bluuebunny/crossref_metadata_2025 huggingface dataset:
N6-methyladenosine with immune infiltration and PD-L1 in hepatocellular carcinoma: novel perspective to personalized diagnosis and treatment
Authors: Shi Yanlong , Wang Yizhu , Zhang Wenning , Niu Kaiyi , Mao Xinyu , Feng Kun , Zhang Yewei
Published: July 2023

Background

Increasing evidence elucidated N6-methyladenosine (m6A) dysregulation participated in regulating RNA maturation, stability, and translation. This study aimed to demystify the crosstalk between m6A regulators and the immune microenvironment, providing a potential therapeutic target for patients with hepatocellular carcinoma (HCC).

Methods

Totals of 371 HCC and 50 normal patients were included in this study. GSE121248 and GSE40367 datasets were used to validate the expression of HNRNPC. The R package “ConsensusClusterPlus” was performed to screen consensus clustering types based on the expression of m6A regulators in HCC. The R package “pheatmap”, “immunedeconv”, “survival”, “survminer” and “RMS” were applied to investigate the expression, immunity, overall survival, and clinical application in different clusters and expression groups. Comprehensive analysis of HNRNPC in pan-cancer was conducted by TIMER2 database. Besides, HNRNPC mRNA and protein expression were verified by qRT-PCR and immunohistochemistry analysis.

Results

Most of m6A regulators were over-expressed excerpt for ZC3H13 in HCC. Three independent clusters were screened based on m6A regulators expression, and the cluster 2 had a favorable prognosis in HCC. Then, the cluster 2 was positively expression in macrophage, hematopoietic stem cell, endothelial cell, and stroma score, while negatively in T cell CD4+ memory and mast cell. We identified HNRNPC was an independent prognostic factor in HCC, and nomogram performed superior application value for clinical decision making. Moreover, PD-L1 was significantly up-regulated in HCC tissues, cluster 1, and cluster 3, and we found PD-L1 expression was positively correlated with HNRNPC. Patients with HCC in high-expression groups was associated with tumor-promoting cells. Besides, HNRNPC was correlated with prognosis, TMB, and immune checkpoints in cancers. Particularly, the experiments confirmed that HNRNPC was positively expression in HCC cells and tissues.

Conclusion

The m6A regulators play irreplaceable roles in prognosis and immune infiltration in HCC, and the relationship of HNRNPC and PD-L1 possesses a promising direction for therapeutic targets of immunotherapy response. Exploration of m6A regulators pattern could be build the prognostic stratification of individual patients and move toward to personalized treatment.
The Russian registry of primary hyperparathyroidism, latest update
Authors: Mokrysheva Natalia G. , Eremkina Anna K. , Elfimova Alina R. , Kovaleva Elena V. , Miliutina Anastasiia P. , Bibik Ekaterina E. , Gorbacheva Anna M. , Dobreva Ekaterina A. , Maganeva Irina S. , Krupinova Julia A. , Salimkhanov Rustam H. , Aboishava Lizaveta A. , Karaseva Elena V. , Melnichenko Galina A. , Dedov Ivan I.
Published: July 2023

Introduction

Until recently no major epidemiological research of primary hyperparathyroidism (PHPT) has been conducted in the Russian Federation, this led to the creation of the Russian online registry. The objective of this study is to estimate the clinical and biochemical profile, classical and non-classical complications, surgical intervention and medical therapy of the patients with different forms of PHPT in the Russian Federation.

Materials and methods

The cross-sectional, observational, continuous study was conducted at the Endocrinology Research Centre (Moscow). The present study explored retrospective data from 6003 patients submitted to the Registry between 12.12.2016 and 25.10.2022 from 81 regions of the Russian Federation (http://pgpt.clin-reg.ru/).

Results

The median age was 59 [60; 66] years with a female:male ratio of 11.7:1. Symptomatic PHPT was observed in 74.3% while asymptomatic form - only in 25.7% of cases. Bone pathology was the predominant clinical manifestation in 62.5% of cases (n=2293), mostly in combination with visceral complications 45.7% (n=1676). The majority of patients (63.3%) had combined visceral disorders including kidney damage in 51.8% and gastroduodenal erosions/ulcers in 32.3% of patients. Symptomatic patients were older (60 [53; 67] vs. 54 [45; 62] years, p<0.001) and had more severe biochemical alterations of calcium-phosphorus metabolism. Cardiovascular disease (СVD) was recorded in 48% of patients, among them the most frequent was arterial hypertension (up to 93.9%). A genetic test was conducted in 183 cases (suspicious for hereditary PHPT) revealing the mutations in MEN1, CDC73, RET genes in 107, 6 and 2 cases, respectively. Surgery was performed in 53.4% of patients with remission achievement in 87%, the relapse/persistence were recorded in 13% of cases. Histological examination revealed carcinoma in 4%, atypical adenoma in 2%, adenoma in 84% and hyperplasia in 11% of cases. Drug therapy was prescribed in 54.0% of cases, most often cholecalciferol.

Conclusion

The detection rate of PHPT has increased in the Russian Federation in recent years. This increase is associated with the start of online registration. However, the majority of patients remain symptomatic with significant alterations of phosphorus-calcium metabolism that indicates delayed diagnosis and requires further modifications of medical care.
Effect of sodium-glucose transporter 2 inhibitors on sarcopenia in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
Authors: Zhang Sha , Qi Zhan , Wang Yidong , Song Danfei , Zhu Deqiu
Published: July 2023

Objective

Sarcopenia has been recognized as the third category of disabling complications in patients with type 2 diabetes mellitus(T2DM), in addition to micro- and macrovascular complications. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are innovative glucose-lowering treatments that have been shown to reduce body weight and enhance cardiovascular and renal outcomes. However, there is vigilance that SGLT2 inhibitors should be taken cautiously because they target skeletal muscle and may raise the risk of sarcopenia. Herein, we conducted a meta-analysis of randomized controlled trials to evaluate the effects of SGLT2 inhibitors on sarcopenia in patients with T2DM.

Method

Relevant studies were obtained from PubMed, Embase, Medicine, Cochrane, and Web of Science databases to determine eligible studies until February 2023, without any language restrictions. A random effects model was utilized irrespective of heterogeneity, and the I2 statistic was used to evaluate study heterogeneity. The differences in results were measured using the weighted average difference (WMD) of the continuous data, along with a 95% confidence interval (CI).

Results

A total of 25 randomized controlled trials with 2,286 participants were included. SGLT2 inhibitors significantly reduced weight-related changes and fat-related changes, including body weight(BW) (WMD= -2.74, 95% CI: -3.26 to -2.23, P<0.01), body mass index(BMI) (WMD= -0.72, 95% CI: -0.95 to -0.49, P<0.01), waist circumference(WC) (WMD= -1.60, 95% CI: -2.99 to -0.22, P=0.02), fat mass(FM)(WMD= -1.49, 95% CI: -2.18 to -0.80, P<0.01), percentage body fat(PBF) (WMD= -1.28, 95% CI: -1.83 to -0.74, P<0.01), visceral fat area(VFA)(WMD= -19.52, 95% CI: -25.90 to -13.14, P<0.01), subcutaneous fat area(SFA)(WMD= -19.11, 95% CI: -31.18 to -7.03, P=0.002), In terms of muscle-related changes, lean mass(LM)(WMD= -0.80, 95% CI: -1.43 to -0.16, P=0.01), and skeletal muscle mass(SMM) (WMD= -0.38, 95% CI: -0.65 to -0.10, P=0.007), skeletal muscle index(SMI) (WMD= -0.12, 95% CI: -0.22 to -0.02, P=0.02)were also significantly reduced. In addition, body water likewise decreased significantly (WMD=-0.96, 95% CI: -1.68 to -0.23, P=0.009).

Conclusions

As one of the most widely used hypoglycemic, SGLT2 inhibitors have beneficial effects on FM and BW weight loss in T2DM, such as BW, BMI, WC, FM, PBF, VFA, and SFA. However, the negative influence on muscle mass paralleled the reduction in FM and BW, and the consequent increased risk of sarcopenia warrants high attention, especially as patients are already predisposed to physical frailty.

Clinical Trial Registration

https://www.crd.york.ac.uk/prospero/#myprospero, identifier PROSPERO (No.CRD 42023396278).
Simulation analysis of rockfall movement characteristics with debris slope using Unity3D based on UAV remote sensing DSM: a case study of the G318 Highway on the Tibetan Plateau
Authors: Ye Tangjin , Tao Wei , Li Hu , Zhang Yu , Liu Ruyuan
Published: July 2023

Rockfalls on debris slopes pose a significant hazard to canyon roads on the Tibetan Plateau. In order to assess risks and develop effective engineering solutions, it is crucial to fully understand the characteristics and processes of rockfall movement. This research utilizes UAVs and three-dimensional (3D) laser scanners to capture images and data, while Pix4D is employed to create a high-precision 3D model from the collected data. Unity3D is utilized to analyze the movement characteristics and deposition positions of rockfall. Various movement characteristic indexes, such as velocity, acceleration, displacement, energy loss, and deposit position, are computed and examined for blocks with different shapes, sizes, instability types on the debris slope, and blocks composed of various slope materials and inclinations. The aim is to obtain insights into the specific movement mechanisms of debris slopes, which differ from conventional slopes. Field experiments have confirmed the effectiveness of the Unity3D simulation approach. Building upon this foundation, a high-precision 3D simulation model for the debris slope of the G318 Highway on the Tibetan Plateau is developed using Unity3D. This model is used to calculate the movement characteristics, energy variation, and deposition positions of rockfall. The findings are then compared with those of common models. The results demonstrate that the high-precision 3D simulation model computed by Unity3D provides more accurate and reasonable results compared to the common model. Moreover, the movement characteristics, energy variation, and deposition positions of rockfall on debris slopes exhibit specific characteristics. By employing Unity3D simulation analysis, a comprehensive understanding of the phenomena and behavior of rockfall on debris slopes can be achieved, enabling the proposal of more reasonable engineering protection measures.
MDSCs in breast cancer: an important enabler of tumor progression and an emerging therapeutic target
Authors: Liu Haoyu , Wang Zhicheng , Zhou Yuntao , Yang Yanming
Published: July 2023

Women worldwide are more likely to develop breast cancer (BC) than any other type of cancer. The treatment of BC depends on the subtype and stage of the cancer, such as surgery, radiotherapy, chemotherapy, and immunotherapy. Although significant progress has been made in recent years, advanced or metastatic BC presents a poor prognosis, due to drug resistance and recurrences. During embryonic development, myeloid-derived suppressor cells (MDSCs) develop that suppress the immune system. By inhibiting anti-immune effects and promoting non-immune mechanisms such as tumor cell stemness, epithelial-mesenchymal transformation (EMT) and angiogenesis, MDSCs effectively promote tumor growth and metastasis. In various BC models, peripheral tissues, and tumor microenvironments (TME), MDSCs have been found to amplification. Clinical progression or poor prognosis are strongly associated with increased MDSCs. In this review, we describe the activation, recruitment, and differentiation of MDSCs production in BC, the involvement of MDSCs in BC progression, and the clinical characteristics of MDSCs as a potential BC therapy target.
Research progress of biomarkers in the prediction of anti-PD-1/PD-L1 immunotherapeutic efficiency in lung cancer
Authors: Wang Luyao , Yang Zongxing , Guo Fucheng , Chen Yurong , Wei Jiarui , Dai Xiangpeng , Zhang Xiaoling
Published: July 2023

Currently, anti-PD-1/PD-L1 immunotherapy using immune checkpoint inhibitors is widely used in the treatment of multiple cancer types including lung cancer, which is a leading cause of cancer death in the world. However, only a limited proportion of lung cancer patients will benefit from anti-PD-1/PD-L1 therapy. Therefore, it is of importance to predict the response to immunotherapy for the precision treatment of patients. Although the expression of PD-L1 and tumor mutation burden (TMB) are commonly used to predict the clinical response of anti-PD-1/PD-L1 therapy, other factors such as tumor-specific genes, dMMR/MSI, and gut microbiome are also promising predictors for immunotherapy in lung cancer. Furthermore, invasive peripheral blood biomarkers including blood DNA-related biomarkers (e.g., ctDNA and bTMB), blood cell-related biomarkers (e.g., immune cells and TCR), and other blood-related biomarkers (e.g., soluble PD-L1 and cytokines) were utilized to predict the immunotherapeutic response. In this review, the current achievements of anti-PD-1/PD-L1 therapy and the potential biomarkers for the prediction of anti-PD-1/PD-L1 immunotherapy in lung cancer treatment were summarized and discussed.
Exploring the mechanical, tribological, and morphological characteristics of areca fiber epoxy composites reinforced with various fillers for multifaceted applications
Authors: Miniappan P. K. , Marimuthu S. , Dharani Kumar S. , Sharma Shubham , Kumar Abhinav , Salah Bashir , Ullah Syed Sajid
Published: July 2023

This investigation is primarily concerned with the effect of fly ash, basalt powder, and tungsten carbide (WC) on the mechanical, microstructural, and tribological behaviour of areca fiber-reinforced composites. The fillers (5–10 wt. %) were included with the areca fiber epoxy reinforced composites. In comparison to areca fiber composites without fillers, the inclusion of fly ash, basalt powder, and WC increased the tensile strength by 33–48.2 MPa. The tensile strength of an A2 composite containing areca fiber (20 wt. %), epoxy (70 wt. %) and basalt powder (10 wt. %) was measured to be 48.2 MPa. Similarly, filler incorporation enhanced flexural, impact, and Shore D hardness properties by up to 21.25%, 13.18%, and 15.66%, respectively. Furthermore, the hybridization of fillers enhanced the mechanical properties and abrasion resistance of areca fiber reinforced composites. The inclusion of filler increases the load-carrying capability and adhesion, as determined by SEM. The river-like pattern demonstrates that ductile failure was dominated in the A5 [areca fiber (20 wt. %), epoxy (70 wt. %), fly ash (5 wt. %) and basalt powder (5 wt. %)] composites. A4 [areca fiber (20 wt. %), epoxy (70 wt. %), fly ash (5 wt. %) and tungsten carbide (5 wt. %)] composite has a lower wear resistance than all other composites. The hybrid filler-reinforced composite exhibits increased wear resistance as a result of the absence of wear detritus and textured surfaces.
Development and validation to predict visual acuity and keratometry two years after corneal crosslinking with progressive keratoconus by machine learning
Authors: Liu Yu , Shen Dan , Wang Hao-yu , Qi Meng-ying , Zeng Qing-yan
Published: July 2023

Purpose

To explore and validate the utility of machine learning (ML) methods using a limited sample size to predict changes in visual acuity and keratometry 2 years following corneal crosslinking (CXL) for progressive keratoconus.

Methods

The study included all consecutive patients with progressive keratoconus who underwent CXL from July 2014 to December 2020, with a 2 year follow-up period before July 2022 to develop the model. Variables collected included patient demographics, visual acuity, spherical equivalence, and Pentacam parameters. Available case data were divided into training and testing data sets. Three ML models were evaluated based on their performance in predicting case corrected distance visual acuity (CDVA) and maximum keratometry (Kmax) changes compared to actual values, as indicated by average root mean squared error (RMSE) and R-squared (R2) values. Patients followed from July 2022 to December 2022 were included in the validation set.

Results

A total of 277 eyes from 195 patients were included in training and testing sets and 43 eyes from 35 patients were included in the validation set. The baseline CDVA (26.7%) and the ratio of steep keratometry to flat keratometry (K2/K1; 13.8%) were closely associated with case CDVA changes. The baseline ratio of Kmax to mean keratometry (Kmax/Kmean; 20.9%) was closely associated with case Kmax changes. Using these metrics, the best-performing ML model was XGBoost, which produced predicted values closest to the actual values for both CDVA and Kmax changes in testing set (R2 = 0.9993 and 0.9888) and validation set (R2 = 0.8956 and 0.8382).

Conclusion

Application of a ML approach using XGBoost, and incorporation of identifiable parameters, considerably improved variation prediction accuracy of both CDVA and Kmax 2 years after CXL for treatment of progressive keratoconus.
Delayed 18F-FDG PET imaging provides better metabolic asymmetry in potential epileptogenic zone in temporal lobe epilepsy
Authors: Hong Yang , Fu Chang , Xing Yazhou , Tao James , Zhao Ting , Wang Na , Chen Yanan , You Yang , Ren Zhe , Hong Yingxing , Wang Qi , Zhao Yibo , Yang Yang , Zhang Jiewen , Xu Junling , Han Xiong
Published: July 2023

Objective

To investigate the value of 18F-FDG positron emission tomography/computed tomography (PET/CT) two time point imaging for the identification of the potential epileptogenic zone (EZ) in temporal lobe epilepsy (TLE).

Methods

Fifty-two patients with TLE were prospectively enrolled in the 18F-FDG PET/CT two time point imaging study. The early imaging was obtained approximately 40 min (43.44 ± 18.04 min) after 18F-FDG injection, and the delayed imaging was obtained about 2 to 3 h (160.46 ± 28.70 min) after the injection. Visual and semi-quantitative analysis of 18F-FDG uptake were performed at the two time points in EZ and contralateral symmetrical region. The mean standardized uptake value (SUVmean) of EZ and contralateral symmetrical region was calculated to determine the asymmetry index (AI) of the early and delayed images, as well as in the MRI positive and negative patient groups.

Results

Semi-quantitative analysis demonstrated that AI of the early and delayed 18F-FDG PET/CT images was 13.47 ± 6.10 and 16.43 ± 6.66, respectively. The ΔAI was 2.95 ± 3.05 in 52 TLE patients between the two time points. The AI of the EZ was significantly elevated in delayed images compared to the early images (p < 0.001). The AI of delayed imaging was also significantly elevated compared to the early imaging in both MRI positive (ΔAI = 2.81 ± 2.54, p < 0.001) and MRI negative (ΔAI = 3.21 ± 3.91, p < 0.003) groups, and more pronounced in MRI negative group. Visual analysis also showed that the delayed imaging appeared to be superior to the early imaging for identification of potential EZ.

Conclusion

Delayed 18F-FDG PET imaging provided significantly better than the early imaging in the identification of potential EZ, which can be valuable during epilepsy pre-surgical evaluation in patients with TLE.
Genomic analysis and chitinase characterization of Vibrio harveyi WXL538: insight into its adaptation to the marine environment
Authors: Ran Lingman , Wang Xiaolei , He Xinxin , Guo Ruihong , Wu Yanhong , Zhang Pingping , Zhang Xiao-Hua
Published: July 2023

Chitin, the most abundant bio-polymer in seawater, may be utilized by various microorganisms as a carbon source. Vibrios have been regarded as one of the main groups of chitin consumers in the marine carbon cycle and chitinase producers. The organisms are widely distributed in the aquatic environment. However, the co-working mechanism between their chitinases, and whether the chitinase’s diversity contributes to their adaption to the environment, needs to be further elucidated. Here, we obtained a chitinolytic strain,Vibrio harveyiWXL538 with eight putative chitinase-coding genes. Five of the genes, i.e., Chi4733, Chi540, Chi4668, Chi5174, and Chi4963, were overexpressed and validated, in which Chi4668, Chi4733 and Chi540 were purified and characterized. The result of Chi4668 was described in our previous study. Endo-chitinase Chi4733 degraded colloidal chitin to produce (GlcNAc)2and minor (GlcNAc)3. The enzymatic activity of Chi4733 was 175.5 U mg−1andKcat/Km was 54.9 s−1M−1. Chi4733 had its maximum activity at 50°C and pH 4–6, activated by Sr2+, Co2+, Ca2+, and Mg2+and inhibited by Al3+, Zn2+, Cu2+, Ni2+, and SDS. Exo-chitinase Chi540 degraded colloidal chitin to (GlcNAc)2. The enzymatic activity of Chi540 was 134.5 U mg−1andKcat/Km was 54.9 s−1M−1. Chi540 had its maximum activity at 60°C and pH 6–8, was activated by Sr2+, Ca2+, and Mg2+but inhibited by K+, Ba2+, Zn2+, Cu2+, Ni2+, SDS and urea. Whole genome analysis ofV. harveyiWXL538 and characterization of its chitinase can provide a better understanding of its adaptability to the changing marine environment.
Genomic characterization of carbapenem-resistant Klebsiella oxytoca complex in China: a multi-center study
Authors: Wan Weimin , Yang Xiaochun , Yu Hua , Wang Min , Jia Wei , Huang Bin , Qu Fen , Shan Bin , Tang Yi-Wei , Chen Liang , Du Hong
Published: July 2023

Carbapenem-resistant (CR) Klebsiella oxytoca complex can be associated with high mortality, emerging as a new threat to the public health. K. oxytoca complex is phylogenetically close to K. pneumoniae, one of most common species associated with multidrug resistance in Enterobacterale. The latest research showed that K. oxytoca is a complex of six species. Currently, the epidemiological and genomic characteristics of CR K. oxytoca complex in China are still unclear. Here, we conducted a multi-center study on 25 CR K. oxytoca complex collected from five representative regions in China. These isolates were, respectively, recovered from respiratory tract (12 cases, 48.0%), abdominal cavity (5 cases, 20.0%), blood (4 cases, 16.0%), urine tract (3 cases, 12.0%) and skin or soft tissue (1 cases, 4.0%). Among them, 32.0% (8/25) of patients infected with K. oxytoca complex had a poor prognosis. In this study, three K. oxytoca complex species were detected, namely K. michiganensis, K. oxytoca and K. pasteurii, among which K. michiganensis was the most common. Three carbapenemase genes were identified, including blaNDM-1 (10, 38.5%), blaKPC-2 (9, 34.6%) and blaIMP (6 blaIMP-4 and 1 blaIMP-8; 7, 26.9%). Subsequent multilocus sequence typing identified various sequence types (STs), among which ST43, ST92 and ST145 were relatively common. Different from the clonal dissemination of high-risk carbapenem-resistant K. pneumoniae strains, our research revealed a polyclonal dissemination characteristic of CR K. oxytoca complex in China. S1-nuclease PFGE and Southern blot experiment showed that carbapenemase genes were encoded in plasmids of different sizes. Two blaNDM-harboring plasmids were subsequently sequenced, and were characterized to be IncX3 and IncC incompatibility groups, respectively. This is the first multi-center study of CR K. oxytoca complex in China, which improved our understanding of the prevalence and antimicrobial resistance characteristics of CR K. oxytoca complex in China.
Microbial community structural and functional differentiation in capped thickened oil sands tailings planted with native boreal species
Authors: Samad Abdul , Degenhardt Dani , Séguin Armand , Morency Marie-Josée , Gagné Patrick , Martineau Christine
Published: July 2023

The oil sands mining operations in Alberta have produced billions of m3 of tailings which must be reclaimed and integrated into various mine closure landforms, including terrestrial landforms. Microorganisms play a central role in nutrient cycling during the reclamation of disturbed landscapes, contributing to successful vegetation restoration and long-term sustainability. However, microbial community succession and response in reconstructed and revegetated tailings remain largely unexplored. This study aimed to monitor the structural and functional responses of microbial communities in tailings subjected to different capping and vegetation strategies over two growing seasons (GS). To achieve this, a column-based greenhouse experiment was conducted to investigate microbial communities in tailings that were capped with a layer (10 or 30 cm) of peat-mineral mix (PMM) and planted with either upland or wetland communities. DNA metabarcoding analysis of the bacterial 16S rRNA gene and fungal ITS2 region as well as shotgun metagenomics were used to asses the impact of treatments on microbial taxonomy and functions, respectively. Results showed that tailings microbial diversity and community composition changed considerably after two GS compared to baseline samples, while communities in the PMM capping layer were much more stable. Likewise, several microbial functions were significantly enriched in tailings after two GS. Interestingly, the impact of capping on bacterial communities in tailings varied depending on the plant community, leading to a higher number of differentially abundant taxa and to a decrease in Shannon diversity and evenness in the upland treatment but not in the wetland treatment. Moreover, while capping in the presence of wetland vegetation increased the energy-related metabolic functions (carbon, nitrogen, and sulfur), these functions were depleted by capping in the upland treatment. Fungi represented a small proportion of the microbial community in tailings, but the relative abundance of several taxa changed over time, while the capping treatments favored the growth of some beneficial taxa, notably the root endophyte Serendipita, in both upland and wetland columns. The results suggest that selecting the right combination of capping material and vegetation type may contribute to improve below-ground microbial processes and sustain plant growth in harsh environments such as oil sands tailings.
Metapangenomic investigation provides insight into niche differentiation of methanogenic populations from the subsurface serpentinizing environment, Samail Ophiolite, Oman
Authors: Thieringer Patrick H. , Boyd Eric S. , Templeton Alexis S. , Spear John R.
Published: July 2023

Serpentinization reactions produce highly reduced waters that have hyperalkaline pH and that can have high concentrations of H2 and CH4. Putatively autotrophic methanogenic archaea have been identified in the subsurface waters of the Samail Ophiolite, Sultanate of Oman, though the strategies to overcome hyperalkaline pH and dissolved inorganic carbon limitation remain to be fully understood. Here, we recovered metagenome assembled genomes (MAGs) and applied a metapangenomic approach to three different Methanobacterium populations to assess habitat-specific functional gene distribution. A Type I population was identified in the fluids with neutral pH, while a Type II and “Mixed” population were identified in the most hyperalkaline fluids (pH 11.63). The core genome of all Methanobacterium populations highlighted potential DNA scavenging techniques to overcome phosphate or nitrogen limitation induced by environmental conditions. With particular emphasis on the Mixed and Type II population found in the most hyperalkaline fluids, the accessory genomes unique to each population reflected adaptation mechanisms suggesting lifestyles that minimize niche overlap. In addition to previously reported metabolic capability to utilize formate as an electron donor and generate intracellular CO2, the Type II population possessed genes relevant to defense against antimicrobials and assimilating potential osmoprotectants to provide cellular stability. The accessory genome of the Mixed population was enriched in genes for multiple glycosyltransferases suggesting reduced energetic costs by adhering to mineral surfaces or to other microorganisms, and fostering a non-motile lifestyle. These results highlight the niche differentiation of distinct Methanobacterium populations to circumvent the challenges of serpentinization impacted fluids through coexistence strategies, supporting our ability to understand controls on methanogenic lifestyles and adaptations within the serpentinizing subsurface fluids of the Samail Ophiolite.
Isolation, characterization, and pathogenicity assessment of Corynebacterium pseudotuberculosis biovar equi strains from alpacas (Vicugna pacos) in China
Authors: Meng Wanyu , Chen Shanyu , Huang Lin , Yang Jinpeng , Zhang Wenqing , Zhong Zhijun , Zhou Ziyao , Liu Haifeng , Fu Hualin , He Tingmei , Peng Guangneng
Published: July 2023

Corynebacterium pseudotuberculosis is a zoonotic pathogen that causes lymphadenitis in humans, livestock, and wildlife. In this study, C. pseudotuberculosis biovar equi strains were isolated from three alpacas. Antibiotic susceptibility tests and pathogenicity tests were also conducted. Moreover, one strain was sequenced using DNBSEQ and Oxford Nanopore technology. The three strains exhibited resistance to aztreonam, fosfomycin, and nitrofurantoin. The median lethal doses (LD50) of strains G1, S2 and BA3 in experimentally infected mice was 1.66 × 105 CFU, 3.78 × 105 CFU and 3.78 × 105 CFU, respectively. The sequencing of strain G1 resulted in the assembly of a chromosomal scaffold comprising 2,379,166 bp with a G + C content of 52.06%. Genome analysis of strain G1 revealed the presence of 48 virulence genes and 5 antibiotic resistance genes (ARGs). Comparative genomic analysis demonstrates a high degree of genetic similarity among C. pseudotuberculosis strains, in contrast to other Corynebacterium species, with a clear delineation between strains belonging to the two biovars (ovis and equi). The data of the present study contribute to a better understanding of the properties of C. pseudotuberculosis biovar equi strains and the potential risk they pose to alpacas and other livestock, as well as the necessity of ongoing surveillance and monitoring of infectious diseases in animals.
Comparative efficacy of five most common traditional Chinese medicine monomers for promoting recovery of motor function in rats with blunt spinal cord injury: a network meta-analysis
Authors: Xu Luchun , Yang Yongdong , Zhong Wenqing , Li Wenhao , Liu Chen , Guo Ziwei , Yu Xing
Published: July 2023

Objective

This research employed a network meta-analysis (NMA) to examine the effectiveness of five traditional Chinese medicine (TCM) monomers for promoting motor function recovery in rats with blunt spinal cord injury (SCI).

Methods

Wangfang, China National Knowledge Infrastructure, Web of Science, Embase, Chinese Scientific Journal Database, PubMed, and the Chinese Biomedical Literature Databases were searched for retrieving relevant articles published from their inception to December 2022. Two reviewers performed screening of search results, data extraction, and literature quality assessment independently.

Results

For this meta-analysis, 59 publications were included. Based on the recovery of motor function at weeks 1, 2, 3, and 4 in NMA, almost all TCM groups had significantly increased positive effects than the negative control animals. In terms of cumulative probability, the tanshinone IIA (TIIA) group ranked first in restoring motor function in the first week after blunt SCI, and the resveratrol (RSV) group ranked first during the last 3 weeks.

Conclusion

The NMA revealed that TCM monomers could effectively restore motor function in the rat model of blunt SCI. In rats with blunt SCI, TIIA may be the most effective TCM monomer during the first week, whereas RSV may be the most effective TCM monomer during the last 3 weeks in promoting motor function recovery. For better evidence reliability in preclinical investigations and safer extrapolation of those findings into clinical settings, further research standardizing the implementation and reporting of animal experiments is required.

Systematic Review Registration

https://inplasy.com/, identifier INPLASY202310070.
Botulinum toxin type A for genitofemoral neuralgia: A case report
Authors: Tereshko Yan , Enrico Belgrado , Christian Lettieri , Dal Bello Simone , Merlino Giovanni , Gigli Gian Luigi , Valente Mariarosaria
Published: July 2023

Genitofemoral neuralgia is an uncommon pain disorder that could be resistant to conventional treatment. A 78-year-old woman with refractory right genitofemoral neuralgia was treated with BoNT/A subcutaneous injections; the treatment was performed three times with significant pain improvement, although temporary, and without adverse events. BoNT/A may be a promising alternative intervention in the setting of genitofemoral neuralgia refractory to oral and/or topical treatment.
Loss of ctnnd2b affects neuronal differentiation and behavior in zebrafish
Authors: Vaz Raquel , Edwards Steven , Dueñas-Rey Alfredo , Hofmeister Wolfgang , Lindstrand Anna
Published: July 2023

Delta-catenin (CTNND2) is an adhesive junction associated protein belonging to the family of p120 catenins. The human gene is located on the short arm of chromosome 5, the region deleted in Cri-du-chat syndrome (OMIM #123450). Heterozygous loss of CTNND2 has been linked to a wide spectrum of neurodevelopmental disorders such as autism, schizophrenia, and intellectual disability. Here we studied how heterozygous loss of ctnnd2b affects zebrafish embryonic development, and larvae and adult behavior. First, we observed a disorganization of neuronal subtypes in the developing forebrain, namely the presence of ectopic isl1-expressing cells and a local reduction of GABA-positive neurons in the optic recess region. Next, using time-lapse analysis, we found that the disorganized distribution of is1l-expressing forebrain neurons resulted from an increased specification of Isl1:GFP neurons. Finally, we studied the swimming patterns of both larval and adult heterozygous zebrafish and observed an increased activity compared to wildtype animals. Overall, this data suggests a role for ctnnd2b in the differentiation cascade of neuronal subtypes in specific regions of the vertebrate brain, with repercussions in the animal’s behavior.
Expression of intra-tumoral necrosis-associated cytokine pattern correlated with prognosis and immune status in glioma
Authors: Zhao Hongtao , Dong Jiawei , Zhang Jiheng , Wang Nan , Liu Zhihui , Yan Xiuwei , Wang Fang , Ji Hang , Hu Shaoshan
Published: July 2023

Intra-tumoral necrosis (ITN) is reported to be an independent prognostic factor in glioma. However, knowledge of ITN is mainly limited to pseudopalisadwe, while its other aspects were neglected. Therefore, a deeper understanding of ITN could be valuable for understanding its exact role in glioma. The only reliable ITN model was time-dependently achieved with the GL261 syngeneic mouse model. The ITN-associated expression pattern was enriched from RNA sequencing. TCGA glioma samples were clustered into a high-expression group (HEG) and a low-expression group (LEG) based on their pattern and their association with prognosis, clinical status, immune status, and therapeutic responsiveness were compared. Mouse glioma with ITN demonstrated invasive histology. Cytokine signaling was significantly enriched in necrotic mouse glioma compared with non-necrotic glioma tissues. Nine pro-inflammatory (IL6, PPBP, IL1A, TNFSF11, CXCL11, CXCL9, CXCL10, CXCL3, and CCL8) and two anti-inflammatory cytokine (IL1RN and IL10) genes were found to be related to ITN-associated cytokine patterns. Comparative analysis showed that HEG had a significantly shorter survival time, five differentially distributed clinical statuses, more infiltrated immune cells, greater expression of immune checkpoints, and better therapeutic responsiveness than LEG. In conclusion, the ITN-associated cytokine pattern is characteristically expressed in glioma with ITN and might indicate necrosis missed in histology diagnosis. Its expression pattern could predict the prognosis, tumor grade, immune status, and therapeutic responsiveness of glioma patients.
Structural and functional understanding of disease-associated mutations in V-ATPase subunit a1 and other isoforms
Authors: Indrawinata Karen , Argiropoulos Peter , Sugita Shuzo
Published: July 2023

The vacuolar-type ATPase (V-ATPase) is a multisubunit protein composed of the cytosolic adenosine triphosphate (ATP) hydrolysis catalyzing V1 complex, and the integral membrane complex, Vo, responsible for proton translocation. The largest subunit of the Vo complex, subunit a, enables proton translocation upon ATP hydrolysis, mediated by the cytosolic V1 complex. Four known subunit a isoforms (a1–a4) are expressed in different cellular locations. Subunit a1 (also known as Voa1), the neural isoform, is strongly expressed in neurons and is encoded by the ATP6V0A1 gene. Global knockout of this gene in mice causes embryonic lethality, whereas pyramidal neuron-specific knockout resulted in neuronal cell death with impaired spatial and learning memory. Recently reported, de novo and biallelic mutations of the human ATP6V0A1 impair autophagic and lysosomal activities, contributing to neuronal cell death in developmental and epileptic encephalopathies (DEE) and early onset progressive myoclonus epilepsy (PME). The de novo heterozygous R740Q mutation is the most recurrent variant reported in cases of DEE. Homology studies suggest R740 deprotonates protons from specific glutamic acid residues in subunit c, highlighting its importance to the overall V-ATPase function. In this paper, we discuss the structure and mechanism of the V-ATPase, emphasizing how mutations in subunit a1 can lead to lysosomal and autophagic dysfunction in neurodevelopmental disorders, and how mutations to the non-neural isoforms, a2–a4, can also lead to various genetic diseases. Given the growing discovery of disease-causing variants of V-ATPase subunit a and its function as a pump-based regulator of intracellular organelle pH, this multiprotein complex warrants further investigation.
Associations between serum trace elements and the risk of nasopharyngeal carcinoma: a multi-center case-control study in Guangdong Province, southern China
Authors: Ge Xin-Yu , Xie Shang-Hang , Wang Hao , Ye Xin , Chen Wenjie , Zhou Hang-Ning , Li Xueqi , Lin Ai-Hua , Cao Su-Mei
Published: July 2023

Background

Associations between trace elements and nasopharyngeal carcinoma (NPC) have been speculated but not thoroughly examined.

Methods

This study registered a total of 225 newly diagnosed patients with NPC and 225 healthy controls matched by sex and age from three municipal hospitals in Guangdong Province, southern China between 2011 and 2015. Information was collected by questionnaire on the demographic characteristics and other possibly confounding lifestyle factors. Eight trace elements and the level of Epstein–Barr virus (EBV) antibody were measured in casual (spot) serum specimens by inductively coupled plasma–mass spectrometry (ICP-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. Restricted cubic splines and conditional logistic regression were applied to assess the relationship between trace elements and NPC risk through single-and multiple-elements models.

Results

Serum levels of chromium (Cr), cobalt (Co), nickel (Ni), arsenic (As), strontium (Sr) and molybdenum (Mo) were not associated with NPC risk. Manganese (Mn) and cadmium (Cd) were positively associated with NPC risk in both single-and multiple-element models, with ORs of the highest tertile compared with the reference categories 3.90 (95% CI, 1.27 to 7.34) for Mn and 2.30 (95% CI, 1.26 to 3.38) for Cd. Restricted cubic splines showed that there was a linear increasing trend between Mn and NPC risk, while for Cd there was a J-type correlation.

Conclusion

Serum levels of Cd and Mn was positively related with NPC risk. Prospective researches on the associations of the two trace elements with NPC ought to be taken into account within the future.
F-ATP synthase inhibitory factor 1 regulates metabolic reprogramming involving its interaction with c-Myc and PGC1α
Authors: Guo Lishu , Gu Zhenglong
Published: July 2023

F-ATP synthase inhibitory factor 1 (IF1) is an intrinsic inhibitor of F-ATP synthase. It is known that IF1 mediates metabolic phenotypes and cell fate, yet the molecular mechanisms through which IF1 fulfills its physiological functions are not fully understood. Ablation of IF1 favors metabolic switch to oxidative metabolism from glycolysis. c-Myc and PGC1α are critical for metabolic reprogramming. This work identified that IF1 interacted with Thr-58 phosphorylated c-Myc, which might thus mediate the activity of c-Myc and promote glycolysis. The interaction of IF1 with PGC1α inhibited oxidative respiration. c-Myc and PGC1α were localized to mitochondria under mitochondrial stress in an IF1-dependent manner. Furthermore, IF1 was found to be required for the protective effect of hypoxia on c-Myc- and PGC1α-induced cell death. This study suggested that the interactions of IF1 with transcription factors c-Myc and PGC1α might be involved in IF1-regulatory metabolic reprogramming and cell fate.
New treatment insights into pancreatic acinar cell carcinoma: case report and literature review
Authors: Zhao Fangrui , Yang Dashuai , Xu Tangpeng , He Jiahui , Guo Jin , Li Xiangpan
Published: July 2023

Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic malignancy with unique clinical, molecular, and morphologic features. The long-term survival of patients with PACC is substantially better than that of patients with ductal adenocarcinoma of the pancreas. Surgical resection is considered the first choice for treatment; however, there is no standard treatment option for patients with inoperable disease. The patient with metastatic PACC reported herein survived for more than 5 years with various treatments including chemotherapy, radiotherapy, antiangiogenic therapy and combined immunotherapy.
Concept and considerations of a medical device: the active noise cancelling incubator
Authors: Jaschke Artur C. , Bos Arend F.
Published: July 2023

Background

An increasingly 24/7 connected and urbanised world has created a silent pandemic of noise-induced hearing loss. Ensuring survival to children born (extremely) preterm is crucial. The incubator is a closed medical device, modifying the internal climate, and thus providing an environment for the child, as safe, warm, and comfortable as possible. While sound outside the incubator is managed and has decreased over the years, managing the noise inside the incubator is still a challenge.

Method

Using active noise cancelling in an incubator will eliminate unwanted sounds (i.e., from the respirator and heating) inside the incubator, and by adding sophisticated algorithms, normal human speech, neonatal intensive care unit music-based therapeutic interventions, and natural sounds will be sustained for the child in the pod. Applying different methods such as active noise cancelling, motion capture, sonological engineering. and sophisticated machine learning algorithms will be implemented in the development of the incubator.

Projected Results

A controlled and active sound environment in and around the incubator can in turn promote the wellbeing, neural development, and speech development of the child and minimise distress caused by unwanted noises. While developing the hardware and software pose individual challenges, it is about the system design and aspects contributing to it. On the one hand, it is crucial to measure the auditory range and frequencies in the incubator, as well as the predictable sounds that will have to be played back into the environment. On the other, there are many technical issues that have to be addressed when it comes to algorithms, datasets, delay, microphone technology, transducers, convergence, tracking, impulse control and noise rejection, noise mitigation stability, detection, polarity, and performance.

Conclusion

Solving a complex problem like this, however, requires a de-disciplinary approach, where each discipline will realise its own shortcomings and boundaries, and in turn will allow for innovations and new avenues. Technical developments used for building the active noise cancellation-incubator have the potential to contribute to improved care solutions for patients, both infants and adults.

Code available at: 10.3389/fped.2023.1187815.
A brief history of crystalloids: the origin of the controversy
Authors: Fernández-Sarmiento Jaime , Casas-Certain Carolina , Ferro-Jackaman Sarah , Solano-Vargas Fabian H. , Domínguez-Rojas Jesús Ángel , Pilar-Orive Francisco Javier
Published: July 2023

Fluid resuscitation with crystalloids has been used in humans for more than 100 years. In patients with trauma, sepsis or shock of any etiology, they can help modify the clinical course of the illness. However, these solutions are medications which are not side-effect free. Recently, they have been questioned in terms of quantity (fluid overload) and their composition. The most frequently used crystalloids, both in high and low-income countries, are 0.9% normal saline (NS) and Ringer's lactate. The first descriptions of the use of sodium and water solutions in humans date from the cholera epidemic which spread throughout Europe in 1831. The composition of the fluids used by medical pioneers at that time differs greatly from the 0.9% NS used routinely today. The term “physiological solution”referred to fluids which did not cause red blood cell hemolysis in amphibians inin vitrostudies years later. 0.9% NS has an acid pH, a more than 40% higher chloride concentration than plasma and a strong ion difference of zero, leading many researchers to consider it an unbalanced solution. In many observational studies and clinical trials, this 0.9% NS composition has been associated with multiple microcirculation and immune response complications, acute kidney injury, and worse clinical outcomes. Ringer’s lactate has less sodium than plasma, as well as other electrolytes which can cause problems in patients with traumatic brain injury. This review provides a brief summary of the most important historical aspects of the origin of the most frequently used intravenous crystalloids today.
Case report: Epstein–Barr virus and constrictive pericarditis—An unusual combination
Authors: Panebianco Mario , Limonjiani Eduard , Formigari Roberto , Bordonaro Veronica , Secinaro Aurelio , Cetrano Enrico , Carotti Adriano , Galletti Lorenzo , Albanese Sonia
Published: July 2023

Constrictive pericarditis is a chronic inflammatory process that can lead to heart failure if not diagnosed and treated correctly. Although Epstein–Barr virus (EBV)–related pericarditis is a very rare condition, it should still be considered for a differential diagnosis. We report the case of an 18-year-old male, who was surgically treated for constrictive pericarditis, in which in situ hybridization to Epstein–Barr virus-encoded RNA (EBER) probe of the excised pericardium led to the subsequent etiological diagnosis of chronic pericarditis caused by EBV.