bluuebunny/crossref_metadata_2025 huggingface dataset:
CX3CR1 But Not CCR2 Expression Is Required for the Development of Autoimmune Peripheral Neuropathy in Mice
Authors: Oladiran Oladayo , Shi Xiang Qun , Fournier Sylvie , Zhang Ji
Published: August 2021

One hallmark of Guillain-Barre syndrome (GBS), a prototypic autoimmune peripheral neuropathy (APN) is infiltration of leukocytes (macrophages and T cells) into peripheral nerves, where chemokines and their receptors play major roles. In this study, we aimed to understand the potential contribution of chemokine receptors CCR2 and CX3CR1 in APN by using a well-established mouse model, B7.2 transgenic (L31) mice, which possesses a predisposed inflammatory background. We crossbred respectively CCR2KO and CX3CR1KO mice with L31 mice. The disease was initiated by partial ligation on one of the sciatic nerves. APN pathology and neurological function were evaluated on the other non-ligated sciatic nerve/limb. Our results revealed that L31/CX3CR1KO but not L31/CCR2KO mice were resistant to APN. CX3CR1 is needed for maintaining circulating monocyte and CD8+ T cell survival. While migration of a significant number of activated CD8+ T cells to peripheral nerves is essential in autoimmune response in nerve, recruitment of monocytes into PNS seems optional. Disease onset is independent of CCR2 mediated blood-derived macrophage recruitment, which can be replaced by compensatory proliferation of resident macrophages in peripheral nerve. CX3CR1 could also contribute to APN via its critical involvement in maintaining nerve macrophage phagocytic ability. We conclude that blockade of CX3CR1 signaling may represent an interesting anti-inflammatory strategy to improve therapeutic management for GBS patients.
Comparison of Efficacy and Safety of Single and Double Immune Checkpoint Inhibitor-Based First-Line Treatments for Advanced Driver-Gene Wild-Type Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis
Authors: Xu Qian , Zhang Xue , Huang Miao , Dai Xin , Gao Jing , Li Song , Sheng Lei , Huang Kai , Wang Jian , Liu Lian
Published: August 2021

Background

Immune checkpoint inhibitors (ICIs) have improved survival for advanced wild-type non-small cell lung cancer (NSCLC) significantly, but few studies compared single ICI (SICI)-based treatments and double ICIs (DICI)-based treatments. We summarized the general efficacy of ICI-related treatments, compared the efficacy and safety of SICI-based [programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors ± chemotherapy (CT)] and DICI-based (PD-1/PD-L1 inhibitors+CTLA-4 inhibitors ± chemotherapy) treatments vs. CT in the first-line treatment.

Methods

We included phase II/III randomized controlled trials (RCTs), including patients with histologically confirmed stage IIIB–IV driver-gene wild-type NSCLC who received first-line ICI-related therapy in at least one arm. PubMed, Embase, and Cochrane Library were searched from January 1, 2005, to December 31, 2020. This network meta-analysis was performed in a Bayesian framework using GEMTC and JAGS package in R.3.6.1. The research was registered with PROSPERO (CRD42020184534).

Results

Twenty RCTs were involved, including 13,032 patients and 17 treatment regimens. The results showed that ICI-based therapies could provide a pooled median overall survival (mOS) (POS) of 15.79 (95% CI: 14.85–16.73) months, and there were no significant differences in OS, progression-free survival (PFS), objective response rate (ORR), and grade 3 or higher adverse events (≥3AEs) between DICI-based treatments (POS: 14.81, 12.11–17.52 months) and SICI-based treatments (POS: 16.17, 14.59–17.74 months) in overall patients. However, DICI-based treatments had significantly prolonged the OS over SICI-based treatments in squamous and PD-L1 <1% subgroups. The ranking of OS benefit by Bayesian surface under the cumulative ranking curve (SUCRA) spectrum showed that DICI+chemotherapy ranked first for overall population and subgroups including squamous, non-squamous, any level of PD-L1 expression, smoking, male, Eastern Cooperative Oncology Group performance status (ECOG PS) = 0/1, age < 65/≥65 while SICI+CT for low tumor mutation burden (TMB), non-smoking, and female subgroups, and DICI for high TMB subgroups.

Conclusions

In the first-line therapy for advanced wild-type NSCLC, both SICI- and DICI-based treatments could bring significant overall advantages over chemotherapy, with comparable outcomes of efficacy and ≥3AEs. DICI-based treatments were more effective than SICI-based treatments in squamous and PD-L1 <1% subgroups. For most populations, DICI+chemotherapy could be the best choice with a survival benefit, while SICI+chemotherapy has established its position actually.

Systematic Review Registration

[PROSPERO], identifier [CRD42020184534].
Lockdown: How the COVID-19 Pandemic Affected the Fishing Activities in the Adriatic Sea (Central Mediterranean Sea)
Authors: Russo Elisabetta , Anelli Monti Marco , Toninato Giacomo , Silvestri Claudio , Raffaetà Alessandra , Pranovi Fabio
Published: August 2021

The coronavirus disease 2019 (COVID-19) has brought a global socio-economic crisis to almost all sectors including the fishery. To limit the infection, governments adopted several containment measures. In Italy, Croatia, and Slovenia, a lockdown period was imposed from March to May 2020, during which many activities, including restaurants had to close or limit their business. All of this caused a strong reduction in seafood requests and consequently, a decrease in fishing activities. The aim of this study is to investigate the effects of the COVID-19 in the Northern and Central Adriatic fleet, by comparing the fishing activities in three periods (before, during, and after the lockdown) of 2019 and 2020. The use of the Automatic Identification System (AIS) data allowed us to highlight the redistribution of the fishing grounds of the trawlers, mainly located near the coasts during the 2020 lockdown period, as well as a reduction of about 50% of fishing effort. This reduction resulted higher for the Chioggia trawlers (−80%) and, in terms of fishing effort decrease, the large bottom otter trawl was the fishing segment mainly affected by the COVID-19 event. Moreover, by analysing the landings of the Chioggia fleet and the Venice lagoon fleets, it was possible to point out a strong reduction both in landings and profits ranging from −30%, for the small-scale fishery operating at sea, to −85%, for the small bottom otter trawl.
Contrasting the Motivations and Wildlife-Related Value Orientations of Recreational Fishers With Participants of Other Outdoor and Indoor Recreational Activities
Authors: Morales-Nin Beatriz , Arlinghaus Robert , Alós Josep
Published: August 2021

Assessing the motivations and wildlife-related value orientations (WVOs) of outdoor recreations, such as recreational fishing (RF), is of key importance to understand the human dimensions of natural resource use and to inform management actions. Using a national random telephone survey, we contrasted the participation rate, the socio-economical profile, and the motivations and WVO of the participants of RF, outdoor recreation (OR), consumptive outdoor recreation (COR), and indoor recreation (IR) in Spain. Participation rates of the four subgroups were 6.6, 15.3, 49.4, and 28.4%, for RF, COR, OR, and IR, respectively. The four subgroups differed in socio-economic characteristics, with women being substantially less involved in RF compared to COR, OR, and IR. Moreover, we found higher incomes and educational degrees of the participants in the three outdoor modalities compared to IR. Motivations to engage in RF, COR, OR, and IR were different. Recreational fishers placed significantly more importance on the motives “to be close to nature,” “to experience tranquility,” “to get away from the usual demands of life,” “to relax psychically,” “to stay with family,” and “to get exercise” compared to the other recreational groups, being very different from the ones to practice IR. We did not find significant differences in the WVO among the participants of the four recreational activities. We conclude that recreational fishing is a widespread recreational activity in Spain, embedded in all the segments of the society, thereby generating substantial psychological benefits, which are not equally produced by other forms of indoor and outdoor recreation.
Deformation of Steel Slag Asphalt Mixtures Under Normal Temperature Water Immersion
Authors: Wang Chao , Zhang Caili
Published: August 2021

To study the deformation resistance of steel slag asphalt mixtures (SSAMs) under rainy conditions, limestone–asphalt mixtures (LAMs) and SSAM were soaked in water at room temperature for 120 days and rutting tests and triaxial compression tests were carried out. The results show that the deformation resistance of SSAM was improved after 120 days of immersion, the cohesion did not decrease significantly, and the internal friction angle increased by 25.1%; the deformation resistance of LAM decreased significantly, the cohesion decreased by 27.1%, and the internal friction angle decreased by 21.1%. To better understand the reason for the increased anti-deformation ability, adhesion tests of asphalt and microscopic studies of the steel slag surface were performed. The experimental results showed that the cohesion of steel slag did not decrease significantly after immersion because of the excellent adhesion between steel slag and asphalt. The increased internal friction angle was caused by calcium hydroxide and other crystals formed on the surface of the steel slag mixture after immersion, which increased the surface roughness of the steel slag aggregates and the internal friction angle of the SSAM. The mechanical properties of semirigid asphalt pavement were analyzed by ANSYS. It was determined that the shear stress of this type of pavement is large, and it can easily produce permanent deformations. Under the influence of moisture, the anti-deformation ability of SSAMs can grow, which promotes the high-temperature deformation resistance of asphalt pavement. Based on a test road used for 2 years, the SSAM pavement exhibited no pavement problems, such as cracking, loosening, or rutting, which indicates good practical road performance.
Contrast-Enhanced Ultrasound Findings of Hepatocellular Carcinoma With Neuroendocrine Carcinoma: A Case Report
Authors: Wang Hong , Yang Dan , Wu Zhenru , Luo Yan , Ling Wenwu
Published: August 2021

Hepatocellular carcinoma (HCC) with the concurrent occurrence of primary hepatic neuroendocrine carcinoma (NEC) of the liver is extremely rare. Preoperative diagnosis of HCC combined with NEC is very difficult. Here, we presented a case report of HCC combined with NEC. A 33-year-old male was admitted to our hospital due to focal liver lesion. To further the diagnosis, he received laboratory tests, conventional ultrasound, contrast-enhanced ultrasound (CEUS), and magnetic resonance imaging (MRI). Grayscale ultrasound showed a hypoechoic nodule with peripheral hypoechoic halo and central small patches of anechoic area in the hepatic segment VI, and the liver background was cirrhosis. In the CEUS, the solid component of the nodule was rapidly homogeneous hyper-enhancement in the arterial phase. Then, the enhancement of the nodule was washed out slowly and gradually; the nodule presented heterogeneously mild enhancement in the portal phase, and slight hypo-enhancement was showed in the late phase. The hypo-enhanced area was mainly located in the surrounding space. Meanwhile, there was a small piece of non-enhanced area within the lesion center in the whole three-phase imaging. MRI showed a lobular contoured mass in segment VI. The patient underwent middle liver resection, splenectomy, and cholecystectomy. The pathological diagnosis was a HCC with NEC. At the time of the preparation of this manuscript, the patient has been alive without recurrence or distant metastases for 6 months since the surgery. We mainly focus on the ultrasound imaging characteristics, especially its enhancement manifestations on CEUS. In this report, since this article is a case report, which is based on the clinical information of the patient and does not involve the patient's privacy, informed consent is not necessary. In addition, the patient agreed to publish the case. To the best of our knowledge, this report is the first to describe the CEUS patterns of the HCC combined with NEC. Herein, we report a case that provides novel insights that will improve clinicians' awareness of the clinical and ultrasound manifestations of this mixed tumor, resulting in improved diagnosis, treatment, and outcomes.
Case Report: Rare Pulmonary Sclerosing Pneumocytoma: Large, Multiple, Metastatic, and Fatal
Authors: Zhang Weidong , Liu Yuanyuan , Chai Yamei , Shi Kefeng , Chen Jialing , Shi Dongfeng , Wu Xiaoming
Published: August 2021

Pulmonary sclerosing pneumocytoma (PSP) is a rare benign or low-grade malignant tumor, but it has the potential to present with multiple lesions, lymph node metastasis, extra-pulmonary metastasis, recurrence and even cause death. Herein, a case of PSP that was huge, presented with multiple lesions and had lymph node as well as extrapulmonary metastases (liver, abdominal cavity, bones) is reported for the first time. This patient was also the first one to die of respiratory and circulatory failure caused by the PSP tumor and its metastases which compressed the mediastinal tissue.
Case Report: SARS-CoV-2 Mother-to-Child Transmission and Fetal Death Associated With Severe Placental Thromboembolism
Authors: Marinho Penélope Saldanha , da Cunha Antonio José Ledo Alves , Chimelli Leila , Avvad-Portari Elyzabeth , Andreiuolo Felipe da Matta , de Oliveira-Szejnfeld Patrícia Soares , Mendes Mayara Abud , Gomes Ismael Carlos , Souza Letícia Rocha Q. , Guimarães Marilia Zaluar , Goldman Suzan Menasce , de Oliveira Mariana Barros Genuíno , Rehen Stevens , Amim Joffre , Tovar-Moll Fernanda , Prata-Barbosa Arnaldo
Published: August 2021

SARS-CoV-2 infection during pregnancy is not usually associated with significant adverse effects. However, in this study, we report a fetal death associated with mild COVID-19 in a 34-week-pregnant woman. The virus was detected in the placenta and in an unprecedented way in several fetal tissues. Placental abnormalities (MRI and anatomopathological study) were consistent with intense vascular malperfusion, probably the cause of fetal death. Lung histopathology also showed signs of inflammation, which could have been a contributory factor. Monitoring inflammatory response and coagulation in high-risk pregnant women with COVID-19 may prevent unfavorable outcomes, as shown in this case.
Ability of a Machine Learning Algorithm to Predict the Need for Perioperative Red Blood Cells Transfusion in Pelvic Fracture Patients: A Multicenter Cohort Study in China
Authors: Huang Xueyuan , Wang Yongjun , Chen Bingyu , Huang Yuanshuai , Wang Xinhua , Chen Linfeng , Gui Rong , Ma Xianjun
Published: August 2021

Background: Predicting the perioperative requirement for red blood cells (RBCs) transfusion in patients with the pelvic fracture may be challenging. In this study, we constructed a perioperative RBCs transfusion predictive model (ternary classifications) based on a machine learning algorithm.

Materials and Methods: This study included perioperative adult patients with pelvic trauma hospitalized across six Chinese centers between September 2012 and June 2019. An extreme gradient boosting (XGBoost) algorithm was used to predict the need for perioperative RBCs transfusion, with data being split into training test (80%), which was subjected to 5-fold cross-validation, and test set (20%). The ability of the predictive transfusion model was compared with blood preparation based on surgeons' experience and other predictive models, including random forest, gradient boosting decision tree, K-nearest neighbor, logistic regression, and Gaussian naïve Bayes classifier models. Data of 33 patients from one of the hospitals were prospectively collected for model validation.

Results: Among 510 patients, 192 (37.65%) have not received any perioperative RBCs transfusion, 127 (24.90%) received less-transfusion (RBCs < 4U), and 191 (37.45%) received more-transfusion (RBCs ≥ 4U). Machine learning-based transfusion predictive model produced the best performance with the accuracy of 83.34%, and Kappa coefficient of 0.7967 compared with other methods (blood preparation based on surgeons' experience with the accuracy of 65.94%, and Kappa coefficient of 0.5704; the random forest method with an accuracy of 82.35%, and Kappa coefficient of 0.7858; the gradient boosting decision tree with an accuracy of 79.41%, and Kappa coefficient of 0.7742; the K-nearest neighbor with an accuracy of 53.92%, and Kappa coefficient of 0.3341). In the prospective dataset, it also had a food performance with accuracy 81.82%.

Conclusion: This multicenter retrospective cohort study described the construction of an accurate model that could predict perioperative RBCs transfusion in patients with pelvic fractures.
Association Between the Health Locus of Control and Medication Adherence: An Observational, Cross-Sectional Study in Primary Care
Authors: Gerland Hanna-Maria E. , Prell Tino
Published: August 2021

Background: Medication non-adherence is an important healthcare issue and a common problem. Many predictors of non-adherence have been found in different settings and cohorts.

Objective: Evaluate the impact of the health locus of control (HLC) on unintentional/intentional non-adherence in primary care.

Methods: In this observational, cross-sectional study, 188 patients (mean age 63.3 ± 14.9 years) were recruited from three primary care practices in Jena, Germany, over 4 months. The study assessed demographic data, self-reported adherence (German Stendal adherence to medication score, SAMS), HLC, and depression.

Results: According to the SAMS total score, 44 (27.5%) were fully adherent, 93 (58.1%) were moderately non-adherent, and 23 (14.4%) were clinically significantly non-adherent. The most common reasons for non-adherence were forgetting to take the medication or lacking knowledge about the prescribed medication. Multiple linear regression revealed that adherence was good in people with external HLC and poor in internal HLC. In particular, intentional non-adherence was positively associated with internal HLC and negatively with fatalistic external HLC. Depression had a negative influence on both intentional and unintentional non-adherence.

Conclusion: HLC is an independent predictor of medication non-adherence and is a promising target for interventions that enhance adherence.
Chronic Obstructive Pulmonary Disease Is Associated With Decreased Quality of Life in Bronchiectasis Patients: Findings From the KMBARC Registry
Authors: Kim Sang Hyuk , Kim Changhwan , Jeong Ina , Lee Seung Jun , Kim Tae Hyung , Lee Chang Youl , Oh Yeon-Mok , Lee Hyun , Kim Youlim
Published: August 2021

Most studies have evaluated the impact of non-cystic fibrosis bronchiectasis (hereafter referred to as bronchiectasis) on quality of life (QoL) in patients with chronic obstructive pulmonary disease (COPD) using COPD cohorts. Accordingly, the impact of COPD on QoL in patients with bronchiectasis is not well-elucidated. We used the Korean Multicenter Bronchiectasis Audit and Research Collaboration (KMBARC) registry between August 2018 and December 2019, a prospective observational cohort that enrolled patients with bronchiectasis in Korea. We evaluated co-occurrence exposure to COPD in bronchiectasis patients, and the primary outcome was QoL according to the Bronchiectasis Health Questionnaire (BHQ). We also investigated factors associated with decreased QoL, defined as the lowest quartile of the total BHQ score. Of 598 patients with bronchiectasis, 372 (62.2%) had COPD. Bronchiectasis patients with COPD had a significantly lower total BHQ score compared with those without COPD [median = 63.1 (interquartile range: 54.8–68.6) vs. 64.8 (57.4–70.8), p = 0.020]. Multivariable analysis revealed that dyspnea [adjusted odds ratio (aOR) = 3.21, 95% confidence interval (CI) = 1.21–8.60], depression (aOR = 1.28, 95% CI = 1.16–1.44), and fatigue (aOR = 1.05, 95% CI = 1.01–1.09) were significantly associated with decreased QoL in bronchiectasis patients with COPD. In conclusion, bronchiectasis patients with COPD had significantly decreased QoL than patients without COPD. In bronchiectasis patients with COPD, dyspnea, depression, and fatigue were associated with decreased QoL.
Antibacterial Activity and Membrane-Targeting Mechanism of Aloe-Emodin Against Staphylococcus epidermidis
Authors: Li Tao , Lu Yan , Zhang Hua , Wang Lei , Beier Ross C. , Jin Yajie , Wang Wenjing , Li Huanrong , Hou Xiaolin
Published: August 2021

The emergence of multidrug-resistant Staphylococcus epidermidis (S. epidermidis) dwarfs the current antibiotic development and calls for the discovery of new antibacterial agents. Aloe-emodin is a plant-derived compound that holds promise to battle against these strains. This work reports the antimicrobial activity of aloe-emodin against S. epidermidis and other Gram-positive pathogenic species, manifesting minimum inhibitory concentrations (MICs) and minimum bactericidal concentration (MBCs) around 4–32 and 32–128 μg/mL, respectively. For Gram-negative bacteria tested, the MICs and MBCs of aloe-emodin were 128–256 and above 1024 μg/mL, respectively. Aloe-emodin at the MBC for 4 h eradicated 96.9% of S. epidermidis cells. Aloe-emodin treatment led to deformities in the morphology of S. epidermidis cells and the destroy of the selective permeability of the cell membranes. Analysis of the transcriptional profiles of aloe-emodin-treated cells revealed changes of genes involved in sulfur metabolism, L-lysine and peptidoglycan biosynthesis, and biofilm formation. Aloe-emodin therefore can safely control Gram-positive bacterial infections and proves to target the bacterial outer membrane.
Microbiological Surveillance of Biogas Plants: Targeting Acetogenic Community
Authors: Singh Abhijeet , Moestedt Jan , Berg Andreas , Schnürer Anna
Published: August 2021

Acetogens play a very important role in anaerobic digestion and are essential in ensuring process stability. Despite this, targeted studies of the acetogenic community in biogas processes remain limited. Some efforts have been made to identify and understand this community, but the lack of a reliable molecular analysis strategy makes the detection of acetogenic bacteria tedious. Recent studies suggest that screening of bacterial genetic material for formyltetrahydrofolate synthetase (FTHFS), a key marker enzyme in the Wood-Ljungdahl pathway, can give a strong indication of the presence of putative acetogens in biogas environments. In this study, we applied an acetogen-targeted analyses strategy developed previously by our research group for microbiological surveillance of commercial biogas plants. The surveillance comprised high-throughput sequencing of FTHFS gene amplicons and unsupervised data analysis with the AcetoScan pipeline. The results showed differences in the acetogenic community structure related to feed substrate and operating parameters. They also indicated that our surveillance method can be helpful in the detection of community changes before observed changes in physico-chemical profiles, and that frequent high-throughput surveillance can assist in management towards stable process operation, thus improving the economic viability of biogas plants. To our knowledge, this is the first study to apply a high-throughput microbiological surveillance approach to visualise the potential acetogenic population in commercial biogas digesters.
Encapsulation of B. bassiana in Biopolymers: Improving Microbiology of Insect Pest Control
Authors: Felizatti Ana Paula , Manzano Roberta Maria , Rodrigues Inajá Marchizeli Wenzel , da Silva Maria Fátima das Graças Fernandes , Fernandes João Batista , Forim Moacir Rossi
Published: August 2021

The fungus Beauveria bassiana is widely used for pest control; however, biostability and dispersion for broth pulverization are limiting factors for its application in the field. In this context, formulation techniques such as microencapsulation are viable alternatives. The aim of this work is to optimize B. bassiana formulations by spray dryer and evaluate its stability and biological activity against Spodoptera cosmioides compared to ionic gelatinization formulations. The fungus was biocompatible with all evaluated biopolymers (lignin, cellulose, starch, humic substances, and alginate). The encapsulation by spray drying was optimized by factorial design in an inlet and outlet air temperature of 120°C and 68°C, respectively; aspirator rate of 35 m3·h−1, feed flow rate of 12 mL·min−1; and drying gas flow at 35 L·h−1. The ionic gelation capsules were obtained using a 0.5% quantity of conidia in a 1% sodium alginate solution dropped into a 0.5 mol·L−1 CaCl2 solution using a peristaltic pump. Spray drying provided smaller microcapsules than those by ionic gelation. Both techniques produced more stable conidia when exposed to temperature and UV-radiation than non-formulated B. bassiana. The formulations prepared by spray drying showed gains at aqueous dispersion. Biological assays against Spodoptera cosmioides showed a mortality rate of up to 90%. These results demonstrate the suitability of encapsulating B. bassiana conidia stably in aqueous dispersion without loss of viability and virulence.
The Effect of tonB Gene on the Virulence of Pseudomonas plecoglossicida and the Immune Response of Epinephelus coioides
Authors: Hu Lingfei , Zhao Lingmin , Zhuang Zhixia , Wang Xiaoru , Fu Qi , Huang Huabin , Lin Lili , Huang Lixing , Qin Yingxue , Zhang Jiaonan , Yan Qingpi
Published: August 2021

Pseudomonas plecoglossicida is the causative agent of “visceral white spot disease” in cultured fish and has resulted in serious economic losses. tonB gene plays a crucial role in the uptake of nutrients from the outer membranes in Gram-negative bacteria. The previous results of our lab showed that the expression of tonB gene of P. plecoglossicida was significantly upregulated in the spleens of infected Epinephelus coioides. To explore the effect of tonB gene on the virulence of P. plecoglossicida and the immune response of E. coioides, tonB gene of P. plecoglossicida was knocked down by RNAi; and the differences between the wild-type strain and the tonB-RNAi strain of P. plecoglossicida were investigated. The results showed that all of the four mutants of P. plecoglossicida exhibited significant decreases in mRNA of tonB gene, and the best knockdown efficiency was 94.0%; the survival rate of E. coioides infected with the tonB-RNAi strain was 20% higher than of the counterpart infected with the wild strain of P. plecoglossicida. Meanwhile, the E. coioides infected with the tonB-RNAi strain of P. plecoglossicida carried less pathogens in the spleen and less white spots on the surface of the spleen; compared with the wild-type strain, the motility, chemotaxis, adhesion, and biofilm formation of the tonB-RNAi strain were significantly attenuated; the transcriptome data of E. coioides infected with the tonB-RNAi strain were different from the counterpart infected with the wild strain of P. plecoglossicida; the antigen processing and presentation pathway and the complement and coagulation cascade pathway were the most enriched immune pathways. The results indicated that tonB was a virulence gene of P. plecoglossicida; tonB gene was involved in the regulation of motility, chemotaxis, adhesion, and biofilm formation; tonB gene affected the immune response of E. coioides to P. plecoglossicida infection.
Organic Selenium Increased Gilts Antioxidant Capacity, Immune Function, and Changed Intestinal Microbiota
Authors: Li Zimei , Dong Yanpeng , Chen Sirun , Jia Xinlin , Jiang Xuemei , Che Lianqiang , Lin Yan , Li Jian , Feng Bin , Fang Zhengfeng , Zhuo Yong , Wang Jianping , Xu Haitao , Wu De , Xu Shengyu
Published: August 2021

Selenium is an indispensable essential micronutrient for humans and animals, and it can affect biological functions by combining into selenoproteins. The purpose of this study was to investigate the effects of 2-hydroxy-4-methylselenobutanoic acid (HMSeBA) on the antioxidant performance, immune function, and intestinal microbiota composition of gilts. From weaning to the 19th day after the second estrus, 36 gilts (Duroc × Landrace × Yorkshire) were assigned to three treatments: control group, sodium selenite group (0.3 mg Se/kg Na2SeO3), and HMSeBA group (0.3 mg Se/kg HMSeBA). Dietary supplementation with HMSeBA improved the gilts tissue selenium content (except in the thymus) and selenoprotein P (SelP1) concentration when compared to the Na2SeO3 or control group. Compared with the control group, the antioxidant enzyme activity in the tissues from gilts in the HMSeBA group was increased, and the concentration of malondialdehyde in the colon had a decreasing trend (p = 0.07). Gilts in the HMSeBA supplemented group had upregulated gene expression of GPX2, GPX4, and SelX in spleen tissue, TrxR1 in thymus; GPX1 and SelX in duodenum, GPX3 and SEPHS2 in jejunum, and GPX1 in the ileum tissues (p < 0.05). In addition, compared with the control group, the expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) in the liver, spleen, thymus, duodenum, ileum, and jejunum of gilts in the HMSeBA group were downregulated (p < 0.05), while the expression of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in the liver, thymus, jejunum, and ileum were upregulated (p < 0.05). Compared with the control group and the Na2SeO3 group, HMSeBA had increased concentration of serum cytokines interleukin-2 (IL-2) and immunoglobulin G (IgG; p < 0.05), increased concentration of intestinal immunoglobulin A (sIgA; p < 0.05), and decreased concentration of serum IL-6 (p < 0.05). Dietary supplementation with HMSeBA also increased the abundance of intestinal bacteria (Ruminococcaceae and Phascolarctobacterium; p < 0.05) and selectively inhibited the abundance of some bacteria (Parabacteroides and Prevotellaceae; p < 0.05). In short, HMSeBA improves the antioxidant performance and immune function of gilts, and changed the structure of the intestinal microflora. And this study provided data support for the application of HMSeBA in gilt and even pig production.
Emergence of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam in a Widespread ST11 Carbapenem-Resistant Klebsiella pneumoniae Clone in China
Authors: Li Xi , Quan Jingjing , Ke Huanhuan , Wu Wenhao , Feng Yu , Yu Yunsong , Jiang Yan
Published: August 2021

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection poses a great threat to public health worldwide, and KPC-2-producing strains are the main factors responsible for resistance to carbapenems in China. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor combination with good activity against KPC-2 carbapenemase and is becoming the most important option for treating KPC-producing CRKP infection. Here, we report the emergence of a novel KPC-2 variant, designated KPC-74, produced by K. pneumoniae strain KP55, that conferred CZA resistance in a patient after CZA exposure. The novel blaKPC–74 variant showed a deletion of 6 nucleotides at positions 712–717 compared with blaKPC–2, and this deletion resulted in the consequent deletion of glycine and valine at positions 239 and 240. Antimicrobial susceptibility testing showed that KP55 presents multidrug resistance, including resistance to CZA and ertapenem, but is susceptible to imipenem, meropenem, and colistin. The blaKPC–74 gene was located on a plasmid, as determined by S1-nuclease pulsed-field gel electrophoresis followed by southern blotting, and confirmed to be 133,766 bp in length by whole-genome sequencing on both the Illumina and MinION platforms. The CZA resistance phenotype of the novel KPC variant was confirmed by both transformation of the blaKPC–74-harboring plasmid and a blaKPC–74 gene cloning assay, showing a 64-fold higher CZA minimum inhibitory concentration (MIC) than the recipient strains. The G239_V240del observed in KPC-74 was outside the omega-loop region but was still close to the active site Ser70 and omega-loop in the protein tertiary structure. The enzyme kinetic parameters and IC50 values further indicated that the hydrolytic activity of the KPC-74 enzyme against ceftazidime was potentiated twofold and that the affinity between KPC-74 and avibactam was alleviated 17-fold compared with that of the KPC-2 allele. This CZA resistance mediated by KPC-74 could be selected after CZA therapy and evolved to be more diverse and heterogeneous. Surveillance of CZA resistance is urgently needed in clinical settings.
HMB Improves Lipid Metabolism of Bama Xiang Mini-Pigs via Modulating the Bacteroidetes-Acetic Acid-AMPKα Axis
Authors: Zheng Jie , Zheng Changbing , Song Bo , Guo Qiuping , Zhong Yinzhao , Zhang Shiyu , Zhang Lingyu , Duan Geyan , Li Fengna , Duan Yehui
Published: August 2021

Here, we used Bama Xiang mini-pigs to explore the effects of different dietary β-hydroxy-β-methylbutyrate (HMB) levels (0, 0.13, 0.64 or 1.28%) on lipid metabolism of adipose tissue. Results showed that HMB decreased the fat percentage of pigs (linearly, P < 0.05), and the lowest value was observed in the 0.13% HMB group. Moreover, the colonic acetic acid concentration and the relative Bacteroidetes abundance were increased in response to HMB supplementation (P < 0.05). Correlation analysis identified a positive correlation between the relative Bacteroidetes abundance and acetic acid production, and a negative correlation between fat percentage and the relative Bacteroidetes abundance or acetic acid production. HMB also upregulated the phosphorylation (p) of AMPKα, Sirt1, and FoxO1, and downregulated the p-mTOR expression. Collectively, these findings indicate that reduced fat percentage in Bama Xiang mini-pigs could be induced by HMB supplementation and the mechanism might be associated with the Bacteroidetes-acetic acid-AMPKα axis.
Insights Into Parkin-Mediated Mitophagy in Alzheimer's Disease: A Systematic Review
Authors: Goudarzi Sepideh , Hosseini Asieh , Abdollahi Mohammad , Haghi-Aminjan Hamed
Published: August 2021

Graphical Abstract

Interactions of PINK1/Parkin pathway with AD-related proteins.
Divergent Connectivity Changes in Gray Matter Structural Covariance Networks in Subjective Cognitive Decline, Amnestic Mild Cognitive Impairment, and Alzheimer’s Disease
Authors: Fu Zhenrong , Zhao Mingyan , He Yirong , Wang Xuetong , Lu Jiadong , Li Shaoxian , Li Xin , Kang Guixia , Han Ying , Li Shuyu
Published: August 2021

Alzheimer’s disease (AD) has a long preclinical stage that can last for decades prior to progressing toward amnestic mild cognitive impairment (aMCI) and/or dementia. Subjective cognitive decline (SCD) is characterized by self-experienced memory decline without any evidence of objective cognitive decline and is regarded as the later stage of preclinical AD. It has been reported that the changes in structural covariance patterns are affected by AD pathology in the patients with AD and aMCI within the specific large-scale brain networks. However, the changes in structural covariance patterns including normal control (NC), SCD, aMCI, and AD are still poorly understood. In this study, we recruited 42 NCs, 35 individuals with SCD, 43 patients with aMCI, and 41 patients with AD. Gray matter (GM) volumes were extracted from 10 readily identifiable regions of interest involved in high-order cognitive function and AD-related dysfunctional structures. The volume values were used to predict the regional densities in the whole brain by using voxel-based statistical and multiple linear regression models. Decreased structural covariance and weakened connectivity strength were observed in individuals with SCD compared with NCs. Structural covariance networks (SCNs) seeding from the default mode network (DMN), salience network, subfields of the hippocampus, and cholinergic basal forebrain showed increased structural covariance at the early stage of AD (referring to aMCI) and decreased structural covariance at the dementia stage (referring to AD). Moreover, the SCN seeding from the executive control network (ECN) showed a linearly increased extent of the structural covariance during the early and dementia stages. The results suggest that changes in structural covariance patterns as the order of NC-SCD-aMCI-AD are divergent and dynamic, and support the structural disconnection hypothesis in individuals with SCD.
Moderate-Intensity Physical Activity, Music and Art Activities Preserved Cognitive Health in Older Adults: An Argument for Social Prescribing Solution
Authors: Arab Ali , Christie Gregory J. , Mansouri Mehrdad , Ahmadzadeh Maryam , Sixsmith Andrew , Ester Martin , Moreno Sylvain
Published: August 2021

Introduction: Rates of dementia are projected to increase over the coming years as global populations age. Without a treatment to slow the progression of dementia, many health policies are focusing on preventing dementia by slowing the rate of cognitive decline with age. However, it is unclear which lifestyle changes in old age meaningfully reduce the rate of cognitive decline associated with aging.

Objectives: Use existing, multi-year longitudinal health data to determine if engagement in a variety of different lifestyle activities can slow the rate of cognitive decline as older adults age.

Method: Data from the English Longitudinal Study of Aging was analyzed using a quasi-experimental, efficient matched-pair design inspired by the clinical trial methodology. Changes in short-term memory scores were assessed over a multi-year interval for groups who undertook one of 11 different lifestyle activities, compared to control groups matched across confounding socioeconomic and lifestyle factors.

Results: Two factors, moderate-intensity physical activity and learning activities, resulted in significant positive impact on cognitive function.

Conclusion: Our analysis brings cognitive benefit arguments in favor of two lifestyle activities, moderate-intensity physical activity and learning activities, while rejecting other factors advanced by the literature such as vigorous-intensity physical activity. Those findings justify and encourage the development of new lifestyle health programs by health authorities and bring forward the new health system solution, social prescribing.
Predicting the Emergence of Major Neurocognitive Disorder Within Three Months After a Stroke
Authors: Aamodt Eva Birgitte , Schellhorn Till , Stage Edwin , Sanjay Apoorva Bharthur , Logan Paige E. , Svaldi Diana Otero , Apostolova Liana G. , Saltvedt Ingvild , Beyer Mona Kristiansen
Published: August 2021

Background: Neurocognitive disorder (NCD) is common after stroke, with major NCD appearing in about 10% of survivors of a first-ever stroke. We aimed to classify clinical- and imaging factors related to rapid development of major NCD 3 months after a stroke, so as to examine the optimal composition of factors for predicting rapid development of the disorder. We hypothesized that the prediction would mainly be driven by neurodegenerative as opposed to vascular brain changes.

Methods: Stroke survivors from five Norwegian hospitals were included from the “Norwegian COgnitive Impairment After STroke” (Nor-COAST) study. A support vector machine (SVM) classifier was trained to distinguish between patients who developed major NCD 3 months after the stroke and those who did not. Potential predictor factors were based on previous literature and included both vascular and neurodegenerative factors from clinical and structural magnetic resonance imaging findings. Cortical thickness was obtained via FreeSurfer segmentations, and volumes of white matter hyperintensities (WMH) and stroke lesions were semi-automatically gathered using FSL BIANCA and ITK-SNAP, respectively. The predictive value of the classifier was measured, compared between classifier models and cross-validated.

Results: Findings from 227 stroke survivors [age = 71.7 (11.3), males = (56.4%), stroke severity NIHSS = 3.8 (4.8)] were included. The best predictive accuracy (AUC = 0.876) was achieved by an SVM classifier with 19 features. The model with the fewest number of features that achieved statistically comparable accuracy (AUC = 0.850) was the 8-feature model. These features ranked by their weighting were; stroke lesion volume, WMH volume, left occipital and temporal cortical thickness, right cingulate cortical thickness, stroke severity (NIHSS), antiplatelet medication intake, and education.

Conclusion: The rapid (<3 months) development of major NCD after stroke is possible to predict with an 87.6% accuracy and seems dependent on both neurodegenerative and vascular factors, as well as aspects of the stroke itself. In contrast to previous literature, we also found that vascular changes are more important than neurodegenerative ones. Although possible to predict with relatively high accuracy, our findings indicate that the development of rapid onset post-stroke NCD may be more complex than earlier suggested.
Reducing the Cognitive Footprint of Brain Tumor Surgery
Authors: Dadario Nicholas B. , Brahimaj Bledi , Yeung Jacky , Sughrue Michael E.
Published: August 2021

The surgical management of brain tumors is based on the principle that the extent of resection improves patient outcomes. Traditionally, neurosurgeons have considered that lesions in “non-eloquent” cerebrum can be more aggressively surgically managed compared to lesions in “eloquent” regions with more known functional relevance. Furthermore, advancements in multimodal imaging technologies have improved our ability to extend the rate of resection while minimizing the risk of inducing new neurologic deficits, together referred to as the “onco-functional balance.” However, despite the common utilization of invasive techniques such as cortical mapping to identify eloquent tissue responsible for language and motor functions, glioma patients continue to present post-operatively with poor cognitive morbidity in higher-order functions. Such observations are likely related to the difficulty in interpreting the highly-dimensional information these technologies present to us regarding cognition in addition to our classically poor understanding of the functional and structural neuroanatomy underlying complex higher-order cognitive functions. Furthermore, reduction of the brain into isolated cortical regions without consideration of the complex, interacting brain networks which these regions function within to subserve higher-order cognition inherently prevents our successful navigation of true eloquent and non-eloquent cerebrum. Fortunately, recent large-scale movements in the neuroscience community, such as the Human Connectome Project (HCP), have provided updated neural data detailing the many intricate macroscopic connections between cortical regions which integrate and process the information underlying complex human behavior within a brain “connectome.” Connectomic data can provide us better maps on how to understand convoluted cortical and subcortical relationships between tumor and human cerebrum such that neurosurgeons can begin to make more informed decisions during surgery to maximize the onco-functional balance. However, connectome-based neurosurgery and related applications for neurorehabilitation are relatively nascent and require further work moving forward to optimize our ability to add highly valuable connectomic data to our surgical armamentarium. In this manuscript, we review four concepts with detailed examples which will help us better understand post-operative cognitive outcomes and provide a guide for how to utilize connectomics to reduce cognitive morbidity following cerebral surgery.
Thresholding Functional Connectivity Matrices to Recover the Topological Properties of Large-Scale Neuronal Networks
Authors: Boschi Alessio , Brofiga Martina , Massobrio Paolo
Published: August 2021

The identification of the organization principles on the basis of the brain connectivity can be performed in terms of structural (i.e., morphological), functional (i.e., statistical), or effective (i.e., causal) connectivity. If structural connectivity is based on the detection of the morphological (synaptically mediated) links among neurons, functional and effective relationships derive from the recording of the patterns of electrophysiological activity (e.g., spikes, local field potentials). Correlation or information theory-based algorithms are typical routes pursued to find statistical dependencies and to build a functional connectivity matrix. As long as the matrix collects the possible associations among the network nodes, each interaction between the neuron i and j is different from zero, even though there was no morphological, statistical or causal connection between them. Hence, it becomes essential to find and identify only the significant functional connections that are predictive of the structural ones. For this reason, a robust, fast, and automatized procedure should be implemented to discard the “noisy” connections. In this work, we present a Double Threshold (DDT) algorithm based on the definition of two statistical thresholds. The main goal is not to lose weak but significant links, whose arbitrary exclusion could generate functional networks with a too small number of connections and altered topological properties. The algorithm allows overcoming the limits of the simplest threshold-based methods in terms of precision and guaranteeing excellent computational performances compared to shuffling-based approaches. The presented DDT algorithm was compared with other methods proposed in the literature by using a benchmarking procedure based on synthetic data coming from the simulations of large-scale neuronal networks with different structural topologies.
The Food Identity of Countries Differs Between Younger and Older Generations: A Cross-Sectional Study in American, European and Asian Countries
Authors: Frez-Muñoz Lucía , Kampen Jarl K. , Fogliano Vincenzo , Steenbekkers Bea L. P. A.
Published: August 2021

Current generations have been strongly influenced by mass communication and massive immigration flows, which may change local lifestyles and perceptions of inhabitants towards traditional foods and beverages (TFBs). TFBs constitute a core element of the cultural identity of a country, although some of them are losing their appeal. In this study, the authors explored the TFBs perceptions of inhabitants in nine countries to determine if their food identity is changing by analysing the TFBs most frequently mentioned by different age cohorts within a country. Six countries were found to have a distinctive core of TFBs shared across age cohorts (homogenous), whereas the remaining showed a heterogeneous pattern. Correspondence and cluster analyses usually grouped younger generations together implying higher similarities among these cohorts. Furthermore, the binary logistic regression analyses performed identified significant differences in the probability of mentioning a specific TFBs across age cohorts per country. Data collected show younger cohorts focusing on TFBs categorised as snacks and foods on-the-go, whereas older cohorts more often refer to time-consuming savoury preparations. The results suggest that lifestyles and current societal trends in food consumption, for example, convenience and healthiness, are impacting the food culture and identity of countries, and therefore play an important role in the variation of TFBs perception and consumption between age cohorts within countries. The results obtained in this study could not only be used by food policymakers and nutritionists to distinguish the current trends that are reshaping the food identity and eating behaviours of the population but also to improve or develop new dietary strategies by age cohorts in the countries studied.