bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicriteria Decision Analysis to Assist in the Selection of Coastal Defence Measures: Involving Coastal Managers and Professionals in the Identification and Weighting of Criteria
Authors: Sauvé Philippe , Bernatchez Pascal , Glaus Mathias
Published: April 2022

Coastal socio-ecological systems are complex adaptive systems with nonlinear changing properties and multi-scale dynamics. They are influenced by unpredictable coastal hazards accentuated by the effects of climate change, and they can quickly be altered if critical thresholds are crossed. Additional pressures come from coastal activities and development, both of which attracting stakeholders with different perspectives and interests. While coastal defence measures (CDMs) have been implemented to mitigate coastal hazards for centuries, a lack of knowledge and tools available to make informed decision has led to coastal managers favouring the choice of seawalls or rock armours with little consideration for socio-ecological systems features, and stakeholders’ priorities. Though it is not currently widely applied in coastal zone management, multicriteria decision analysis (MCDA) is a tool that can be useful to facilitate decision making. PROMETHEE, an outranking method, was chosen to support the multicriteria decision analysis for the evaluation of CDMs in the context of four study sites characterized by distinct environmental features. The aim was to determine the relevance and benefits of a MCDA by integrating coastal zone stakeholders in a participatory decision-making process in order to select CDMs that are better adapted to the whole socio-ecological system. First, in a series of five workshops, stakeholders were asked to identify and weigh criteria that were relevant to their local conditions. Second and third, CDMs were evaluated in relation to each criterion within the local context, then, hierarchized. Initial results show that vegetation came first in three of the four sites, while rock armour ranked first in the fourth site. A post-evaluation of the participatory process indicated that the weighting phase is an effective way to integrate local knowledge into the decision-making process, but the identification of criteria could be streamlined by the presentation of a predefined list from which participants could make a selection. This would ensure criteria that are standardized, and in a format that is compatible with the MCDA. Coupled with a participatory process MCDA proved to be a flexible methodology that can synthetize multiple aspects of the problem, and contribute in a meaningful way to the coastal engineering and management decision-making process.
Broadband and Dual-Polarized Terahertz Wave Anomalous Refraction Based on a Huygens’ Metasurface
Authors: Ran Jia , Xie Mingli , Wen Dandan , Zhang Xiaolei , Xue Chunhua
Published: April 2022

Terahertz wavefront manipulation is one of the key terahertz technologies. While few of the research works on terahertz wavefront manipulation has broadband and dual-polarized responses. Here a broadband dual-polarized Huygens’ metasurface is proposed to realize high efficient terahertz wave anomalous refraction. By constructing simultaneous electric and magnetic responses in a bi-layer metasurface to produce Huygens’ resonance, broadband and large phase changes for dual-polarized terahertz wave are achieved. A phase change over 300° with transmission magnitude beyond 0.75 is realized between 0.4 THz and 1 THz. An array made of the metasurface with phase gradient is designed to achieve a 14.0° anomalous refraction for two orthogonal linear polarized waves at 0.93 THz. The structure consists of only two metal layers, providing a simple and high-efficiency design scheme for achieving efficient dual-polarized terahertz wavefront manipulation.
New Insights Into an Overlooked Entity: Long-Term Outcomes of Membranous Lupus Nephritis From a Single Institution Inception Cohort
Authors: Kapsia Eleni , Marinaki Smaragdi , Michelakis Ioannis , Liapis George , Sfikakis Petros P. , Tektonidou Maria G. , Boletis John
Published: April 2022

Introduction

Pure membranous lupus nephritis (MLN) accounts for 10–20% of total cases of lupus nephritis and is generally associated with a better patient and renal survival compared to proliferative classes. Studies of MLN are limited by small sample size and heterogeneity of included populations since patients with pure MLN and those with mixed classes are usually examined together.

Aim of the Study

To describe clinical and laboratory characteristics of patients with pure MLN, therapeutic regimens, response to treatment, renal relapses, and their long-term renal survival and to define prognostic factors of remission and relapse.

Methods

We retrospectively studied an inception cohort of 27 patients with histologically proven pure MLN. Clinical, laboratory and therapeutical parameters were recorded at diagnosis, at different time points (3–6–9–12–18–24–36–72 months) during the course of the disease, at time of renal flare, and at last follow up visit.

Results

48.1% (13/27) of patients were treated with mycophenolic acid (MPA), 29.6% (8/27) with cyclophosphamide (CYC), and 3.7% (1/27) with cyclosporine (all in combination with corticosteroids). Five patients (18.5%) did not receive any immunosuppressive treatment. Mean duration of treatment was 4.7 ± 2.3 years. Median time to complete remission was 9 months (IQR = 7) and median time to partial remission was 4 months (IQR = 4). No clinical or laboratory parameter was found to be significantly associated with time to remission. Time to remission was not significantly affected by either of the two treatment regimens (CYC and MPA) (p = 0.43). Renal flare was observed in 6 (22%) of the 27 patients in a median time of 51 months (IQR = 63). Proteinuria >1 g/24 h at 1 year significantly correlated with risk of flare (OR 20, p = 0.02). After a median follow up period of 77 months, all patients had an eGFR > 60 ml/min/1.73 m2 (mean eGFR 100 ± 32 ml/min/1.73 m2).

Conclusions

In a small cohort of patients with pure MLN, long-term renal survival was very good. With the limitation of the small sample size, we could not find any baseline clinical, biochemical or therapeutic factor that could predict time to remission. Proteinuria > 1 g/24 h at 1 year should be further examined in larger cohorts as a possible predictor of flare.
Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte Injury
Authors: He Xu , Sun Tao , Zhang Pei , Xia Zhengkun , Gao Chunlin , Ren Hongqi , Ji Daxi
Published: April 2022

Histone deacetylases (HDACs) inhibitors are promising therapeutic agents against proteinuric kidney diseases, here, we investigated the effect of MC1568, a selective inhibitor of HDAC class IIa, on the development and progression of nephrotic syndrome in a murine model induced by Adriamycin (ADR). In kidney tissues of FSGS patients, all four members of HDAC IIa were significantly upregulated in podocytes. In ADR-treated cultured human podocyte, expression of HDAC IIa were induced, meanwhile inhibition of HDAC IIa with MC1568 restored cytoskeleton structure and suppressed expression of desmin and α-SMA. In mice, administration of MC1568 at 14 days after ADR ameliorated proteinuria and podocyte injury, also decreased expression of Fibronectin and α-SMA. Mechanistically, MC1568 inhibited ADR induced β-catenin activation in vitro and in vivo. Together, these finding demonstrate that HDAC IIa inhibition ameliorates podocyte injury and proteinuria, which provide a possibility that MC1568 may be used in nephrotic syndrome.
COVID-19 Autopsies Reveal Underreporting of SARS-CoV-2 Infection and Scarcity of Co-infections
Authors: Schwab Nathalie , Nienhold Ronny , Henkel Maurice , Baschong Albert , Graber Anne , Frank Angela , Mensah Nadine , Koike Jacqueline , Hernach Claudia , Sachs Melanie , Daun Till , Zsikla Veronika , Willi Niels , Junt Tobias , Mertz Kirsten D.
Published: April 2022

Coronavirus disease 2019 (COVID-19) mortality can be estimated based on reliable mortality data. Variable testing procedures and heterogeneous disease course suggest that a substantial number of COVID-19 deaths is undetected. To address this question, we screened an unselected autopsy cohort for the presence of SARS-CoV-2 and a panel of common respiratory pathogens. Lung tissues from 62 consecutive autopsies, conducted during the first and second COVID-19 pandemic waves in Switzerland, were analyzed for bacterial, viral and fungal respiratory pathogens including SARS-CoV-2. SARS-CoV-2 was detected in 28 lungs of 62 deceased patients (45%), although only 18 patients (29%) were reported to have COVID-19 at the time of death. In 23 patients (37% of all), the clinical cause of death and/or autopsy findings together with the presence of SARS-CoV-2 suggested death due to COVID-19. Our autopsy results reveal a 16% higher SARS-CoV-2 infection rate and an 8% higher SARS-CoV-2 related mortality rate than reported by clinicians before death. The majority of SARS-CoV-2 infected patients (75%) did not suffer from respiratory co-infections, as long as they were treated with antibiotics. In the lungs of 5 patients (8% of all), SARS-CoV-2 was found, yet without typical clinical and/or autopsy findings. Our findings suggest that underreporting of COVID-19 contributes substantially to excess mortality. The small percentage of co-infections in SARS-CoV-2 positive patients who died with typical COVID-19 symptoms strongly suggests that the majority of SARS-CoV-2 infected patients died from and not with the virus.
BasS/BasR Two-Component System Affects the Sensitivity of Escherichia coli to Plantaricin BM-1 by Regulating the Tricarboxylic Acid Cycle
Authors: Liu Yifei , Wang Yawen , Chen Xinyue , Jin Junhua , Liu Hui , Hao Yanling , Zhang Hongxing , Xie Yuanhong
Published: April 2022

Plantaricin BM-1, a class IIa bacteriocin produced by Lactiplantibacillus plantarum BM-1, exhibits significant antibacterial activity against many gram-positive and gram-negative bacteria. However, the mechanism underlying the action of class IIa bacteriocins against gram-negative bacteria remains to be explored. This study aimed to investigate the role of the BasS/BasR two-component system (TCS) in Escherichia coli (E. coli) K12 response to plantaricin BM-1. The IC50 values for plantaricin BM-1 in E. coli K12, basS mutant (E. coli JW4073), and basR mutant (E. coli JW4074) strains were found to be 10.85, 8.94, and 7.62 mg/mL, respectively. Growth curve experiments showed that mutations in the BasS/BasR TCS led to an increase in the sensitivity of E. coli K12 to plantaricin BM-1 and that after gene complementation, the complemented mutant strain regained its original sensitivity. Proteomic analysis showed that 100 and 26 proteins were upregulated and 62 and 58 proteins were downregulated in E. coli JW4073 and E. coli JW4074, respectively. These differential proteins, which exhibited different molecular functions and participated in different molecular pathways, were mainly concentrated in the cytoplasm. More specifically, mutations in basS and basR were found to affect the synthesis and metabolism of many substances in E. coli, including many important amino acids and enzymes involved in cellular activities. In addition, 14 proteins, including 8 proteins involved in the tricarboxylic acid (TCA) cycle, were found to be downregulated in both E. coli JW4073 and E. coli JW4074. Growth curve experiments showed that the deletion of these proteins could increase the sensitivity of E. coli to plantaricin BM-1. Therefore, we speculate that TCA pathway regulation may be an important mechanism by which the BasS/BasR TCS regulates the sensitivity of E. coli to plantaricin BM-1. This finding will facilitate the determination of the mechanism underlying the action of class IIa bacteriocins against gram-negative bacteria.
The Role of Lipids in Allergic Sensitization: A Systematic Review
Authors: Hopkins Georgina V. , Cochrane Stella , Onion David , Fairclough Lucy C.
Published: April 2022

Background:Immunoglobulin E (IgE)-mediated allergies are increasing in prevalence, with IgE-mediated food allergies currently affecting up to 10% of children and 6% of adults worldwide. The mechanisms underpinning the first phase of IgE-mediated allergy, allergic sensitization, are still not clear. Recently, the potential involvement of lipids in allergic sensitization has been proposed, with reports that they can bind allergenic proteins and act on immune cells to skew to a T helper type 2 (Th2) response.

Objectives:The objective of this systematic review is to determine if there is strong evidence for the role of lipids in allergic sensitization.

Methods:Nineteen studies were reviewed, ten of which were relevant to lipids in allergic sensitization to food allergens, nine relevant to lipids in aeroallergen sensitization.

Results:The results provide strong evidence for the role of lipids in allergies. Intrinsic lipids from allergen sources can interact with allergenic proteins to predominantly enhance but also inhibit allergic sensitization through various mechanisms. Proposed mechanisms included reducing the gastrointestinal degradation of allergenic proteins by altering protein structure, reducing dendritic cell (DC) uptake of allergenic proteins to reduce immune tolerance, regulating Th2 cytokines, activating invariant natural killer T (iNKT) cells through CD1d presentation, and directly acting upon toll-like receptors (TLRs), epithelial cells, keratinocytes, and DCs.

Conclusion:The current literature suggests intrinsic lipids are key influencers of allergic sensitization. Further research utilising human relevantin vitromodels and clinical studies are needed to give a reliable account of the role of lipids in allergic sensitization.
Locomotor Pattern and Force Generation Modulated by Ionic Channels: A Computational Study of Spinal Networks Underlying Locomotion
Authors: Zhang Qiang , Cheng Yi , Zhou Mei , Dai Yue
Published: April 2022

Locomotion is a fundamental movement in vertebrates produced by spinal networks known as central pattern generators (CPG). During fictive locomotion cat lumbar motoneurons (MNs) exhibit changes in membrane properties, including hyperpolarization of voltage threshold, reduction of afterhyperpolarization and input resistance, and amplification of nonlinear membrane properties. Both modeling and electrophysiological studies suggest that these changes can be produced by upregulating voltage-gated sodium channel (VGSC), persistent sodium (NaP), or L-type calcium channel (LTCC) or downregulating delayed-rectifier potassium (K(DR)) or calcium-dependent potassium channel (KCa) in spinal MNs. Further studies implicate that these channel modulations increase motor output and facilitate MN recruitment. However, it remains unknown how the channel modulation of CPG networks or MN pools affects the rhythmic generation of locomotion and force production of skeletal muscle during locomotion. In order to investigate this issue, we built a two-level CPG model composed of excitatory interneuron pools (Exc-INs), coupled reciprocally with inhibitory interneuron pools (Inh-INs), and projected to the flexor-extensor MN pools innervating skeletal muscles. Each pool consisted of 100 neurons with membrane properties based on cat spinal neurons. VGSC, K(DR), NaP, KCa, LTCC, and H-current channels were included in the model. Simulation results showed that (1) upregulating VGSC, NaP, or LTCC or downregulating KCa in MNs increased discharge rate and recruitment of MNs, thus facilitating locomotor pattern formation, increased amplitude of electroneurogram (ENG) bursting, and enhanced force generation of skeletal muscles. (2) The same channel modulation in Exc-INs increased the firing frequency of the Exc-INs, facilitated rhythmic generation, and increased flexor-extensor durations of step cycles. (3) Contrarily, downregulation of NaP or LTCC in MNs or Exc-INs or both CPG (Exc-INs and Inh-INs) and MNs disrupted locomotor pattern and reduced or even blocked the ENG bursting of MNs and force generation of skeletal muscles. (4) Pharmacological experiments showed that bath application of 25 μM nimodipine or 2 μM riluzole completely blocked fictive locomotion in isolated rat spinal cord, consistent with simulation results. We concluded that upregulation of VGSC, NaP, or LTCC or downregulation of KCa facilitated rhythmic generation and force production during walking, with NaP and LTCC playing an essential role.
An Adaptive Information Security System for 5G-Enabled Smart Grid Based on Artificial Neural Network and Case-Based Learning Algorithms
Authors: Jiang Chengzhi , Xu Hao , Huang Chuanfeng , Huang Qiwei
Published: April 2022

With the deployment of 5G Internet of Things (IoT) in the power system, the efficiency of smart grid is improved by increasing two-way interactions in different layers in smart grid. However, it introduces more attack interfaces that the traditional information security system in smart grid cannot response in time. The neuroscience-inspired models have shown their effectiveness in solving security and optimization problems in smart grid. How to improve the security mechanism in smart grid while taking into account the optimization of data transmission efficiency using neuroscience-inspired algorithms is the problem to be solved in this study. Therefore, an information security system based on artificial neural network (ANN) and improved multiple protection model is proposed. Based on the ANN algorithm, the link state sample space is used to train the model to obtain the optimal transmission path in 5G power communication network. Integrating the intelligent link state module, the zero-trust security protection platform using case-based learning algorithm is designed and taken as the first protection, the network security logical isolation facility is taken as the second protection, and the forward and backward isolation facilities are set as the third protection to achieve the strengthened security of 5G IoT in smart grid. The experimental results show the efficiency and effectiveness of the proposed algorithms. In addition, the experimental results also show that the proposed system can resist malicious terminal access, terminal hijacking, data tampering and eavesdropping, protocol fuzzy, and denial-of-service attacks, so as to reduce the security risks of 5G IoT in smart grid. Since the proposed system can be easily integrated into the existing smart grid structure in China, the proposed system can provide a reference for the design and implementation of 5G IoT in smart grid.
Is Resting State Functional MRI Effective Connectivity in Movement Disorders Helpful? A Focused Review Across Lifespan and Disease
Authors: Sussman Bethany L. , Wyckoff Sarah N. , Heim Jennifer , Wilfong Angus A. , Adelson P. David , Kruer Michael C. , Gonzalez Maria Jose , Boerwinkle Varina L.
Published: April 2022

In the evolving modern era of neuromodulation for movement disorders in adults and children, much progress has been made recently characterizing the human motor network (MN) with potentially important treatment implications. Herein is a focused review of relevant resting state fMRI functional and effective connectivity of the human motor network across the lifespan in health and disease. The goal is to examine how the transition from functional connectivity to dynamic effective connectivity may be especially informative of network-targeted movement disorder therapies, with hopeful implications for children.
Relatively Early and Late-Onset Neuromyelitis Optica Spectrum Disorder in Central China: Clinical Characteristics and Prognostic Features
Authors: Yu Jinbei , Yan Shuai , Niu Pengpeng , Teng Junfang
Published: April 2022

Background

We aimed to analyze the clinical characteristics and prognostic features of Chinese patients with relatively late-onset neuromyelitis optica spectrum disorder (RLO-NMOSD>40 years of age at disease onset), compared with patients with relatively early onset NMOSD (REO-NMOSD, ≤ 40 years of age at disease onset).

Methods

We retrospectively reviewed the medical records of patients with NMOSD in central China (with disease courses longer than 3 years) between January 2012 and January 2021. We further analyzed the clinical and prognostic differences between patients with REO-NMOSD and RLO-NMOSD.

Results

A total of 71 patients were included in this study. The results showed that 39 (54.9%) of the patients had RLO-NMOSD. The patients with RLO-NMOSD had higher expanded disability status scale (EDSS) scores than patients with REO-NMOSD at the initial (5.0 vs. 3.0, p = 0.01), 3-month (4.0 vs. 2.5, p = 0.001), 1-year (4.0 vs. 2.5, p = 0.003), 3rd-year (3.5 vs. 3.0, p = 0.0017), and final follow-up (4.0 vs. 2.5, P = 0.002) time points. The EDSS scores of visual function were 2.0 (1.0–3.0) in REO-NMOSD and 3.0 (2.0–3.0) in RLO-NMOSD (p = 0.038) at the final follow-up time point. The locations of spinal cord lesions at transverse myelitis (TM) onset were prone to cervical cord in patients with REO-NMOSD. There were no between-group treatment differences. The risk of requiring a cane to walk (EDSS score of 6.0) increased as the age of disease onset increased: for every 10-year increase in the age of disease onset, the risk of needing a cane to walk increased by 65% [hazard ratio (HR) = 1.65, 95% CI 1.15–2.38, p = 0.007]. Another significant predictor identified in the multivariate analysis was annualized relapse rate (ARR) (HR = 2.01, 95% CI 1.09–3.71, p = 0.025). In addition, we observed a positive correlation between age at onset and EDSS scores at the final follow-up (Spearman's r = 0.426, p < 0.0001) time point. EDSS scores at different periods were significantly different between patients with RLO-NMOSD and REO-NMOSD with anti-aquaporin-4 (AQP4) IgG positive.

Conclusion

The patients with RLO-NMOSD developed more severe disabilities than patients with REO-NMOSD at a variety of time periods. All of the patients may experience recurrent aggravated symptoms after their first year, with only patients with REO-NMOSD partly recovering from the 3rd year. The age at onset and ARR were the main predictors of outcomes.
NEK1 Variants in a Cohort of Italian Patients With Amyotrophic Lateral Sclerosis
Authors: Riva Nilo , Pozzi Laura , Russo Tommaso , Pipitone Giovanni Battista , Schito Paride , Domi Teuta , Agosta Federica , Quattrini Angelo , Carrera Paola , Filippi Massimo
Published: April 2022

Introduction

In the last few years, different studies highlighted a significant enrichment of NEK1 loss of function (LoF) variants in amyotrophic lateral sclerosis (ALS), and an additional role for the p.Arg261His missense variant in the disease susceptibility. Several other missense variants have been described so far, whose pathogenic relevance remains however unclear since many of them have been reported in both patients and controls. This study aimed to investigate the presence of NEK1 variants and their correlation with phenotype in a cohort of Italian patients with ALS.

Methods

We sequenced a cohort of 350 unrelated Italian patients with ALS by next-generation sequencing (NGS) and then we analyzed the clinical features of NEK1 carriers.

Results

We detected 20 different NEK1 rare variants (four LoF and 16 missense) in 33 unrelated patients with sporadic ALS (sALS). The four LoF variants (two frameshift and two splice-site variants) were all novel. The p.Arg261His missense variant was enriched in the patients’ cohort (p < 0.001). Excluding this variant from counting, the difference in the frequency of NEK1 rare missense variants between patients and controls was not statistically significant. NEK1 carriers had a higher frequency of flail arm (FA) phenotype compared with the other patients of the cohort (29.2% vs. 6.4%). Nine NEK1 carriers (37.5%) also harbored variants in other ALS-related genes.

Conclusion

This study confirms that NEK1 LoF and p.Arg261. His missense variants are associated with ALS in an Italian ALS cohort and suggests a correlation between the presence of NEK1 variants and FA phenotype.
Functional Connectivity Underlying Symptoms in Preschool Boys With Autism: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Lan Zhihong , Xu Shoujun , Yu Xiangrong , Yu Zhenjie , Li Meng , Chen Feng , Liu Yu , Wang Tianyue , Wu Yunfan , Gan Yungen , Jiang Guihua
Published: April 2022

Background

Single-sex children have been regarded as one of the best subjects to understand the abnormal development patterns of autism spectrum disorders (ASDs). However, the functional connectivity (FC) behind their symptoms is still unknown.

Methods

Based on FC analysis, the acquired resting-state functional magnetic resonance imaging (rs-fMRI) data sets, including 86 boys with ASD and 54 normal controls (NC), were used to detect the neural synchronous activity between brain regions. Pearson correlation analysis was used to evaluate the relationship between the abnormal FC value and clinical features.

Results

Individuals with ASD showed enhanced FC between the right calcarine and the right lingual gyrus (LG). The right medial orbital frontal cortex also showed increased FC with bilateral inferior temporal gyrus (ITG) [two-tailed, voxel-level p < 0.001, gaussian random field (GRF) correction, cluster-level p < 0.05]. We did not find a correlation between the abnormal FC value and clinical scales.

Conclusion

Our study reveals a possible relationship between atypical visual attention and poor learning ability in subjects with ASD, and delayed social language development may be a secondary symptom to ASD.
Hypocholesterolemia and Inflammatory Biomarkers Act as Predictors of Severe Vitamin D Deficiency in Patients With Crohn’s Disease: A Clinical Analysis of 862 Patients in China
Authors: Lu Jie , Yu Fei , Huang Jun , Yu Haitao , Li Fengying , Le Zhi’an , Cheng Yulan , Zhang Qi , Li Guiling , Xie Xinyou , Tang Huifang , Zhang Jun
Published: April 2022

Background

In this study, we enrolled 862 patients with Crohn’s disease (CD) in China to investigate the correlation between serum vitamin D (SVD) and serum lipids, inflammatory biomarkers, and important clinical parameters.

Materials and Methods

25(OH)D was measured by LS/MS/MS. Correlation analysis, chi-square tests, and logistic regression analysis were performed to determine the correlations between vitamin D and potential risk factors when vitamin D levels were lower than 10 ng/mL or 20 ng/mL.

Results

The incidence of severe vitamin D deficiency (SVD < 10 ng/mL) in patients with CD was significantly higher than that in healthy controls (28.9 vs. 9.5%). Multinomial logistic regression analysis showed that penetrating disease [odds ratio (OR) = 2.18], low levels of high-density lipoprotein cholesterol (HDL) (OR = 1.91), high erythrocyte sedimentation rate (OR = 1.73), and platelet count (PLT) (OR = 2.71) were regarded as predictors of severe vitamin D deficiency, while only PLT (OR = 1.90) and HDL (OR = 1.76) were considered as predictors of mild vitamin D deficiency (SVD 10–20 ng/mL).

Conclusion

Our results confirm a higher incidence of severe vitamin D deficiency in patients with CD in China and show that vitamin D deficiency could result from the combined effects of penetrating disease, inflammation, and low levels of HDL.
Potential Application of Tea Polyphenols to the Prevention of COVID-19 Infection: Based on the Gut-Lung Axis
Authors: Xu Lei , Ho Chi-Tang , Liu Yanan , Wu Zufang , Zhang Xin
Published: April 2022

Coronavirus disease 2019 (COVID-19) disrupts the intestinal micro-ecological balance, and patients often develop the intestinal disease. The gut is the largest immune organ in the human body; intestinal microbes can affect the immune function of the lungs through the gut-lung axis. It has been reported that tea polyphenols (TPs) have antiviral and prebiotic activity. In this review, we discussed TPs reduced lung-related diseases through gut-lung axis by inhibiting dysbiosis. In addition, we also highlighted the preventive and therapeutic effects of TPs on COVID-19 complications, further demonstrating the importance of research on TPs for the prevention and treatment of COVID-19 in humans. Based on this understanding, we recommend using TPs to regulate the gut microbiota to prevent or alleviate COVID-19 through the gut-lung axis.
Construction of an Immune-Related lncRNA Signature That Predicts Prognosis and Immune Microenvironment in Osteosarcoma Patients
Authors: He Yi , Zhou Haiting , Xu Haoran , You Hongbo , Cheng Hao
Published: April 2022

Osteosarcoma is one of the most common bone tumors in teenagers. We hope to provide a reliable method to predict the prognosis of osteosarcoma and find potential targets for early diagnosis and precise treatment. To address this issue, we performed a detailed bioinformatics analysis based on the Cancer Genome Atlas (TCGA). A total of 85 osteosarcoma patients with gene expression data and clinicopathological features were included in this study, which was considered the entire set. They were randomly divided into a train set and a test set. We identified six lncRNAs (ELFN1-AS1, LINC00837, OLMALINC, AL669970.3, AC005332.4 and AC023157.3), and constructed a signature that exhibited good predictive ability of patient survival and metastasis. What’s more, we found that risk score calculated by the signature was positively correlated to tumor purity, CD4+ naive T cells, and negatively correlated to CD8+ T cells. Furthermore, we investigated each lncRNA in the signature and found that these six lncRNAs were associated with tumorigenesis and immune cells in the tumor microenvironment. In conclusion, we constructed and validated a signature, which had good performance in the prediction of survival, metastasis and immune microenvironment. Our study indicated possible mechanisms of these lncRNAs in the development of osteosarcoma, which may provide new insights into the precise treatment of osteosarcoma.
Effectiveness and Safety of Toripalimab Combination Therapies for Patients With Chemo-Resistant Choriocarcinoma
Authors: Liu Xiaomei , Li Xiuqin , Qu Hui , Zhang Shiyue , Zhang Ruizhe , Du Zhenhua
Published: April 2022

Toripalimab as a novel PD-1 inhibitor has presented its promising efficacy in patients who developed chemo-refractory carcinomas, whereas no study has ever investigated the effectiveness of toripalimab in chemo-resistant choriocarcinoma. Here we reported the effectiveness and safety data of 4 patients with chemo-resistant choriocarcinoma who underwent PD-1 antibody therapy by toripalimab and individualized chemotherapies. From January 2019 to August 2020, 4 patients with choriocarcinoma were admitted in Shengjing Hospital of China Medical University. The patients’ age ranged from 29 to 52 years with a median of 36 years. All the patients achieved CR after the combined therapy of toripalimab with individualized chemotherapies according to the decreased serum β-hcg level. Two of the four patients were observed with treatment-related adverse events (AEs), including one grade I skin rash and one grade I pruritus. Our cases showed that toripalimab combined with chemotherapy presented a tolerable safety profile and promising effectiveness in patients with chemo-resistant choriocarcinoma, indicating its potential as salvage therapy for this subset of patients.
Case Report: 18F-FDG PET/CT and Laparoscopic Nephron Sparing Surgery in the Management of Bleeding From Renal Metastases of Choriocarcinoma
Authors: Du Yuancheng , Zhang Xueping , Sun Shengyang , Sun Meihong , Yang Dongyu , Yu Xinyuan , Li Kehao , Ma Jie , Li Yongxiang , Ge Jinming , Liu Changqing , Qiao Liang
Published: April 2022

Choriocarcinoma is a cancer that usually occurs in the uterus during pregnancy. Although choriocarcinoma with renal metastasis and spontaneous renal hemorrhage is very rare, it can occur. We describe a rare case of metastatic choriocarcinoma, wherein the patient presented with acute abdominal pain due to a subcapsular hematoma secondary to a bleeding renal metastasis. We performed a laparoscopic nephron sparing surgery to remove the tumor and control the bleeding. A retrospective analysis revealed that metastasis was detected on 18F-fluorodeoxyglucose PET/CT, but not on CT alone. To our knowledge, a case of choriocarcinoma with such symptoms and treatment has not been described in recent literature. Our case illustrates that acute bleeding from a renal metastasis can be effectively managed by laparoscopic nephron sparing surgery. It also demonstrates the advantage 18F-FDG PET/CT may have in the evaluation of metastatic choriocarcinoma.
SCLC Treatment in the Immuno-Oncology Era: Current Evidence and Unmet Needs
Authors: Belluomini Lorenzo , Calvetti Lorenzo , Inno Alessandro , Pasello Giulia , Roca Elisa , Vattemi Emanuela , Veccia Antonello , Menis Jessica , Pilotto Sara
Published: April 2022

Small cell lung cancer (SCLC) represents about 13%–15% of all lung cancers. It has a particularly unfavorable prognosis and in about 70% of cases occurs in the advanced stage (extended disease). Three phase III studies tested the combination of immunotherapy (atezolizumab, durvalumab with or without tremelimumab, and pembrolizumab) with double platinum chemotherapy, with practice-changing results. However, despite the high tumor mutational load and the chronic pro-inflammatory state induced by prolonged exposure to cigarette smoke, the benefit observed with immunotherapy is very modest and most patients experience disease recurrence. Unfortunately, biological, clinical, or molecular factors that can predict this risk have not yet been identified. Thanks to these clinically meaningful steps forward, SCLC is no longer considered an “orphan” disease. Innovative treatment strategies and combinations are currently under investigation to further improve the expected prognosis of patients with SCLC. Following the recent therapeutic innovations, we have reviewed the available literature data about SCLC management, with a focus on current unmet needs and potential predictive factors. In detail, the role of radiotherapy; fragile populations, such as elderly or low-performance status patients (ECOG PS 2), usually excluded from randomized studies; predictive factors of response useful to optimize and guide therapeutic choices; and new molecular targets and future combinations have been explored and revised.
Retrospective Analysis of the Accuracy of High-Frequency Ultrasound for Pancreaticobiliary Maljunction in Pediatrics at a Single Center
Authors: Xu Qiuchen , Liu Min , Wu Qiumei , Ling Wen , Guo Shan
Published: April 2022

Objective

To determine the clinical value of high-frequency ultrasonography (US) in the evaluation and diagnosis of pancreaticobiliary maljunction (PBM) among children.

Methods

The clinical subjects consisted of 31 pediatric patients who were diagnosed with PBM from January 2015 to May 2021 in Fujian Provincial Maternity and Children's Hospital. The primary outcomes included diagnosis accuracy, imaging characteristics of each type of PBM based on JSPBM, time length of operation, and cost of service. Secondary outcomes were the serum amylase and bilirubin levels.

Results

The diagnostic accuracy of US was 90.3% and comparable to the other imaging methods—MRCP (82.6%), IOC (79.2%), and ERCP (100%), respectively. The time length of operation and direct cost were significantly lower than other imaging pathways. Stenotic type (A) is associated with a high internal diameter of CBD, and dilated channel type (C) presents increased internal diameter and length of CC as well as internal diameter of PD. There were higher levels of the serum bilirubin seen in type A and of serum amylase in type C compared with others.

Conclusion

High-frequency US is a safe, cost-effective, and non-invasive imaging tool for the diagnosis and evaluation of PBM in pediatrics.
Case Report: SARS-CoV-2 Associated Acute Interstitial Nephritis in an Adolescent
Authors: Azukaitis Karolis , Besusparis Justinas , Laurinavicius Arvydas , Jankauskiene Augustina
Published: April 2022

Acute interstitial nephritis (AIN) has been recently recognized as one of the infrequent kidney involvement phenotypes among adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although SARS-CoV-2 associated intrinsic kidney disease has been scarcely reported in children, only one case of AIN temporally associated with the infection has been described in the pediatric population so far. We presented a case of a 12-year old boy who presented with fatigue, anorexia, and polydipsia following an RT-PCR that confirmed SARS-CoV-2 infection seven weeks prior to admission. Initial workup revealed increased serum creatinine (235 μmol/L), glucosuria, low-molecular-weight proteinuria, mild leukocyturia, and microhematuria with hyaline and granular casts on microscopy. Antibodies against the SARS-CoV-2 S protein receptor-binding domain confirmed prior infection with high titers. Kidney biopsy showed diffuse active interstitial nephritis with negative immunofluorescence and positive immunohistochemistry for SARS-CoV-2 in the inflammatory cells within the interstitium. Electron microscopy revealed several SARS-CoV-2-like particles. Kidney function continued to deteriorate despite several days of supportive therapy only (peak serum creatinine 272 μmol/L); thus, treatment with methylprednisolone pulse-dose therapy was initiated and was followed by oral prednisolone with gradual tapering. Kidney function completely recovered after 3 weeks post-discharge and remained normal after 11 weeks of follow-up (last estimated glomerular filtration rate 106 ml/min/1.73 m2) with only residual microhematuria. Our case adds to the emerging evidence of SARS-CoV-2 as a potential etiological agent of AIN in children and also suggests that interstitial kidney injury may result from secondary inflammatory damage. Epidemiological history, serologic testing, and SARS-CoV-2 detection in biopsy should be considered in the work-up of children with AIN of unknown etiology.
Something Is Changing in Viral Infant Bronchiolitis Approach
Authors: Bottau Paolo , Liotti Lucia , Laderchi Eleonora , Palpacelli Alessandra , Calamelli Elisabetta , Colombo Carlotta , Serra Laura , Cazzato Salvatore
Published: April 2022

Acute Viral Bronchiolitis is one of the leading causes of hospitalization in the first 12–24 months of life. International guidelines on the management of bronchiolitis broadly agree in recommending a minimal therapeutic approach, not recommending the use of bronchodilators. Guidelines, generally, consider bronchiolitis as a “unique disease” and this runs the risk of not administering therapy in some patients who could benefit from the use of bronchodilators, for instance, in those who will develop asthma later in their life and face first episode in the age of bronchiolitis. Today, there is growing evidence that bronchiolitis is not a single illness but can have different “endotypes” and “phenotypes,” based on age, personal or family history of atopy, etiology, and pathophysiological mechanism. There is evidence that some phenotypes of bronchiolitis are more strongly associated with asthma features and are linked to higher risk for asthma development. In these populations, possible use of bronchodilators might have a better impact. Age seems to be the main feature to suggest a good response to a bronchodilator-trial, because, among children > 6 months old with bronchiolitis, the presence of a subset of patients with virus-induced wheezing or the first episode of asthma is more likely. While waiting for new research to define the relationship between therapeutic options and different phenotypes, a bronchodilator-trial (using short-acting β2 agonists with metered-dose inhalers and valved holding chambers) seems appropriate in every child with bronchiolitis and age > 6 months.
Pharmacodynamic Evaluation of Zoliflodacin Treatment of Neisseria gonorrhoeae Strains With Amino Acid Substitutions in the Zoliflodacin Target GyrB Using a Dynamic Hollow Fiber Infection Model
Authors: Jacobsson Susanne , Golparian Daniel , Oxelbark Joakim , Franceschi Francois , Brown David , Louie Arnold , Drusano George , Unemo Magnus
Published: April 2022

Novel antimicrobials for effective treatment of uncomplicated gonorrhea are essential, and the first-in-class, oral spiropyrimidinetrione DNA gyrase B inhibitor zoliflodacin appears promising. Using our newly developed Hollow Fiber Infection Model (HFIM), the pharmacodynamics of zoliflodacin was examined. A clinical zoliflodacin-susceptible N. gonorrhoeae strain, SE600/18 (harbouring a GyrB S467N amino acid substitution; MIC = 0.25 mg/L), and SE600/18-D429N (zoliflodacin-resistant mutant with a second GyrB substitution, D429N, selected in the HFIM experiments; zoliflodacin MIC = 2 mg/L), were examined. Dose-range experiments, simulating zoliflodacin single oral dose regimens of 0.5, 1, 2, 3, and 4 g, were performed for SE600/18. For SE600/18-D429N, dose-range experiments, simulating zoliflodacin single oral 2, 3, 4, and 6 g doses, and zoliflodacin oral dose-fractionation experiments with 4, 6, and 8 g administered as q12 h were performed. Both strains grew well in the untreated HFIM growth control arms and mostly maintained growth at 1010–1011 CFU/ml for 7 days. Zoliflodacin 3 and 4 g single dose oral regimens successfully eradicated SE600/18 and no growth was recovered during the 7-days experiments. However, the single oral 0.5, 1, and 2 g doses failed to eradicate SE600/18, and zoliflodacin-resistant populations with a GyrB D429N substitution were selected with all these doses. The zoliflodacin-resistant SE600/18-D429N mutant was not eradicated with any examined treatment regimen. However, this in vitro-selected zoliflodacin-resistant mutant was substantially less fit compared to the zoliflodacin-susceptible SE600/18 parent strain. In conclusion, the rare clinical gonococcal strains with GyrB S467N substitution are predisposed to develop zoliflodacin resistance and may require treatment with zoliflodacin ≥3 g. Future development may need to consider the inclusion of diagnostics directed at identifying strains resistant or predisposed to resistance development at a population level and to strengthen surveillance (phenotypically and genetically), and possibly also at the patient level to guide treatment.
SIRT1 Is Involved in the Neuroprotection of Pterostilbene Against Amyloid β 25–35-Induced Cognitive Deficits in Mice
Authors: Zhu Lin , Lu Fangjin , Zhang Xiaoran , Liu Siyuan , Mu Ping
Published: April 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposits and neurofibrillary tangles. Pterostilbene (PTE), a bioactive component mainly in blueberries, is found to have neuroprotective properties. However, the specific underlying mechanisms of PTE in protecting AD remain unclear. Herein, we explored its effects on Aβ25–35-induced neuronal damage in vivo and in vitro and further compared the roles with its structural analog resveratrol (RES) in improving learning–memory deficits. We found that intragastric administration of PTE (40 mg/kg) displayed more effective neuroprotection on Aβ25–35-induced cognitive dysfunction assessed using the novel object test, Y-maze test, and Morris water maze test. Then, we found that PTE improved neuronal plasticity and alleviated neuronal loss both in vivo and in vitro. Additionally, PTE upregulated the expression of sirtuin-1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (Nrf2) and the level of superoxide dismutase (SOD), and inhibited mitochondria-dependent apoptosis in the Aβ25–35-treated group. However, SIRT1 inhibitor EX527 reversed the neuroprotection and induced a drop in mitochondrial membrane potential in PTE-treated primary cortical neurons. Our data suggest that PTE’s enhancing learning–memory ability and improving neuroplasticity might be related to inhibiting mitochondria-dependent apoptosis via the antioxidant effect regulated by SIRT1/Nrf2 in AD.
Hydrocarbon Charge History of the Upper Paleozoic, Ordos Basin as Revealed by Fluid Inclusions
Authors: Cao Qing , Wei Xinshan , Chen Zhangxing , Zhao Jingzhou , Tang Mingju
Published: April 2022

The petrographic characteristics of fluid inclusions of the main gas-bearing intervals of the Upper Paleozoic in the Ordos Basin are analyzed by means of plane-polarized light, fluorescence microscopy, and microthermometry. With the burial history of the basin, the charging and enrichment of natural gas in low-permeability reservoirs are also studied through a comparison of parameters such as the homogenization temperature and freezing temperature of aqueous inclusions associated with hydrocarbon inclusions. A comprehensive analysis of the assemblage characteristics, components, and temperature of fluid inclusions of the Upper Paleozoic shows that the abundance, attitude, and composition of gaseous hydrocarbon inclusions can reflect petroleum enrichment in low-permeability reservoirs. The homogenization temperature and freezing temperature of aqueous inclusions associated with gaseous hydrocarbon inclusions show no obvious discontinuities, indicating that natural gas charging was a long and continuous process since the Late Triassic to Early Cretaceous (210–100 Ma) and natural gas accumulation mainly occurred during the Early Cretaceous (125–100 Ma).
Nematicity and Glassy Behavior Probed by Nuclear Magnetic Resonance in Iron-Based Superconductors
Authors: Curro N. J. , Kissikov T. , Tanatar M. A. , Prozorov R. , Bud’ko S. L. , Canfield P. C.
Published: April 2022

Nuclear magnetic resonance provides a wealth of information about the magnetic and nematic degrees of freedom in the iron-based superconductors. A striking observation is that the spin lattice relaxation rate is inhomogeneous with a standard deviation that correlates with the nematic susceptibility. Moreover, the spin lattice relaxation is strongly affected by uniaxial strain, and in doped samples it depends sensitively upon the history of the applied strain. These observations suggest that quenched strain fields associated with doping atoms induce a nematic glass in the iron pnictide materials.
Bulked Segregant RNA Sequencing Revealed Difference Between Virulent and Avirulent Brown Planthoppers
Authors: Guan Wei , Shan Junhan , Gao Mingyang , Guo Jianping , Wu Di , Zhang Qian , Wang Jing , Chen Rongzhi , Du Bo , Zhu Lili , He Guangcun
Published: April 2022

The brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most devastating insect pests of rice (Oryza sativa L.), but BPH populations have varying degrees of virulence to rice varieties carrying different resistance genes. To help efforts to characterize these variations we applied bulked segregant RNA sequencing (BSR-seq) to identify differentially expressed genes (DEGs) and genetic loci associated with BPH virulence to YHY15 rice plants carrying the resistance gene Bph15. BPHs that are highly virulent or avirulent to these plants were selected from an F2 population to form two contrasting bulks, and BSR-seq identified 751 DEGs between the bulks. Genes associated with carbohydrate, amino acid and nucleotide metabolism, the endocrine system, and signal transduction were upregulated in the avirulent insects when they fed on these plants. The results also indicated that shifts in lipid metabolism and digestive system pathways were crucial for the virulent BPHs’ adaptation to the resistant rice. We identified 24 single-nucleotide polymorphisms (SNPs) in 21 genes linked with BPH virulence. Possible roles of genes apparently linked to BPH virulence are discussed. Our results provide potentially valuable information for further studies of BPH virulence mechanisms and development of robust control strategies.