bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and characterization of the ferroptosis-related ceRNA network in irreversible pulpitis
Authors: Xie Qiuyan , Yu Hongwen , Liu Zining , Zhou Bangyi , Fang Fuchun , Qiu Wei , Wu Hongle
Published: May 2023

Background

The role of ferroptosis in irreversible pulpitis (IP) remains unclear. The competing endogenous RNA (ceRNA) theory that has been widely investigated is rarely used studied in IP. Hub lncRNAs selected from a ceRNA network may provide a novel hypothesis for the interaction of ferroptosis and IP.

Methods

Differentially expressed genes (DEGs) were intersected with 484 ferroptosis markers to identify differentially expressed ferroptosis-related genes (DE-FRGs). Functional analysis and protein−protein interaction (PPI) networks were constructed to reveal the functions of DE-FRGs. Then, coexpression analyses were conducted between DE-FRGs and DElncRNAs to define ferroptosis-related DElncRNAs (FR-DElncRNAs). Predictions of DE-FRG- and FR-DElncRNA-related miRNAs were obtained, and members of both groups were selected. Additionally, two ceRNA networks consisting of FR-DElncRNAs, miRNAs and DE-FRGs from upregulated and downregulated groups were built. Finally, the hub lncRNAs of the ceRNA networks were used for immuno-infiltration analysis and qPCR verification.

Results

According to the results of PCA and clustering analysis, 5 inflamed and 5 healthy pulp tissue samples were selected for analysis. The intersection of DEGs with 484 ferroptosis marker genes identified 72 DE-FRGs. The response to stimulus, cellular process, signaling, localization, and biological regulation pathways related to DE-FRGs were enriched. In total, 161 downregulated and 40 upregulated FR-DElncRNAs were chosen by coexpression analysis for further investigation. The MultimiR package and starBase were used to predict miRNAs of DE-FRGs and FR-DElncRNAs, respectively. The upregulated ceRNA network contained 2 FR-DElncRNAs (↑), 19 miRNAs (↓) and 22 DE-FRGs (↑). The downregulated network contained 44 FR-DElncRNAs (↓), 251 miRNAs (↑) and 10 DE-FRGs (↓). Six hub lncRNAs were identified based on the MCC method (LUCAT1 and AC106897.1 ↑; LINC00943, AL583810.1, AC068888.1, and AC125257.1↓). In addition, strong relationships between hub lncRNAs and immune cells were shown by immune infiltration analysis. Finally, validated by qPCR assays of the pulp tissue of IP patients, the expression levels in clinical samples were consistent with the microarray data.

Conclusion

Two ceRNA networks were comprehensively constructed, and 6 hub lncRNAs were identified. These genes provide novel insights into the relationship between ferroptosis and IP. Intriguingly, the LINC00943/hsa-miR-29a-3p/PDK4 axis was deemed to be the key node in this network.
Broad-scale spatial distribution patterns of soft-sediment macrobenthic communities in the Red Sea
Authors: Carvalho Susana , Alsaffar Zahra , Ellis Joanne , Alghamdi Hamed , Cúrdia João
Published: May 2023

In sub-tropical and tropical regions, the diversity patterns of soft-sediment macrobenthic communities are still poorly understood, particularly when compared to temperate shelf environments. The present study investigates spatial patterns of variability in macrobenthic distribution along the eastern Red Sea margin, and the role of sediment composition and other explanatory variables in determining such patterns. This study has two main objectives: (i) to produce a baseline characterization of the Saudi Arabian Red Sea macrobenthic infauna, particularly along the central and southern regions, (ii) to assess the relative contribution of two major processes driving macrobenthic communities (i.e., dispersal-based and environmental filtering), based on changes on beta-diversity components (turnover and nestedness) across multiple scales (up to ~600km), using relevant modeling methodologies. Shallow soft-sediment macrobenthic communities in the Red Sea showed extremely high small-scale variability, highlighted by the percentage of rare species (44% of species present at a single sample) and the dominance of turnover (species replacement) over nestedness. Our results also suggest a strong influence of broad- over fine-scale variation in the species composition. However, sedimentary characteristics, particularly grain-size, played a critical role governing the distribution patterns of soft-sediment macrobenthic communities in the Red Sea. Our findings highlight the importance of regional factors in shaping the macrofaunal community composition whilst also highlighting the role of high species diversity at local scales. The current results suggest the need for conservation measures from regional levels (to maintain genetic diversity) to local levels (to preserve the high occurrence of rare species). To our knowledge, no other study investigated the distribution of Red Sea marine species over large spatial scales combining modeling methods and the partitioning of beta-diversity. The current approach applied to soft-sediment macroinvertebrates can be extended to other marine communities since conservation strategies can be more effective when mechanisms governing species distribution are considered.
An extracellular protease containing a novel C-terminal extension produced by a marine-originated haloarchaeon
Authors: Han Dong , Hou Jing , Cui Heng-Lin
Published: May 2023

Marine microorganisms have long been acknowledged as a significant reservoir of enzymes required for industrial use. In this study, a novel extracellular protease HslHlyB derived from marine-originated haloarchaeon Halostella pelagica DL-M4T was identified. HslHlyB contained polycystic kidney disease (PKD) domain and pre-peptidase C-terminal (PPC) domain at the C-terminus. Truncation and replacement of the C-terminal extension (CTE) of HslHlyB demonstrated the importance of the CTE in maintaining the protease activity secreted by haloarchaeon. HslHlyB and HslHlyBΔCTE were expressed in Escherichia coli BL21(DE3), and purified by high-affinity column refolding and gel filtration chromatography. The molecular masses of HslHlyB and HslHlyBΔCTE were 42 kDa and 20 kDa, respectively. The optimum catalytic reaction conditions were 50°C, pH 8.5, NaCl 3.5 M and 50°C, pH 7.5, NaCl 3 M, respectively. They showed good stability and hydrolysis capabilities towards a wide range of protein substrates. HslHlyBΔCTE showed higher catalytic reaction rate and better thermal stability than the wild type against azocasein and tetrapeptide substrate. The hydrolysates of soybean protein hydrolyzed by HslHlyBΔCTE had smaller average molecular masses and shorter average peptide chain lengths than those by HslHlyB. These results indicated the diversity of halolysins from marine-originated haloarchaea to harness organic nitrogen in the marine environment and provided promising candidates for application in various industries.
How does the Niger river warm coastal waters in the northern Gulf of Guinea?
Authors: Topé G. D. A. , Alory G. , Djakouré S. , Da-Allada C.Y. , Jouanno J. , Morvan G.
Published: May 2023

To highlight the processes by which the Niger River warms the coastal waters in the eastern part of the northern Gulf of Guinea upwelling, two simulations of the NEMO model at high resolution were used over the period 2010 - 2017. The first simulation is realistic while the second is a simulation in which the effects of the Niger River are not taken into account. The first step was to evaluate the outputs of the models, using satellite products and in situ observations. The average states of the Sea Surface Temperature, Salinity, Height, zonal current and vertical profiles of temperature and salinity showed the ability of the model to reproduce correctly the physical characteristics of the study area. The analysis of the heat balance terms of the two simulations showed that vertical diffusion and meridional advection processes are the causes of the warming induced by the Niger River. The stratification and vertical shear of the horizontal currents reveal that the river acts by inhibiting the upwelling of cold water induced by vertical diffusion. The river reinforces the stratification and prevents vertical shearing of horizontal currents at the bottom of the mixed layer.
Underwater terrain positioning method based on Markov random field for unmanned underwater vehicles
Authors: Chen Pengyun , Liu Ying , Chen Xiaolong , Ma Teng , Zhang Lei
Published: May 2023

Underwater terrain-matching navigation technologies have become a popular topic for the high-precision positioning and navigation of autonomous underwater vehicles. This paper proposes an underwater terrain-matching positioning method based on a Markov random field model, which is based on real-time terrain data obtained using a multi-beam echo sounder. It focuses on the strong correlation between adjacent terrain data, which can improve terrain adaptability and matching accuracy. Playback simulation tests were conducted based on actual sea trial data, and the results showed that the proposed method has good positioning performance, which can correct the cumulative errors of inertial navigation systems. The results demonstrated the usability of the proposed method for positioning correction in underwater engineering applications.
Predicting total lung capacity from spirometry: a machine learning approach
Authors: Beverin Luka , Topalovic Marko , Halilovic Armin , Desbordes Paul , Janssens Wim , De Vos Maarten
Published: May 2023

Background and objective

Spirometry patterns can suggest that a patient has a restrictive ventilatory impairment; however, lung volume measurements such as total lung capacity (TLC) are required to confirm the diagnosis. The aim of the study was to train a supervised machine learning model that can accurately estimate TLC values from spirometry and subsequently identify which patients would most benefit from undergoing a complete pulmonary function test.

Methods

We trained three tree-based machine learning models on 51,761 spirometry data points with corresponding TLC measurements. We then compared model performance using an independent test set consisting of 1,402 patients. The best-performing model was used to retrospectively identify restrictive ventilatory impairment in the same test set. The algorithm was compared against different spirometry patterns commonly used to predict restriction.

Results

The prevalence of restrictive ventilatory impairment in the test set is 16.7% (234/1402). CatBoost was the best-performing machine learning model. It predicted TLC with a mean squared error (MSE) of 560.1 mL. The sensitivity, specificity, and F1-score of the optimal algorithm for predicting restrictive ventilatory impairment was 83, 92, and 75%, respectively.

Conclusion

A machine learning model trained on spirometry data can estimate TLC to a high degree of accuracy. This approach could be used to develop future smart home-based spirometry solutions, which could aid decision making and self-monitoring in patients with restrictive lung diseases.
Frailty as a risk marker of adverse lower urinary symptom outcomes in patients with benign prostatic hyperplasia undergoing transurethral resection of prostate
Authors: Ren Xiang , Wang Jing , Wang Zhixian , Yin Yisheng , Li Xing , Tian Yiqun , Guo Zihao , Zeng Xiaoyong
Published: May 2023

Purpose

Lower urinary symptoms (LUTS) may persist in a proportion of patients with benign prostatic hyperplasia (BPH) following transurethral resection of prostate (TURP), which is a major cause of reduced quality-of-life. We aimed to investigate the effect of frailty on LUTS in patients with BPH treated with TURP.

Methods

We longitudinally evaluated LUTS and health-related quality-of-life (HRQOL) in patients with BPH treated with TURP from February 2019 and January 2022 using International Prostate Symptom Score (IPSS) and Short Form-8 (SF-8), respectively. Patients were divided into frail and non-frail groups according to the Fried phenotype (FP). The primary purpose was comparing the outcomes of LUTS and HRQOL between two groups. Secondary purposes were investigating the frailty as a preoperative predictor of postoperative adverse LUTS outcomes following TURP using logistic regression analysis. A 1:2 propensity score matching (PSM) was performed to reduce the effects of selection bias and potential confounders.

Results

Of the 567 patients enrolled, 495 (87.3%) patients were non-frail (FP = 0–2), and the remaining 72 (12.7%) patients were classified into the frail group. There were no significant differences in body mass index (BMI), urine white blood cell (UWBC), creatinine, prostate-specific antigen (PSA) and prostate volume in both groups at baseline (all p > 0.05). However, patients with frailty were older, higher comorbidity rates, lower peak flow rates and lower HRQOL. In the frail group, although LUTS and HRQOL at 6 months following TURP improved significantly compared to those at baseline, it did not show a significant improvement compared with the non-frail group (both p < 0.001). Moreover, multivariable logistic regression analysis demonstrated that preoperative frailty was significantly associated with poor LUTS improvement in both the entire cohort and PSM subset (both p < 0.05), whereas age and comorbidities were not after PSM analysis.

Conclusion

In patients with frail or non-frail, TURP for BPH provides overall good results. However, frail individuals are at higher risk of postoperative adverse LUTS outcomes. Frailty has the potential to be a strong objective tool for risk stratification and should be considered during the perioperative evaluation.
Establishment of a triplex TaqMan quantitative real-time PCR assay for simultaneous detection of Cymbidium mosaic virus, Odontoglossum ringspot virus and Cymbidium ringspot virus
Authors: Sun Aiqing , Wang Lihua , Zhang Yiping , Yang Xiumei , Wei Yi , Yang Dong , Li Wenhan , Wu Xuewei
Published: May 2023

Orchids are significant ornamental plants whose viral infection results in substantial economic damage. Cymbidium mosaic virus (CymMV), Odontoglossum ringspot virus (ORSV), and Cymbidium ringspot virus (CymRSV) represent three important and prevalent orchid viruses. The detection system proposed in this study uses a triplex TaqMan quantitative real-time PCR assay to identify CymMV, ORSV, and CymRSV in a simultaneous manner. We designed specific primers and probes for CymMV, ORSV, and CymRSV, with amplified sequences of 156 bp, 148 bp, and 145 bp, respectively. The minimum detection limit of the triplex qRT-PCR assay for CymMV and CymRSV was 1 copy/assay, and the minimum detection limit was 10 copies/assay for ORSV. The minimum stable detection limits for CymMV, ORSV, and CymRSV were 10, 102, and 102 copies/assay, respectively. Therefore, this system exhibited higher sensitivity (approximately 10 to 104-fold) than RT–PCR. The intra-and interassay CVs of Cq values are less than 0.55 and 0.95%, respectively, indicating that the triplex assay is highly reliable and accurate. In addition, 66 samples from five different orchid genera were analyzed using the established assay and gene chip. The detection results demonstrated that the triplex probe qRT–PCR demonstrated higher sensitivity than the gene chip, indicating that the triplex real-time PCR assay could be used for the detection of field samples. Our findings suggest that the triplex real-time RT–PCR detection system represents a rapid, simple, and accurate tool for detecting CymMV, ORSV, and CymRSV on orchids.
Malassezia pachydermatis from brown bear: A comprehensive analysis reveals novel genotypes and distribution of all detected variants in domestic and wild animals
Authors: Hađina Suzana , Bruvo Mađarić Branka , Kazazić Snježana , Paradžik Tina , Reljić Slaven , Pinter Ljiljana , Huber Đuro , Vujaklija Dušica
Published: May 2023

Malassezia pachydermatis (phylum Basidiomycota, class Malasseziomycetes) is a zoophilic opportunistic pathogen with recognized potential for invasive infections in humans. Although this pathogenic yeast is widespread in nature, it has been primarily studied in domestic animals, so available data on its genotypes in the wild are limited. In this study, 80 yeast isolates recovered from 42 brown bears (Ursus arctos) were identified as M. pachydermatis by a culture-based approach. MALDI-TOF mass spectrometry (MS) was used to endorse conventional identification. The majority of samples exhibited a high score fluctuation, with 42.5% of isolates generating the best scores in the range confident only for genus identification. However, the use of young biomass significantly improved the identification of M. pachydermatis at the species confidence level (98.8%). Importantly, the same MALDI-TOF MS efficiency would be achieved regardless of colony age if the cut-off value was lowered to ≥1.7. Genotyping of LSU, ITS1, CHS2, and β-tubulin markers identified four distinct genotypes in M. pachydermatis isolates. The most prevalent among them was the genotype previously found in dogs, indicating its transmission potential and adaptation to distantly related hosts. The other three genotypes are described for the first time in this study. However, only one of the genotypes consisted of all four loci with bear-specific sequences, indicating the formation of a strain specifically adapted to brown bears. Finally, we evaluated the specificity of the spectral profiles of the detected genotypes. MALDI-TOF MS exhibited great potential to detect subtle differences between all M. pachydermatis isolates and revealed distinct spectral profiles of bear-specific genotypes.
Off-label use of antimicrobials among hospitalized children: a retrospective study of 3,406 patients
Authors: Tang Lin , Zhao Kai , Hou Ning
Published: May 2023

Introduction

Off-label drug use is a global problem for which many countries and regions have issued legal provisions or reached an expert consensus. Off-label use is sometimes a necessity, especially since antibacterial drugs have become one of the most widely used drugs in pediatric settings and the issue of causing antimicrobial resistance has increasingly become unavoidable. It also poses additional risks, such as adverse drug reactions.

Methods

Our study analyzed the antimicrobial prescriptions of pediatric inpatients in a large Chinese hospital in the first half of 2021. This retrospective investigation included 6,829 prescriptions, including 2,294 off-label prescriptions. We performed descriptive analyses of prescription antimicrobial agents among pediatric populations and reported the percentages and frequencies.

Results

It was found that off-label use of antibiotics was present in many children (n = 1,665, 48.9%) and was most common in newborns (n  = 328, 82.8%). Among the commonly used antibiotics in pediatric patients, cephalosporins (n  = 2,778, 40.7%) accounted for a relatively low proportion of offlabel use (n  = 360, 15.7%), while macrolides (n  = 628, 27.4%) and penicillins (n  = 610, 26.6%) accounted for a higher proportion. The off-label type mainly referred to the appropriate population (46.5%) and dosage (dose, 10.0%; frequency of administration, 48.3%).

Discussion

Off-label use was due to imperfect labels, improper medications, or medication errors. Only a few consensuses could apply to pediatric patients. More clinical trials are required to update the consensus, and drug labels must be continuously improved. The prescription behavior of doctors is also needed to be regulated. Rational use of drugs, especially antimicrobials, is the responsibility of all people, including the states, medical institutions, and individuals.
Venetoclax is a potent hepsin inhibitor that reduces the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells
Authors: Rodenas Maria Carmen , Peñas-Martínez Julia , Pardo-Sánchez Irene , Zaragoza-Huesca David , Ortega-Sabater Carmen , Peña-García Jorge , Espín Salvador , Ricote Guillermo , Montenegro Sofía , Ayala-De La Peña Francisco , Luengo-Gil Ginés , Nieto Andrés , García-Molina Francisco , Vicente Vicente , Bernardi Francesco , Lozano María Luisa , Mulero Victoriano , Pérez-Sánchez Horacio , Carmona-Bayonas Alberto , Martínez-Martínez Irene
Published: May 2023

Introduction: Hepsin is a type II transmembrane serine protease and its expression has been linked to greater tumorigenicity and worse prognosis in different tumors. Recently, our group demonstrated that high hepsin levels from primary tumor were associated with a higher risk of metastasis and thrombosis in localized colorectal cancer patients. This study aims to explore the molecular role of hepsin in colorectal cancer.

Methods: Hepsin levels in plasma from resected and metastatic colorectal cancer patients were analyzed by ELISA. The effect of hepsin levels on cell migration, invasion, and proliferation, as well as on the activation of crucial cancer signaling pathways, was performed in vitro using colorectal cancer cells. A thrombin generation assay determined the procoagulant function of hepsin from these cells. A virtual screening of a database containing more than 2000 FDA-approved compounds was performed to screen hepsin inhibitors, and selected compounds were tested in vitro for their ability to suppress hepsin effects in colorectal cancer cells. Xenotransplantation assays were done in zebrafish larvae to study the impact of venetoclax on invasion promoted by hepsin.

Results: Our results showed higher plasma hepsin levels in metastatic patients, among which, hepsin was higher in those suffering thrombosis. Hepsin overexpression increased colorectal cancer cell invasion, Erk1/2 and STAT3 phosphorylation, and thrombin generation in plasma. In addition, we identified venetoclax as a potent hepsin inhibitor that reduced the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells. Interestingly, pretreatment with Venetoclax of cells overexpressing hepsin reduced their invasiveness in vivo.

Discussion: Our results demonstrate that hepsin overexpression correlates with a more aggressive and prothrombotic tumor phenotype. Likewise, they demonstrate the antitumor role of venetoclax as a hepsin inhibitor, laying the groundwork for molecular-targeted therapy for colorectal cancer.
Exercise program to reduce the risk of cognitive decline and physical frailty in older adults: study protocol for an open label double-arm clinical trial
Authors: Noguchi-Shinohara Moeko , Yokoyama Kunihiko , Komatsu Junji , Masuda Kazumi , Kouno Mitsunobu , Yoshita Mitsuhiro , Ono Kenjiro
Published: May 2023

Objective

It is a big problem that many older adults are physically inactive. Well-known benefits of physical exercise include a decrease in the risk of cognitive decline and physical frailty. Therefore, this study aims to examine whether our proposed exercise program can prevent cognitive decline and improve physical function in the elderly.

Methods

This study will include nondemented older adults (n = 103) without regular exercise habits. The trial will include a physical exercise training program (once a week) and nutritional lectures (once a month) over 5 months and follow-up for ≥1 year. The primary endpoint is the program’s efficacy in preventing cognitive decline, as assessed by changes in the memory performance index of the mild cognitive impairment (MCI) screen; the secondary endpoints are the incidence of MCI and dementia, physical testing, and frailty proportion. In the exploratory phase of the study, we will elucidate the underlying diseases causing MCI in community-dwelling older adults by neuroimaging.

Discussion

This double-arm trial that aims to assess the impact of physical exercise on nondemented older adults’ cognitive and physical function. Furthermore, our newly developed exercise program will be easy for older adults to undertake.

Clinical Trial Registration: https://clinicaltrials.gov/, identifier [jRCT 1040220140].
Association between handgrip strength asymmetry and cognitive function across ethnicity in rural China: a cross-sectional study
Authors: Feng Wenjing , Ma Mingfeng , Gao Hanshu , Yuan Wei , Li Ruixue , Guo Hui , Gu Cuiying , Sun Zhaoqing , Zhang Yao , Zheng Liqiang
Published: May 2023

Background

Recently, the association between handgrip strength (HGS) asymmetry and cognition has been revealed, but evidences are still scarce. Particularly, the association between asymmetric HGS and cognitive performance in various cognitive domains is unclear and whether this association is stable across ethnic groups is unknown.

Method

The population was from a longitudinal study in rural areas of Fuxin, Liaoning, China. The Chinese version of Montreal Cognitive Assessment-Basic (MOCA-BC) was used to evaluate the cognitive function. The HGS ratio was calculated as maximal non-dominant HGS divided by maximal dominant HGS. HGS ratio <0.9 or >1.1 was classified as asymmetric dominant/non-dominant HGS, respectively. Generalized linear models were used to analyze the relationship between asymmetric HGS and cognitive function adjusted for HGS, handedness, wave, age, sex, education, ethnicity, smoking, drinking, physical labor level, BMI, hypertension, diabetes and dyslipidemia.

Result

A total of 2,969 participants ≥50 years were included in this study. Adjusted for HGS and other confunding variables, there was an inverted U-shaped association between HGS ratio and MoCA-BC scores (Pnon–linear = 0.004). The association between HGS ratio and MoCA-BC scores was inconsistent among ethnic groups (Pinteraction = 0.048). In Han, only asymmetric non-dominant HGS was associated with lower cognitive scores [β = −0.67, 95% confidence interval (CI): −1.26 ∼−0.08, P = 0.027]; in Mongolians, asymmetric dominant HGS(β = −0.60, 95% CI: −1.35 ∼ 0.15, P = 0.115) and asymmetric non-dominant HGS (β = −0.56, 95% CI: −1.42 ∼ 0.31, P = 0.206) were all associated with lower cognitive scores, although no statistical significance was found. Asymmetric non-dominant HGS and lower HGS, but not asymmetric dominant HGS were all independently associated with impairment of Delayed Recall (OR = 1.35, 95% CI: 1.05 ∼ 1.74; OR per 5 kg decrease = 1.10, 95% CI: 1.01 ∼ 1.21) and Fluency (OR = 1.43, 95% CI: 1.15 ∼ 1.78; OR per 5 kg decrease = 1.10, 95% CI: 1.02 ∼ 1.19). Both asymmetric dominant HGS (OR = 1.34, 95% CI: 1.07 ∼ 1.67) and lower HGS (OR per 5 kg decrease = 1.21, 95% CI: 1.10 ∼ 1.32) were associated with impairment of visuoperception.

Conclusion

HGS and HGS asymmetry were all independently related to lower global cognitive performance. The association between HGS asymmetry and cognitive function varies among ethnic groups.
Case report: Unusual patient with dermatomyositis associated with SARS-CoV-2 infection
Authors: Niedzielska Joanna , Chaszczewska-Markowska Monika , Chojdak-Łukasiewicz Justyna , Berezowski Jakub , Kalra Seema , Jazwiec Przemysław
Published: May 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a major challenge for clinicians. SARS-CoV-2 infection results in coronavirus disease 2019 (COVID-19), and it is best known for its respiratory symptoms. It can also result in several extrapulmonary manifestations such as neurological complications potentially experienced during the course of COVID-19. The association of dermatomyositis (DM) with COVID-19 pathogenesis has not been well-studied. This study aimed to present a previously healthy 37-year-old man, a soldier by profession, with symptoms of DM on the 4th day from the onset of COVID-19. The patient presented DM symptoms with both skin and muscle manifestations. The patient suffered from cough, fever, and fatigue to begin with, and reverse-transcription polymerase chain reaction (RT-PCR) reported positive for SARS-CoV-2 infection. The laboratory findings showed, intra alia, elevated muscle enzymes CK 8253 U/l (N: <145 U/l), a positive test for myositis-specific autoantibodies (anti-Mi-2), electrodiagnostic tests exhibited features of myopathy, with the presence of muscle and skin symptoms. The patient improved with corticosteroids and immunosuppressive agent therapy. In summary, the association between COVID-19 and the development of multi-system autoimmune disorders such as DM remains unclear. Nevertheless, viral infections such as SARS-CoV-2 may likely serve as a trigger.
Extreme prematurity and perinatal risk factors related to extremely preterm birth are associated with complex patterns of regional brain volume alterations at 10 years of age: a voxel-based morphometry study
Authors: Kvanta Hedvig , Bolk Jenny , Broström Lina , Fernández de Gamarra-Oca Lexuri , Padilla Nelly , Ådén Ulrika
Published: May 2023

Objective

Structural brain volumetric differences have been investigated previously in very preterm children. However, children born extremely preterm, at the border of viability, have been studied to a lesser degree. Our group previously analyzed children born extremely preterm at term using voxel-based morphometry. In this study, we aimed to examine regional gray and white matter differences for children born extremely preterm derived from the same cohort during childhood. We also aimed to explore the effect of perinatal risk factors on brain volumes in the same group.

Methods

At 10 years of age, 51 children born extremely preterm (before 27 weeks and 0 days) and 38 term-born controls with high-quality 3.0 Tesla magnetic resonance images were included. Statistical analyses using voxel-based morphometry were conducted on images that were normalized using age-specific templates, modulated, and smoothed. Analyses were also performed in stratified groups of children born extremely preterm in the absence or presence of perinatal risk factors that have previously been shown to be associated with volumetric differences at term.

Results

We found volumetric decreases in gray and white matter in the temporal lobes, gray matter decreases in the precuneus gyri, and white matter decreases in the anterior cingulum for children born extremely preterm (all p < 0.001, and pfwe < 0.05). Gray and white matter increases were predominantly observed in the right posterior cingulum and occipital lobe (all p < 0.001, and pfwe < 0.05). Of the examined perinatal risk factors, intraventricular hemorrhage grades I-II compared with no intraventricular hemorrhage and patent ductus arteriosus ligation compared with no treated patent ductus arteriosus or patent ductus arteriosus treated with ibuprofen led to volumetric differences at 10 years of age (all p < 0.001, and pfwe < 0.05).

Conclusions

Children born extremely preterm exhibit volumetric alterations in a pattern overlapping that previously found at term, where many regions with differences are the main hubs of higher order networks. Some, but not all, risk factors known to be associated with structural alterations at term were associated with alterations at 10 years of age.
An online survival predictor in glioma patients using machine learning based on WHO CNS5 data
Authors: Ye Liguo , Gu Lingui , Zheng Zhiyao , Zhang Xin , Xing Hao , Guo Xiaopeng , Chen Wenlin , Wang Yaning , Wang Yuekun , Liang Tingyu , Wang Hai , Li Yilin , Jin Shanmu , Shi Yixin , Liu Delin , Yang Tianrui , Liu Qianshu , Deng Congcong , Wang Yu , Ma Wenbin
Published: May 2023

Background

The World Health Organization (WHO) CNS5 classification system highlights the significance of molecular biomarkers in providing meaningful prognostic and therapeutic information for gliomas. However, predicting individual patient survival remains challenging due to the lack of integrated quantitative assessment tools. In this study, we aimed to design a WHO CNS5-related risk signature to predict the overall survival (OS) rate of glioma patients using machine learning algorithms.

Methods

We extracted data from patients who underwent an operation for histopathologically confirmed glioma from our hospital database (2011–2022) and split them into a training and hold-out test set in a 7/3 ratio. We used biological markers related to WHO CNS5, clinical data (age, sex, and WHO grade), and prognosis follow-up information to identify prognostic factors and construct a predictive dynamic nomograph to predict the survival rate of glioma patients using 4 kinds machine learning algorithms (RF, SVM, XGB, and GLM).

Results

A total of 198 patients with complete WHO5 molecular data and follow-up information were included in the study. The median OS time of all patients was 29.77 [95% confidence interval (CI): 21.19–38.34] months. Age, FGFR2, IDH1, CDK4, CDK6, KIT, and CDKN2A were considered vital indicators related to the prognosis and OS time of glioma. To better predict the prognosis of glioma patients, we constructed a WHO5-related risk signature and nomogram. The AUC values of the ROC curves of the nomogram for predicting the 1, 3, and 5-year OS were 0.849, 0.835, and 0.821 in training set, and, 0.844, 0.943, and 0.959 in validation set. The calibration plot confirmed the reliability of the nomogram, and the c-index was 0.742 in training set and 0.775 in validation set. Additionally, our nomogram showed a superior net benefit across a broader scale of threshold probabilities in decision curve analysis. Therefore, we selected it as the backend for the online survival prediction tool (Glioma Survival Calculator, https://who5pumch.shinyapps.io/DynNomapp/), which can calculate the survival probability for a specific time of the patients.

Conclusion

An online prognosis predictor based on WHO5-related biomarkers was constructed. This therapeutically promising tool may increase the precision of forecast therapy outcomes and assess prognosis.
Emotional sounds in space: asymmetrical representation within early-stage auditory areas
Authors: Grisendi Tiffany , Clarke Stephanie , Da Costa Sandra
Published: May 2023

Evidence from behavioral studies suggests that the spatial origin of sounds may influence the perception of emotional valence. Using 7T fMRI we have investigated the impact of the categories of sound (vocalizations; non-vocalizations), emotional valence (positive, neutral, negative) and spatial origin (left, center, right) on the encoding in early-stage auditory areas and in the voice area. The combination of these different characteristics resulted in a total of 18 conditions (2 categories x 3 valences x 3 lateralizations), which were presented in a pseudo-randomized order in blocks of 11 different sounds (of the same condition) in 12 distinct runs of 6 min. In addition, two localizers, i.e., tonotopy mapping; human vocalizations, were used to define regions of interest. A three-way repeated measure ANOVA on the BOLD responses revealed bilateral significant effects and interactions in the primary auditory cortex, the lateral early-stage auditory areas, and the voice area. Positive vocalizations presented on the left side yielded greater activity in the ipsilateral and contralateral primary auditory cortex than did neutral or negative vocalizations or any other stimuli at any of the three positions. Right, but not left area L3 responded more strongly to (i) positive vocalizations presented ipsi- or contralaterally than to neutral or negative vocalizations presented at the same positions; and (ii) to neutral than positive or negative non-vocalizations presented contralaterally. Furthermore, comparison with a previous study indicates that spatial cues may render emotional valence more salient within the early-stage auditory areas.
Developmental patterning of peptide transcription in the central circadian clock in both sexes
Authors: Carmona-Alcocer Vania , Brown Lindsey S. , Anchan Aiesha , Rohr Kayla E. , Evans Jennifer A.
Published: May 2023

Introduction

Neuropeptide signaling modulates the function of central clock neurons in the suprachiasmatic nucleus (SCN) during development and adulthood. Arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) are expressed early in SCN development, but the precise timing of transcriptional onset has been difficult to establish due to age-related changes in the rhythmic expression of each peptide.

Methods

To provide insight into spatial patterning of peptide transcription during SCN development, we used a transgenic approach to define the onset of Avp and Vip transcription. Avp-Cre or Vip-Cre males were crossed to Ai9+/+ females, producing offspring in which the fluorescent protein tdTomato (tdT) is expressed at the onset of Avp or Vip transcription. Spatial patterning of Avp-tdT and Vip-tdT expression was examined at critical developmental time points spanning mid-embryonic age to adulthood in both sexes.

Results

We find that Avp-tdT and Vip-tdT expression is initiated at different developmental time points in spatial subclusters of SCN neurons, with developmental patterning that differs by sex.

Conclusions

These data suggest that SCN neurons can be distinguished into further subtypes based on the developmental patterning of neuropeptide expression, which may contribute to regional and/or sex differences in cellular function in adulthood.
Deciphering the mechanism of jujube vinegar on hyperlipoidemia through gut microbiome based on 16S rRNA, BugBase analysis, and the stamp analysis of KEEG
Authors: Duan Guofeng , Li Lijuan
Published: May 2023

Background

Growing data indicate that the gut microbiome may contribute to the rising incidence of hyperlipoidemia. Jujube vinegar lowers lipids, protects the liver, and reduces oxidant capacity, however, it is unknown whether this is due to the gut flora. To further research the role of the gut microbiome in treating hyperlipidemia with jujube vinegar, we looked into whether the action of jujube vinegar is related to the regulation of the gut microbiome.

Method

Thirty male ICR mice were used. The control group (CON), the high-fat diet (HFD) group, and the vinegar group (VIN) each consisted of ten female ICR mice fed consistently for eight weeks. For each treatment, we kept track of body mass, liver index, blood lipid levels, and oxidative stress state. We also analyzed mouse feces using high-throughput 16srRNA sequencing to examine the relationship between jujube vinegar’s hypolipidemic effect and antioxidant activity and how it affects the gut microbiome.

Results

Jujube vinegar reduced body weight by 19.92%, serum TC, TG, and LDL-C by 25.09%, 26.83%, and 11.66%, and increased HDL-C by 1.44 times, serum AST and ALT decreased by 26.36% and 34.87% respectively, the blood levels of SOD and GSH-Px increased 1.35-fold and 1.60-fold, respectively. While blood MDA decreased 33.21%, the liver’s SOD and GSH-Px increased 1.32-fold and 1.60-fold, respectively, and the liver’s MDA decreased 48.96% in HFD mice. The gut microbiome analysis revealed that jujube vinegar increased the intestinal microbial ASV count by 13.46%, and the F/B (Firmicutes/Bacteroidota) ratio by 2.08-fold in high-fat diet mice, and the proportion was significantly inversely correlated with TC, TG, and LDL-C and positively correlated with HDL-C. Biomarker bacteria in the vinegar group included Lactobacillaceae and Lactobacillus, which correlated favorably with HDL-C, SOD, and GSH-Px and negatively with LDL-C, TC, and TG. Jujube vinegar increased the abundance of the Aerobic, Contains Mobile Elements, and Facultative Aerobic by 2.84 times, 1.45 times, and 2.40 times, while decreased the abundance of Potential pathogens by 44.72%, according to the BugBase study. The KEGG analysis showed that jujube vinegar was predominantly reflected in the biological process of gene function and related to signal transduction pathways, including glucagon signaling system, HIF-1 signaling pathway, adipocytokine signaling pathway, amino sugar, and nucleotide sugar metabolism, and so forth.

Conclusion

Based on these findings, jujube vinegar may reduce hyperlipoidemia by controlling the gut microbiome and enhancing antioxidant capacity.
Deciphering immune microenvironment and cell evasion mechanisms in human gliomas
Authors: Rafii Soumaya , Kandoussi Sarah , Ghouzlani Amina , Naji Oumayma , Reddy Konala Priyanka , Ullah Sadiqi Rizwan , Badou Abdallah
Published: May 2023

Gliomas are considered one of the most malignant cancers in the body. Despite current therapies, including surgery, chemotherapy, and radiotherapy, these tumors usually recur with more aggressive and resistant phenotypes. Indeed, the survival following these conventional therapies is very poor, which makes immunotherapy the subject of active research at present. The anti-tumor immune response could also be considered a prognostic factor since each stage of cancer development is regulated by immune cells. However, glioma microenvironment contains malignant cells that secrete numerous chemokines, cytokines and growth factors, promoting the infiltration of immunosuppressive cells into the tumor, which limit the functioning of the immune system against glioma cells. Recently, researchers have been able to reverse the immune resistance of cancer cells and thus activate the anti-tumor immune response through different immunotherapy strategies. Here, we review the general concept of glioma’s immune microenvironment and report the impact of its distinct components on the anti-tumor immune response. We also discuss the mechanisms of glioma cell evasion from the immune response and pinpoint some potential therapeutic pathways, which could alleviate such resistance.
Ubiquitination-related biomarkers in metastatic melanoma patients and their roles in tumor microenvironment
Authors: Zhang Li , Shi Zhehao , Zhang Fan , Chen Bin , Qiu Wei , Cai Lei , Lin Xiaohua
Published: May 2023

Background

Skin cutaneous melanoma (SKCM) is the deadliest type of cutaneous malignancy. Ubiquitination is a process of protein sorting and degradation that exhibits multiple functions in the progression of various tumors. This study aimed to characterize a set of genes for ubiquitination in SKCM.

Methods

The expression patterns of ubiquitin-associated genes (URGs) and the corresponding clinical information in SKCM tissues were comprehensively analyzed based on The Cancer Genome Atlas (TCGA) database. We performed univariate and multivariate Cox proportional regression models to characterize the risk scores and identify four critical genes related to prognostic ubiquitination (HCLS1, CORO1A, NCF1 and CCRL2), which were used to construct the prognostic signatures. We also studied the effects of HCLS1, CORO1A and CCRL2 on tumor metastasis-related indicators at the cellular level through in vitro experiments.

Results

SKCM patients in the low-risk group showing a longer survival than those in the high-risk group. Characteristic risk scores correlated with several clinicopathological variables and reflected the infiltration of multiple immune cells. In addition, the knockdown of CLS1, CORO1A and CCRL2 affected cellular malignant biological behavior through the EMT signaling pathway.

Conclusion

This study provides a novel and prospective strategy to improve the clinical survival of SKCM patients.
Crosstalk between arginine, glutamine, and the branched chain amino acid metabolism in the tumor microenvironment
Authors: Wetzel Tanner J. , Erfan Sheila C. , Figueroa Lucas D. , Wheeler Leighton M. , Ananieva Elitsa A.
Published: May 2023

Arginine, glutamine, and the branched chain amino acids (BCAAs) are a focus of increased interest in the field of oncology due to their importance in the metabolic reprogramming of cancer cells. In the tumor microenvironment (TME), these amino acids serve to support the elevated biosynthetic and energy demands of cancer cells, while simultaneously maintaining the growth, homeostasis, and effector function of tumor-infiltrating immune cells. To escape immune destruction, cancer cells utilize a variety of mechanisms to suppress the cytotoxic activity of effector T cells, facilitating T cell exhaustion. One such mechanism is the ability of cancer cells to overexpress metabolic enzymes specializing in the catabolism of arginine, glutamine, and the BCAAs in the TME. The action of such enzymes supplies cancer cells with metabolic intermediates that feed into the TCA cycle, supporting energy generation, or providing precursors for purine, pyrimidine, and polyamine biosynthesis. Armed with substantial metabolic flexibility, cancer cells redirect amino acids from the TME for their own advantage and growth, while leaving the local infiltrating effector T cells deprived of essential nutrients. This review addresses the metabolic pressure that cancer cells exert over immune cells in the TME by up-regulating amino acid metabolism, while discussing opportunities for targeting amino acid metabolism for therapeutic intervention. Special emphasis is given to the crosstalk between arginine, glutamine, and BCAA metabolism in affording cancer cells with metabolic dominance in the TME.
COVID-19 musculoskeletal involvement in children
Authors: Giraudo Chiara , Fichera Giulia , Pilati Lucia , Cortinovis Anna Laura , Cavallin Celeste , Bertin Sofia , Zuliani Monica , Cecchin Diego
Published: May 2023

Since the early phases of the COVID-19 pandemic, it has become clear that children are affected by mild respiratory symptoms rather than the critical pneumonia typical in adults. Nevertheless, it took longer to understand that pediatric patients with SARS-COV2 may develop a severe multisystem inflammatory response (a.k.a. multisystem inflammatory syndrome in children (MIS-C)), which can include musculoskeletal symptoms, and/or arthritis and myositis independently from MIS-C. Diagnostic imaging significantly contributed to the assessment of pulmonary disease due to COVID-19 but it has been rarely applied to evaluate musculoskeletal involvement in children with or without previous rheumatic diseases. Despite the paucity of radiological literature, muscle edema at magnetic resonance and synovitis at ultrasound have been described. Further use of diagnostic imaging for children with articular and muscular symptoms due to COVID-19 is strongly encouraged.
A review of nanomaterials from synthetic and natural molecules for prospective breast cancer nanotherapy
Authors: Kumar Pankaj , Mangla Bharti , Javed Shamama , Ahsan Waquar , Musyuni Pankaj , Sivadasan Durgaramani , Alqahtani Saad S. , Aggarwal Geeta
Published: May 2023

Breast cancer being one of the most frequent cancers in women accounts for almost a quarter of all cancer cases. Early and late-stage breast cancer outcomes have improved dramatically, with considerable gains in overall survival rate and disease-free state. However, the current therapy of breast cancer suffers from drug resistance leading to relapse and recurrence of the disease. Also, the currently used synthetic and natural agents have bioavailability issues which limit their use. Recently, nanocarriers-assisted delivery of synthetic and natural anticancer drugs has been introduced to the breast cancer therapy which alienates the limitations associated with the current therapy to a great extent. Significant progress has lately been made in the realm of nanotechnology, which proved to be vital in the fight against drug resistance. Nanotechnology has been successfully applied in the effective and improved therapy of different forms of breast cancer including invasive, non-invasive as well as triple negative breast cancer (TNBC), etc. This review presents a comprehensive overview of various nanoformulations prepared for the improved delivery of synthetic and natural anticancer drugs alone or in combination showing better efficacy and pharmacokinetics. In addition to this, various ongoing and completed clinical studies and patents granted on nanotechnology-based breast cancer drug delivery are also reviewed.