bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic value of autoantibodies and novel automated methods of their detection
Authors: Tkachenko O. Yu. , Lapin S. V. , Masing A. V. , Blinova T. V. , Moshnikova A. N. , Kuznetsova D. A. , Kholopova I. V.
Published: April 2022

Autoantibodies (aAb) are human immunoglobulins that can specifically bind to antigenic epitopes of molecules of their own body. Most of AATs have diagnostic value and are serological markers, as well as reflect the main mechanisms of loss of tolerance and inflammation in patients with autoimmune diseases. Indirect immunofluorescence (IIF) was the first method used to detect aAb. During the 1970s and 1980s, there was an evolution in qualitative methods with the introduction of immunoblotting or dot blotting, and second generation quantitative immunometric assays (radioimmunoassay,, enzyme-linked immunosorbent assay (ELISA), fluoroimmunoassay, immunochemiluminescence assay) were suggested. The growing number of aAbs, as well as the growing request for aAb research in general, has fueled the development of automated and multiplex testing. An example is the Chorus trio multi-parameter automatic station (Italy), which combines the ELISA method and the complement fixation reaction (CFR) on one platform. The advantages of this device include a large panel of tests, minimal labor costs, the ability to use the analyzer to perform analyzes in the “cito” mode, perform CFR tests in an automatic mode, high accuracy and reproducibility of results, and a compact design of the analyzer. The Chorus trio multi-parameter automatic station has been implemented into the routine practice of our laboratory for the diagnosis of autoimmune diseases as a confirmatory test. Thus, the effectiveness of new technologies, the possibility of automation and an increase in the speed and quality of testing, as well as the extensive information provided by innovative multi-parameter systems, will bring significant benefits for clinical laboratory diagnostics and clinicians.
Decellularization in Tissue Engineering and Regenerative Medicine: Evaluation, Modification, and Application Methods
Authors: Neishabouri Afarin , Soltani Khaboushan Alireza , Daghigh Faezeh , Kajbafzadeh Abdol-Mohammad , Majidi Zolbin Masoumeh
Published: April 2022

Reproduction of different tissues using scaffolds and materials is a major element in regenerative medicine. The regeneration of whole organs with decellularized extracellular matrix (dECM) has remained a goal despite the use of these materials for different purposes. Recently, decellularization techniques have been widely used in producing scaffolds that are appropriate for regenerating damaged organs and may be able to overcome the shortage of donor organs. Decellularized ECM offers several advantages over synthetic compounds, including the preserved natural microenvironment features. Different decellularization methods have been developed, each of which is appropriate for removing cells from specific tissues under certain conditions. A variety of methods have been advanced for evaluating the decellularization process in terms of cell removal efficiency, tissue ultrastructure preservation, toxicity, biocompatibility, biodegradability, and mechanical resistance in order to enhance the efficacy of decellularization methods. Modification techniques improve the characteristics of decellularized scaffolds, making them available for the regeneration of damaged tissues. Moreover, modification of scaffolds makes them appropriate options for drug delivery, disease modeling, and improving stem cells growth and proliferation. However, considering different challenges in the way of decellularization methods and application of decellularized scaffolds, this field is constantly developing and progressively moving forward. This review has outlined recent decellularization and sterilization strategies, evaluation tests for efficient decellularization, materials processing, application, and challenges and future outlooks of decellularization in regenerative medicine and tissue engineering.
Association Between Lipoprotein(a) and Calcific Aortic Valve Disease: A Systematic Review and Meta-Analysis
Authors: Liu Qiyu , Yu Yanqiao , Xi Ruixi , Li Jingen , Lai Runmin , Wang Tongxin , Fan Yixuan , Zhang Zihao , Xu Hao , Ju Jianqing
Published: April 2022

Background

Preliminary studies indicated that enhanced plasma levels of lipoprotein(a) [lp(a)] might link with the risk of calcific aortic valve disease (CAVD), but the clinical association between them remained inconclusive. This systematic review and meta-analysis were aimed to determine this association.

Methods

We comprehensively searched PubMed, Embase, Web of Science, and Scopus databases for studies reporting the incidence of CAVD and their plasma lp(a) concentrations. Pooled risk ratio (RR) and 95% confidence interval (95% CI) were calculated to evaluate the effect of lp(a) on CAVD using the random-effects model. Subgroup analyses by study types, countries, and the level of adjustment were also conducted. Funnel plots, Egger's test and Begg's test were conducted to evaluate the publication bias.

Results

Eight eligible studies with 52,931 participants were included in this systematic review and meta-analysis. Of these, four were cohort studies and four were case-control studies. Five studies were rated as high quality, three as moderate quality. The pooled results showed that plasma lp(a) levels ≥50 mg/dL were associated with a 1.76-fold increased risk of CAVD (RR, 1.76; 95% CI, 1.47–2.11), but lp(a) levels ≥30 mg/dL were not observed to be significantly related with CAVD (RR, 1.28; 95% CI, 0.98–1.68). We performed subgroup analyses by study type, the RRs of cohort studies revealed lp(a) levels ≥50 mg/dL and lp(a) levels ≥30 mg/dL have positive association with CAVD (RR, 1.70; 95% CI, 1.39–2.07; RR 1.38; 95% CI, 1.19–1.61).

Conclusion

High plasma lp(a) levels (≥50 mg/dL) are significantly associated with increased risk of CAVD.
Comparative Evaluation of Chiglitazar and Sitagliptin on the Levels of Retinol-Binding Protein 4 and Its Correlation With Insulin Resistance in Patients With Type 2 Diabetes
Authors: Zhou Yunting , Wang Huiying , Wang Yuming , Xu Xiaohua , Li Fengfei , Zhou Junming , Shan Ting , Huang Rong , Cai Tingting , Liu Xiaomei , Su Xiaofei , Li Huiqin , Ma Jianhua
Published: April 2022

Aims

We evaluated the efficacy and significant changes in the levels of retinol-binding protein 4 (RBP-4) and insulin resistance in patients with type 2 diabetes mellitus (T2DM) treated with chiglitazar versus sitagliptin.

Methods

Eighty-one T2DM patients with haemoglobin A1c (HbA1c) level of 7.5%–10.0% were selected. Based on the study criteria, patients were randomly assigned to receive chiglitazar (32 mg), chiglitazar (48 mg), or sitagliptin (100 mg) orally for 24 weeks. Sociodemographic and anthropometric characteristics, lipid profiles, glucose profiles, and serum RBP-4 levels were determined at baseline and at the end of the therapy.

Results

After treatment for 24 weeks, significant changes in fasting blood glucose (FBG), fasting insulin (Fins), 2 h-blood glucose (2h-BG), the score values of insulin resistance/insulin secretion/β cell function (HOMA-IR, HOMA-IS, and HOMA-β), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), and RBP-4 levels were detected in patients with chiglitazar administration and sitagliptin administration. Changes in RBP-4 levels were positively correlated with changes in HOMA-IR and 2 h-BG in linear regression.

Conclusions

Chiglitazar showed a greater improvement in parameters of diabetes than sitagliptin, and changes in serum RBP-4 levels were associated with changes in insulin-sensitizing parameters.

Clinical Trial Registration

ClinicalTrials.gov, CT.gov identifier: NCT02173457.
Outcome of Endoscopic Transsphenoidal Surgery for Recurrent or Residual Pituitary Adenomas and Comparison to Non-Recurrent or Residual Cohort by Propensity Score Analysis
Authors: Gong Xuan , Zhuo Yang , Yuan Huichun , Yang Kui , Li Chuntao , Feng Songshan , Zhang Mingyu , Li Zhenyan , Zhou Hongshu , Liu Zhixiong
Published: April 2022

Objective

To evaluate the long-term outcomes and safety of endoscopic transsphenoidal surgery (ETS) in recurrent and residual pituitary adenomas (rrPAs), as well as the predictors of gross total resection (GTR) and intraoperative CSF leakage. Furthermore, to compare outcomes and complications with non-rrPAs cohort.

Methods

Clinical and radiological characteristics of patients with rrPAs who underwent ETS were collected between 2017 and 2020. Data of patients with non-rrPAs were collected from 2019 to 2020. Logistic regression analyses were performed to investigate the factors influencing gross total resection (GTR) and intraoperative CSF leakage. Between-group comparisons of outcomes and complications were performed through propensity score analysis.

Results

We enrolled 73 patients with rrPAs. GTR was achieved in 41 (56.1%) cases; further, GTR or near-total resection was achieved in 93.2% of patients. The mean tumor volumes for GTR and non-GTR cases were 6.2 ±7.2 cm3 and 11.1 ±9.1 cm3, respectively. Multivariate regression analysis of the GTR rate in patients with rrPAs revealed that Knosp grade was an independent factor (odds ratio [OR] = 0.324; p=0.005). Moreover, previous transcranial surgery and non-functional pituitary adenomas were risk factors for intraoperative CSF leakage in patients with rrPAs (OR=6.450, p=0.019 and OR=7.472, p=0.012, respectively). After propensity score matching, There was no significant difference in the GTR rate between patients with rrPAs and patients with non-rrPAs. Contrastingly, patients with rrPAs had a higher rate of intraoperative CSF leakage and longer postoperative hospital stay than patients with non-rrPAs. During the follow-up, vision improved in 9 (22.0%) and 24 (62.5%) patients with rrPAs and non-rrPAs, respectively. Although there was a trend that reoperation of rrPAs involved a lower hypopituitarism recovery rate and biochemical remission rate, as well as a higher hypopituitarism rate, there was no statistically significant between-group difference.

Conclusions

Knosp grade was an independent factor for GTR in endoscopic transsphenoidal surgery in patients with rrPAs. Previous transcranial surgery and non-functional PAs were risk factors for intraoperative CSF leakage. Although associated with longer hospital stay, rrPAs did not associate with lower GTR rate or more frequent postoperative complications than non-rrPAs cohort.
The Causal Association Between Obesity and Primary Open-Angle Glaucoma: A Two-Sample Mendelian Randomization Study
Authors: Lin Yi , Zhu Xiaomin , Luo Wangdu , Jiang Bingcai , Lin Qianyi , Tang Min , Li Xiangji , Xie Lin
Published: April 2022

The correlation between obesity and primary open-angle glaucoma (POAG) has not yet been fully established. The aim of this study was to investigate the causal relationship between obesity and POAG by a two-sample Mendelian randomization (MR) study. In this study, body mass index (BMI), an index to evaluate general obesity, and waist and hip circumference, indices to evaluate abdominal obesity, were selected as exposures in MR analysis. Single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables (IVs). Summary data from genome-wide association studies (GWASs) based on a European ancestry by Locke et al., with regard to BMI, and Shungin et al., with regard to waist and hip circumference, were used. Genetic predictors of POAG were obtained from public GWAS summary data. To assess the causal effect of obesity on POAG, the inverse variance-weighted (IVW) method was used as the primary method, and other methods, such as MR–Egger, weighted median, simple mode, and weighted mode, were also used as complementary analyses. Finally, we performed Cochran’s Q statistic to assess heterogeneity, and sensitivity analysis was performed to evaluate the reliability and stability of the MR results. MR analysis showed that BMI has a positive effect on the risk of POAG, with 1 standard deviation (SD) increase in BMI; the risk of POAG increases by approximately 90.9% [OR = 1.909; 95% CI= (1.225, 2.975); p = 0.0042)] (analyzed by IVW); there were no heterogeneity and pleiotropy in the result; and waist circumference also had a positive effect on the risk of POAG [OR = 2.319; 95% CI= (1.071, 5.018); p = 0.033)] analyzed by weighted median. As hip circumference increases, with 1 SD increase in hip circumference, the risk of POAG increases by approximately 119% [OR = 2.199; 95% CI= (1.306, 3.703); p = 0.00305)] estimated by IVW, there were not heterogeneity and pleiotropy as for the result. Our study for the first time confirms that obesity might increase the risk of POAG using two-sample MR analysis. These results might provide guidance on the prevention and treatment of POAG.
Comprehensive Analyses of Mutation-Derived Long-Chain Noncoding RNA Signatures of Genome Instability in Kidney Renal Papillary Cell Carcinoma
Authors: Li Jian , Wei Shimei , Zhang Yan , Lu Shuangshuang , Zhang Xiaoxu , Wang Qiong , Yan Jiawei , Yang Sanju , Chen Liying , Liu Yunguang , Huang Zhijing
Published: April 2022

Background: The role of long-chain noncoding RNA (lncRNA) in genomic instability has been demonstrated to be increasingly importance. Therefore, in this study, lncRNAs associated with genomic instability were identified and kidney renal papillary cell carcinoma (KIRP)-associated predictive features were analysed to classify high-risk patients and improve individualised treatment.

Methods: The training (n = 142) and test (n = 144) sets were created using raw RNA-seq and patient’s clinical data of KIRP obtained from The Cancer Genome Atlas (TCGA).There are 27 long-chain noncoding RNAs (lncRNAs) that are connected with genomic instability, these lncRNAs were identified using the ‘limma’ R package based on the numbers of somatic mutations and lncRNA expression profiles acquired from KIRP TCGA cohort. Furthermore, Cox regression analysis was carried out to develop a genome instability-derived lncRNA-based gene signature (GILncSig), whose prognostic value was confirmed in the test cohort as well as across the entire KIRP TCGA dataset.

Results: A GILncSig derived from three lncRNAs (BOLA3-AS1, AC004870, and LINC00839), which were related with poor KIRP survival, was identified, which was split up into high- and low-risk groups. Additionally, the GILncSig was found to be an independent prognostic predictive index in KIRP using univariate and multivariate Cox analysis. Furthermore, the prognostic significance and characteristics of GilncSig were confirmed in the training test and TCGA sets. GilncSig also showed better predictive performance than other prognostic lncRNA features.

Conclusion: The function of lncRNAs in genomic instability and the genetic diversity of KIRP were elucidated in this work. Moreover, three lncRNAs were screened for prediction of the outcome of KIRP survival and novel insights into identifying cancer biomarkers related to genomic instability were discussed.
Combinatorial Herpes Simplex Vaccine Strategies: From Bedside to Bench and Back
Authors: Chentoufi Aziz A. , Dhanushkodi Nisha R. , Srivastava Ruchi , Prakash Swayam , Coulon Pierre-Gregoire A. , Zayou Latifa , Vahed Hawa , Chentoufi Hiba A. , Hormi-Carver Kathy K. , BenMohamed Lbachir
Published: April 2022

The development of vaccines against herpes simplex virus type 1 and type 2 (HSV1 and HSV-2) is an important goal for global health. In this review we reexamined (i) the status of ocular herpes vaccines in clinical trials; and (ii) discusses the recent scientific advances in the understanding of differential immune response between HSV infected asymptomatic and symptomatic individuals that form the basis for the new combinatorial vaccine strategies targeting HSV; and (iii) shed light on our novel “asymptomatic” herpes approach based on protective immune mechanisms in seropositive asymptomatic individuals who are “naturally” protected from recurrent herpetic diseases. We previously reported that phenotypically and functionally distinct HSV-specific memory CD8+T cell subsets in asymptomatic and symptomatic HSV-infected individuals. Moreover, a better protection induced following a prime/pull vaccine approach that consists of first priming anti-viral effector memory T cells systemically and then pulling them to the sites of virus reactivation (e.g., sensory ganglia) and replication (e.g., eyes and vaginal mucosa), following mucosal administration of vectors expressing T cell-attracting chemokines. In addition, we reported that a combination of prime/pull vaccine approach with approaches to reverse T cell exhaustion led to even better protection against herpes infection and disease. Blocking PD-1, LAG-3, TIGIT and/or TIM-3 immune checkpoint pathways helped in restoring the function of antiviral HSV-specific CD8+T cells in latently infected ganglia and increased efficacy and longevity of the prime/pull herpes vaccine. We discussed that a prime/pull vaccine strategy that use of asymptomatic epitopes, combined with immune checkpoint blockade would prove to be a successful herpes vaccine approach.
Exploring Changes in Fishery Emissions and Organic Carbon Impacts Associated With a Recovering Stock
Authors: Martin Angela Helen , Ferrer Erica M. , Hunt Corallie A. , Bleeker Katinka , Villasante Sebastián
Published: April 2022

International objectives for sustainable development and biodiversity conservation require restoring fish populations to healthy levels and reducing fishing impacts on marine ecosystems. At the same time, governments, retailers, and consumers are increasingly motivated to reduce the carbon footprint of food. These concerns are reflected in measures of the EU Common Fisheries Policy (CFP) and the CFP Reform Regulation, which highlighted a need to move from traditional single-stock management toward an ecosystem approach to fisheries management (EAF). Using publicly available landings and effort data combined with estimates of adult population biomass, we develop methods to explore the potential for lowering emissions intensity and impacts on organic carbon stocks through ending overfishing and rebuilding stocks. We use the recent recovery of European hake (Merluccius merluccius) stocks in the Northeast Atlantic as a case study. With a focus on the hake fisheries of France, Spain, and the United Kingdom, we compare 2008 and 2016 fishing years. We make an initial estimate of the influence of changing stock status on greenhouse gas emissions during the fishery phase from fuel use and investigate the potential disturbance of organic carbon in the ecosystem, specifically via identification of bottom trawling overlap with organic-rich muddy sediments, and directly on storage in hake biomass. Our findings indicate that recovery of the hake stock was associated with reductions in overall emissions intensity from fuel and proportional impact on hake populations, however, total emissions from both fuel and landings increased, as did likely disturbance of sedimentary organic carbon in surface sediments due to benthic trawling. Ultimately, the aims of this analysis are to further explore the climate impacts of fisheries and overfishing, and to inform development of EAF in the EU.
Semi-Active Controllable Stiffness Engine Mount Utilizing Natural Rubber-Based Magnetorheological Elastomers
Authors: Mat Song Rusdi , Mazlan Saiful Amri , Johari Norhasnidawani , Imaduddin Fitrian , Abdul Aziz Siti Aishah , Abd Fatah Abdul Yasser , Ubaidillah U.
Published: April 2022

This study proposes the design and fabrication of a natural rubber-based magnetorheological elastomer (NR-MRE) engine mount as a new device in absorbing the vibration originated from the automotive engine. The conceptual design was performed through a simulation process by Finite Element Method Magnetics to analyze the magnetic field distribution. The simulation result had indicated that the device was capable of generating an equivalent magnetic field density of 0.31 T at the effective area. The MRE was prepared by utilizing 60 wt% of carbonyl iron particles (CIPs), and the cavity was filled by compression molding. The MRE compound was tested based on its basic mechanical properties, while the MRE engine mounts were tested under a static compression load at off- and on-state conditions. It was observed that the compound possessed a good tensile strength for a load bearer matrix with an average of 12.65 MPa. Subsequently, the results of the static compression load had showed that the MRE engine mounts recorded an increase of 12% in the force generated as compared to conventional engine mounts at an off-state condition. Meanwhile, at an on-state condition of 2.4 A, the MRE engine mounts recorded an increase in the force generated with 106%. The study has demonstrated that the proposed device can be one of the potential candidates for vibration control applications due to its stiffness controllability.
Different Surgical Approaches for Early-Stage Ovarian Cancer Staging. A Large Monocentric Experience
Authors: Cianci Stefano , Capozzi Vito Andrea , Rosati Andrea , Rumolo Valerio , Corrado Giacomo , Uccella Stefano , Gueli Alletti Salvatore , Riccò Matteo , Fagotti Anna , Scambia Giovanni , Cosentino Francesco
Published: April 2022

Introduction

Ovarian cancer is the third most frequent gynecological cancer. In early stage ovarian cancer (ESOC) comprehensive surgical staging is recommended. Surgical staging is traditionally approached by laparotomy, although minimally invasive surgery can be a valid alternative in selected patients. This study aims to analyze the surgical and oncological outcomes of three different surgical approaches in a large series of patients.

Methods

We retrospectively included all histologically proven ESOC cases treated between January 2014 and December 2017. ESOC was defined as stage IA to IIB according to the 2018 FIGO staging system. Subjects were divided into groups 1, 2, and 3, based on the surgical approach (open abdominal, laparoscopic, or robotic, respectively).

Results

Within patients enrolled during the study period, 455 met the inclusion criteria. No difference in intraoperative complications was recorded in the three groups (p = 0.709). Conversely, a significant difference occurred in postoperative complications (16.2 vs. 3.8 vs. 11.1%, in groups 1, 2, and 3 respectively, p = 0.004). No difference was found in overall survival (OS) (32 vs. 31 vs. 25 months, p = 0.481) and disease-free survival (DFS) (26 vs. 29 vs. 24 months, p = 0.178) in groups 1, 2, and 3, respectively. At univariate analysis FIGO stage I (p = 0.004) showed a lower recurrence rate compared to FIGO stage II.

Conclusion

No significant difference was found in OS and DFS among the three groups (open, laparoscopic, and robotic). The minimally invasive approach showed lower rate of complications than the laparotomic approach.
EMDS-6: Environmental Microorganism Image Dataset Sixth Version for Image Denoising, Segmentation, Feature Extraction, Classification, and Detection Method Evaluation
Authors: Zhao Peng , Li Chen , Rahaman Md Mamunur , Xu Hao , Ma Pingli , Yang Hechen , Sun Hongzan , Jiang Tao , Xu Ning , Grzegorzek Marcin
Published: April 2022

Environmental microorganisms (EMs) are ubiquitous around us and have an important impact on the survival and development of human society. However, the high standards and strict requirements for the preparation of environmental microorganism (EM) data have led to the insufficient of existing related datasets, not to mention the datasets with ground truth (GT) images. This problem seriously affects the progress of related experiments. Therefore, This study develops theEnvironmental Microorganism Dataset Sixth Version(EMDS-6), which contains 21 types of EMs. Each type of EM contains 40 original and 40 GT images, in total 1680 EM images. In this study, in order to test the effectiveness of EMDS-6. We choose the classic algorithms of image processing methods such as image denoising, image segmentation and object detection. The experimental result shows that EMDS-6 can be used to evaluate the performance of image denoising, image segmentation, image feature extraction, image classification, and object detection methods. EMDS-6 is available at thehttps://figshare.com/articles/dataset/EMDS6/17125025/1.
In vitro Activity of Antivirulence Drugs Targeting the las or pqs Quorum Sensing Against Cystic Fibrosis Pseudomonas aeruginosa Isolates
Authors: Collalto Diletta , Giallonardi Giulia , Fortuna Alessandra , Meneghini Carlo , Fiscarelli Ersilia , Visca Paolo , Imperi Francesco , Rampioni Giordano , Leoni Livia
Published: April 2022

The chronic lung infection caused by Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis (CF) patients. Antivirulence drugs targeting P. aeruginosa quorum sensing (QS) systems are intensively studied as antibiotics substitutes or adjuvants. Previous studies, carried out in non-CF P. aeruginosa reference strains, showed that the old drugs niclosamide and clofoctol could be successfully repurposed as antivirulence drugs targeting the las and pqs QS systems, respectively. However, frequent emergence of QS-defective mutants in the CF lung undermines the use of QS inhibitors in CF therapy. Here, QS signal production and susceptibility to niclosamide and clofoctol have been investigated in 100 P. aeruginosa CF isolates, with the aim of broadening current knowledge on the potential of anti-QS compounds in CF therapy. Results showed that 85, 78, and 69% of the CF isolates from our collection were proficient for the pqs, rhl, and las QS systems, respectively. The ability of both niclosamide and clofoctol to inhibit QS and virulence in vitro was highly variable and strain-dependent. Niclosamide showed an overall low range of activity and its negative effect on las signal production did not correlate with a decreased production of virulence factors. On the other hand, clofoctol displayed a broader QS inhibitory effect in CF isolates, with consequent reduction of the pqs-controlled virulence factor pyocyanin. Overall, this study highlights the importance of testing new antivirulence drugs against large panels of P. aeruginosa CF clinical isolates before proceeding to further pre-clinical studies and corroborates previous evidence that strains naturally resistant to QS inhibitors occur among CF isolates. However, it is also shown that resistance to pqs inhibitors is less frequent than resistance to las inhibitors, thus supporting the development of pqs inhibitors for antivirulence therapy in CF.
Growth and Persistence of an Aerobic Microbial Community in Wyoming Bentonite MX-80 Despite Anoxic in situ Conditions
Authors: Burzan Niels , Murad Lima Roberta , Frutschi Manon , Janowczyk Andrew , Reddy Bharti , Rance Andrew , Diomidis Nikitas , Bernier-Latmani Rizlan
Published: April 2022

Microbial activity has the potential to enhance the corrosion of high-level radioactive waste disposal canisters, which, in the proposed Swiss deep geological repository, will be embedded in bentonite and placed in the Opalinus Clay (OPA) rock formation. A total of 12 stainless steel cylindrical vessels (referred to as modules) containing bentonite were deployed in an anoxic borehole in OPA for up to 5.5 years. Carbon steel coupons were embedded in the bentonite. Individual modules were retrieved after 1, 1.5, 2.5, and 5.5 years. Enumeration of aerobic and anaerobic heterotrophs and sulfate-reducing bacteria (SRB) revealed microbial growth for 1.5 years followed by a decline or stagnation in microbial viability. It was surprising to observe the growth of aerobic heterotrophs followed by their persistent viability in bentonite, despite the nominally anoxic conditions. In contrast, SRB numbers remained at very low levels. DNA-based amplicon sequencing confirmed the persistence of aerobes and the relatively low contribution of anaerobes to the bentonite microbiome. Bentonite dry density, in situ exposure time, and bioavailable trapped oxygen are observed to shape the bentonite microbial community in the clay.
Discovery of Early-Branching Wolbachia Reveals Functional Enrichment on Horizontally Transferred Genes
Authors: Weyandt Nicholas , Aghdam Shiva A. , Brown Amanda M. V.
Published: April 2022

Wolbachiais a widespread endosymbiont of insects and filarial nematodes that profoundly influences host biology.Wolbachiahas also been reported in rhizosphere hosts, where its diversity and function remain poorly characterized. The discovery that plant-parasitic nematodes (PPNs) hostWolbachiastrains with unknown roles is of interest evolutionarily, ecologically, and for agriculture as a potential target for developing new biological controls. The goal of this study was to screen communities for PPN endosymbionts and analyze genes and genomic patterns that might indicate their role. Genome assemblies revealed 1 out of 16 sampled sites had nematode communities hosting aWolbachiastrain, designatedwTex, that has highly diverged as one of the early supergroup L strains. Genome features, gene repertoires, and absence of known genes for cytoplasmic incompatibility, riboflavin, biotin, and other biosynthetic functions placedwTex between mutualist C + D strains and reproductive parasite A + B strains. Functional terms enriched in group L included protoporphyrinogen IX, thiamine, lysine, fatty acid, and cellular amino acid biosynthesis, while dN/dS analysis suggested the strongest purifying selection on arginine and lysine metabolism, and vitamin B6, heme, and zinc ion binding, suggesting these as candidate roles in PPNWolbachia. Higher dN/dS pathways between group L,wPni from aphids,wFol from springtails, andwCfeT from cat fleas suggested distinct functional changes characterizing these earlyWolbachiahost transitions. PPNWolbachiahad several putative horizontally transferred genes, including a lysine biosynthesis operon like that of the mitochondrial symbiontMidichloria, a spirochete-like thiamine synthesis operon shared only withwCfeT, an ATP/ADP carrier important inRickettsia, and a eukaryote-like gene that may mediate plant systemic acquired resistance through the lysine-to-pipecolic acid system. The Discovery of group L-like variants from global rhizosphere databases suggests diverse PPNWolbachiastrains remain to be discovered. These findings support the hypothesis of plant-specialization as key to shaping earlyWolbachiaevolution and present new functional hypotheses, demonstrating promise for future genomics-based rhizosphere screens.
D-Allulose (D-Psicose) Biotransformation From Allitol by a Newly Found NAD(P)-Dependent Alcohol Dehydrogenase From Gluconobacter frateurii NBRC 3264 and the Enzyme Characterization
Authors: Wen Xin , Lin Huibin , Ning Yuhang , Liu Guangwen , Ren Yilin , Li Can , Zhang Chengjia , Lin Jianqun , Song Xin , Lin Jianqiang
Published: April 2022

The NAD(P)-dependent alcohol dehydrogenase (ADH) gene was cloned from Gluconobacter frateurii NBRC 3264 and expressed in Escherichia coli BL21 star (DE3). The expressed enzyme was purified and the characteristics were investigated. The results showed that this ADH can convert allitol into D-allulose (D-psicose), which is the first reported enzyme with this catalytic ability. The optimum temperature and pH of this enzyme were 50°C and pH 7.0, respectively, and the enzyme showed a maximal activity in the presence of Co2+. At 1 mM Co2+ and allitol concentrations of 50, 150, and 250 mM, the D-allulose yields of 97, 56, and 38%, respectively, were obtained after reaction for 4 h under optimal conditions, which were much higher than that obtained by using the epimerase method of about 30%.
An Efficient Evaluation System Accelerates α-Helical Antimicrobial Peptide Discovery and Its Application to Global Human Genome Mining
Authors: Liu Licheng , Wang Caiyun , Zhang Mengyue , Zhang Zixuan , Wu Yingying , Zhang Yixuan
Published: April 2022

Antimicrobial peptides (AMPs), as an important part of the innate immune system of an organism, is a kind of promising drug candidate for novel antibiotics due to their unique antibacterial mechanism. However, the discovery of novel AMPs is facing a great challenge due to the complexity of systematic experiments and the poor predictability of antimicrobial activity. Here, a novel and comprehensive screening system, the Multiple Descriptor Multiple Strategy (MultiDS), was proposed based on 59 physicochemical and structural parameters, three strategies, and four algorithms for the mining of α-helical AMPs. This approach was applied to mine the encrypted peptide antibiotics from the global human genome, including introns and exons. A library of approximately 70 billion peptides with 15–25 amino acid residues was screened by the MultiDS system and generated a list of peptides with the Multiple Descriptor Index (MD index) scores, which was the core part of the MultiDS system. Sixty peptides with top MD scores were chemically synthesized and experimentally tested their antimicrobial activity against 10 kinds of Gram-positive bacteria, Gram-negative bacteria (including drug-resistant pathogens). A total of fifty-nine out of 60 (98.3%) peptides exhibited antimicrobial activity (MIC ≤ 64 μg/mL), and 24 out of 60 (40%) peptides showed high activity (MIC ≤ 2 μg/mL), validating the MultiDS system was an effective and predictive screening tool with high hit rate and superior antimicrobial activity. For further investigation, AMPs S1, S2, and S3 with the highest MD scores were used to treat the skin infection mouse models in vivo caused by Escherichia coli, drug-resistance Escherichia coli, and Staphylococcus aureus, respectively. All of S1, S2, and S3 showed comparable therapeutic effects on promoting infection healing to or even better than the positive drug levofloxacin. A mechanism study discovered that rapid bactericidal action was caused by cell membrane disruption and content leakage. The MultiDS system not only provides a high-throughput approach that allows for the mining of candidate AMPs from the global genome sequence but also opens up a new route to accelerate the discovery of peptide antibiotics.
Comparative Biophysical and Ultrastructural Analysis of Melanins Produced by Clinical Strains of Different Species From the Trichosporonaceae Family
Authors: de Andrade Iara Bastos , Araújo Glauber Ribeiro de Sousa , Brito-Santos Fábio , Figueiredo-Carvalho Maria Helena Galdino , Zancopé-Oliveira Rosely Maria , Frases Susana , Almeida-Paes Rodrigo
Published: April 2022

Melanin is one of the most studied virulence factors in pathogenic fungi. This pigment protects them from a series of both environmental and host stressors. Among basidiomycetes, Cryptococcus neoformans and Trichosporon asahii are known to produce melanin in the presence of phenolic precursors. Other species from the Trichosporonaceae family also produce this pigment, but the extent to this production among the clinically relevant species is unknown. For this reason, the aim of this study was to verify the production of melanin by different Trichosporonaceae species of clinical interest and to compare their pigments with the ones from C. neoformans and T. asahii, which are more prevalent in human infections. Melanin was produced in a minimal medium supplemented with 1 mM L-dihydroxyphenylalanine (L-DOPA). Pigment was evaluated using scanning electron microscopy, Zeta potential measurements, and energy-dispersive X-ray spectroscopy. It was found that, besides C. neoformans and T. asahii, Trichosporon japonicum, Apiotrichum montevideense, Trichosporon inkin, Trichosporon faecale, Cutaneotrichosporon debeurmannianum, and Cutaneotrichosporon arboriformis also produce melanin-like particles in the presence of L-DOPA. Melanin particles have negative charge and are smaller than original cells. Variations in color, fluorescence, and chemical composition was noticed between the studied strains. All melanins presented carbon, oxygen, sodium, and potassium in their composition. Melanins from the most pathogenic species also presented iron, zinc, and copper, which are important during parasitism. Biophysical properties of these melanins can confer to the Trichosporonaceae adaptive advantages to both parasitic and environmental conditions of fungal growth.
The Comparative Efficacy of Non-ergot Dopamine Agonist and Potential Risk Factors for Motor Complications and Side Effects From NEDA Use in Early Parkinson's Disease: Evidence From Clinical Trials
Authors: Wu Chunxiao , Guo Hongji , Xu Yingshan , Li Luping , Li Xinyu , Tang Chunzhi , Chen Dongfeng , Zhu Meiling
Published: April 2022

Background/Objectives

Non-ergot dopamine agonist (NEDA) are recommended as the first-line treatment for patients with early Parkinson's disease (PD) because of their efficacy in treating PD motor symptoms. However, systematic evaluations of the risk of motor complications induced by NEDA and risk factors potentially associated with motor complications are still lacking.

Methods

Medline, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were searched for potentially eligible randomized controlled trials. The incidence of motor complications (dyskinesia, motor fluctuations), impulsive-compulsive behaviors and adverse events and clinical disability rating scale (UPDRS) scores were evaluated using standard meta-analytic methods. Metaregression was conducted on the incidence of motor complications (dyskinesia) with treatment duration and NEDA dose as covariates.

Results

Patients treated with NEDA had significantly lower UPDRS total scores, motor scores and activity of daily living (ADL) scores than those receiving a placebo (weighted mean difference (WMD) −4.81, 95% CI −6.57 to −3.05; WMD −4.901, 95% CI −7.03 to −2.77; WMD −1.52, 95% CI −2.19 to −0.84, respectively). Patients in the NEDA and NEDA+open Levodopa (LD) groups had lower odds for dyskinesia than patients in the LD group (OR = 0.21, 95% CI: 0.15–0.29; OR = 0.31, 95% CI 0.24–0.42, respectively). Metaregressions indicated that the mean LD dose of the NEDA group increased, and the odds of developing dyskinesia increased (p = 0.012). However, the odds of developing dyskinesia in the NEDA group were not related to treatment duration (p = 0.308). PD patients treated with NEDA or NEDA+open LD had a lower risk of wearing-off implications than those treated with LD (all p < 0.05). No significant difference was found between the NEDA and placebo groups in impulsive-compulsive behavior development (p > 0.05). Patients in the NEDA group were more likely to suffer somnolence, edema, constipation, dizziness, hallucinations, nausea and vomiting than those in the placebo or LD group.

Conclusion

NEDA therapy reduces motor symptoms and improves ADLs in early PD. The odds of developing motor complications were lower with NEDA than with LD, and dyskinesia increased with increasing LD equivalent dose and was not influenced by NEDA treatment duration. Therefore, long-term treatment with an appropriate dosage of NEDA might be more suitable than LD for early PD patients.

Registration

PROSPERO CRD42021287172.
Practice Effects in Mild Cognitive Impairment Increase Reversion Rates and Delay Detection of New Impairments
Authors: Sanderson-Cimino Mark , Elman Jeremy A. , Tu Xin M. , Gross Alden L. , Panizzon Matthew S. , Gustavson Daniel E. , Bondi Mark W. , Edmonds Emily C. , Eppig Joel S. , Franz Carol E. , Jak Amy J. , Lyons Michael J. , Thomas Kelsey R. , Williams McKenna E. , Kremen William S.
Published: April 2022

Objective

Cognitive practice effects (PEs) can delay detection of progression from cognitively unimpaired to mild cognitive impairment (MCI). They also reduce diagnostic accuracy as suggested by biomarker positivity data. Even among those who decline, PEs can mask steeper declines by inflating cognitive scores. Within MCI samples, PEs may increase reversion rates and thus impede detection of further impairment. Within an MCI sample at baseline, we evaluated how PEs impact prevalence, reversion rates, and dementia progression after 1 year.

Methods

We examined 329 baseline Alzheimer’s Disease Neuroimaging Initiative MCI participants (mean age = 73.1; SD = 7.4). We identified test-naïve participants who were demographically matched to returnees at their 1-year follow-up. Since the only major difference between groups was that one completed testing once and the other twice, comparison of scores in each group yielded PEs. PEs were subtracted from each test to yield PE-adjusted scores. Biomarkers included cerebrospinal fluid phosphorylated tau and amyloid beta. Cox proportional models predicted time until first dementia diagnosis using PE-unadjusted and PE-adjusted diagnoses.

Results

Accounting for PEs increased MCI prevalence at follow-up by 9.2% (272 vs. 249 MCI), and reduced reversion to normal by 28.8% (57 vs. 80 reverters). PEs also increased stability of single-domain MCI by 12.0% (164 vs. 147). Compared to PE-unadjusted diagnoses, use of PE-adjusted follow-up diagnoses led to a twofold increase in hazard ratios for incident dementia. We classified individuals as false reverters if they reverted to cognitively unimpaired status based on PE-unadjusted scores, but remained classified as MCI cases after accounting for PEs. When amyloid and tau positivity were examined together, 72.2% of these false reverters were positive for at least one biomarker.

Interpretation

Even when PEs are small, they can meaningfully change whether some individuals with MCI retain the diagnosis at a 1-year follow-up. Accounting for PEs resulted in increased MCI prevalence and altered stability/reversion rates. This improved diagnostic accuracy also increased the dementia-predicting ability of MCI diagnoses.
Intracerebral Hemorrhage: The Effects of Aging on Brain Injury
Authors: Watson Noah , Bonsack Frederick , Sukumari-Ramesh Sangeetha
Published: April 2022

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high rates of mortality and morbidity. ICH patients often suffer devastating and debilitating neurological impairments, from which the majority of victims are unable to fully recover to functional independence. Unfortunately, there is no established medical therapy for ICH, which is partly attributed to the lack of understanding of the complex pathology of the disorder. Despite advanced age being a major risk factor of ICH, most preclinical studies on ICH employed young animal subjects. Due to this discrepancy, the molecular level changes in the aging brain after ICH are largely unknown, limiting the translation of preclinical studies into potential human treatments. The purpose of this review is to highlight the effects of advanced age on ICH- induced brain injury and recovery and to draw attention to current knowledge gaps, which warrant further investigation.
Age Related Changes in Muscle Mass and Force Generation in the Triple Transgenic (3xTgAD) Mouse Model of Alzheimer’s Disease
Authors: Xu Hongyang , Bhaskaran Shylesh , Piekarz Katarzyna M. , Ranjit Rojina , Bian Jan , Kneis Parker , Ellis Aubrey , Bhandari Suyesha , Rice Heather C. , Van Remmen Holly
Published: April 2022

Emerging evidence suggests that patients with Alzheimer’s disease (AD) may show accelerated sarcopenia phenotypes. To investigate whether pathological changes associated with neuronal death and cognitive dysfunction also occur in peripheral motor neurons and muscle as a function of age, we used the triple transgenic mouse model of AD (3xTgAD mice) that carries transgenes for mutant forms of APP, Tau, and presenilin proteins that are associated with AD pathology. We measured changes in motor neurons and skeletal muscle function and metabolism in young (2 to 4 month) female control and 3xTgAD mice and in older (18–20 month) control and 3xTgAD female mice. In older 3xTgAD mice, we observed a number of sarcopenia-related phenotypes, including significantly fragmented and denervated neuromuscular junctions (NMJs) associated with a 17% reduction in sciatic nerve induced vs. direct muscle stimulation induced contractile force production, and a 30% decrease in gastrocnemius muscle mass. On the contrary, none of these outcomes were found in young 3xTgAD mice. We also measured an accumulation of amyloid-β (Aβ) in both skeletal muscle and neuronal tissue in old 3xTgAD mice that may potentially contribute to muscle atrophy and NMJ disruption in the older 3xTgAD mice. Furthermore, the TGF-β mediated atrophy signaling pathway is activated in old 3xTgAD mice and is a potential contributing factor in the muscle atrophy that occurs in this group. Perhaps surprisingly, mitochondrial oxygen consumption and reactive oxygen species (ROS) production are not elevated in skeletal muscle from old 3xTgAD mice. Together, these results provide new insights into the effect of AD pathological mechanisms on peripheral changes in skeletal muscle.
Shedding Light on Inter-Individual Variability of Olfactory Circuits in Drosophila
Authors: Rihani Karen , Sachse Silke
Published: April 2022

Inter-individual differences in behavioral responses, anatomy or functional properties of neuronal populations of animals having the same genotype were for a long time disregarded. The majority of behavioral studies were conducted at a group level, and usually the mean behavior of all individuals was considered. Similarly, in neurophysiological studies, data were pooled and normalized from several individuals. This approach is mostly suited to map and characterize stereotyped neuronal properties between individuals, but lacks the ability to depict inter-individual variability regarding neuronal wiring or physiological characteristics. Recent studies have shown that behavioral biases and preferences to olfactory stimuli can vary significantly among individuals of the same genotype. The origin and the benefit of these diverse “personalities” is still unclear and needs to be further investigated. A perspective taken into account the inter-individual differences is needed to explore the cellular mechanisms underlying this phenomenon. This review focuses on olfaction in the vinegar fly Drosophila melanogaster and summarizes previous and recent studies on odor-guided behavior and the underlying olfactory circuits in the light of inter-individual variability. We address the morphological and physiological variabilities present at each layer of the olfactory circuitry and attempt to link them to individual olfactory behavior. Additionally, we discuss the factors that might influence individuality with regard to olfactory perception.
Large-N Rat Data Enables Phenotyping of Risky Decision-Making: A Retrospective Analysis of Brain Injury on the Rodent Gambling Task
Authors: Vonder Haar Cole , Frankot Michelle A. , Reck A. Matthew , Milleson Virginia , Martens Kris M.
Published: April 2022

Decision-making is substantially altered after brain injuries. Patients and rats with brain injury are more likely to make suboptimal, and sometimes risky choices. Such changes in decision-making may arise from alterations in how sensitive individuals are to outcomes. To assess this, we compiled and harmonized a large dataset from four studies of TBI, each of which evaluated behavior on the Rodent Gambling Task (RGT). We then determined whether the following were altered: (1) sensitivity to overall contingencies, (2) sensitivity to immediate outcomes, or (3) general choice phenotypes. Overall sensitivity was evaluated using the matching law, immediate sensitivity by looking at the probability of switching choices given a win or loss, and choice phenotypes by k-means clustering. We found significant reductions in sensitivity to the overall outcomes and a bias toward riskier alternatives in TBI rats. However, the substantial individual variability led to poor overall fits in matching analyses. We also found that TBI caused a significant reduction in the tendency to repeatedly choose a given option, but no difference in win- or loss-specific sensitivity. Finally, clustering revealed 5 distinct decision-making phenotypes and TBI reduced membership in the “optimal” type. The current findings support a hypothesis that TBI reduces sensitivity to contingencies. However, in the case of tasks such as the RGT, this is not a simple shift to indiscriminate or less discriminate responding. Rather, TBI rats are more likely to develop suboptimal preferences and frequently switch choices. Treatments will have to consider how this behavior might be corrected.