bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional choroidal vascularity index in central serous chorioretinopathy using ultra-widefield swept-source optical coherence tomography angiography
Authors: Zeng Qiaozhu , Luo Lan , Yao Yuou , Tu Shu , Yang Zhi , Zhao Mingwei
Published: September 2022

Background

To map and compare the three-dimensional choroidal vascularity index (3D-CVI) in eyes with unilateral central serous chorioretinopathy (CSC), fellow eyes and control eyes using ultra-widefield swept source optical coherence tomography (UWF SS-OCTA).

Methods

In this prospective observational study, the 3D-CVIs were measured in 9 subfields or 1 × 1 mm grids by the UWF SS-OCTA with a viewing angle of horizontal 24 × vertical 20 mm. The proportions of vortex vein anastomoses and their corresponding CVI in the central regions were compared among the CSC, fellow and control eyes. Correlations of CVI and vascular density of the large choroidal vessel layer/choriocapillaris layer/choroidal thickness (CT) were also assessed.

Results

Thirty-two eyes in 32 patients with unilateral CSC and 32 normal eyes were included in the study. The mean CVI in the eyes with CSC was significantly greater than that in the fellow eyes of CSC and control eyes (41.99 ± 3.56% vs. 40.38 ± 3.855%, P = 0.003; 41.99 ± 3.56% vs. 38.93 ± 4.067%, P = 0.004, respectively). The CVIs in superotemporal, inferotemporal and inferonasal regions were significantly higher in CSC eyes than control eyes (P = 0.03, P = 0.02, P = 0.008). In CSC eyes, there was a linear positive correlation between 3D-CVI and vascular density of the large choroidal vessel layer and CT in all subfields. The proportion of vortex vein anastomoses in CSC was 25/32 (78.1%), and significantly higher in fellow and control eyes (P < 0.001). The average central CVI was significantly higher in CSC eyes with anastomoses than in CSC eyes without anastomoses (42.8 ± 5.1% vs. 38.4 ± 2.7%, P = 0.039). CVIs in superior, central, inferior, superonasal, nasal and inferonasal regions were significantly correlated with vortex vein anastomoses (P < 0.05), regardless of CSC, fellow or healthy eyes. In addition, whether there were vortex vein anastomoses, CVI in superotemporal region was significantly higher in eyes with CSC (P = 0.002) and fellow eyes (P = 0.014), compared to control eyes. No significant correlation was found between hypertension and CVIs in the three groups.

Conclusion

Remodeling of choroidal drainage routes by venous anastomosis between superior and inferior vortex veins may be common in CSC. The 3D-CVI could be a comprehensive parameter to evaluate the choroid vasculature and help understand the pathogenesis of pachychoroid spectrum disease.
Behçet uveitis: Current practice and future perspectives
Authors: Aboul Naga Shereen H. , Hassan Lameece Moustafa , El Zanaty Radwa T. , Refaat Mohammad , Amin Rana H. , Ragab Gaafar , Soliman Mahmoud M.
Published: September 2022

Described as early as Hippocrates in his “Third Book of Endemic Diseases,” Behçet's Disease (BD), also known as “The Silk Road Disease” following its initial demographics, consists of a triad of recurrent oro-genital ulcers and associated uveitis. Current demographics and rising percentages of patients seen far beyond the Silk Road in Ocular Inflammatory Disease and Uveitis Clinics list BD uveitis as one of the frontliners of non-infectious autoinflammatory eye diseases. Clinical features of BD and juvenile-onset BD are detailed alongside various approaches in classification and suggested algorithms for diagnosis that are outlined in this review. With the ongoing Human Microbiome Project and studies such as the MAMBA study, the role of the human microbiome in BD is highlighted in the pathophysiology of BD to include the current research and literature perspective. Furthermore, with the advancement of recent diagnostic and investigative techniques, especially in the field of Optical Coherence Tomography (OCT), disease-related characteristics are updated to encompass SD, EDI and OCT-angiography characteristics of BD. Having entered the era of biologic therapy, the role of various specific cytokine-blocking biologic drugs, such as TNF-α inhibitors (e.g., adalimumab, infliximab), interferon α-2a inhibitors, IL-6 and IL-1 inhibitors are presented and contrasted alongside the conventional immunosuppressant drugs and the classic old gold standard: corticosteroids (systemic or local). Finally, with the ongoing SARS-CoV-2 pandemic, it was not possible to conclude the review without reviewing the latest evidence-based literature reporting BD morbidity in this era, the observed pattern and treatment recommendations as well as those related to reported post-vaccine complications and emergence of BD.
Case report: Nocardia farcinica pneumonia in early-stage post liver transplantation
Authors: Pan Bing , Wang Fang-Fei , He Qiang
Published: September 2022

Background

Liver transplantation is a well-established treatment for end-stage liver disease. The evolution of immunosuppressants has supported the recent advances in this field. However, this leads to immunosuppression and increases the risk for infections. Nocardia is an aerobic gram-positive bacillus, which can cause multi-systemic or multi-organ infections. Nocardia is an opportunistic pathogen that principally affects immunosuppressed patients.

Case presentation

Herein, we present a case of Nocardia farcinica pneumonia in a patient at early-stage post-liver transplantation. Following appropriate microbiological tests and imaging, the diagnosis was finally confirmed. A full recovery was achieved after optimal antibiotic therapy of sulfamethoxazole, minocycline, and amikacin.

Conclusions

Nocardia farcinica pneumonia is a rare and life-threatening disease, especially in patients after liver transplantation. Imaging and microbiological tests are helpful for the early diagnosis of the disease. Trimethoprim-sulfamethoxazole (TMP-SMX) as part of first-line therapy for nocardiosis is recommended.
The diversity analysis and gene function prediction of intestinal bacteria in three equine species
Authors: Bao Wuyundalai , Yu Jinghe , He Yuxing , Liu Mingchao , Yang Xiaofeng
Published: September 2022

The intestinal flora has a variety of physiological functions involved in the regulation of host metabolism, immunity and endocrinology, and plays an important role in maintaining the health of the host. In this study, we used high-throughput sequencing technology to analyze the intestinal bacterial diversity and their gene functions in three equine species of the genus Shetland Pony (SP), Mongolian Wild Ass (MA), and Plain Zebra (PZ) in captivity in two wildlife parks in Inner Mongolia Autonomous Region, China. The results showed that only the SP intestinal bacterial abundance index (Chao1) was significantly different (P < 0.05) between the same species in the two wildlife parks, but neither the intestinal bacterial diversity index (Shannon) nor the community composition were significantly different (P > 0.05). The bacterial abundance index (Chao1) was significantly higher in MA than SP (P < 0.05) and highly significantly higher than PZ (P < 0.01); the bacterial diversity index (Shannon) was higher in MA than PZ, but there was no significant difference, but both MA and PZ were significantly higher than SP (P < 0.05). Moreover, the intestinal bacterial community composition was significantly different among the three equine species (P = 0.001). The dominant bacterial phyla for SP, MA, and PZ were Firmicutes and Bacteroidota; among them, the bacterial family with the highest relative abundance was Lachnospiraceae and the bacterial genus was Rikenellaceae_RC9_gut_group. Analysis of the metabolic gene functions of intestinal bacteria revealed that the highest relative abundance at Pathway level 2 was for global and overview maps; at Pathway level 3, the highest relative abundance was for biosynthesis of secondary metabolites. In sum, the intestinal bacterial community composition and diversity of the above three equine species differed significantly, but their metabolic gene functions were similar. Moreover, the results of this manuscript fill the gap in the study of intestinal bacterial diversity in SP, MA, and PZ. It also provides a reference for the study of the dominant bacteria in the intestinal microorganisms of these three equine species and the discovery of novel functional genes.
Susceptibility-guided vs. empirical 10-day quadruple treatment for Helicobacter pylori-infected patients: A prospective clinical trial of first-line therapy
Authors: Li Peiwei , Jin Jing , Chen Yan , Ma Jianjuan , Du Qin , Han Yuehua
Published: September 2022

Background

The increasing antimicrobial resistance of Helicobacter pylori (H. pylori) has resulted in a fall in cure rates. We aimed to assess the effectiveness of first-line susceptibility-guided therapy and furazolidone-based quadruple therapy for H. pylori-infected patients.

Methods

Subjects with H. pylori-infection were randomly assigned to either 10-day susceptibility-guided treatment or empiric treatment in a 2:1 ratio. Susceptibility-guided therapy was based on susceptibility to clarithromycin, and patients with susceptible strains received clarithromycin 500 mg twice daily and otherwise minocycline 100 mg twice a day was administered. Patients in the empiric therapy group was treated with furazolidone 100 mg twice a day. During treatment, all patients were given esomeprazole 20 mg twice daily, colloidal bismuth pectin 200 mg twice daily, and amoxicillin 1 g twice daily.

Results

A total of 248 patients were screened and 201 were finally included. Empiric and susceptibility-guided regimens were both successful with per-protocol eradication rates of 90.5% (57/63) vs. 88.5% (108/122) (p = 0.685) and intent-to-treat eradication rates of 85.1% (57/67) vs. 80.6% (108/134) (p = 0.435). No significant difference in eradication rates were observed among the furazolidone group, clarithromycin group and minocycline group.

Conclusion

Both susceptibility-guided therapy and quadruple therapy containing furazolidone can achieve good eradication rates. For population with a high rate of resistance, quadruple therapy containing furazolidone and bismuth may be a more practical choice for first-line treatment.
Short-term application of chicken manure under different nitrogen rates alters structure and co-occurrence pattern but not diversity of soil microbial community in wheat field
Authors: Jin Haiyang , Zhang Deqi , Yan Yaqian , Yang Cheng , Fang Baoting , Li Xiangdong , Shao Yunhui , Wang Hanfang , Yue Junqin , Wang Yanjing , Cheng Hongjian , Shi Yanhua , Qin Feng
Published: September 2022

Manure application is an effective way to improve the utilization efficiency of organic resources and alleviate the adverse effects of long-term application of chemical fertilizers. However, the impact of applying manure under different nitrogen rates on soil microbial community in wheat field remains unclear. Treatments with and without chicken manure application under three nitrogen rates (N 135, 180 and 225 kg⋅hm–2) were set in wheat field. Soil organic carbon, available nutrients, and abundance, diversity, structure and co-occurrence pattern of soil microbial community at wheat maturity were investigated. Compared with no manure application, chicken manure application increased the soil organic carbon and available phosphorus, while the effects on soil mineral nitrogen and available potassium varied with different nitrogen rates. Chicken manure application significantly increased soil bacterial abundance under the nitrogen fertilization of 135 and 225 kg⋅hm–2, increased soil fungal abundance under the nitrogen fertilization of 135 kg⋅hm–2, but decreased soil fungal abundance under the nitrogen fertilization of 180 and 225 kg⋅hm–2 (P < 0.05). There was no significant difference in alpha diversity indices of soil microbial communities between treatments with and without chicken manure application under different nitrogen rates (P > 0.05). Chicken manure application and its interaction with nitrogen rate significantly changed soil bacterial and fungal community structures (P < 0.05). There were significantly different taxa of soil microbial communities between treatments with and without chicken manure application. Chicken manure application reduced the ecological network complexity of soil bacterial community and increased that of soil fungal community. In summary, the responses of soil available nutrients and microbial abundance to applying chicken manure varied with different nitrogen rates. One growing season application of chicken manure was sufficient to alter the soil microbial community structure, composition and co-occurrence pattern, whereas not significantly affected soil microbial community diversity.
The role of structural dynamics in the thermal adaptation of hyperthermophilic enzymes
Authors: Fusco Giuliana , Bemporad Francesco , Chiti Fabrizio , Dobson Christopher M. , De Simone Alfonso
Published: September 2022

Proteins from hyperthermophilic organisms are evolutionary optimised to adopt functional structures and dynamics under conditions in which their mesophilic homologues are generally inactive or unfolded. Understanding the nature of such adaptation is of crucial interest to clarify the underlying mechanisms of biological activity in proteins. Here we measured NMR residual dipolar couplings of a hyperthermophilic acylphosphatase enzyme at 80°C and used these data to generate an accurate structural ensemble representative of its native state. The resulting energy landscape was compared to that obtained for a human homologue at 37°C, and additional NMR experiments were carried out to probe fast (15N relaxation) and slow (H/D exchange) backbone dynamics, collectively sampling fluctuations of the two proteins ranging from the nanosecond to the millisecond timescale. The results identified key differences in the strategies for protein-protein and protein-ligand interactions of the two enzymes at the respective physiological temperatures. These include the dynamical behaviour of a β-strand involved in the protection against aberrant protein aggregation and concerted motions of loops involved in substrate binding and catalysis. Taken together these results elucidate the structure-dynamics-function relationship associated with the strategies of thermal adaptation of protein molecules.
Plasma metabolomics and lipidomics signatures of motoric cognitive risk syndrome in community-dwelling older adults
Authors: Li Wanmeng , Sun Xuelian , Liu Yu , Ge Meiling , Lu Ying , Liu Xiaolei , Zhou Lixing , Liu Xiaohui , Dong Biao , Yue Jirong , Xue Qianli , Dai Lunzhi , Dong Birong
Published: September 2022

Introduction

Motoric cognitive risk syndrome (MCR) is characterized by subjective cognitive complaints (SCCs) and slow gait (SG). Metabolomics and lipidomics may potentiate disclosure of the underlying mechanisms of MCR.

Methods

This was a cross-sectional study from the West China Health and Aging Trend cohort study (WCHAT). The operational definition of MCR is the presence of SCCs and SG without dementia or mobility disability. The test and analysis were based on untargeted metabolomics and lipidomics, consensus clustering, lasso regression and 10-fold cross-validation.

Results

This study enrolled 6,031 individuals for clinical analysis and 577 plasma samples for omics analysis. The overall prevalence of MCR was 9.7%, and the prevalence of MCR-only, assessed cognitive impairment-only (CI-only) and MCR-CI were 7.5, 13.3, and 2.1%, respectively. By consensus clustering analysis, MCR-only was clustered into three metabolic subtypes, MCR-I, MCR-II and MCR-III. Clinically, body fat mass (OR = 0.89, CI = 0.82–0.96) was negatively correlated with MCR-I, and comorbidity (OR = 2.19, CI = 1.10–4.38) was positively correlated with MCR-III. Diabetes mellitus had the highest ORs above 1 in MCR-II and MCR-III (OR = 3.18, CI = 1.02–9.91; OR = 2.83, CI = 1.33–6.04, respectively). The risk metabolites of MCR-III showed relatively high similarity with those of cognitive impairment. Notably, L-proline, L-cystine, ADMA, and N1-acetylspermidine were significantly changed in MCR-only, and PC(40:3), SM(32:1), TG(51:3), eicosanoic acid(20:1), methyl-D-galactoside and TG(50:3) contributed most to the prediction model for MCR-III.

Interpretation

Pre-dementia syndrome of MCR has distinct metabolic subtypes, and SCCs and SG may cause different metabolic changes to develop MCR.
Clinical relevance of biomarkers, new therapeutic approaches, and role of post-translational modifications in the pathogenesis of Alzheimer’s disease
Authors: Mumtaz Ibtisam , Ayaz Mir Owais , Khan Mohamad Sultan , Manzoor Umar , Ganayee Mohd Azhardin , Bhat Aadil Qadir , Dar Ghulam Hassan , Alghamdi Badrah S. , Hashem Anwar M. , Dar Mohd Jamal , Ashraf Gulam Md. , Maqbool Tariq
Published: September 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder that causes progressive loss of cognitive functions like thinking, memory, reasoning, behavioral abilities, and social skills thus affecting the ability of a person to perform normal daily functions independently. There is no definitive cure for this disease, and treatment options available for the management of the disease are not very effective as well. Based on histopathology, AD is characterized by the accumulation of insoluble deposits of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs). Although several molecular events contribute to the formation of these insoluble deposits, the aberrant post-translational modifications (PTMs) of AD-related proteins (like APP, Aβ, tau, and BACE1) are also known to be involved in the onset and progression of this disease. However, early diagnosis of the disease as well as the development of effective therapeutic approaches is impeded by lack of proper clinical biomarkers. In this review, we summarized the current status and clinical relevance of biomarkers from cerebrospinal fluid (CSF), blood and extracellular vesicles involved in onset and progression of AD. Moreover, we highlight the effects of several PTMs on the AD-related proteins, and provide an insight how these modifications impact the structure and function of proteins leading to AD pathology. Finally, for disease-modifying therapeutics, novel approaches, and targets are discussed for the successful treatment and management of AD.
The gut–microbiota–brain changes across the liver disease spectrum
Authors: Higarza Sara G. , Arboleya Silvia , Arias Jorge L. , Gueimonde Miguel , Arias Natalia
Published: September 2022

Gut microbiota dysbiosis plays a significant role in the progression of liver disease, and no effective drugs are available for the full spectrum. In this study, we aimed to explore the dynamic changes of gut microbiota along the liver disease spectrum, together with the changes in cognition and brain metabolism. Sprague–Dawley rats were divided into four groups reflecting different stages of liver disease: control diet (NC); high-fat, high-cholesterol diet (HFHC), emulating non-alcoholic steatohepatitis; control diet + thioacetamide (NC + TAA), simulating acute liver failure; and high-fat, high-cholesterol diet + thioacetamide (HFHC + TAA) to assess the effect of the superimposed damages. The diet was administered for 14 weeks and the thioacetamide was administrated (100 mg/kg day) intraperitoneally over 3 days. Our results showed changes in plasma biochemistry and liver damage across the spectrum. Differences in gut microbiota at the compositional level were found among the experimental groups. Members of the Enterobacteriaceae family were most abundant in HFHC and HFHC + TAA groups, and Akkermansiaceae in the NC + TAA group, albeit lactobacilli genus being dominant in the NC group. Moreover, harm to the liver affected the diversity and bacterial community structure, with a loss of rare species. Indeed, the superimposed damage group (HFHC + TAA) suffered a loss of both rare and abundant species. Behavioral evaluation has shown that HFHC, NC + TAA, and HFHC + TAA displayed a worsened execution when discriminating the new object. Also, NC + TAA and HFHC + TAA were not capable of recognizing the changes in place of the object. Furthermore, working memory was affected in HFHC and HFHC + TAA groups, whereas the NC + TAA group displayed a significant delay in the acquisition. Brain oxidative metabolism changes were observed in the prefrontal, retrosplenial, and perirhinal cortices, as well as the amygdala and mammillary bodies. Besides, groups administered with thioacetamide presented an increased oxidative metabolic activity in the adrenal glands. These results highlight the importance of cross-comparison along the liver spectrum to understand the different gut–microbiota–brain changes. Furthermore, our data point out specific gut microbiota targets to design more effective treatments, though the liver–gut–brain axis focused on specific stages of liver disease.
Convolutional-de-convolutional neural networks for recognition of surgical workflow
Authors: Chen Yu-wen , Zhang Ju , Wang Peng , Hu Zheng-yu , Zhong Kun-hua
Published: September 2022

Computer-assisted surgery (CAS) has occupied an important position in modern surgery, further stimulating the progress of methodology and technology. In recent years, a large number of computer vision-based methods have been widely used in surgical workflow recognition tasks. For training the models, a lot of annotated data are necessary. However, the annotation of surgical data requires expert knowledge and thus becomes difficult and time-consuming. In this paper, we focus on the problem of data deficiency and propose a knowledge transfer learning method based on artificial neural network to compensate a small amount of labeled training data. To solve this problem, we propose an unsupervised method for pre-training a Convolutional-De-Convolutional (CDC) neural network for sequencing surgical workflow frames, which performs neural convolution in space (for semantic abstraction) and neural de-convolution in time (for frame level resolution) simultaneously. Specifically, through neural convolution transfer learning, we only fine-tuned the CDC neural network to classify the surgical phase. We performed some experiments for validating the model, and it showed that the proposed model can effectively extract the surgical feature and determine the surgical phase. The accuracy (Acc), recall, precision (Pres) of our model reached 91.4, 78.9, and 82.5%, respectively.
Extracting default mode network based on graph neural network for resting state fMRI study
Authors: Wang Donglin , Wu Qiang , Hong Don
Published: September 2022

Functional magnetic resonance imaging (fMRI)-based study of functional connections in the brain has been highlighted by numerous human and animal studies recently, which have provided significant information to explain a wide range of pathological conditions and behavioral characteristics. In this paper, we propose the use of a graph neural network, a deep learning technique called graphSAGE, to investigate resting state fMRI (rs-fMRI) and extract the default mode network (DMN). Comparing typical methods such as seed-based correlation, independent component analysis, and dictionary learning, real data experiment results showed that the graphSAGE is more robust, reliable, and defines a clearer region of interests. In addition, graphSAGE requires fewer and more relaxed assumptions, and considers the single subject analysis and group subjects analysis simultaneously.
Asynchronous excitatory neuron development in an isogenic cortical spheroid model of Down syndrome
Authors: Li Zhen , Klein Jenny A. , Rampam Sanjeev , Kurzion Ronni , Campbell Natalie Baker , Patel Yesha , Haydar Tarik F. , Zeldich Ella
Published: September 2022

The intellectual disability (ID) in Down syndrome (DS) is thought to result from a variety of developmental deficits such as alterations in neural progenitor division, neurogenesis, gliogenesis, cortical architecture, and reduced cortical volume. However, the molecular processes underlying these neurodevelopmental changes are still elusive, preventing an understanding of the mechanistic basis of ID in DS. In this study, we used a pair of isogenic (trisomic and euploid) induced pluripotent stem cell (iPSC) lines to generate cortical spheroids (CS) that model the impact of trisomy 21 on brain development. Cortical spheroids contain neurons, astrocytes, and oligodendrocytes and they are widely used to approximate early neurodevelopment. Using single cell RNA sequencing (scRNA-seq), we uncovered cell type-specific transcriptomic changes in the trisomic CS. In particular, we found that excitatory neuron populations were most affected and that a specific population of cells with a transcriptomic profile resembling layer IV cortical neurons displayed the most profound divergence in developmental trajectory between trisomic and euploid genotypes. We also identified candidate genes potentially driving the developmental asynchrony between trisomic and euploid excitatory neurons. Direct comparison between the current isogenic CS scRNA-seq data and previously published datasets revealed several recurring differentially expressed genes between DS and control samples. Altogether, our study highlights the power and importance of cell type-specific analyses within a defined genetic background, coupled with broader examination of mixed samples, to comprehensively evaluate cellular phenotypes in the context of DS.
Image registration and appearance adaptation in non-correspondent image regions for new MS lesions detection
Authors: Andresen Julia , Uzunova Hristina , Ehrhardt Jan , Kepp Timo , Handels Heinz
Published: September 2022

Manual detection of newly formed lesions in multiple sclerosis is an important but tedious and difficult task. Several approaches for automating the detection of new lesions have recently been proposed, but they tend to either overestimate the actual amount of new lesions or to miss many lesions. In this paper, an image registration convolutional neural network (CNN) that adapts the baseline image to the follow-up image by spatial deformations and simulation of new lesions is proposed. Simultaneously, segmentations of new lesions are generated, which are shown to reliably estimate the real new lesion load and to separate stable and progressive patients. Several applications of the proposed network emerge: image registration, detection and segmentation of new lesions, and modeling of new MS lesions. The modeled lesions offer the possibility to investigate the intensity profile of new lesions.
Advances on immunoregulation effect of astragalus polysaccharides
Authors: Wang Xin-Yi , Wang Rong-Can , Qu Zheng-Yi , Zhu Yan-Zhu , Li Ya-Li
Published: September 2022

Astragalus membranaceus (AM) is a traditional chinese medicine (TCM) with active substances such as saponins and polysaccharides, The most abundant active ingredient is astragalus polysaccharides (APS). It is a natural extract with multiple activities such as anti-viral, anti-tumor and the immune-enhancing effects. In recent years, studies on the role of APS in immunomodulatory direction have been increasing, and numerous studies have shown that APS has a better immune enhancing effect. This paper outlines the immunomodulatory effects of APS in terms of immune cells, nonspecific immunity, anti-viral immunity, anti-tumor effects, and applications in animal production, which would provide a base for the further applications of APS. Herein, this current review intends to describe the immunomodulatory effects of APS with underlying mechanisms of therapeutic effects.
Positive effects of dietary fiber from sweet potato [Ipomoea batatas (L.) Lam.] peels by different extraction methods on human fecal microbiota in vitro fermentation
Authors: Cao Yan , Tian Baoming , Zhang Zhiguo , Yang Kai , Cai Ming , Hu Weiwei , Guo Yang , Xia Qile , Wu Weicheng
Published: September 2022

The purpose of this study was to compare the effects of sweet potato peels dietary fiber obtained by different extraction methods on intestinal health. Specifically, four different dietary fibers were extracted by hot water, microwave, ultrasonic and subcritical water methods. And the prebiotics effects of sweet potato peels dietary fibers were explored in an in vitro fermentation model, by determining intestinal gas content, short-chain fatty acid content, pH, ammonia content and the gut microbiota composition. The results showed that dietary fiber obtained by four different extraction methods could be utilized by GM and improve human health by increasing the abundance of beneficial bacteria (e.g., Bifidobacterium, Faecalibacterium, and Prevotella) and reducing the abundance of harmful bacteria (e.g., Proteobacteria, Romboutsia and Dorea), enhancing the relative abundance of SCFA-producing bacteria, promoting the production of short-chain fatty acids, reducing intestinal pH from 6.89 to 4.63 and ammonia. Among them, dietary fiber extracted by ultrasound is better than the other three extraction methods. This study suggests that all the four different extraction methods are available for sweet potato peels dietary fiber, and the extracted dietary fiber could be served as potential functional foods with great development value. In addition, it is beneficial to reduce the environmental pollution of sweet potato peels and improve the high-value processing and utilization of sweet potato by-products.
Phase 2 randomized controlled trial of intravenous or intraperitoneal paclitaxel plus mFOLFOX6 vs. mFOLFOX6 as first-line treatment of advanced gastric cancer
Authors: Zhao Shen , Su Liyu , Chen Yigui , Li Xiaofeng , Lin Peicheng , Chen Wujin , Fang Wenzheng , Zhu Jinfeng , Li Hui , Ren Liping , Liu Jie , Hong Yanni , Lin Shaowei , Fan Nanfeng , Lin Rongbo
Published: September 2022

Objective

We conducted a phase 2 trial to compare the safety and efficacy of intravenous paclitaxel or intraperitoneal paclitaxel plus mFOLFOX6 vs. mFOLFOX6 in untreated advanced gastric cancer.

Methods

Participants with untreated advanced gastric cancer were randomly assigned (1:1:1) to: intravenous paclitaxel 135 mg/m2 or intraperitoneal paclitaxel 80 mg/m2 plus mFOLFOX6 omitting bolus fluorouracil; or mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil 400 mg/m2 bolus, fluorouracil 2,400 mg/m2 46-h continuous infusion). Treatment was every 14 days for up to 9 cycles followed by S-1 maintenance. The primary outcome was progression-free survival.

Results

Of 90 enrolled participants, 30 in the intravenous paclitaxel group, 29 in the intraperitoneal paclitaxel group, and 30 in the mFOLFOX6 group were included in the analyses. The median progression-free survival was 6.52, 5.83, and 4.55 months, respectively, for the intravenous paclitaxel group, intraperitoneal paclitaxel group, and mFOLFOX6 group. The hazard ratios were 0.56 (95% CI: 0.33–0.94; p = 0.026) and 0.56 (95% CI: 0.33–0.96; p = 0.037), respectively, for the intravenous paclitaxel group and the intraperitoneal paclitaxel group vs. the mFOLFOX6 group. The most common grade 3/4 adverse events for the intravenous paclitaxel group, intraperitoneal paclitaxel group, and mFOLFOX6 group, respectively, were neutropenia (30.0%, 34.5%, 33.3%), diarrhea (13.3%, 20.7%, 13.3%), and leukopenia (10.0%, 13.8%, 10.0%). No treatment-related death occurred.

Conclusion

The findings of this phase 2 trial suggest that adding intravenous paclitaxel or intraperitoneal paclitaxel to mFOLFOX6 for untreated advanced gastric cancer improved progression-free survival with manageable adverse events.
An isolated pulmonary nodule secondary to Streptococcus intermedius infection in an otherwise healthy 10-year-old boy: A case report and literature review
Authors: Huang Meixia , Li Shuxian , Wu Xiling , Xu Dan , Tang Lanfang , Chen Zhimin
Published: September 2022

Streptococcus intermedius, as a Gram-positive commensal bacterium, tends to cause various infections, such as brain and liver abscesses, endocarditis, and empyema, especially in immunocompromised patients. However, an isolated pulmonary nodule caused by S. intermedius in previously healthy individuals without traditional risk factors is rarely reported. Herein, we present a case of a 10-year-old immunocompetent boy referred to our department with a 5-day history of intermittent, left-sided chest pain. Chest X-ray and computed tomography revealed a left lung nodule. Although his blood, sputum, and bronchoalveolar lavage fluid cultures were negative, metagenomic next-generation sequencing (mNGS) showed only the presence of S. intermedius in ultrasonography-guided lung biopsy tissue and pleural fluid (416 and 110 reads, respectively). He was then successfully treated with appropriate intravenous antibiotics and avoided surgical intervention. To the best of our knowledge, this is the first report of S. intermedius-related pulmonary nodule confirmed by mNGS analysis in healthy children. For achieving proper diagnosis and treatment, infection with S. intermedius should be included in the differential diagnosis when coming across such a similar pulmonary nodule. mNGS, as a valuable supplement to conventional culture methods, is an essential diagnostic tool for identifying pathogens without typical characteristics.
Pediatric neurosurgery AC-after COVID-19: What has really changed? A review of the literature
Authors: Noris Alice , Peraio Simone , Di Rita Andrea , Ricci Zaccaria , Spezzani Chiara , Lenge Matteo , Giordano Flavio
Published: September 2022

The COVID-19 outbreak has dramatically changed the organization of Pediatric Neurosurgery all over the world. The departments involved developed similar plans to maintain emergency surgeries without reducing clinical activities. The Association of Pediatric Neurosurgeons wrote different memoranda to detail the surgical procedures not to be postponed with special attention given to high-risk pathology for COVID-19 contamination, like trans-naso-sphenoidal surgery. On this basis, we have conducted a complete literature review focusing on many topics: hospital organization, patients and parents screening, surgical indication criteria, outpatient clinic and teleconsultation, telematic conference and meeting, fellowship and training, and virtual multidisciplinary meeting.
Risk factors for admission to the pediatric critical care unit among children hospitalized with COVID-19 in France
Authors: Prévost Blandine , Retbi Aurélia , Binder-Foucard Florence , Borde Aurélie , Bruandet Amélie , Corvol Harriet , Gilleron Véronique , Le Bourhis-Zaimi Maggie , Lenne Xavier , Muller Joris , Ouattara Eric , Séguret Fabienne , Tran Ba Loc Pierre , Tezenas du Montcel Sophie
Published: September 2022

Background

COVID-19 infection is less severe among children than among adults; however, some patients require hospitalization and even critical care. Using data from the French national medico-administrative database, we estimated the risk factors for critical care unit (CCU) admissions among pediatric COVID-19 hospitalizations, the number and characteristics of the cases during the successive waves from January 2020 to August 2021 and described death cases.

Methods

We included all children (age < 18) hospitalized with COVID-19 between January 1st, 2020, and August 31st, 2021. Follow-up was until September 30th, 2021 (discharge or death). Contiguous hospital stays were gathered in “care sequences.” Four epidemic waves were considered (cut off dates: August 11th 2020, January 1st 2021, and July 4th 2021). We excluded asymptomatic COVID-19 cases, post-COVID-19 diseases, and 1-day-long sequences (except death cases). Risk factors for CCU admission were assessed with a univariable and a multivariable logistic regression model in the entire sample and stratified by age, whether younger than 2.

Results

We included 7,485 patients, of whom 1988 (26.6%) were admitted to the CCU. Risk factors for admission to the CCU were being younger than 7 days [OR: 3.71 95% CI (2.56–5.39)], being between 2 and 9 years old [1.19 (1.00–1.41)], pediatric multisystem inflammatory syndrome (PIMS) [7.17 (5.97–8.6)] and respiratory forms [1.26 (1.12–1.41)], and having at least one underlying condition [2.66 (2.36–3.01)]. Among hospitalized children younger than 2 years old, prematurity was a risk factor for CCU admission [1.89 (1.47–2.43)]. The CCU admission rate gradually decreased over the waves (from 31.0 to 17.8%). There were 32 (0.4%) deaths, of which the median age was 6 years (IQR: 177 days–15.5 years).

Conclusion

Some children need to be more particularly protected from a severe evolution: newborns younger than 7 days old, children aged from 2 to 13 years who are more at risk of PIMS forms and patients with at least one underlying medical condition.
Osthole: An up-to-date review of its anticancer potential and mechanisms of action
Authors: Yang Shaojie , Dai Wanlin , Wang Jingnan , Zhang Xiaolin , Zheng Yuting , Bi Shiyuan , Pang Liwei , Ren Tengqi , Yang Ye , Sun Yang , Zheng Zhuyuan , Wu Shuodong , Kong Jing
Published: September 2022

With its high incidence and mortality rates, cancer is one of the largest health problems worldwide. Investigating various cancer treatment options has been the focus of many domestic and international researchers, and significant progress has been made in the study of the anticancer effects of traditional Chinese medicines. Osthole, a coumarin compound extracted from Cnidium monnieri (L.) Cuss., has become a new research hotspot. There have been many reports on its anticancer effects, and recent studies have elucidated that its underlying mechanism of action mainly involves inhibiting cancer cell proliferation, inducing cancer cell apoptosis, inhibiting invasion and migration of cancer cells, inhibiting cancer angiogenesis, increasing sensitivity to chemotherapy drugs, and reversing multidrug resistance of cancer cells. This mini-review summarizes the research progress on the anticancer effects of osthole in recent years.
Network pharmacology-based investigation and experimental validation of the mechanism of scutellarin in the treatment of acute myeloid leukemia
Authors: Huang Zhe , Yang Yan , Fan Xianming , Ma Wenzhe
Published: September 2022

Background: It has been demonstrated that scutellarin, a natural flavone compound from Scutellaria lateriflora and Scutellaria barbata, exerts selective cytotoxicity against a range of cancer cells. However, the underlining mechanism of scutellarin on acute myeloid leukemia (AML) remains elusive.

Methods: In this study, the combination of network pharmacology and experimental verification was performed to identify the pharmacological mechanisms of scutellarin for AML therapy. The public databases, such as PharmMapper, UniProt, OMIM, GeneCards, DrugBank and PharmGkb database, were used to sceen the potential targets of scutellarin and AML. The protein-protein interaction (PPI), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted to uncover the mechanism of scutellarin in the treatment of AML. Finally, the network pharmacological results were further confirmed by in vitro and in vivo experiments.

Results: First and foremost, we totally obtained 289 target genes for scutellarin and 10998 disease targets for AML. 253 overlapping genes were preliminarily considered the potential targets of scutellarin for AML treatment. The results of PPI network analysis, GO analysis and KEGG pathway enrichment demonstrated that the anti-AML effect of scutellarin may focused on MAPK signaling pathway. Furthermore, the cytologic tests suggested that scutellarin can inhibit AML cells proliferation through the mediation of JNK/Caspase-3 pathway. Meanwhile, pretreatment with the JNK inhibitor SP600125 rescued scutellarin-induced apoptosis. Similarly, scutellarin obviously suppressed subcutaneous xenograft growth in nude mice via regulating the JNK/Caspase-3 signaling pathway.

Conclusion: In this study, we integrated network pharmacology-based prediction and experimental validation and revealed the importance of the JNK pathway in scutellarin-mediated AML treatment.
Sex difference in circulating PCSK9 and its clinical implications
Authors: Jia Fang , Fei Si-Fan , Tong De-Bing , Xue Cong , Li Jian-Jun
Published: September 2022

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a proprotein convertase that increases plasma low-density lipoprotein cholesterol (LDL-C) levels by triggering the degradation of LDL receptors (LDLRs). Beyond the regulation of circulating LDL-C, PCSK9 also has direct atherosclerotic effects on the vascular wall and is associated with coronary plaque inflammation. Interestingly, emerging data show that women have higher circulating PCSK9 concentrations than men, suggesting that the potential roles of PCSK9 may have different impacts according to sex. In this review, we summarize the studies concerning sex difference in circulating levels of PCSK9. In addition, we report on the sex differences in the relations of elevated circulating PCSK9 levels to the severity and prognosis of coronary artery disease, the incidence of type 2 diabetes mellitus, and neurological damage after cardiac arrest and liver injury, as well as inflammatory biomarkers and high-density lipoprotein cholesterol (HDL-C). Moreover, sex difference in the clinical efficacy of PCSK9 inhibitors application are reviewed. Finally, the underlying mechanisms of sex difference in circulating PCSK9 concentrations and the clinical implications are also discussed.
The contribution of ion channels to shaping macrophage behaviour
Authors: Selezneva Anna , Gibb Alasdair J. , Willis Dean
Published: September 2022

The expanding roles of macrophages in physiological and pathophysiological mechanisms now include normal tissue homeostasis, tissue repair and regeneration, including neuronal tissue; initiation, progression, and resolution of the inflammatory response and a diverse array of anti-microbial activities. Two hallmarks of macrophage activity which appear to be fundamental to their diverse cellular functionalities are cellular plasticity and phenotypic heterogeneity. Macrophage plasticity allows these cells to take on a broad spectrum of differing cellular phenotypes in response to local and possibly previous encountered environmental signals. Cellular plasticity also contributes to tissue- and stimulus-dependent macrophage heterogeneity, which manifests itself as different macrophage phenotypes being found at different tissue locations and/or after different cell stimuli. Together, plasticity and heterogeneity align macrophage phenotypes to their required local cellular functions and prevent inappropriate activation of the cell, which could lead to pathology. To execute the appropriate function, which must be regulated at the qualitative, quantitative, spatial and temporal levels, macrophages constantly monitor intracellular and extracellular parameters to initiate and control the appropriate cell signaling cascades. The sensors and signaling mechanisms which control macrophages are the focus of a considerable amount of research. Ion channels regulate the flow of ions between cellular membranes and are critical to cell signaling mechanisms in a variety of cellular functions. It is therefore surprising that the role of ion channels in the macrophage biology has been relatively overlooked. In this review we provide a summary of ion channel research in macrophages. We begin by giving a narrative-based explanation of the membrane potential and its importance in cell biology. We then report on research implicating different ion channel families in macrophage functions. Finally, we highlight some areas of ion channel research in macrophages which need to be addressed, future possible developments in this field and therapeutic potential.
Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments
Authors: Liu Zhi-Mei , Yang Ming-Hui , Yu Kun , Lian Zheng-Xing , Deng Shou-Long
Published: September 2022

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) rapidly infects humans and animals which make coronavirus disease 2019 (COVID-19) a grievous epidemic worldwide which broke out in 2020. According to data analysis of the other coronavirus family, for instance severe acute respiratory syndrome SARS coronavirus (SARS-CoV), can provide experience for the mutation of SARS-CoV-2 and the prevention and treatment of COVID-19. Toll-like receptors (TLRs) as a pattern recognition receptor (PRRs), have an indispensable function in identifying the invader even activate the innate immune system. It is possible for organism to activate different TLR pathways which leads to secretion of proinflammatory cytokines such as Interleukin 1 (IL-1), Interleukin 6 (IL-6), Tumor necrosis factor α (TNFα) and type Ⅰ interferon. As a component of non-specific immunity, TLRs pathway may participate in the SARS-CoV-2 pathogenic processes, due to previous works have proved that TLRs are involved in the invasion and infection of SARS-CoV and MERS to varying degrees. Different TLR, such as TLR2, TLR4, TLR7, TLR8 and TLR9 probably have a double-sided in COVID-19 infection. Therefore, it is of great significance for a correctly acknowledging how TLR take part in the SARS-CoV-2 pathogenic processes, which will be the development of treatment and prevention strategies.
Data-driven computational models of ventricular-arterial hemodynamics in pediatric pulmonary arterial hypertension
Authors: Tossas-Betancourt Christopher , Li Nathan Y. , Shavik Sheikh M. , Afton Katherine , Beckman Brian , Whiteside Wendy , Olive Mary K. , Lim Heang M. , Lu Jimmy C. , Phelps Christina M. , Gajarski Robert J. , Lee Simon , Nordsletten David A. , Grifka Ronald G. , Dorfman Adam L. , Baek Seungik , Lee Lik Chuan , Figueroa C. Alberto
Published: September 2022

Pulmonary arterial hypertension (PAH) is a complex disease involving increased resistance in the pulmonary arteries and subsequent right ventricular (RV) remodeling. Ventricular-arterial interactions are fundamental to PAH pathophysiology but are rarely captured in computational models. It is important to identify metrics that capture and quantify these interactions to inform our understanding of this disease as well as potentially facilitate patient stratification. Towards this end, we developed and calibrated two multi-scale high-resolution closed-loop computational models using open-source software: a high-resolution arterial model implemented using CRIMSON, and a high-resolution ventricular model implemented using FEniCS. Models were constructed with clinical data including non-invasive imaging and invasive hemodynamic measurements from a cohort of pediatric PAH patients. A contribution of this work is the discussion of inconsistencies in anatomical and hemodynamic data routinely acquired in PAH patients. We proposed and implemented strategies to mitigate these inconsistencies, and subsequently use this data to inform and calibrate computational models of the ventricles and large arteries. Computational models based on adjusted clinical data were calibrated until the simulated results for the high-resolution arterial models matched within 10% of adjusted data consisting of pressure and flow, whereas the high-resolution ventricular models were calibrated until simulation results matched adjusted data of volume and pressure waveforms within 10%. A statistical analysis was performed to correlate numerous data-derived and model-derived metrics with clinically assessed disease severity. Several model-derived metrics were strongly correlated with clinically assessed disease severity, suggesting that computational models may aid in assessing PAH severity.