined with a modified Glenn–Anderson procedure, while 44 patients (Group B) underwent a two-step repair consisting of tunica vaginalis flap-covering using the Duplay technique and the modified Glenn–Anderson procedure. The two groups were compared on operation time, length of postoperative hospital stay, postoperative complications, and associated costs.

Results

All operations were successful in both groups. No statistical difference was observed between the two groups in incidence of stenosis of the urinary meatus (2.38% vs. 4.54%, P = 0.279), urethral stricture (2.38% vs. 2.27%, P = 0.948), urinary fistula (7.14% vs. 6.82%, P = 0.907), or urinary infection (7.14% vs. 4.55%, P = 0.309). Additionally, there was no statistical difference between the groups in operation time (63.21 ± 5.20 vs. 62.07 ± 4.47 min, P = 0.059), postoperative off-bed time (7.02 ± 1.32 vs. 6.84 ± 1.20 days, P = 0.456), or duration of hospitalization (10.55 ± 1.15 vs. 10.15 ± 1.45 days, P = 0.092). However, Group B patients underwent an additional second-stage operation, incurring extra costs. Three months after surgery, Group A were judged more positively on the PPPS (specifically receiving higher scores on shaft skin and general appearance) by both the parents (shaft skin: 2.10 ± 0.82 vs. 1.93 ± 0.62, P = 0.024; general appearance: 2.16 ± 0.91 vs. 1.93 ± 0.72, P = 0.042) and the surgeon (shaft skin: 2.42 ± 0.70 vs. 2.25 ± 0.58, P = 0.025; general appearance: 2.38 ± 0.69 vs. 2.29 ± 0.51, P = 0.041). In most cases, the parents and surgeon were satisfied with the appearance of the genitals after one-stage repair.

Conclusion

The advantages of the novel repair technique include use of a single-stage operation, producing a better appearance at a lower cost. The tunica vaginalis flap-covering method is not only demonstrated to be safe and effective, but it is also a simpler method than the conventional operation.
Adjunctive granisetron therapy in patients with sepsis or septic shock (GRANTISS): A single-center, single-blinded, randomized, controlled clinical trial
Authors: Guan Jianbin , Liao Yuping , Guo Yuexun , Yu Shuang , Wei Rongjuan , Niu Mengwei , Gan Jianwei , Zhang Lu , Li Tong , Lv Jin , Shichen Maoyou , Chang Ping , Chen Peng , Liu Zhanguo
Published: December 2022

Background: In preclinical experiments, we demonstrated that the 5-HT3 receptor antagonist granisetron results in reduced inflammation and improved survival in septic mice. This randomized controlled trial was designed to assess the efficacy and safety of granisetron in patients with sepsis.

Methods: Adult patients with sepsis and procalcitonin ≥ 2 ng/ml were randomized in a 1:1 ratio to receive intravenous granisetron (3 mg every 8 h) or normal saline at the same volume and frequency for 4 days or until intensive care unit discharge. The primary outcome was 28-day all-cause mortality. Secondary outcomes included the duration of supportive therapies for organ function, changes in sequential organ failure assessment scores over 96 h, procalcitonin reduction rate over 96 h, the incidence of new organ dysfunction, and changes in laboratory variable over 96 h. Adverse events were monitored as the safety outcome.

Results: The modified intention-to-treat analysis included 150 septic patients. The 28-day all-cause mortalities in the granisetron and placebo groups were 34.7% and 35.6%, respectively (odds ratio, 0.96; 95% CI, 0.49–1.89). No differences were observed in secondary outcomes. In the subgroup analysis of patients without abdominal or digestive tract infections, the 28-day mortality in the granisetron group was 10.9% lower than mortality in the placebo group. Adverse events were not statistically different between the groups.

Conclusion: Granisetron did not improve 28-day mortality in patients with sepsis. However, a further clinical trial targeted to septic patients without abdominal/digestive tract infections perhaps is worthy of consideration.