bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of platelet-rich plasma in spinal surgery
Authors: Wang Hengyi , Zhu Jianshu , Xia Yuanliang , Li Yuehong , Fu Changfeng
Published: March 2023

With the aging of the population and changes in lifestyle, the incidence of spine-related diseases is increasing, which has become a major global public health problem; this results in a huge economic burden on the family and society. Spinal diseases and complications can lead to loss of motor, sensory, and autonomic functions. Therefore, it is necessary to identify effective treatment strategies. Currently, the treatment of spine-related diseases includes conservative, surgical, and minimally invasive interventional therapies. However, these treatment methods have several drawbacks such as drug tolerance and dependence, adjacent spondylosis, secondary surgery, infection, nerve injury, dural rupture, nonunion, and pseudoarthrosis. Further, it is more challenging to promote the regeneration of the interstitial disc and restore its biomechanical properties. Therefore, clinicians urgently need to identify methods that can limit disease progression or cure diseases at the etiological level. Platelet-rich plasma (PRP), a platelet-rich form of plasma extracted from venous blood, is a blood-derived product. Alpha granules contain a large number of cytokines, such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), epidermal growth factor, platelet factor 4 (PF-4), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β (TGF-β). These growth factors allow stem cell proliferation and angiogenesis, promote bone regeneration, improve the local microenvironment, and enhance tissue regeneration capacity and functional recovery. This review describes the application of PRP in the treatment of spine-related diseases and discusses the clinical application of PRP in spinal surgery.
Transcriptome landscape comparison of periodontium in developmental and renewal stages
Authors: Deng Yuwei , Luo Nan , Xie Ming , He Ling , Jiang Ruixue , Hu Nan , Wen Jin , Jiang Xinquan
Published: March 2023

Objectives

Periodontium regeneration remains a significant challenge in clinics and research, and it is essential to understand the stage-specific biological process in situ. However, differing findings have been reported, and the mechanism has yet to be elucidated. The periodontium of adult mice molars is considered to be stable remodeling tissue. At the same time, the continuously growing incisors and the developing dental follicle (DF) of postnatal mice highly represent fast remodeling tissue. In this study, we attempted to explore different clues of temporal and spatial comparisons to provide improved references for periodontal regeneration.

Methods

Periodontal tissues from the developing periodontium (DeP) of postnatal mice, and continuously growing periodontium (CgP) and stable remodeling periodontium (ReP) of adult mice were isolated and compared using RNA sequencing. Based on the Dep and CgP separately compared with the ReP, differentially expressed genes and signaling pathways were analyzed using GO, KEGG databases, and Ingenuity Pathway Analysis (IPA). The results and validation were obtained by immunofluorescence staining and RT-PCR assays. Data were expressed as means ± standard deviation (SD) and analyzed by GraphPad Prism 8 software package, and one-way ANOVA was used to test multiple groups.

Results

Principal component analysis showed that the three groups of periodontal tissue were successfully isolated and had distinct expression profiles. A total of 792 and 612 DEGs were identified in the DeP and CgP groups compared with the ReP. Upregulated DEGs in the DeP were closely related to developmental processes, while the CgP showed significantly enhanced cellular energy metabolism. The DeP and CgP showed a common downregulation of the immune response, with activation, migration, and recruitment of immune cells. IPA and further validation jointly suggested that the MyD88/p38 MAPK pathway played an essential regulatory role in periodontium remodeling.

Conclusion

Tissue development, energy metabolism, and immune response were critical regulatory processes during periodontal remodeling. Developmental and adult stages of periodontal remodeling showed different expression patterns. These results contribute to a deeper understanding of periodontal development and remodeling and may provide references for periodontal regeneration.
Investigating the growth of carbon traces in cardboard in oil-paper insulation
Authors: Zhang Zhanlong , Pan Xiaomei , Dong Zijian , Zhong Jiarong , Wang Xuemeng
Published: March 2023

A large amount of contaminants are collected on the cardboard surface of the valve-side bushing outlet of a converter transformer that has been operating for a long period, and can cause the performance of the oil–paper insulation to degrade. The analysis of their energy spectrum has shown that these contaminants contain free carbon. To investigate causes of the formation of these carbon traces, the authors of this study analyze their law of growth on the surface of the insulating paper in the presence of pure insulating oil and insulating oil containing carbon particles. We examined the influence of carbon tracks of different lengths on the breakdown voltage along the surface of the oil–paper insulation. The results showed that carbonization on the surface of the insulating paper generated carbon traces in pure insulating oil and eventually led to the formation of conductive channels. Moreover, carbon traces were generated by carbon particles deposited on the surface of the insulating paper in insulating oil containing carbon particles. The carbon traces grew from the high-voltage electrode to the ground electrode along the direction of the electric field in both types of oils. The formation of the conductive channel through the poles of the paper in insulating oil containing carbon particles required a lower voltage and a shorter discharge time than that in pure insulating oil. As the concentration of the carbon particles increased, the rate of growth of carbon traces on the surface of the insulating paper increased such that the oil–paper insulation failed earlier than otherwise. Long carbon traces were formed on the surface of the insulating paper in case of a high concentration of carbon particles under the DC pre-pressure mode, and this led to a reduction in the breakdown voltage along the surface of the oil–paper insulation.
Irrigation suitability and health risk assessment of groundwater resources in the Firozabad industrial area of north-central India: An integrated indexical, statistical, and geospatial approach
Authors: Saraswat Anuj , Nath Triyugi , Omeka Michael E. , Unigwe Chinanu O. , Anyanwu Ifeanyi E. , Ugar Samuel I. , Latare Ashish , Raza Md Basit , Behera Biswaranjan , Adhikary Partha P. , Scopa Antonio , AbdelRahman Mohamed A. E.
Published: March 2023

The recent global upsurge in anthropogenic activities has resulted in a decline in the quality of water. This by extension has resulted in increased ubiquity of water pollution in terms of sources. The application of traditional water quality assessment methods usually involves the use of conventional water quality parameters and guideline values. This may be associated with bias and errors during the computation of various sub-indices. Hence, to overcome this limitation, it is critical to have a visual appraisal of the water quality in terms of source and human health risks exposure for sustainable water resource management and informed decision-making. Therefore, the present study has integrated multiple water quality assessment indices, spatio-temporal, and statistical models to assess the suitability of fifty groundwater samples (n = 50) within the Firozabad industrial area for irrigation and drinking; as well as the likely health risks from oral intake and dermal contact by inhabitants. Electrical conductivity (mean = 1,576.6 μs/cm), total hardness (mean = 230.9 mg/L), dissolved sodium (mean = 305.1 mg/L) chloride (mean = 306.1 mg/L) and fluoride (mean = 1.52 mg/L) occurred in the water at concentrations above the recommended standards; attributed influxes from agricultural and industrial wastewater. The pollution index of groundwater and water quality index revealed that 100% of the groundwater samples are extremely polluted; this was also supported by the joint multivariate statistical analyses. The majority of the irrigational water quality indices (sodium adsorption ratio, Kelly’s Ratio, permeability index, percent sodium) revealed that the long-term use of the groundwater for irrigation in the area will result in reduced crop yield unless remedial measures are put in place. Higher Hazard index (HI > 1) for nitrate and fluoride ingestion was recorded in water for the children population compared to adult; an indication that the children population is more predisposed to health risks from the oral intake of water. Generally, risk levels from ingestion appear to increase in the western and north-eastern parts of the study area. From the findings of this study, it is highly recommended that adequate agricultural practices, land use, and water treatment regulatory strategies be put in place for water quality sustainability for enhanced agricultural production and human health protection.
The role of long non-coding RNA in abdominal aortic aneurysm
Authors: Xu Yi , Yang Shuofei , Xue Guanhua
Published: March 2023

The abdominal aortic aneurysm (AAA) is characterized by segmental expansion of the abdominal aorta and a high mortality rate. The characteristics of AAA suggest that apoptosis of smooth muscle cells, the production of reactive oxygen species, and inflammation are potential pathways for the formation and development of AAA. Long non-coding RNA (lncRNA) is becoming a new and essential regulator of gene expression. Researchers and physicians are focusing on these lncRNAs to use them as clinical biomarkers and new treatment targets for AAAs. LncRNA studies are beginning to emerge, suggesting that they may play a significant but yet unidentified role in vascular physiology and disease. This review examines the role of lncRNA and their target genes in AAA to increase our understanding of the disease’s onset and progression, which is crucial for developing potential AAA therapies.
Construction and immunogenicity of an mRNA vaccine against chikungunya virus
Authors: Liu Jingjing , Lu Xishan , Li Xingxing , Huang Weijin , Fang Enyue , Li Wenjuan , Liu Xiaohui , Liu Minglei , Li Jia , Li Ming , Zhang Zelun , Song Haifeng , Ying Bo , Li Yuhua
Published: March 2023

Chikungunya fever (CHIKF) has spread to more than 100 countries worldwide, with frequent outbreaks in Europe and the Americas in recent years. Despite the relatively low lethality of infection, patients can suffer from long-term sequelae. Until now, no available vaccines have been approved for use; however, increasing attention is being paid to the development of vaccines against chikungunya virus (CHIKV), and the World Health Organization has included vaccine development in the initial blueprint deliverables. Here, we developed an mRNA vaccine using the nucleotide sequence encoding structural proteins of CHIKV. And immunogenicity was evaluated by neutralization assay, Enzyme-linked immunospot assay and Intracellular cytokine staining. The results showed that the encoded proteins elicited high levels of neutralizing antibody titers and T cell-mediated cellular immune responses in mice. Moreover, compared with the wild-type vaccine, the codon-optimized vaccine elicited robust CD8+ T-cell responses and mild neutralizing antibody titers. In addition, higher levels of neutralizing antibody titers and T-cell immune responses were obtained using a homologous booster mRNA vaccine regimen of three different homologous or heterologous booster immunization strategies. Thus, this study provides assessment data to develop vaccine candidates and explore the effectiveness of the prime-boost approach.
Adrenergic receptor signaling regulates the CD40-receptor mediated anti-tumor immunity
Authors: Singh Akansha , Ranjan Ashish
Published: March 2023

Introduction

Anti-CD40 agonistic antibody (αCD40), an activator of dendritic cells (DC) can enhance antigen presentation and activate cytotoxic T-cells against poorly immunogenic tumors. However, cancer immunotherapy trials also suggest that αCD40 is only moderately effective in patients, falling short of achieving clinical success. Identifying factors that decrease αCD40 immune-stimulating effects can aid the translation of this agent to clinical reality.

Method/Results

Here, we reveal that β-adrenergic signaling on DCs directly interferes with αCD40 efficacy in immunologically cold head and neck tumor model. We discovered that β-2 adrenergic receptor (β2AR) activation rewires CD40 signaling in DCs by directly inhibiting the phosphorylation of IκBα and indirectly by upregulating levels of phosphorylated-cAMP response element-binding protein (pCREB). Importantly, the addition of propranolol, a pan β-Blocker reprograms the CD40 pathways, inducing superior tumor regressions, increased infiltration of cytotoxic T-cells, and a reduced burden of regulatory T-cells in tumors compared to monotherapy.

Conclusion

Our study highlights an important mechanistic link between stress-induced β2AR signaling and reduced αCD40 efficacy in cold tumors, providing a new combinatorial approach to improve clinical outcomes in patients.
SnoRNA and lncSNHG: Advances of nucleolar small RNA host gene transcripts in anti-tumor immunity
Authors: Xiao Hao , Feng Xin , Liu Mengjun , Gong Hanwen , Zhou Xiao
Published: March 2023

The small nucleolar RNA host genes (SNHGs) are a group of genes that can be transcript into long non-coding RNA SNHG (lncSNHG) and further processed into small nucleolar RNAs (snoRNAs). Although lncSNHGs and snoRNAs are well established to play pivotal roles in tumorigenesis, how lncSNHGs and snoRNAs regulate the immune cell behavior and function to mediate anti-tumor immunity remains further illustrated. Certain immune cell types carry out distinct roles to participate in each step of tumorigenesis. It is particularly important to understand how lncSNHGs and snoRNAs regulate the immune cell function to manipulate anti-tumor immunity. Here, we discuss the expression, mechanism of action, and potential clinical relevance of lncSNHGs and snoRNAs in regulating different types of immune cells that are closely related to anti-tumor immunity. By uncovering the changes and roles of lncSNHGs and snoRNAs in different immune cells, we aim to provide a better understanding of how the transcripts of SNHGs participate in tumorigenesis from an immune perspective.
Lipocalin-2 and neutrophil activation in pancreatic cancer cachexia
Authors: Deng Min , Aberle Merel R. , van Bijnen Annemarie A. J. H. M. , van der Kroft Gregory , Lenaerts Kaatje , Neumann Ulf P. , Wiltberger Georg , Schaap Frank G. , Olde Damink Steven W. M. , Rensen Sander S.
Published: March 2023

Background

Cancer cachexia is a multifactorial syndrome characterized by body weight loss and systemic inflammation. The characterization of the inflammatory response in patients with cachexia is still limited. Lipocalin-2, a protein abundant in neutrophils, has recently been implicated in appetite suppression in preclinical models of pancreatic cancer cachexia. We hypothesized that lipocalin-2 levels could be associated with neutrophil activation and nutritional status of pancreatic ductal adenocarcinoma (PDAC) patients.

Methods

Plasma levels of neutrophil activation markers calprotectin, myeloperoxidase, elastase, and bactericidal/permeability-increasing protein (BPI) were compared between non-cachectic PDAC patients (n=13) and cachectic PDAC patients with high (≥26.9 ng/mL, n=34) or low (<26.9 ng/mL, n=34) circulating lipocalin-2 levels. Patients’ nutritional status was assessed by the patient-generated subjective global assessment (PG-SGA) and through body composition analysis using CT-scan slices at the L3 level.

Results

Circulating lipocalin-2 levels did not differ between cachectic and non-cachectic PDAC patients (median 26.7 (IQR 19.7-34.8) vs. 24.8 (16.6-29.4) ng/mL, p=0.141). Cachectic patients with high systemic lipocalin-2 levels had higher concentrations of calprotectin, myeloperoxidase, and elastase than non-cachectic patients or cachectic patients with low lipocalin-2 levels (calprotectin: 542.3 (355.8-724.9) vs. 457.5 (213.3-606.9), p=0.448 vs. 366.5 (294.5-478.5) ng/mL, p=0.009; myeloperoxidase: 30.3 (22.1-37.9) vs. 16.3 (12.0-27.5), p=0.021 vs. 20.2 (15.0-29.2) ng/mL, p=0.011; elastase: 137.1 (90.8-253.2) vs. 97.2 (28.8-215.7), p=0.410 vs. 95.0 (72.2-113.6) ng/mL, p=0.006; respectively). The CRP/albumin ratio was also higher in cachectic patients with high lipocalin-2 levels (2.3 (1.3-6.0) as compared to non-cachectic patients (1.0 (0.7-4.2), p=0.041). Lipocalin-2 concentrations correlated with those of calprotectin (rs=0.36, p<0.001), myeloperoxidase (rs=0.48, p<0.001), elastase (rs=0.50, p<0.001), and BPI (rs=0.22, p=0.048). Whereas no significant correlations with weight loss, BMI, or L3 skeletal muscle index were observed, lipocalin-2 concentrations were associated with subcutaneous adipose tissue index (rs=-0.25, p=0.034). Moreover, lipocalin-2 tended to be elevated in severely malnourished patients compared with well-nourished patients (27.2 (20.3-37.2) vs. 19.9 (13.4-26.4) ng/mL, p=0.058).

Conclusions

These data suggest that lipocalin-2 levels are associated with neutrophil activation in patients with pancreatic cancer cachexia and that it may contribute to their poor nutritional status.
Artificial intelligence in colposcopic examination: A promising tool to assist junior colposcopists
Authors: Wu Aiyuan , Xue Peng , Abulizi Guzhalinuer , Tuerxun Dilinuer , Rezhake Remila , Qiao Youlin
Published: March 2023

Introduction

Well-trained colposcopists are in huge shortage worldwide, especially in low-resource areas. Here, we aimed to evaluate the Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) to detect abnormalities based on digital colposcopy images, especially focusing on its role in assisting junior colposcopist to correctly identify the lesion areas where biopsy should be performed.

Materials and methods

This is a hospital-based retrospective study, which recruited the women who visited colposcopy clinics between September 2021 to January 2022. A total of 366 of 1,146 women with complete medical information recorded by a senior colposcopist and valid histology results were included. Anonymized colposcopy images were reviewed by CAIADS and a junior colposcopist separately, and the junior colposcopist reviewed the colposcopy images with CAIADS results (named CAIADS-Junior). The diagnostic accuracy and biopsy efficiency of CAIADS and CAIADS-Junior were assessed in detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+), CIN3+, and cancer in comparison with the senior and junior colposcipists. The factors influencing the accuracy of CAIADS were explored.

Results

For CIN2 + and CIN3 + detection, CAIADS showed a sensitivity at ~80%, which was not significantly lower than the sensitivity achieved by the senior colposcopist (for CIN2 +: 80.6 vs. 91.3%, p = 0.061 and for CIN3 +: 80.0 vs. 90.0%, p = 0.189). The sensitivity of the junior colposcopist was increased significantly with the assistance of CAIADS (for CIN2 +: 95.1 vs. 79.6%, p = 0.002 and for CIN3 +: 97.1 vs. 85.7%, p = 0.039) and was comparable to those of the senior colposcopists (for CIN2 +: 95.1 vs. 91.3%, p = 0.388 and for CIN3 +: 97.1 vs. 90.0%, p = 0.125). In detecting cervical cancer, CAIADS achieved the highest sensitivity at 100%. For all endpoints, CAIADS showed the highest specificity (55–64%) and positive predictive values compared to both senior and junior colposcopists. When CIN grades became higher, the average biopsy numbers decreased for the subspecialists and CAIADS required a minimum number of biopsies to detect per case (2.2–2.6 cut-points). Meanwhile, the biopsy sensitivity of the junior colposcopist was the lowest, but the CAIADS-assisted junior colposcopist achieved a higher biopsy sensitivity.

Conclusion

Colposcopic Artificial Intelligence Auxiliary Diagnostic System could assist junior colposcopists to improve diagnostic accuracy and biopsy efficiency, which might be a promising solution to improve the quality of cervical cancer screening in low-resource settings.
A novel lytic polysaccharide monooxygenase from enrichment microbiota and its application for shrimp shell powder biodegradation
Authors: Zhang Yang , Pan Delong , Xiao Peiyao , Xu Qianqian , Geng Fan , Zhang Xinyu , Zhou Xiuling , Xu Hong
Published: March 2023

Lytic polysaccharide monooxygenases (LPMO) are expected to change the current status of chitin resource utilization. This study reports that targeted enrichment of the microbiota was performed with chitin by the selective gradient culture technique, and a novel LPMO (M2822) was identified from the enrichment microbiota metagenome. First, soil samples were screened based on soil bacterial species and chitinase biodiversity. Then gradient enrichment culture with different chitin concentrations was carried out. The efficiency of chitin powder degradation was increased by 10.67 times through enrichment, and chitin degradation species Chitiniphilus and Chitinolyticbacter were enriched significantly. A novel LPMO (M2822) was found in the metagenome of the enriched microbiota. Phylogenetic analysis showed that M2822 had a unique phylogenetic position in auxiliary activity (AA) 10 family. The analysis of enzymatic hydrolysate showed that M2822 had chitin activity. When M2822 synergized with commercial chitinase to degrade chitin, the yield of N-acetyl glycosamine was 83.6% higher than chitinase alone. The optimum temperature and pH for M2822 activity were 35°C and 6.0. The synergistic action of M2822 and chitin-degrading enzymes secreted by Chitiniphilus sp. LZ32 could efficiently hydrolyze shrimp shell powder. After 12 h of enzymatic hydrolysis, chitin oligosaccharides (COS) yield reached 4,724 μg/mL. To our knowledge, this work is the first study to mine chitin activity LPMO in the metagenome of enriched microbiota. The obtained M2822 showed application prospects in the efficient production of COS.
Combination of organic acids benzoate, butyrate, caprylate, and sorbate provides a novel antibiotics-independent treatment option in the combat of acute campylobacteriosis
Authors: Du Ke , Foote Minnja S. , Mousavi Soraya , Buczkowski Agnes , Schmidt Sebastian , Peh Elisa , Kittler Sophie , Bereswill Stefan , Heimesaat Markus M.
Published: March 2023

Introduction

The food-borne Gram-negative bacterial pathogenCampylobacter jejunimay cause the acute enterocolitis syndrome campylobacteriosis in infected humans. Given that humanC. jejuniinfections are rising globally which hold also true for resistance rates against antibiotic compounds such as macrolides and fluoroquinolones frequently prescribed for the treatment of severe infectious enteritis, novel antibiotics-independent therapeutic strategies are needed. Distinct organic acids are well known for their health-beneficial including anti-microbial and immunomodulatory properties. In our present study, we investigated potential pathogen-lowering and anti-inflammatory effects of benzoic acid, butyric acid, caprylic acid, and sorbic acid either alone or in combination during acute murine campylobacteriosis.

Methods

Therefore, secondary abiotic IL-10–/–mice were perorally infected withC. jejunistrain 81–176 and subjected to a 4-day-course of respective organic acid treatment.

Results and discussion

On day 6 post-infection, mice from the combination cohort displayed slightly lower pathogen loads in the duodenum, but neither in the stomach, ileum nor large intestine. Remarkably, the clinical outcome ofC. jejuniinduced acute enterocolitis was significantly improved after combined organic acid treatment when compared to the placebo control group. In support, the combinatory organic acid treatment dampened both, macroscopic and microscopic inflammatory sequelae ofC. jejuniinfection as indicated by less colonic shrinkage and less pronounced histopathological including apoptotic epithelial cell changes in the colon on day 6 post-infection. Furthermore, mice from the combination as compared to placebo cohort exhibited lower numbers of innate and adaptive immune cells such as neutrophilic granulocytes, macrophages, monocytes, and T lymphocytes in their colonic mucosa and lamina propria, respectively, which also held true for pro-inflammatory cytokine secretion in the large intestines and mesenteric lymph nodes. Notably, the anti-inflammatory effects were not restricted to the intestinal tract, but could also be observed systemically given pro-inflammatory mediator concentrations inC. jejuniinfected mice from the combination organic acid treatment that were comparable to basal values. In conclusion, ourin vivostudy provides first evidence that an oral application of distinct organic acids in combination exhibits pronounced anti-inflammatory effects and hence, constitutes a promising novel antibiotics-independent therapeutic strategy in the combat of acute campylobacteriosis.
Remnant cholesterol and mild cognitive impairment: A cross-sectional study
Authors: Zhang Qiaoyang , Huang Shan , Cao Yin , Dong Guanzhong , Chen Yun , Zhu Xuanyan , Yun Wenwei , Zhang Min
Published: March 2023

Objective

Emerging evidence suggests that elevated remnant cholesterol (RC) correlates with several health conditions. To explore the association of plasma RC with MCI incidence and the relationship between plasma RC and different domains of cognition in MCI patients.

Methods

Thirty-six MCI patients and 38 cognitively healthy controls (HC) were enrolled in the present cross-sectional study. Using total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C) as the formula for calculating fasting RC. Cognition was assessed using the Chinese version of the Montreal cognitive assessment (MoCA), Auditory Verbal Learning Test (AVLT), Digit Symbol Substitution Test (DSST), Trail Making Test (TMT), and Rey-Osterrieth Complex Figure Test (ROCF).

Results

Compared to healthy controls, MCI patients had a higher level of RC, the median difference in RC levels between these two groups was 8.13 mg/dl (95.0%CI: 0.97–16.1). Concurrently, plasma RC level was positively associated with MCI risk (OR = 1.05, 95%CI: 1.01–1.10). Notably, elevated RC level was correlated with impaired cognition in MCI patients, such as DSST (pr = −0.45, p = 0.008), ROCF- Long Delayed Recall (pr = −0.45, p = 0.008), AVLT-Immediate Recall (pr = −0.38, p = 0.028), and TMT-A (pr = 0.44, p = 0.009). Conversely, no significant correlation was found between RC and the AVLT-Long Delayed Recall test.

Conclusion

This study found that plasma remnant cholesterol was associated with MCI. Further large longitudinal studies are needed in the future to confirm the results and clarify the cause-and-effect relationship.
LPS-stimulated microglial cells promote ganglion cell death in organotypic cultures of quail embryo retina
Authors: Sierra-Martín Ana , Navascués Julio , Neubrand Veronika E. , Sepúlveda M. Rosario , Martín-Oliva David , Cuadros Miguel A. , Marín-Teva José L.
Published: March 2023

During development microglia colonize the central nervous system (CNS) and play an important role in programmed cell death, not only because of their ability to remove dead cells by phagocytosis, but also because they can promote the death of neuronal and glial cells. To study this process, we used as experimental systems the developing in situ quail embryo retina and organotypic cultures of quail embryo retina explants (QEREs). In both systems, immature microglia show an upregulation of certain inflammatory markers, e.g., inducible NO synthase (iNOS), and nitric oxide (NO) under basal conditions, which can be further enhanced with LPS-treatment. Hence, we investigated in the present study the role of microglia in promoting ganglion cell death during retinal development in QEREs. Results showed that LPS-stimulation of microglia in QEREs increases (i) the percentage of retinal cells with externalized phosphatidylserine, (ii) the frequency of phagocytic contacts between microglial and caspase-3-positive ganglion cells, (iii) cell death in the ganglion cell layer, and (iv) microglial production of reactive oxygen/nitrogen species, such as NO. Furthermore, iNOS inhibition by L-NMMA decreases cell death of ganglion cells and increases the number of ganglion cells in LPS-treated QEREs. These data demonstrate that LPS-stimulated microglia induce ganglion cell death in cultured QEREs by a NO-dependent mechanism. The fact that phagocytic contacts between microglial and caspase-3-positive ganglion cells increase suggests that this cell death might be mediated by microglial engulfment, although a phagocytosis-independent mechanism cannot be excluded.
Traditional Chinese Manual Therapy (Tuina) reshape the function of default mode network in patients with lumbar disc herniation
Authors: Chen Xiao-Min , Wen Ya , Chen Shao , Jin Xin , Liu Chen , Wang Wei , Kong Ning , Ling Dong-Ya , Huang Qin , Chai Jin-Er , Zhao Xiao-Lei , Li Jie , Xu Mao-Sheng , Jiang Zhong , Du Hong-Gen
Published: March 2023

Purpose

Investigating the changes of regional homogeneity (ReHo) values and both static and dynamic functional connectivity (FC) before and after Traditional Chinese Manual Therapy (Tuina) in patients with lumbar disk herniation (LDH) through resting-state functional magnetic resonance imaging (RS-fMRI). Based on this, we observe the effect of Tuina on the above abnormal changes.

Methods

Patients with LDH (n = 27) and healthy controls (HCs) (n = 28) were recruited. The functional magnetic resonance imaging (fMRI) scanning was performed two times in LDH patients, before Tuina (time point 1, LDH-pre) and after the sixth Tuina (time point 2, LDH-pos). And for one time in HCs which received no intervention. The ReHo values were compared between LDH-pre and HCs. The significant clusters detected by ReHo analysis were selected as seeds to calculate static functional connectivity (sFC). We also applied the sliding-window to perform dynamic functional connectivity (dFC). To evaluate the Tuina effect, the mean ReHo and FC values (both static and dynamic) were extracted from significant clusters and compared between LDH and HCs.

Results

In comparison to HCs, LDH patients displayed decreased ReHo in the left orbital part middle frontal gyrus (LO-MFG). For sFC analysis, no significant difference was found. However, we found decreased dFC variance between LO-MFG and the left Fusiform, and increased dFC variance in the left orbital inferior frontal gyrus and left precuneus. Both ReHo and dFC values revealed after Tuina, the brain activities in LDH patients were similar to HCs.

Conclusion

The present study characterized the altered patterns of regional homogeneity in spontaneous brain activity and those of functional connectivity in patients with LDH. Tuina can reshape the function of the default mode network (DMN) in LDH patients, which may contribute to the analgesic effect of Tuina in LDH patients.
Quantification of tumor induced motor cortical plasticity using navigated transcranial magnetic stimulation in patients with adult-type diffuse gliomas
Authors: Almeida Cesar Cimonari de , Neville Iuri Santana , Hayashi Cintya Yukie , Gomes dos Santos Alexandra , Brunoni André Russowsky , Teixeira Manoel Jacobsen , Paiva Wellingson Silva
Published: March 2023

Introduction

The evaluation of brain plasticity can provide relevant information for the surgical planning of patients with brain tumors, especially when it comes to intrinsic lesions such as gliomas. Neuronavigated transcranial magnetic stimulation (nTMS) is a non-invasive tool capable of providing information about the functional map of the cerebral cortex. Although nTMS presents a good correlation with invasive intraoperative techniques, the measurement of plasticity still needs standardization. The present study evaluated objective and graphic parameters in the quantification and qualification of brain plasticity in adult patients with gliomas in the vicinity of the motor area.

Methods

This is a prospective observational study that included 35 patients with a radiological diagnosis of glioma who underwent standard surgical treatment. nTMS was performed with a focus on the motor area of the upper limbs in both the affected and healthy cerebral hemispheres in all patients to obtain data on motor thresholds (MT) and graphical evaluation by three-dimensional reconstruction and mathematical analysis of parameters related to the location and displacement of the motor centers of gravity (ΔL), dispersion (SDpc) and variability (VCpc) of the points where there was a positive motor response. Data were compared according to the ratios between the hemispheres of each patient and stratified according to the final pathology diagnosis.

Results

The final sample consisted of 14 patients with a radiological diagnosis of low-grade glioma (LGG), of which 11 were consistent with the final pathology diagnosis. The normalized interhemispheric ratios of ΔL, SDpc, VCpc, and MT were significantly relevant for the quantification of plasticity (p < 0.001). The graphic reconstruction allows the qualitative evaluation of this plasticity.

Conclusion

The nTMS was able to quantitatively and qualitatively demonstrate the occurrence of brain plasticity induced by an intrinsic brain tumor. The graphic evaluation allowed the observation of useful characteristics for the operative planning, while the mathematical analysis made it possible to quantify the magnitude of the plasticity.
Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol
Authors: Zhai Weihang , Jiao Haoyang , Zhuang Yutong , Yang Yi , Zhang Jinling , Wang Yifei , Wang Yu , Zhao Ya-nan , Zhang Shuai , He Jianghong , Rong Peijing
Published: March 2023

Background

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique. Several studies have reported the effectiveness of taVNS in patients with disorders of consciousness (DOC); however, differences in the modulation paradigm have led to inconsistent treatment outcomes.

Methods/design

This prospective exploratory trial will include 15 patients with a minimally conscious state (MCS) recruited according to the coma recovery scale-revised (CRS-R). Each patient will receive 5 different frequencies of taVNS (1, 10, 25, 50, and 100 Hz); sham stimulation will be used as a blank control. The order of stimulation will be randomized, and the patients’ CRS-R scores and resting electroencephalography (EEG) before and after stimulation will be recorded.

Discussion

The overall study of taVNS used in treating patients with DOC is still in the preliminary stage of exploration. Through this experiment, we aim to explore the optimal stimulation frequency parameters of taVNS for the treatment of DOC patients. Furthermore, we expect to achieve a stable improvement of consciousness in DOC patients by continuously optimizing the neuromodulation paradigm of taVNS for the treatment of DOC patients.

Clinical trial registration

https://www.chictr.org.cn/index.aspx, identifier ChiCTR 2200063828.
Computational models of autonomic regulation in gastric motility: Progress, challenges, and future directions
Authors: Athavale Omkar N. , Avci Recep , Cheng Leo K. , Du Peng
Published: March 2023

The stomach is extensively innervated by the vagus nerve and the enteric nervous system. The mechanisms through which this innervation affects gastric motility are being unraveled, motivating the first concerted steps towards the incorporation autonomic regulation into computational models of gastric motility. Computational modeling has been valuable in advancing clinical treatment of other organs, such as the heart. However, to date, computational models of gastric motility have made simplifying assumptions about the link between gastric electrophysiology and motility. Advances in experimental neuroscience mean that these assumptions can be reviewed, and detailed models of autonomic regulation can be incorporated into computational models. This review covers these advances, as well as a vision for the utility of computational models of gastric motility. Diseases of the nervous system, such as Parkinson’s disease, can originate from the brain-gut axis and result in pathological gastric motility. Computational models are a valuable tool for understanding the mechanisms of disease and how treatment may affect gastric motility. This review also covers recent advances in experimental neuroscience that are fundamental to the development of physiology-driven computational models. A vision for the future of computational modeling of gastric motility is proposed and modeling approaches employed for existing mathematical models of autonomic regulation of other gastrointestinal organs and other organ systems are discussed.
Bringing synapses into focus: Recent advances in synaptic imaging and mass-spectrometry for studying synaptopathy
Authors: Hindley Nicole , Sanchez Avila Anna , Henstridge Christopher
Published: March 2023

Synapses are integral for healthy brain function and are becoming increasingly recognized as key structures in the early stages of brain disease. Understanding the pathological processes driving synaptic dysfunction will unlock new therapeutic opportunities for some of the most devastating diseases of our time. To achieve this we need a solid repertoire of imaging and molecular tools to interrogate synaptic biology at greater resolution. Synapses have historically been examined in small numbers, using highly technical imaging modalities, or in bulk, using crude molecular approaches. However, recent advances in imaging techniques are allowing us to analyze large numbers of synapses, at single-synapse resolution. Furthermore, multiplexing is now achievable with some of these approaches, meaning we can examine multiple proteins at individual synapses in intact tissue. New molecular techniques now allow accurate quantification of proteins from isolated synapses. The development of increasingly sensitive mass-spectrometry equipment means we can now scan the synaptic molecular landscape almost in totality and see how this changes in disease. As we embrace these new technical developments, synapses will be viewed with clearer focus, and the field of synaptopathy will become richer with insightful and high-quality data. Here, we will discuss some of the ways in which synaptic interrogation is being facilitated by methodological advances, focusing on imaging, and mass spectrometry.
Bioavailability of calcium in an enriched postbiotic system compared to calcium citrate in healthy postmenopausal females; A randomized, double-blind, comparator-controlled, crossover study
Authors: Friling Marina , Haber Adi , Furman-Assaf Sharon , Israel David , Harari Gil , Evans Malkanthi , Crowley David C. , Ouwehand Arthur C. , Ivanir Eran
Published: March 2023

Introduction

Bioavailability of calcium is an important consideration when designing supplements for achieving adequate calcium intake, mainly in high-risk, and aged populations. Alternative supplementation strategies may be able to circumvent absorption issues commonly seen with calcium supplements. The objective of this study was to assess the bioavailability of a single serving of two calcium formulations vs. comparator product in healthy postmenopausal women.

Methods

A total of 24 participants between 45 and 65 years were enrolled in a randomized, double-blind, three-phase, crossover study, with a 7-day washout period between phases. The bioavailability of calcium from calcium-carrying Saccharomyces cerevisiae (Ca-SC) or calcium-carrying Lactobacillus (Ca-LAB) in the form of postbiotic products versus calcium citrate, a conventional salt-based calcium supplement, was determined. Each product provided 630 mg of calcium and 400 IU of vitamin D3. After a 14-h (overnight) fast followed by a single dose of product with a standard low-calcium breakfast, both serum and urine calcium concentrations were assessed for up to 8 and 24 h, respectively.

Results

Ca-LAB resulted in greater calcium bioavailability, demonstrated by significantly higher area under the curve and peak concentration both in blood and urine, and total calcium mass excreted in urine. The bioavailability of calcium was similar for Ca-SC and calcium citrate except for the peak concentration value that was significantly higher for calcium citrate. Both Ca-LAB and Ca-SC were well tolerated with no significant difference in adverse events between the products during the study.

Discussion

These findings suggest that calcium enriched in a Lactobacillus-based postbiotic system is associated with higher levels of bioavailability as compared to calcium citrate, while a calcium-enriched yeast-based postbiotic does not influence calcium absorption.
Trends in dietary supplement use among athletes selected for doping controls
Authors: Lauritzen Fredrik , Gjelstad Astrid
Published: March 2023

Background

Dietary supplements (DS) may be beneficial for athletes in certain situations, whereas incorrect or excessive use may impair performance, pose a risk to the athlete's health and cause positive doping tests by containing prohibited substances. To provide athletes with relevant and tailored information on safe supplement use, a better knowledge about DS trends over time and between sport disciplines are needed.

Methods

This study examines the use of DS among athletes who have participated in doping controls by extracting information derived from 10,418 doping control forms (DCF) collected by Anti-Doping Norway from 2015 to 2019.

Results

Overall, 51% of the DCFs contained information about at least one DS. National level athletes (NLA) more often reported using DS than recreational athletes (RA) (53 vs. 47%, p < 0.001). Athletes in strength and power (71%), VO2max endurance (56%) and muscular endurance sports (55%) had the highest proportion of DCFs with information about DS. Medical supplements were the most used supplement category for both genders and across all sports. Dietary supplements with a high risk of containing doping substances were most common among male, RA in strength and power sports. There were small and non-significant year-to-year variations in the prevalence of athletes using DS, while the number of products used concomitantly peaked in 2017 before declining in 2019 (2.30 vs. 2.08, p < 0.01). The use of medical supplements and ergogenic substances increased slightly for both NLA and RA from 2015 to 2019, while the use of all other supplement categories declined.

Conclusion

Half of the 10,418 DCFs contained information about DS, with variations within the athlete population. DS with high risk of containing prohibited substances were mostly seen in sport disciplines requiring a high degree of specialization in strength/power, including powerlifting and weightlifting, as well as in some team sports, such as cheerleading and american football.
Multidisciplinary team diagnosis and treatment of pancreatic cancer: Current landscape and future prospects
Authors: Yao Weirong , Chen Xiaoliang , Fan Bin , Zeng Lin , Zhou Zhiyong , Mao Zhifang , Shen Qinglin
Published: March 2023

The pathogenesis of pancreatic cancer has not been completely clear, there is no highly sensitive and specific detection method, so early diagnosis is very difficult. Despite the rapid development of tumor diagnosis and treatment, it is difficult to break through in the short term and the overall 5-year survival rate of pancreatic cancer is less than 8%. In the face of the increasing incidence of pancreatic cancer, in addition to strengthening basic research, exploring its etiology and pathogenesis, it is urgent to optimize the existing diagnosis and treatment methods through standard multidisciplinary team (MDT), and formulate personalized treatment plan to achieve the purpose of improving the curative effect. However, there are some problems in MDT, such as insufficient understanding and enthusiasm of some doctors, failure to operate MDT according to the system, lack of good communication between domestic and foreign peers, and lack of attention in personnel training and talent echelon construction. It is expected to protect the rights and interests of doctors in the future and ensure the continuous operation of MDT. To strengthen the research on the diagnosis and treatment of pancreatic cancer, MDT can try the Internet +MDT mode to improve the efficiency of MDT.
Dosiomics and radiomics to predict pneumonitis after thoracic stereotactic body radiotherapy and immune checkpoint inhibition
Authors: Kraus Kim Melanie , Oreshko Maksym , Bernhardt Denise , Combs Stephanie Elisabeth , Peeken Jan Caspar
Published: March 2023

Introduction

Pneumonitis is a relevant side effect after radiotherapy (RT) and immunotherapy with checkpoint inhibitors (ICIs). Since the effect is radiation dose dependent, the risk increases for high fractional doses as applied for stereotactic body radiation therapy (SBRT) and might even be enhanced for the combination of SBRT with ICI therapy. Hence, patient individual pre-treatment prediction of post-treatment pneumonitis (PTP) might be able to support clinical decision making. Dosimetric factors, however, use limited information and, thus, cannot exploit the full potential of pneumonitis prediction.

Methods

We investigated dosiomics and radiomics model based approaches for PTP prediction after thoracic SBRT with and without ICI therapy. To overcome potential influences of different fractionation schemes, we converted physical doses to 2 Gy equivalent doses (EQD2) and compared both results. In total, four single feature models (dosiomics, radiomics, dosimetric, clinical factors) were tested and five combinations of those (dosimetric+clinical factors, dosiomics+radiomics, dosiomics+dosimetric+clinical factors, radiomics+dosimetric+clinical factors, radiomics+dosiomics+dosimetric+clinical factors). After feature extraction, a feature reduction was performed using pearson intercorrelation coefficient and the Boruta algorithm within 1000-fold bootstrapping runs. Four different machine learning models and the combination of those were trained and tested within 100 iterations of 5-fold nested cross validation.

Results

Results were analysed using the area under the receiver operating characteristic curve (AUC). We found the combination of dosiomics and radiomics features to outperform all other models with AUCradiomics+dosiomics, D = 0.79 (95% confidence interval 0.78-0.80) and AUCradiomics+dosiomics, EQD2 = 0.77 (0.76-0.78) for physical dose and EQD2, respectively. ICI therapy did not impact the prediction result (AUC ≤ 0.5). Clinical and dosimetric features for the total lung did not improve the prediction outcome.

Conclusion

Our results suggest that combined dosiomics and radiomics analysis can improve PTP prediction in patients treated with lung SBRT. We conclude that pre-treatment prediction could support clinical decision making on an individual patient basis with or without ICI therapy.