bluuebunny/crossref_metadata_2025 huggingface dataset:
Probabilistic planning for ligament-balanced TKA—Identification of critical ligament properties
Authors: Bartsoen Laura , Faes Matthias G. R. , Wirix-Speetjens Roel , Moens David , Jonkers Ilse , Sloten Jos Vander
Published: November 2022

Total knee arthroplasty (TKA) failures are often attributed to unbalanced knee ligament loading. The current study aims to develop a probabilistic planning process to optimize implant component positioning that achieves a ligament-balanced TKA. This planning process accounts for both subject-specific uncertainty, in terms of ligament material properties and attachment sites, and surgical precision related to the TKA process typically used in clinical practice. The consequent uncertainty in the implant position parameters is quantified by means of a surrogate model in combination with a Monte Carlo simulation. The samples for the Monte Carlo simulation are generated through Bayesian parameter estimation on the native knee model in such a way that each sample is physiologically relevant. In this way, a subject-specific uncertainty is accounted for. A sensitivity analysis, using the delta-moment-independent sensitivity measure, is performed to identify the most critical ligament parameters. The designed process is capable of estimating the precision with which the targeted ligament-balanced TKA can be realized and converting this into a success probability. This study shows that without additional subject-specific information (e.g., knee kinematic measurements), a global success probability of only 12% is estimated. Furthermore, accurate measurement of reference strains and attachment sites critically improves the success probability of the pre-operative planning process. To allow more precise planning, more accurate identification of these ligament properties is required. This study underlines the relevance of investigating in vivo or intraoperative measurement techniques to minimize uncertainty in ligament-balanced pre-operative planning results, particularly prioritizing the measurement of ligament reference strains and attachment sites.
Evaluation of unsulfated biotechnological chondroitin in a knee osteoarthritis mouse model as a potential novel functional ingredient in nutraceuticals and pharmaceuticals
Authors: Cimini Donatella , Boccella Serena , Alfano Alberto , Stellavato Antonietta , Paino Salvatore , Schiraldi Chiara , Guida Francesca , Perrone Michela , Donniacuo Maria , Tirino Virginia , Desiderio Vincenzo , Rinaldi Barbara
Published: November 2022

Osteoarthritis is a very disabling disease that can be treated with both non-pharmacological and pharmacological approaches. In the last years, pharmaceutical-grade chondroitin sulfate (CS) and glucosamine emerged as symptomatic slow-acting molecules, effective in pain reduction and improved function in patients affected by osteoarthritis. CS is a sulfated glycosaminoglycan that is currently produced mainly by extraction from animal tissues, and it is commercialized as a pharmaceutical-grade ingredient and/or food supplement. However, public concern on animal product derivatives has prompted the search for alternative non-extractive production routes. Thus, different approaches were established to obtain animal-free natural identical CS. On the other hand, the unsulfated chondroitin, which can be obtained via biotechnological processes, demonstrated promising anti-inflammatory properties in vitro, in chondrocytes isolated from osteoarthritic patients. Therefore, the aim of this study was to explore the potential of chondroitin, with respect to the better-known CS, in an in vivo mouse model of knee osteoarthritis. Results indicate that the treatment with biotechnological chondroitin (BC), similarly to CS, significantly reduced the severity of mechanical allodynia in an MIA-induced osteoarthritic mouse model. Decreased cartilage damage and a reduction of inflammation- and pain-related biochemical markers were also observed. Overall, our data support a beneficial activity of biotechnological unsulfated chondroitin in the osteoarthritis model tested, thus suggesting BC as a potential functional ingredient in pharmaceuticals and nutraceuticals with the advantage of avoiding animal tissue extraction.
Integration of cancer stemness and neoantigen load to predict responsiveness to anti-PD1/PDL1 therapy
Authors: Luo Kunpeng , Liu Shuqiang , Shen Xiuyun , Xu Jincheng , Shi Chunpeng , Chao Yuqiu , Wen Zhengchao , Zhang Kejiao , Wang Ru , Liu Bing , Jiang Yanan
Published: November 2022

Background: Anti-programmed cell death 1/programmed cell death ligand 1 (PD1/PDL1) therapy is an important part of comprehensive cancer therapy. However, many patients suffer from non-response to therapy. Tumor neoantigen burden (TNB) and cancer stemness play essential roles in the responsiveness to therapy. Therefore, the identification of drug candidates for anti-PD1/PDL1 therapy remains an unmet need.

Methods: Three anti-PD1/PDL1 therapy cohorts were obtained from GEO database and published literatures. Cancer immune characteristics were analyzed using CIBERSORTX, GSVA, and ESTIMATE. WGCNA was employed to identify the gene modules correlated with cancer TNB and stemness. A machine-learning method was used to construct the immunotherapy resistance score (TSIRS). Pharmacogenomic analysis was conducted to explore the potential alternative drugs for anti-PD1/PDL1 therapy resistant patients. CCK-8 assay, EdU assay and wound healing assay were used to validate the effect of the predicted drug on cancer cells.

Results: The therapy response and non-response cancer groups have different microenvironment features. TSIRS was developed based on tumor neoantigen and stemness. TSIRS can effectively predict the outcomes of patients with anti-PD1/PDL1 therapy in training, validation and meta cohorts. Meanwhile, TSIRS can reflect the characteristics of tumor microenvironment during anti-PD1/PDL1 therapy. PF-4708671 is identified as a potential alternative drug for patients with resistance to anti-PD1/PDL1 therapy. It possesses significant inhibitive effect on the proliferation and migration of BGC-823 cells.

Conclusion: TSIRS is an effective tool in the identification of candidate patients who will be benefit from anti-PD1/PDL1 therapy. Small molecule drug PF-4708671 has the potential to be used in anti-PD1/PDL1 therapy resistant patients.
Modern Hopfield Networks for graph embedding
Authors: Liang Yuchen , Krotov Dmitry , Zaki Mohammed J.
Published: November 2022

The network embedding task is to represent a node in a network as a low-dimensional vector while incorporating the topological and structural information. Most existing approaches solve this problem by factorizing a proximity matrix, either directly or implicitly. In this work, we introduce a network embedding method from a new perspective, which leverages Modern Hopfield Networks (MHN) for associative learning. Our network learns associations between the content of each node and that node's neighbors. These associations serve as memories in the MHN. The recurrent dynamics of the network make it possible to recover the masked node, given that node's neighbors. Our proposed method is evaluated on different benchmark datasets for downstream tasks such as node classification, link prediction, and graph coarsening. The results show competitive performance compared to the common matrix factorization techniques and deep learning based methods.
The association between body mass index and risk of preoperative oxygenation impairment in patients with the acute aortic syndrome
Authors: Zhang Chiyuan , Shi Ruizheng , Zhang Guogang , Bai Hui , Zhang Yanfeng , Zhang Lei , Chen Xuliang , Fu Zuli , Lin Guoqiang , Xu Qian
Published: November 2022

Objective

The study aimed to determine the relationship between body mass index (BMI) and the risk of acute aortic syndrome (AAS) with preoperative oxygenation impairment.

Methods

A meta-analysis of published observational studies involving BMI and AAS with preoperative oxygenation impairment was conducted. A total of 230 patients with AAS were enrolled for retrospective analysis. All patients were divided into 2 groups (Non-oxygenation impairment group and Oxygenation impairment group). Logistic regression analysis was performed to assess the relation between BMI and the risk of preoperative oxygenation impairment after the onset of AAS. Dose-response relationship curve and subgroup analysis were conducted to test the reliability of BMI as an independent factor of it.

Results

For the meta-analysis, the quantitative synthesis indicated that excessive BMI increased the risk of preoperative oxygenation impairment (OR: 1.30, 95% CI: 1.05-1.60, Pheterogeneity = 0.001). For the retrospective analysis, a significant association was observed after adjusting for a series of variables. BMI was significantly related to preoperative oxygenation impairment after the onset of AAS (OR: 1.34, 95% CI: 1.15-1.56, p <0.001), and compared with normal weight group (18.5 kg/m2 ≤ BMI < 23.0 kg/m2), the individuals with excessive BMI were at higher risk of preoperative oxygenation impairment for the obese group (BMI ≥ 25 kg/m2) (OR: 17.32, 95% CI: 4.03-74.48, p <0.001). A J-shape curve in dose-response relationship analysis further confirmed their positive correlation. Subgroup analysis showed that diastolic blood pressure (DBP) ≥ 90mmHg carried an excess risk of preoperative oxygenation impairment in obese patients.

Conclusion

Excessive BMI was an independent risk factor for AAS with preoperative oxygenation impairment.
Effects of organic fertilizer incorporation practices on crops yield, soil quality, and soil fauna feeding activity in the wheat-maize rotation system
Authors: Zhou Zhongkai , Zhang Siyu , Jiang Na , Xiu Weiming , Zhao Jianning , Yang Dianlin
Published: November 2022

The decline in soil quality is becoming a significant process of soil degradation. Optimizing organic fertilizer incorporation practices in cropland is essential to enhancing crop productivity and soil health. However, that requires a comprehensive understanding of crop yield and soil quality reaction across an application gradient of organic fertilizer. We investigated the effect of organic fertilizer incorporation practices on crop yield, soil quality, and fauna feeding activity from fluvo-aquic soils on wheat (Triticum aestivum)-maize (Zea mays) rotation field. The six treatments included were unfertilized N control (UC), traditional chemical fertilizer application (TF, 600 N kg ha−1 year−1), and recommended chemical fertilization (RF, 400 N kg ha−1 year−1) with no organic fertilizer application rate, low-level 15.0 (RFLO), medium-level 30.0 (RFMO), and high-level 45.0 t ha−1 year−1(RFHO) application, respectively. The research findings show that the yield with organic fertilizer incorporation treatments increased 26.4%–44.6% for wheat and 12.5%–40.8% for maize compared to RF plots. The long-term organic fertilizer incorporation rate increased organic carbon from 54.7% to 110.6% versus UC plots and 27.9%–74.0% versus chemical fertilizer (TF and RF) treatments, and the total nitrogen content of soil increased from 41.8% to 59.2%, and 24.6%–39.2%. The long-term inorganic fertilizer combined with organic fertilizer incorporation practices significantly enhanced soil sucrose (30.1%–51.9%), urease (28.4%–38.3%), and β-1,4-glucosidase (34.6%–122.4%) activity. Still, nitrite reductase, polyphenol oxidase, and catalase significantly lower 27.3%–49.9%, 8.5%–26.3% and 23.3%–34.3% than single applications of inorganic N fertilizer groups. Meanwhile, the results showed that organic fertilizer incorporation practices improved soil fauna feeding activity by 35.2%–42.5%, and the excessive application of inorganic N fertilizer reduced the activity level of soil fauna.
Influence of financial subsidies on innovation efficiency of start-up enterprises
Authors: Zhou Yuzhong , Wang Liming , Ren Hang , Wang Lun , Zhang Shihan , Aamir Muhammad
Published: November 2022

The start-up period is the most difficult period for enterprises to survive and innovate. How will government subsidies affect the innovation efficiency of enterprises in the start-up period? And, is there any heterogeneity? The academic research is still relatively preliminary and controversial. This study adopts the cash flow method to screen a sample of start-ups from Chinese GEM, STAR Market and SME board-listed companies from 2010 to 2020 for empirical research. The study found that financial subsidies can generally promote the innovation efficiency of start-ups, but there is also significant heterogeneity by industry, region and whether the subsidies are sustainable. Financial subsidies generally have a signaling effect that facilitates startups to attract external capital, and this effect is most significant in the industrial sector. Overall, fiscal decentralization negatively regulates the effect of subsidies on the innovation efficiency of start-ups, especially in the public utilities and industrial sectors. The government subsidies are relatively insignificant to improve the innovation efficiency of start-up enterprises in non-first-tier cities, especially in small and medium-sized cities, and the multiplier effect is relatively small. The effect of non-sustainable subsidies is not significant because they cannot produce a long-term mechanism and thus are difficult to influence future expectations and decisions. The subsidy effect is not significant in other industries outside the industrial sector, and the lower the level of industry competition, the weaker the signaling effect of enterprise credit, the less conducive to its access to external innovation resources to enhance innovation efficiency through the signaling effect of government subsidies. Moreover, financial decentralization does not improve the innovation efficiency of government subsidies as expected, but weakens the innovation efficiency of fiscal subsidies for start-up enterprises in general. The study proposed that the government (especially the small and medium-sized city government) should optimize the business environment and financial capital allocation, change the supervision and management mechanism, improve the efficiency of capital utilization and reduce the crowding out effect. The government’s subsidy policy should be further standardized and refined.
Construction of an immune-related ceRNA network to screen for potential diagnostic markers for autism spectrum disorder
Authors: Sun Jing-Jing , Chen Bo , Yu Tao
Published: November 2022

Purpose: The diagnosis of autism spectrum disorder (ASD) is reliant on evaluation of patients’ behavior. We screened the potential diagnostic and therapeutic targets of ASD through bioinformatics analysis.

Methods: Four ASD-related datasets were downloaded from the Gene Expression Omnibus database. The “limma” package was employed to analyze differentially expressed messenger (m)RNAs, long non-coding (lnc)RNAs, and micro (mi)RNAs between ASD patients and healthy volunteers (HVs). We constructed a competing endogenous-RNA (ceRNA) network. Enrichment analyses of key genes were undertaken using the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes database. The ImmucellAI database was used to analyze differences in immune-cell infiltration (ICI) in ASD and HV samples. Synthetic analyses of the ceRNA network and ICI was done to obtain a diagnostic model using LASSO regression analysis. Analyses of receiver operating characteristic (ROC) curves were done for model verification.

Results: The ceRNA network comprised 49 lncRNAs, 30 miRNAs, and 236 mRNAs. mRNAs were associated with 41 cellular components, 208 biological processes, 39 molecular functions, and 35 regulatory signaling pathways. Significant differences in the abundance of 10 immune-cell species between ASD patients and HVs were noted. Using the ceRNA network and ICI results, we constructed a diagnostic model comprising five immune cell-associated genes: adenosine triphosphate-binding cassette transporter A1 (ABCA1), DiGeorge syndrome critical region 2 (DGCR2), glucose-fructose oxidoreductase structural domain gene 1 (GFOD1), glutaredoxin (GLRX), and SEC16 homolog A (SEC16A). The diagnostic performance of our model was revealed by an area under the ROC curve of 0.923. Model verification was done using the validation dataset and serum samples of patients.

Conclusion:ABCA1, DGCR2, GFOD1, GLRX, and SEC16A could be diagnostic biomarkers and therapeutic targets for ASD.
Construction and validation of an angiogenesis-related scoring model to predict prognosis, tumor immune microenvironment and therapeutic response in hepatocellular carcinoma
Authors: Tang Bo , Zhang Xinyuan , Yang Xiaozhou , Wang Wenling , Li Rongkuan , Liu Yu
Published: November 2022

Background

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with high morbidity and mortality. Identifying an effective marker for predicting the prognosis and therapeutic response is extremely meaningful. Angiogenesis-related genes (ARGs) play important roles in the tumor progression and immune-suppressive microenvironment formation.

Methods

The differential expressed ARGs associated with the prognosis of HCC were identified in the TCGA dataset. Univariate Cox and least absolute shrinkage selection operator (LASSO) regression were applied to construct a ARGs Scoring model. The prognostic value of the ARGs Scoring model was assessed by Cox regression, Kaplan-Meier (KM) and ROC curve analyses. Then the model was further validated in an external dataset, ICGC dataset. The patients were split into two groups based on the ARGs Score and the clinical features were compared. TIMER, CIBERSORT and xCell algorithms were utilized to analyze the correlation between the ARGs Score and tumor immune microenvironment (TIME). Furthermore, we analyzed the efficacy of the model in predicting the therapeutic response for immunotherapy, targeted therapy and TACE treatment in different cohorts.

Results

A total of 97 differential expressed ARGs were identified relating to the prognosis of HCC patients from the TCGA dataset. Then the ARGs Scoring model based on a 9-gene signature was constructed using the Cox and LASSO regression analyses. Higher ARGs Score had a poor clinical outcome and was considered to be an independent prognostic predictor for HCC in the multivariate Cox analysis. The ARGs Score was related to the enrichment of various immune cells, such as CD4+ T cells, Treg, macrophage, neutrophil and dendritic cells, exhibiting a more immunosuppressive phenotype. Higher ARGs Score was correlated with higher expression of immune checkpoint genes and poor response to immunotherapy. Furthermore, higher ARGs Score indicated poor therapeutic response in the sorafenib and TACE treatment cohorts, individually.

Conclusions

The ARGs Scoring model exhibited robust predictive value for the prognosis and TIME for HCC patients. Higher ARGs Score indicated poor therapeutic response of the immunotherapy, sorafenib and TACE treatment. The ARGs Scoring model could be used as a biomarker to help physicians to develop more individualized treatment for HCC patients.
Cytokine-mediated crosstalk between cancer stem cells and their inflammatory niche from the colorectal precancerous adenoma stage to the cancerous stage: Mechanisms and clinical implications
Authors: Cui Guanglin , Wang Ziqi , Liu Hanzhe , Pang Zhigang
Published: November 2022

The majority of colorectal cancers (CRCs) are thought to arise from precancerous adenomas. Upon exposure to diverse microenvironmental factors, precancerous stem cells (pCSCs) undergo complex genetic/molecular changes and gradually progress to form cancer stem cells (CSCs). Accumulative evidence suggests that the pCSC/CSC niche is an inflammatory dominated milieu that contains different cytokines that function as the key communicators between pCSCs/CSCs and their niche and have a decisive role in promoting CRC development, progression, and metastasis. In view of the importance and increasing data about cytokines in modulating pCSCs/CSC stemness properties and their significance in CRC, this review summarizes current new insights of cytokines, such as interleukin (IL)-4, IL-6, IL-8, IL-17A, IL-22, IL-23, IL-33 and interferon (IFN)-γ, involving in the modulation of pCSC/CSC properties and features in precancerous and cancerous lesions and discusses the possible mechanisms of adenoma progression to CRCs and their therapeutic potential.
Comprehensive 18F-FDG PET-based radiomics in elevating the pathological response to neoadjuvant immunochemotherapy for resectable stage III non-small-cell lung cancer: A pilot study
Authors: Cui Yingpu , Lin Yaobin , Zhao Zerui , Long Hao , Zheng Lie , Lin Xiaoping
Published: November 2022

Purpose

To develop a comprehensive PET radiomics model to predict the pathological response after neoadjuvant toripalimab with chemotherapy in resectable stage III non-small-cell lung cancer (NSCLC) patients.

Methods

Stage III NSCLC patients who received three cycles of neoadjuvant toripalimab with chemotherapy and underwent 18F-FDG PET/CT were enrolled. Baseline 18F-FDG PET/CT was performed before treatment, and preoperative 18F-FDG PET/CT was performed three weeks after the completion of neoadjuvant treatment. Surgical resection was performed 4–5 weeks after the completion of neoadjuvant treatment. Standardized uptake value (SUV) statistics features and radiomics features were derived from baseline and preoperative PET images. Delta features were derived. The radiologic response and metabolic response were assessed by iRECIST and iPERCIST, respectively. The correlations between PD-L1 expression, driver-gene status, peripheral blood biomarkers, and the pathological responses (complete pathological response [CPR]; major pathological response [MPR]) were assessed. Associations between PET features and pathological responses were evaluated by logistic regression.

Results

Thirty patients underwent surgery and 29 of them performed preoperative PET/CT. Twenty patients achieved MPR and 16 of them achieved CPR. In univariate analysis, five SUV statistics features and two radiomics features were significantly associated with pathological responses. In multi-variate analysis, SUVmax, SUVpeak, SULpeak, and End-PET-GLDM-LargeDependenceHighGrayLevelEmphasis (End-GLDM-LDHGLE) were independently associated with CPR. SUVpeak and SULpeak performed better than SUVmax and SULmax for MPR prediction. No significant correlation, neither between the radiologic response and the pathological response, nor among PD-L1, driver gene status, and baseline PET features was found. Inflammatory response biomarkers by peripheral blood showed no difference in different treatment responses.

Conclusion

The logistic regression model using comprehensive PET features contributed to predicting the pathological response after neoadjuvant toripalimab with chemotherapy in resectable stage III NSCLC patients.
Onchocerciasis: Current knowledge and future goals
Authors: Frallonardo Luisa , Di Gennaro Francesco , Panico Gianfranco Giorgio , Novara Roberta , Pallara Elisabetta , Cotugno Sergio , Guido Giacomo , De Vita Elda , Ricciardi Aurelia , Totaro Valentina , Camporeale Michele , De Iaco Giuseppina , Bavaro Davide Fiore , Lattanzio Rossana , Patti Giulia , Brindicci Gaetano , Papagni Roberta , Pellegrino Carmen , Santoro Carmen Rita , Segala Francesco Vladimiro , Putoto Giovanni , Nicastri Emanuele , Saracino Annalisa
Published: November 2022

Human Onchocerciasis, caused by infection by the filarial nematode Onchocerca volvulus, is a neglected public health disease that affects millions of people in the endemic regions of sub-Saharan Africa and Latin America. It is also called river blindness because the Blackflies that transmit infection breeds in rapidly flowing fresh water streams and rivers. This review features state-of-the-art data on the parasite, its endobacteria Wolbachia, the prevalence of the infection and its geographical distribution, its diagnostics, the interaction between the parasite and its host, and the pathology of Onchocerciasis. By development and optimization of the control measures, transmission by the vector has been interrupted in foci of countries in the Americas (Colombia, Ecuador, Mexico, and Guatemala)and inSudan, followed by Onchocerciasis eliminations. The current state and future perspectives for vector control and elimination strategy are described.
Exploring the multimodal role of Cnicus benedictus extract in the modulation of growth, hematobiochemical, histopathological, antioxidative performance, and immune-related gene expression of Oreochromis niloticus challenged with Aeromonas hydrophila
Authors: Salah Abdallah S. , El-Nagar Sahar H. , Elsheshtawy Ahmed , Al-Dhuayan Ibtesam , Fouad Alamira Marzouk , Alnamshan Mashael M. , Kadira Hossam I. , Alaqeel Nouf K. , El-Shobokshy Set A. , Shukry Mustafa , Abd-Elhafeez Hanan H.
Published: November 2022

This study explored the growth efficiency and the intracellular pathways by which Cnicus benedictus extract (CBE) acts. It investigated the antioxidant effects and efficacy of CBE as a fish supplement in attenuation of Aeromonas hydrophila in Oreochromis niloticus fish. Mono-sex Nile tilapia fish (n = 225) were randomly allocated to five groups in triplicate aquaria (n = 3 tanks per group, 15 fish per tank, with 120 L of water per tank) with a daily water exchange rate of 20%. After adaption for 2 weeks and body weight measuring, the experimental groups were fed isonitrogenous and isocaloric diets with different dosages of the ethanolic extract of C. benedictus for 10 weeks. The five groups were identified as the control group (CBE0.0), which was fed on the basal diet, while the second (CBE0.1), the third (CBE0.2), the fourth (CBE0.4), and the fifth (CBE0.6) groups were fed the basal diet supplemented with 0.1%, 0.2%, 0.4%, and 0.6% of C. benedictus extract, respectively. After the 10-week feeding trial was completed, the fish were inoculated with the PCR-identified pathogenic A. hydrophila in a challenge trial which lasted 15 days. A. hydrophila, one of the septicemic bacteria, causes severe economic losses, high mortality rates, and hemorrhages in Nile tilapia and other cultured freshwater fishes worldwide. The CBE was found to significantly increase the body mass, weight gain, and the specific growth rate, as well as the protein efficiency ratio of the fish. Increased survival percentage, accompanied by post challenge lymphocytosis with decreased liver enzyme levels, increased total protein, and improved kidney function markers were also seen. Additionally, CBE supplementation showed significant increases in phagocytic activity, phagocytic index, and lysosomal activity post challenge, accompanied by increases in antioxidant activity and the mRNA expression of cytokines genes hsp70 and tlr7 mRNA. The desirable effects of CBE treatment were confirmed by a histopathological examination of the height of intestinal villi and enterocytes lining the middle intestine and increases in the size of liver cells. We conclude that CBE increases the growth performance and modulates the antioxidant, inflammatory, stress, and immune-related genes in Nile tilapia. Moreover, the dietary inclusion of 0.42–0.47% CBE showed a better protective effect with the A. hydrophila challenge.
WLLP: A weighted reconstruction-based linear label propagation algorithm for predicting potential therapeutic agents for COVID-19
Authors: Chen Langcheng , Lin Dongying , Xu Haojie , Li Jianming , Lin Lieqing
Published: November 2022

The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV) has led to a huge health and economic crises. However, the research required to develop new drugs and vaccines is very expensive in terms of labor, money, and time. Owing to recent advances in data science, drug-repositioning technologies have become one of the most promising strategies available for developing effective treatment options. Using the previously reported human drug virus database (HDVD), we proposed a model to predict possible drug regimens based on a weighted reconstruction-based linear label propagation algorithm (WLLP). For the drug–virus association matrix, we used the weighted K-nearest known neighbors method for preprocessing and label propagation of the network based on the linear neighborhood similarity of drugs and viruses to obtain the final prediction results. In the framework of 10 times 10-fold cross-validated area under the receiver operating characteristic (ROC) curve (AUC), WLLP exhibited excellent performance with an AUC of 0.8828 ± 0.0037 and an area under the precision-recall curve of 0.5277 ± 0.0053, outperforming the other four models used for comparison. We also predicted effective drug regimens against SARS-CoV-2, and this case study showed that WLLP can be used to suggest potential drugs for the treatment of COVID-19.
Bacteriophage-mediated manipulations of microbiota in gastrointestinal diseases
Authors: El Haddad Lynn , Mendoza Jesus F. , Jobin Christian
Published: November 2022

Although some gastrointestinal diseases could be managed using various antibiotics regimen, this therapeutic approach lacks precision and damages the microbiota. Emerging literature suggests that phages may play a key role in restoring the gut microbiome balance and controlling disease progression either with exogenous phage intervention or filtered fecal transplantation or even engineered phages. In this review, we will discuss the current phage applications aiming at controlling the bacterial population and preventing infection, inflammation, and cancer progression in the context of gastrointestinal diseases.
Factors influencing successful establishment of exotic Pinus radiata seedlings with co-introduced Lactarius deliciosus or local ectomycorrhizal fungal communities
Authors: Wang Ran , Wang Yanliang , Guerin-Laguette Alexis , Zhang Peng , Colinas Carlos , Yu Fuqiang
Published: November 2022

An introduction of exotic or non-native trees may fail due to a lack of suitable fungal partners. We planted exotic Pinus radiata in Xifeng, Guizhou Southwest China. Strategies to introduce P. radiata seedlings either colonized with an ectomycorrhizal fungus (EcMF), Lactarius deliciosus, or expect them to form familiar/new associations with local EcMF in a new habitat were studied to know how P. radiata could be successfully established over a period of 2.5 years. Plant height and needle nutrient acquisition, the persistence of the co-introduced L. deliciosus, and fungal community composition in rhizosphere soil and root tips were analyzed. In addition, a greenhouse bioassay experiment of local soil to assess the differences in the EcMF community between exotic and native pine seedlings was also conducted. The current results demonstrated that P. radiata could establish in the Xifeng plantation with or without co-introduced L. deliciosus. The co-introduced L. deliciosus might be naturalized with P. radiata in the new area since it has been fruited for 2 years with high relative abundance in mycorrhizosphere soil. L. deliciosus pre-colonization significantly altered the mycorrhizosphere fungal composition and it had a positive correlation with nitrogen acquisition of P. radiata. Host identity had no effect on fungal composition since exotic P. radiata and native P. massoniana recruited similar local fungal communities in early establishment or in plantation. The cosmopolitan species Suillus placidus, with high relative abundance, formed a familiar association with P. radiata. The greenhouse bioassay experiment further showed that Suillus sp. contributed relatively higher total extracellular enzymes by forming ectomycorrhizas with P. radiata and the same type of ectomycorrhiza of P. radiata and P. massoniana showed different enzymatic functions. Our study indicated that exotic P. radiata could be a suitable tree capable to get established successfully in the Xifeng plantation either by interaction with the co-introduced L. deliciosus or with a local EcMF, but we should be cautious about large-scale planting of P. radiata. L. deliciosus persisted in plantation and more attention should be paid to local EcMF community changes induced by the introduced L. deliciosus.
Defining Paenibacillus azoreducens (P8) and Acetobacter pasteurianus (UMCC 2951) strains performances in producing acetic acid
Authors: Krusong Warawut , La China Salvatore , Pothimon Ruttipron , Gullo Maria
Published: November 2022

In this study, spore-forming bacteria isolated from saccharified rice were selected for producing acetic acid. From the screening of 15 strains, P8 strain was chosen as a candidate. The strain was identified as Paenibacillus azoreducens by 16S rRNA analysis (99.85% similarity with P. azoreducens CM1T). Acetic acid is the main component of vinegar but also an industrial commodity produced by chemical synthesis. Sustainable routes for obtaining acetic acid are of great interest for decreasing the environmental impact generated by chemical syntheses. Biological acetic acid production is effective for vinegar production by acetic acid bacteria, but it cannot economically compete with the chemical synthesis for producing it as a pure commodity. Considering the need to improve the yield of pure acetic acid produced by microbial conversions, in this study, P8 strain was chosen for designing processes in different fermentation conditions. Tests were conducted in single and semi-continuous systems, using rice wine as substrate. Acetic acid produced by P8 strain was compared with that of Acetobacter pasteurianus (UMCC 2951), a strain known for producing acetic acid from rice wine. Even though the fermentation performances of P. azoreducens P8 were slightly lower than those of acetic acid bacteria usually used for vinegar production, results highlight its suitability for producing acetic acid. The final acetic acid produced by P. azoreducens P8 was 73 g/L, in a single stage fermentation, without losses. In nine cycles of semi-continuous regime the average of acetification rate was 0.814 (g/L/days). Two main attributes of P. azoreducens P8 are of relevance for producing acetic acid, namely the ability to grow at temperature higher (+ 37°C), than mesophilic acetic acid bacteria, and the absence of cytoplasmic assimilation of acetic acid. These features allow to design multiple strains cultures, in which P. azoreducens can acts as a helper strain. Based on our results, the new isolate P. azoreducens P8 can be propagated in fermenting broths for boosting acetic acid production, under the selected conditions, and used in combination with acetic acid bacteria to produce biological acetic acid, as a non-food grade commodity.
Pyroptosis in spinal cord injury
Authors: Yin Jian , Gong Ge , Wan Wenhui , Liu Xinhui
Published: November 2022

Spinal cord injury (SCI) often brings devastating consequences to patients and their families. Pathophysiologically, the primary insult causes irreversible damage to neurons and glial cells and initiates the secondary damage cascade, further leading to inflammation, ischemia, and cells death. In SCI, the release of various inflammatory mediators aggravates nerve injury. Pyroptosis is a new pro-inflammatory pattern of regulated cell death (RCD), mainly mediated by caspase-1 or caspase-11/4/5. Gasdermins family are pore-forming proteins known as the executor of pyroptosis and the gasdermin D (GSDMD) is best characterized. Pyroptosis occurs in multiple central nervous system (CNS) cell types, especially plays a vital role in the development of SCI. We review here the evidence for pyroptosis in SCI, and focus on the pyroptosis of different cells and the crosstalk between them. In addition, we discuss the interaction between pyroptosis and other forms of RCD in SCI. We also summarize the therapeutic strategies for pyroptosis inhibition, so as to provide novel ideas for improving outcomes following SCI.
Perineuronal nets restrict transport near the neuron surface: A coarse-grained molecular dynamics study
Authors: Hanssen Kine Ødegård , Malthe-Sørenssen Anders
Published: November 2022

Perineuronal nets (PNNs) are mesh-like extracellular matrix structures that wrap around certain neurons in the central nervous system. They are hypothesized to stabilize memories in the brain and act as a barrier between cell and extracellular space. As a means to study the impact of PNNs on diffusion, the nets were approximated by negatively charged polymer brushes and simulated by coarse-grained molecular dynamics. Diffusion constants of single neutral and single charged particles were obtained in directions parallel and perpendicular to the brush substrate. The results for the neutral particle were compared to different theories of diffusion in a heuristic manner. Diffusion was found to be considerably reduced for brush spacings smaller than 10 nm, with a pronounced anisotropy for dense brushes. The exact dynamics of the chains was found to have a negligible impact on particle diffusion. The resistance of the brush proved small compared to typical values of the membrane resistance of a neuron, indicating that PNNs likely contribute little to the total resistance of an enwrapped neuron.
Case report: Implantation metastasis following stereotactic biopsy of pineal parenchymal tumor of intermediate differentiation in an adult patient: An exceptionally rare complication
Authors: Tandean Steven , Siahaan Andre Marolop Pangihutan , Loe Michael Lumintang , Indharty Rr Suzy , Julijamnasi  , Sitorus Mega Sari , Japardi Iskandar , July Julius
Published: November 2022

Implantation metastasis following stereotactic biopsy in the brain had been reported as a rare complication. A 36-years-old female patient was treated with ventriculoperitoneal (VP) shunt and stereotactic biopsy of a pineal parenchymal tumor of intermediate differentiation (PPTID) with hydrocephalus. The patient underwent five cycles of radiotherapy on the pineal area. Seven years after the procedure, the patient developed left hemiparesis with the brain MRI findings showing an enhanced mass along the biopsy tract. Craniotomy tumor removal was carried out and the pathological assessment was consistent with those of the PPTID. Radiation on metastase area and craniospinal was subsequently performed. The patient was disease-free during the 2-year follow-up assessments. The potential occurrence of implantation metastasis following the stereotactic biopsy of PPTID should be considered in the treatment plan and follow-up assessments and evaluations. Expanding the radiation area to cover the entire biopsy tract may be favorable to lower the risk of implantation metastasis.
Deep brain stimulation in Early Onset Parkinson's disease
Authors: Krause Patricia , Reimer Johanna , Kaplan Jonathan , Borngräber Friederike , Schneider Gerd-Helge , Faust Katharina , Kühn Andrea A.
Published: November 2022

Introduction

Subthalamic Deep Brain Stimulation (STN-DBS) is a safe and well-established therapy for the management of motor symptoms refractory to best medical treatment in patients with Parkinson's disease (PD). Early intervention is discussed especially for Early-onset PD (EOPD) patients that present with an age of onset ≤ 45–50 years and see themselves often confronted with high psychosocial demands.

Methods

We retrospectively assessed the effect of STN-DBS at 12 months follow-up (12-MFU) in 46 EOPD-patients. Effects of stimulation were evaluated by comparison of disease-specific scores for motor and non-motor symptoms including impulsiveness, apathy, mood, quality of life (QoL), cognition before surgery and in the stimulation ON-state without medication. Further, change in levodopa equivalent dosage (LEDD) after surgery, DBS parameter, lead localization, adverse and serious adverse events as well as and possible additional clinical features were assessed.

Results

PD-associated gene mutations were found in 15% of our EOPD-cohort. At 12-MFU, mean motor scores had improved by 52.4 ± 17.6% in the STIM-ON/MED-OFF state compared to the MED-OFF state at baseline (p = 0.00; n = 42). These improvements were accompanied by a significant 59% LEDD reduction (p < 0.001), a significant 6.6 ± 16.1 points reduction of impulsivity (p = 0.02; n = 35) and a significant 30 ± 50% improvement of QoL (p = 0.01). At 12-MFU, 9 patients still worked full- and 6 part-time. Additionally documented motor and/or neuropsychiatric features decreased from n = 41 at baseline to n = 14 at 12-MFU.

Conclusion

The present study-results demonstrate that EOPD patients with and without known genetic background benefit from STN-DBS with significant improvement in motor as well as non-motor symptoms. In line with this, patients experienced a meaningful reduction of additional neuropsychiatric features. Physicians as well as patients have an utmost interest in possible predictors for the putative DBS outcome in a cohort with such a highly complex clinical profile. Longitudinal monitoring of DBS-EOPD-patients over long-term intervals with standardized comprehensive clinical assessment, accurate phenotypic characterization and documentation of clinical outcomes might help to gain insights into disease etiology, to contextualize genomic information and to identify predictors of optimal DBS candidates as well as those in danger of deterioration and/or non-response in the future.
Vestibular dysfunction is an important contributor to the aging of visuospatial ability in older adults–Data from a computerized test system
Authors: Zhang Xuehao , Huang Yan , Xia Yuqi , Yang Xiaotong , Zhang Yanmei , Wei Chaogang , Ying Hang , Liu Yuhe
Published: November 2022

Background

A convergence of research supports a key role of the vestibular system in visuospatial ability. However, visuospatial ability may decline with age. This work aims to elucidate the important contribution of vestibular function to visuospatial ability in old adults through a computerized test system.

Methods

Patients with a clinical history of recurrent vertigo and at least failed one vestibular test were included in this cross-sectional study. Healthy controls of three age groups: older, middle-aged, and young adults were also involved. Visuospatial cognitive outcomes including spatial memory, spatial navigation, and mental rotation of all the groups were recorded. Comparing the performance of the visuospatial abilities between patients and age-matched controls as well as within the controls.

Results

A total of 158 individuals were enrolled. Results showed that patients performed worse than the age-matched controls, with the differences in the forward span (p < 0.001), the time of the maze 8 × 8 (p = 0.009), and the time of the maze 12 × 12 (p = 0.032) being significant. For the differences in visuospatial cognitive outcomes within the controls, the younger group had a significantly better performance than the other groups. The older group and the middle-aged group had comparable performances during all the tests.

Conclusions

Older patients with vestibular dysfunction had more difficulties during visuospatial tasks than age-matched controls, especially in spatial memory and spatial navigation. Within the controls, younger adults did much better than other age groups, while older adults behaved similarly to middle-aged adults. It is a valuable attempt to computerize the administration of tests for visuospatial ability.
BDNF rs10501087, rs1491850 and rs11030094 polymorphisms associated with delayed progression in early-stage Parkinson's disease
Authors: Fischer D. Luke , Auinger Peggy , Goudreau John L. , Paumier Katrina L. , Cole-Strauss Allyson , Kemp Christopher J. , Lipton Jack W. , Sortwell Caryl E.
Published: November 2022

Parkinson's disease (PD) is heterogenous in its presentation, progression and response to therapies. Genetic polymorphisms may account for some of this variability. Several single nucleotide polymorphisms (SNPs) in the brain-derived neurotrophic factor gene BDNF have been associated with differing clinical outcomes from different dopaminergic replacement strategies, and one of these, the rs6265 SNP, has been associated with a milder clinical phenotype in the unmedicated, early-stage of PD. We examined if other BDNF SNPs with potential pharmacogenetic effects also are associated with different rates of disease progression. The Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) study was analyzed retrospectively. DNA samples (n = 217) were genotyped for the BDNF rs908867, rs11030094, rs10501087, rs1157659, and rs1491850 SNPs, and the primary endpoint was time to initiate symptomatic pharmacotherapy. Genotypes were compared using the Cox proportional hazard ratio (HR) with baseline age, sex, site, time since PD diagnosis and rs6265 genotype as covariates. The primary endpoint was associated with a delay with three SNPs: rs10501087 [HR (95% Confidence Interval) = 28.3 (3.6–223.1, p = 0.002) and 7.6 (1.9–29.8, p = 0.004) for T/T and T/C subjects, respectively, vs. C/C subjects], rs1491850 [HR = 3.3 (1.3–8.4, p = 0.04) and 2.8 (1.3–6.4, p = 0.03) for T/T and T/C subjects, respectively, vs. C/C subjects] and rs11030094 [HR = 2.5 (1.1–5.6, p = 0.03) and 2.0 (1.3–6.4, p = 0.03) for A/A and A/G subjects, respectively, vs. G/G subjects]. From the primary endpoint, specific rs10501087, rs1491850, and rs11030094 SNP genotypes are associated with a slower rate of PD progression in the unmedicated state. A prospective clinical trial examining many BDNF SNPs is warranted.
Short-term and long-term outcomes in patients with cryptococcal meningitis after ventriculoperitoneal shunt placement
Authors: Wen Junxian , Yin Rui , Chang Jianbo , Chen Yihao , Dong Xiying , Cao Wei , Ma Xiaojun , Li Taisheng , Wei Junji
Published: November 2022

Objective

The purpose of this study was to assess the short-term and long-term outcomes of ventriculoperitoneal shunt (VPS) placement in patients with cryptococcal meningitis (CM).

Methods

We performed a retrospective analysis of all patients with CM admitted to the Peking Union Medical College Hospital from September 1990 to January 2021. We collected related clinical features to analyze the short- and long-term outcomes of VPS at 1 month and 1 year at least the following therapy, respectively. Overall survival (OS) was compared with all patients and a subgroup of critically ill cases by the Kaplan–Meier method with the log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors.

Results

We enrolled 98 patients, fifteen of whom underwent VPS. Those who received VPS had a lower cerebrospinal fluid (CSF) Cryptococcus burden (1:1 vs. 1:16; p = 0.046), lower opening pressures (173.3 mmH2 O vs. 224 mmH2O; p = 0.009) at lumbar punctures, and a lower incidence of critical cases (6.7 vs. 31.3%; p = 0.049). According to our long-term follow-up, no significant difference was shown in the Barthel Index (BI) between the two groups. Two patients in the VPS group suffered postoperative complications and had to go through another revision surgery. According to survival analysis, overall survival (OS) between the VPS and non-VPS groups was not significantly different. However, the Kaplan–Meier plots showed that critical patients with VPS had better survival in OS (p < 0.009). Multivariable analyses for critical patients showed VPS was an independent prognostic factor.

Conclusion

A VPS could reduce the intracranial pressure (ICP), decrease the counts of Cryptococcus neoformans by a faster rate and reduce the number of critical cases. The VPS used in critical patients with CM has a significant impact on survival, but it showed no improvement in the long-term Barthel Index (BI) vs. the conservative treatment and could lead to postoperative complications.