bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances of Pyridinone in Medicinal Chemistry
Authors: Lin Shibo , Liu Chun , Zhao Xiaotian , Han Xiao , Li Xuanhao , Ye Yongqin , Li Zheyu
Published: March 2022

Pyridinones have been adopted as an important block in medicinal chemistry that could serve as hydrogen bond donors and acceptors. With the help of feasible synthesis routes via established condensation reactions, the physicochemical properties of such a scaffold could be manipulated by adjustment of polarity, lipophilicity, and hydrogen bonding, and eventually lead to its wide application in fragment-based drug design, biomolecular mimetics, and kinase hinge-binding motifs. In addition, most pyridinone derivatives exhibit various biological activities ranging from antitumor, antimicrobial, anti-inflammatory, and anticoagulant to cardiotonic effects. This review focuses on recent contributions of pyridinone cores to medicinal chemistry, and addresses the structural features and structure–activity relationships (SARs) of each drug-like molecule. These advancements contribute to an in-depth understanding of the potential of this biologically enriched scaffold and expedite the development of its new applications in drug discovery.
SARS-CoV-2 Diagnostics Based on Nucleic Acids Amplification: From Fundamental Concepts to Applications and Beyond
Authors: Vindeirinho João M. , Pinho Eva , Azevedo Nuno F. , Almeida Carina
Published: March 2022

COVID-19 pandemic ignited the development of countless molecular methods for the diagnosis of SARS-CoV-2 based either on nucleic acid, or protein analysis, with the first establishing as the most used for routine diagnosis. The methods trusted for day to day analysis of nucleic acids rely on amplification, in order to enable specific SARS-CoV-2 RNA detection. This review aims to compile the state-of-the-art in the field of nucleic acid amplification tests (NAATs) used for SARS-CoV-2 detection, either at the clinic level, or at the Point-Of-Care (POC), thus focusing on isothermal and non-isothermal amplification-based diagnostics, while looking carefully at the concerning virology aspects, steps and instruments a test can involve. Following a theme contextualization in introduction, topics about fundamental knowledge on underlying virology aspects, collection and processing of clinical samples pave the way for a detailed assessment of the amplification and detection technologies. In order to address such themes, nucleic acid amplification methods, the different types of molecular reactions used for DNA detection, as well as the instruments requested for executing such routes of analysis are discussed in the subsequent sections. The benchmark of paradigmatic commercial tests further contributes toward discussion, building on technical aspects addressed in the previous sections and other additional information supplied in that part. The last lines are reserved for looking ahead to the future of NAATs and its importance in tackling this pandemic and other identical upcoming challenges.
Effects of Short-Chain Fatty Acid Modulation on Potentially Diarrhea-Causing Pathogens in Yaks Through Metagenomic Sequencing
Authors: Li Kun , Zeng Zhibo , Liu Juanjuan , Pei Lulu , Wang Yaping , Li Aoyun , Kulyar Muhammad Fakhar-e-Alam , Shahzad Muhammad , Mehmood Khalid , Li Jiakui , Qi Desheng
Published: March 2022

Short-chain fatty acids (SCFA) are principal nutrient substrates of intestinal epithelial cells that regulate the epithelial barrier in yaks. Until now, metagenomics sequencing has not been reported in diarrheal yaks. Scarce information is available regarding the levels of fecal SCFA and diarrhea in yaks. So, our study aims to identify the potential pathogens that cause the emerging diarrhea and explore the potential relationship of short-chain fatty acids in this issue. We estimated diarrhea rate in yaks after collecting an equal number of fecal samples from affected animals. Metagenomics sequencing and quantitative analysis of SCFA were performed, which revealed 15%–25% and 5%–10% prevalence of diarrhea in yak’s calves and adults, respectively. Violin box plot also showed a higher degree of dispersion in gene abundance distribution of diarrheal yaks, as compared to normal yaks. We found 366,163 significant differential abundance genes in diarrheal yaks, with 141,305 upregulated and 224,858 downregulated genes compared with normal yaks via DESeq analysis. Metagenomics binning analysis indicated the higher significance of bin 33 (Bacteroidales) (p < 0.05) in diarrheal animals, while bin 10 (p < 0.0001), bin 30 (Clostridiales) (p < 0.05), bin 51 (Lactobacillales) (p < 0.05), bin 8 (Lachnospiraceae) (p < 0.05), and bin 47 (Bacteria) (p < 0.05) were significantly higher in normal yaks. At different levels, a significant difference in phylum (n = 4), class (n = 8), oder (n = 8), family (n = 16), genus (n = 17), and species (n = 30) was noticed, respectively. Compared with healthy yaks, acetic acid (p < 0.01), propionic acid (p < 0.01), butyric acid (p < 0.01), isobutyric acid (p < 0.01), isovaleric acid (p < 0.05), and caproic acid (p < 0.01) were all observed significantly at a lower rate in diarrheal yaks. In conclusion, besides the increased Staphylococcus aureus, Babesia ovata, Anaplasma phagocytophilum, Bacteroides fluxus, viruses, Klebsiella pneumonia, and inflammation-related bacteria, the decrease of SCFA caused by the imbalance of intestinal microbiota was potentially observed in diarrheal yaks.
Influence of Pre-treatment Saliva Microbial Diversity and Composition on Nasopharyngeal Carcinoma Prognosis
Authors: Du Yun , Feng Ruimei , Chang Ellen T. , Debelius Justine W. , Yin Li , Xu Miao , Huang Tingting , Zhou Xiaoying , Xiao Xue , Li Yancheng , Liao Jian , Zheng Yuming , Huang Guangwu , Adami Hans-Olov , Zhang Zhe , Cai Yonglin , Ye Weimin
Published: March 2022

Background

The human microbiome has been reported to mediate the response to anticancer therapies. However, research about the influence of the oral microbiome on nasopharyngeal carcinoma (NPC) survival is lacking. We aimed to explore the effect of oral microbiota on NPC prognosis.

Methods

Four hundred eighty-two population-based NPC cases in southern China between 2010 and 2013 were followed for survival, and their saliva samples were profiled using 16s rRNA sequencing. We analyzed associations of the oral microbiome diversity with mortality from all causes and NPC.

Results

Within- and between-community diversities of saliva were associated with mortality with an average of 5.29 years follow-up. Lower Faith’s phylogenetic diversity was related to higher all-cause mortality [adjusted hazard ratio (aHR), 1.52 (95% confidence interval (CI), 1.06–2.17)] and NPC-specific mortality [aHR, 1.57 (95% CI, 1.07–2.29)], compared with medium diversity, but higher phylogenetic diversity was not protective. The third principal coordinate (PC3) identified from principal coordinates analysis (PCoA) on Bray–Curtis distance was marginally associated with reduced all-cause mortality [aHR, 0.85 (95% CI, 0.73–1.00)], as was the first principal coordinate (PC1) from PCoA on weighted UniFrac [aHR, 0.86 (95% CI, 0.74–1.00)], but neither was associated with NPC-specific mortality. PC3 from robust principal components analysis was associated with lower all-cause and NPC-specific mortalities, with HRs of 0.72 (95% CI, 0.61–0.85) and 0.71 (95% CI, 0.60–0.85), respectively.

Conclusions

Oral microbiome may be an explanatory factor for NPC prognosis. Lower within-community diversity was associated with higher mortality, and certain measures of between-community diversity were related to mortality. Specifically, candidate bacteria were not related to mortality, suggesting that observed associations may be due to global patterns rather than particular pathogens.
Ascorbic Acid Ameriolates Liver Damage by Myeloperoxidase Oxidative Products in a Hamster Model of Amoebic Liver Abscess
Authors: Cruz-Baquero Andrea , Jarillo-Luna Rosa Adriana , Cárdenas-Jaramillo Luz María , Drago-Serrano Maria Elisa , Serrano-Luna José de Jesús , Pacheco-Yépez Judith
Published: March 2022

Entamoeba histolytica is a protozoan-pathogen-causing amoebic liver abscess (ALA). After amoeba establishment in the liver, it causes abundant infiltrate of neutrophils. Liver tissue damage by neutrophils results in part from anti-amoebic oxidative intermediates, including reactive oxygen species (ROS), reactive nitrogen species (RNS), and hypochlorous acid (HOCl), derived from the myeloperoxidase (MPO) enzyme. Ascorbic acid (ASC) is an antioxidant that acts as a scavenger for ROS and NOS-derived free radicals. No previous information regarding the effect of ASC concerning the participation of MPO in an experimental model of ALA in hamsters has been reported. Thus, the aim of the present work was to analyze the effect of ASC on acute ALA development and to measure the activity and gene expression of the MPO enzyme. Hamsters were treated with ASC (800 mg/kg) and then intrahepatically inoculated with E. histolytica trophozoites. Animals were sacrificed at 3, 6, and 12 h post-inoculation (p.i.), and liver samples were collected. The percentage of lesions, amoeba in situ count, MPO activity, and mpo gene expression were ascertained. Compared to ALA hamsters without ASC treatment as the control group (CT), the ALA group treated with ASC had a significant decrease in liver lesions (all p.i. hours) and viable amoeba count (12 h p.i.) and an increase in MPO activity (12 h p.i.) and mpo gene expression (6 h/12 h p.i.). These data suggest that ASC ameliorated liver damage caused by oxidizing products via modulation of mpo expression and activity.
A Deep Learning System for Fully Automated Retinal Vessel Measurement in High Throughput Image Analysis
Authors: Shi Danli , Lin Zhihong , Wang Wei , Tan Zachary , Shang Xianwen , Zhang Xueli , Meng Wei , Ge Zongyuan , He Mingguang
Published: March 2022

Motivation

Retinal microvasculature is a unique window for predicting and monitoring major cardiovascular diseases, but high throughput tools based on deep learning for in-detail retinal vessel analysis are lacking. As such, we aim to develop and validate an artificial intelligence system (Retina-based Microvascular Health Assessment System, RMHAS) for fully automated vessel segmentation and quantification of the retinal microvasculature.

Results

RMHAS achieved good segmentation accuracy across datasets with diverse eye conditions and image resolutions, having AUCs of 0.91, 0.88, 0.95, 0.93, 0.97, 0.95, 0.94 for artery segmentation and 0.92, 0.90, 0.96, 0.95, 0.97, 0.95, 0.96 for vein segmentation on the AV-WIDE, AVRDB, HRF, IOSTAR, LES-AV, RITE, and our internal datasets. Agreement and repeatability analysis supported the robustness of the algorithm. For vessel analysis in quantity, less than 2 s were needed to complete all required analysis.
Non-alcoholic Fatty Liver Disease and the Risk of Incident Atrial Fibrillation in Young Adults: A Nationwide Population-Based Cohort Study
Authors: Choi JungMin , Lee So-Ryoung , Choi Eue-Keun , Ahn Hyo-Jeong , Kwon Soonil , Park Sang-Hyeon , Lee HuiJin , Chung Jaewook , Han MinJu , Lee Seung-Woo , Han Kyung-Do , Oh Seil , Lip Gregory Y. H.
Published: March 2022

Background

Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease including cardiovascular. However, the association between NAFLD and the risk of incident atrial fibrillation (AF), especially in young adults, remains unclear. We aimed to evaluate the association between NAFLD as assessed by the fatty liver index (FLI) and the risk of AF in young adults.

Methods

We identified individuals aged 20–39 years who underwent health examinations conducted by the Korean National Health Insurance Corporation between January 2009 and December 2012. Individuals with significant liver disease, heavy alcohol consumption, or prevalent AF were excluded. We categorized based on FLI: <30, 30 to <60, and ≥60. Incident AF was evaluated as the primary outcome.

Results

We included 5,333,907 subjects (mean age, 31 ± 5 years; men, 57%). During a mean follow-up of 7.4 ± 1.1 years, 12,096 patients had newly diagnosed AF (incidence rate 0.31 per 1,000 person-years). After adjustment, subjects with FLI 30 to <60 and FLI ≥60 showed a higher risk of AF compared to those with FLI <30 (hazard ratio [HR] 1.21, 95% confidence interval [CI, 1.15–1.27] and HR 1.47, 95% CI [1.39–1.55], p < 0.001, respectively). In women, the increased AF risk was accentuated in the higher FLI group than in the individuals with FLI <30, compared with men (p-for-interaction = 0.023). A higher incident AF risk in the higher FLI groups was consistently observed in various subgroups.

Conclusion

Among young adults, NAFLD assessed using FLI was positively correlated with the AF risk. These findings support the evidence of AF screening in young adults with high FLI scores.
The Impact of Geohazards on Sustainable Development of Rural Mountain Areas in the Upper Reaches of the Min River
Authors: He Yanfen , Ding Mingtao , Liu Kang , Lei Min
Published: March 2022

There is a coupling mechanism among geohazards, rural settlements, and cultivated land in mountainous areas in the upper reaches of the Min River by analyzing geohazards data, settlements data and cultivated land data. Geohazards change the landform and provide material basis and space for the occurrence and development of cultivated land and settlements. However, human production and life are not only stressed by geohazards, but also one of the main factors inducing geohazards. The Settlements in the upper reaches of the Min River can be categorized into production-stressed settlements and life-stressed settlements. With the transformation of the social economy and society’s attention to the ecological function of the region, geohazards risk management of life-stressed settlements is of more importance. The “two-wheel-drive” strategy of new urbanization and rural revitalization provides opportunities for rural development in mountainous areas and also changes the role of land in human-land relationships. To fully consider natural capital in the sustainable livelihoods of farmers, it is necessary to evaluate the risk degree of geohazards in settlements at the small catchment scale and improving the external connectivity of the settlements, which is the key for promoting the optimization of natural environmental assets in these mountain settlements.
Correlation of Adiponectin Gene Polymorphisms rs266729 and rs3774261 With Risk of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Authors: Zheng Yong-Tian , Xiao Tian-Mei , Wu Chan-Xian , Cheng Jin-Yan , Li Le-Yu
Published: March 2022

Background

Increasing evidence has suggested an association of adiponectin gene polymorphisms rs1501299, rs2241766, rs266729 and rs3774261 with risk of nonalcoholic fatty liver disease (NAFLD). This correlation has been extensively meta-analyzed for the first two polymorphisms, but not the second two.

Methods

The PubMed, EMBASE, Google Scholar, and China National Knowledge Infrastructure databases were searched for relevant literature. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

A total of 10 case-control studies on rs266729 (2,619 cases and 1,962 controls) and 3 case-control studies on rs3774261 (562 cases and 793 controls) were included. Meta-analysis showed that rs266729 was associated with significantly higher NAFLD risk based on the following five models: allelic, OR 1.72, 95% CI 1.34-2.21, P < 0.001; recessive, OR 2.35, 95% CI 1.86-2.95, P < 0.001; dominant, OR 1.84, 95% CI 1.34-2.53, P < 0.001; homozygous, OR 2.69, 95% CI 1.84-3.92, P < 0.001; and heterozygous, OR 1.72, 95% CI 1.28-2.32, P < 0.001. This association between rs266729 and NAFLD risk remained significant for all five models among studies with Asian, Chinese and Caucasian samples. The rs2241766 polymorphism was associated with significantly higher NAFLD risk according to the recessive model (OR 1.87, 95% CI 1.15-3.04, P = 0.01).

Conclusion

Polymorphisms rs266729 and rs3774261 in the adiponectin gene may be risk factors for NAFLD. These findings may pave the way for novel therapeutic strategies, but they should be verified in large, well-designed studies.
Design of Back-to-Back Converter Interface for Electric Spring in a Distribution System
Authors: Deepika K. K. , Kumar J. Vijaya , Pinni Srinivasa Varma , Sura Srinivasa Rao , Sankar R. S. Ravi
Published: March 2022

In a distribution system, the erratic output power of distributed generation causes fluctuations in the available power to critical loads on the demand side. A novel electric spring (ES) with back-to-back converter configuration is proposed. Besides PCC voltage regulation and power control, the proposed converter integrates the ES to the grid without compromising the DC link voltage and the quality of the grid current. It comprises an instantaneous DC link voltage control, active power control, PCC voltage control, and a hysteresis band current control. The systematic design of the parameters in the configuration is detailed. Simulations were performed in MATLAB/Simulink, and a series of comparative analyses at various control stages were demonstrated. The quality of the grid current was analyzed with PI, PR, and hysteresis band current controllers. It was established that the hysteresis band current controller gave the best performance. Similarly, the DC link voltage was efficiently regulated with the instantaneous DC link voltage controller than the conventional controller.
Recent Advances in Anode Metallic Catalysts Supported on Conducting Polymer-Based Materials for Direct Alcohol Fuel Cells
Authors: Halim El Mahdi , Chemchoub Sanaa , El Attar Anas , Salih Fatima Ezzahra , Oularbi Larbi , EL RHAZI Mama
Published: March 2022

Sustainable energy development is a major challenge, particularly when considering population increase, rising energy demands resulting from the excessive use of nonrenewable fossil fuels, and growing consequences on global pollution and climate change. It is critical to continue to develop new sources of renewable and clean energy. Direct alcohol fuel cell (DAFC) represents a technological approach that meets all the requirements in terms of energy conversion with good electrical efficiency and lower emissions of pollutants. However, it largely suffers from the poisoning of the anode catalyst caused by the accumulation of intermediate products. In this context, this review is devoted to discussing the recent progress in anode catalysts based on conducting polymers (CPs) materials for direct alcohol fuel cells, especially direct methanol and ethanol fuel cells, from the viewpoint of synthesis techniques, morphology, and catalytic performance. In the first part of this review, we will explore the most commonly used methods for preparing metal-conducting polymer-based nanocomposites, including the key factors influencing their morphology regardless of the application. The catalytic performances of mono-, bi-, and tri-metal catalysts deposited on conducting polymer-based supports for the electrooxidation of methanol and ethanol reactions are examined in detail in the second and third parts of this review. We also highlight the effect of the introduction of carbon nanomaterials into conducting polymer supports on the electrical properties and on the performance of the catalysts. Development of anode materials using nanostructured conducting polymers-based support plays a vital role in reducing catalyst loadings and should therefore shed light on the wide-scale commercialization of DAFCs. In a nutshell, this review will give readers a thorough understanding of the principles of direct alcohol fuel cells, new advancements in electrode materials based on non-precious metals, and the main challenges that should be dealt with.
Reconsidering the “War on Rats”: What We Know From Over a Century of Research Into Municipal Rat Management
Authors: Lee Michael J. , Byers Kaylee A. , Stephen Craig , Patrick David M. , Corrigan Robert , Iwasawa Stefan , Himsworth Chelsea G.
Published: March 2022

To sustainably control urban rat infestations, management efforts need to encompass large areas of urban centers. Therefore, the objective of this review and narrative synthesis was to collate what is known about municipal-scale rat management. We explored the management frameworks that have been used at a large scale in cities and we describe the expectations of experts who have designed and implemented these frameworks. We found that there has been a persistent “war on rats” paradigm driving this literature since the early 1900s. Not only was there little quantitative evidence to support this paradigm and associated methodologies, but together, they failed to meet the expectations of those who designed and implemented them due to real-world constraints (i.e., limited resources). To improve the field of municipal management, we identify two distinct options. First, stakeholders may continue to wage the “war on rats” while improving existing strategies within this paradigm. Key pathways forward include developing evaluation metrics aligned with program objectives, establishing the cost-effectiveness of methodologies, and improving control efficacy. Second, we suggest a new paradigm, one that considers that rat management is a complex system that must be approached by first mapping its complexity to highlight and prioritize the many complex upstream determinants of infestations. This perspective highlights how rat management may be a wicked problem for which there is no overarching solution and instead can only be managed by making incremental gains in individual components of the problem over time. Importantly, we propose an alternative management objective that places a priority on improving the overall health of the community, instead of on eliminating rats, and we stress that management goals must address stakeholders’ goals as their investment is essential for a sustained program.
A Novel Hierarchical Clustering Approach for Joint Analysis of Multiple Phenotypes Uncovers Obesity Variants Based on ARIC
Authors: Fu Liwan , Wang Yuquan , Li Tingting , Yang Siqian , Hu Yue-Qing
Published: March 2022

Genome-wide association studies (GWASs) have successfully discovered numerous variants underlying various diseases. Generally, one-phenotype one-variant association study in GWASs is not efficient in identifying variants with weak effects, indicating that more signals have not been identified yet. Nowadays, jointly analyzing multiple phenotypes has been recognized as an important approach to elevate the statistical power for identifying weak genetic variants on complex diseases, shedding new light on potential biological mechanisms. Therefore, hierarchical clustering based on different methods for calculating correlation coefficients (HCDC) is developed to synchronously analyze multiple phenotypes in association studies. There are two steps involved in HCDC. First, a clustering approach based on the similarity matrix between two groups of phenotypes is applied to choose a representative phenotype in each cluster. Then, we use existing methods to estimate the genetic associations with the representative phenotypes rather than the individual phenotypes in every cluster. A variety of simulations are conducted to demonstrate the capacity of HCDC for boosting power. As a consequence, existing methods embedding HCDC are either more powerful or comparable with those of without embedding HCDC in most scenarios. Additionally, the application of obesity-related phenotypes from Atherosclerosis Risk in Communities via existing methods with HCDC uncovered several associated variants. Among these, UQCC1-rs1570004 is reported as a significant obesity signal for the first time, whose differential expression in subcutaneous fat, visceral fat, and muscle tissue is worthy of further functional studies.
Unsupervised Multi-Omics Data Integration Methods: A Comprehensive Review
Authors: Vahabi Nasim , Michailidis George
Published: March 2022

Through the developments of Omics technologies and dissemination of large-scale datasets, such as those from The Cancer Genome Atlas, Alzheimer’s Disease Neuroimaging Initiative, and Genotype-Tissue Expression, it is becoming increasingly possible to study complex biological processes and disease mechanisms more holistically. However, to obtain a comprehensive view of these complex systems, it is crucial to integrate data across various Omics modalities, and also leverage external knowledge available in biological databases. This review aims to provide an overview of multi-Omics data integration methods with different statistical approaches, focusing onunsupervised learningtasks, including disease onset prediction, biomarker discovery, disease subtyping, module discovery, and network/pathway analysis. We also briefly review feature selection methods, multi-Omics data sets, and resources/tools that constitute critical components for carrying out the integration.
An Evolutionary Insight Into the Heterogeneous Severity Pattern of the SARS-CoV-2 Infection
Authors: Raza Rabail Zehra , Abbasi Sumra Wajid
Published: March 2022

The ongoing pandemic of COVID-19 has elaborated an idiosyncratic pattern of SARS-CoV-2-induced symptoms in the human host. Some populations have succumbed to the SARS-CoV-2 infection in large numbers during this pandemic, whereas others have shown a resilient side by manifesting only milder or no symptoms at all. This observation has relayed the onus of the heterogeneous pattern of SARS-CoV-2-induced critical illness among different populations to the host genetic factors. Here, the evolutionary route was explored and three genetic loci, i.e., rs10735079, rs2109069, and rs2236757, associated with COVID-19 were analyzed. Among the three, the risk allele A at genetic locus rs2236757 residing in the IFNAR2 gene was observed to have undergone recent positive selection in the African population.
The Genomic Architecture of Hidradenitis Suppurativa—A Systematic Review
Authors: Pace Nikolai Paul , Mintoff Dillon , Borg Isabella
Published: March 2022

Hidradenitis suppurativa is a chronic, suppurative condition of the pilosebaceous unit manifesting as painful nodules, abscesses, and sinus tracts mostly in, but not limited to, intertriginous skin. Great strides have been made at elucidating the pathophysiology of hidradenitis suppurativa, which appears to be the product of hyperkeratinization and inflammation brought about by environmental factors and a genetic predisposition. The identification of familial hidradenitis suppurativa has sparked research aimed at identifying underlying pathogenic variants in patients who harbor them. The objective of this review is to provide a broad overview of the role of genetics in various aspects of hidradenitis suppurativa, specifically the pathophysiology, diagnosis, and clinical application.
A Pyramidal Feature Fusion Model on Swimming Crab Portunus trituberculatus Re-identification
Authors: Zhang Kejie , Xin Yu , Shi Ce , Xie Zhijun , Ren Zhiming
Published: March 2022

Swimming crab Portunus trituberculatus is a vital crab species in coastal areas of China. In this study, an individual re-identification method based on Pyramidal Feature Fusion Model (PFFM) for P. trituberculatus was proposed. This method took the carapace texture of P. trituberculatus as a “biological fingerprint” and extracted carapace texture features, including global features and local features, to identify P. trituberculatus. Furthermore, this method utilized a weight adaptive module to improve re-identification (ReID) accuracy for the P. trituberculatus individuals with the incomplete carapace. To strengthen the discrimination of the extracted features, triplet loss was adopted in the model training process to improve the effectiveness of P. trituberculatus ReID. Furthermore, three experiments, i.e., PFFM on the effect of pyramidal model, P. trituberculatus features analysis, and comparisons to the State-of-the-Arts, were carried out to evaluate PFFM performance. The results showed that the mean average precision (mAP) and Rank-1 values of the proposed method reached 93.2 and 93% in the left half occlusion case, and mAP and Rank-1 values reached 71.8 and 75.4% in the upper half occlusion case. By using the experiments, the effectiveness and robustness of the proposed method were verified.
Plasma Circulating Vitamin C Levels and Risk of Endometrial Cancer: A Bi-Directional Mendelian Randomization Analysis
Authors: Peng Haoxin , Wu Xiangrong , Wen Yaokai
Published: March 2022

Background

Observational studies indicated that circulating vitamin C (VitC) levels may be correlated with the risk of endometrial cancer (EC). However, the causal effects and direction between them were still unclear.

Methods

In this study, 11 single nucleotide polymorphisms (SNPs) robustly correlated with plasma VitC levels were extracted from the latest genome-wide association study (GWAS), containing 52,018 individuals. Genetic data of EC were obtained from the Endometrial Cancer Association Consortium (ECAC) (12,906 cases and 108,979 controls). An inverse-variance weighted method was utilized as the primary analysis of Mendelian randomization (MR), supplemented by the weighted median, MR Pleiotropy Residual Sum and Outlier test (MR-PRESSO), and MR-Egger methods. Additional sensitivity analyses excluding 3 SNPs with secondary phenotypes were conducted to rule out the possible pleiotropic effects. Potential impacts of several risk factors of EC, such as obesity, body mass index (BMI), hypertension, and diabetes on VitC levels, were assessed. We additionally evaluated the effects of VitC on LDL cholesterol levels, HDL cholesterol levels, and triglycerides levels to probe into the possible mediators in the VitC-EC pathway.

Results

Genetically predicted higher plasma VitC levels (per 1 SD increase, approximately 20 μmol/L) were causally associated with an increased risk of EC overall [odds ratio (OR) 1.374, 95%CI1.128–1.674,p= 0.0016], supported by complementary sensitivity analyses. In the subgroup analyses, genetically predicted higher levels of VitC were associated with a tendency of increased risks of both endometrioid (ORSD1.324, 95%CI0.959–1.829,p= 0.0881) and non-endometrioid histology (ORSD1.392, 95%CI0.873–2.220,p= 0.1647) while without statistical significance. The association remained significant after the exclusion of the three pleiotropic SNPs (ORSD1.394, 95%CI1.090–1.784,p= 0.0082). The confounders and mediators were unlikely to affect the VitC-EC relationship. The causal effect of EC on VitC levels was not supported (OR1.001, 95%CI0.998–1.004,p= 0.4468).

Conclusions

This bi-directional MR study demonstrated a causal risk role of higher circulating VitC at physiological levels on an increased risk of EC, which was independent of confounders and mediators. Further studies are warranted to elucidate the possible mechanisms.
β-Thalassemia Intermedia: Interaction of α-Globin Gene Triplication With β-thalassemia Heterozygous in Spain
Authors: Ropero Paloma , González Fernández Fernando Ataúlfo , Nieto Jorge M. , Torres-Jiménez Williana Melissa , Benavente Celina
Published: March 2022

Objectives

To verify with hematimetric data that the diagnosis and clinical grade of β-TI can be established when a triplication of alpha genes (αααanti 3.7) and heterozygous β-thalassemia coexist.

Materials and Methods

Retrospective study in which 73 patients of Caucasian origin participated, who simultaneously showed a triplication or quadruplication of genes α and β-thalassemia.

Screening for the most frequent α-thalassemia mutations as well as gene triplication (αααanti 3.7) was carried out by multiplex PCR followed by reverse hybridization with a commercial Alpha-Globin StripAssay kit and confirmed by MLPA (Multiplex ligation-dependent probe amplification). The molecular diagnosis of β-thalassemia was carried out by automatic sequencing according to the Sanger method.

Results

The genotypes have been classified into three groups according to the number of α globin genes and the severity of the alteration in the β globin gene. All had a mutation in the HBB gene (β0-thalassemia, β+-thalassemia severe, and β+-thalassemia mild). Group I patients who have coherent 6 α genes and groups II and III with 5 α globin genes. In group III, the patients were carriers of mutations affecting the β and δ globin genes. The most significant hematological parameters were hemoglobin levels, MCV, RDW, and the percentage of Hb F.

Conclusions

In group I, regardless of the distribution of the 6 α globin genes, homozygous triplication (ααα/ααα) or heterozygous quadruplication (αααα/αα), the association with heterozygous β-thalassemia results in severe to moderate anemia that may or may not require transfusion therapy, is the severity of the HBB gene mutation that would determine the clinical variation. Group II patients phenotypically behaved like mild thalassemia intermedia, except for one case that presented thalassemic trait because it also presented an associated α-thalassemia (ααα/-α3.7). Finally, group III patients behaved as a thalassemic trait since all were carriers of mutations that increase the overexpression of γ genes.
Tumor Microenvironment Shapes Colorectal Cancer Progression, Metastasis, and Treatment Responses
Authors: Li Jun , Chen Dawei , Shen Minhong
Published: March 2022

Colorectal cancer (CRC) is one of the most devastating diseases that accounts for numerous deaths worldwide. Tumor cell-autonomous pathways, such as the oncogenic signaling activation, significantly contribute to CRC progression and metastasis. Recent accumulating evidence suggests that the CRC microenvironment also profoundly promotes or represses this process. As the roles of the tumor microenvironment (TME) in CRC progression and metastasis is gradually uncovered, the importance of these non-cell-autonomous signaling pathways is appreciated. However, we are still at the beginning of this TME function exploring process. In this review, we summarize the current understanding of the TME in CRC progression and metastasis by focusing on the gut microbiota and host cellular and non-cellular components. We also briefly discuss TME-remodeling therapies in CRC.
Emergence of Resistant Escherichia coli Mutants in Microfluidic On-Chip Antibiotic Gradients
Authors: Nagy Krisztina , Dukic Barbara , Hodula Orsolya , Ábrahám Ágnes , Csákvári Eszter , Dér László , Wetherington Miles T. , Noorlag Janneke , Keymer Juan E. , Galajda Péter
Published: March 2022

Spatiotemporal structures and heterogeneities are common in natural habitats, yet their role in the evolution of antibiotic resistance is still to be uncovered. We applied a microfluidic gradient generator device to study the emergence of resistant bacteria in spatial ciprofloxacin gradients. We observed biofilm formation in regions with sub-inhibitory concentrations of antibiotics, which quickly expanded into the high antibiotic regions. In the absence of an explicit structure of the habitat, this multicellular formation led to a spatial structure of the population with local competition and limited migration. Therefore, such structures can function as amplifiers of selection and aid the spread of beneficial mutations. We found that the physical environment itself induces stress-related mutations that later prove beneficial when cells are exposed to antibiotics. This shift in function suggests that exaptation occurs in such experimental scenarios. The above two processes pave the way for the subsequent emergence of highly resistant specific mutations.
Prevalence and Diversity of Staphylococcus aureus and Staphylococcal Enterotoxins in Raw Milk From Northern Portugal
Authors: Oliveira Ricardo , Pinho Eva , Almeida Gonçalo , Azevedo Nuno F. , Almeida Carina
Published: March 2022

Staphylococcus aureus and staphylococcal enterotoxins are a serious public health concern associated with hospital and community-acquired illnesses. Dairy animals frequently shed S. aureus into the milk supply which can lead to food poisoning in humans. This study aims to investigate the prevalence and genetic diversity of S. aureus and staphylococcal enterotoxins in raw milk from the main dairy region of mainland Portugal. S. aureus was found in 53.0% (95% CI: 40.6–65.4%) of 100 raw cow’s milk samples collected from bulk cooling tanks. The highest contamination level was 3.4 log10 CFU.mL–1, and in some samples more than one S. aureus strain was identified. Staphylococcal enterotoxins (SEA-SEE) were detected in one sample. Spa typing revealed 62 distinct S. aureus isolates, being t529 (17.7%, 95% CI: 8.2–27.3%) and t1403 (16.1%, 95% CI: 7.0–25.3%) the predominant types, commonly associated with livestock infection or carriage. The antimicrobial susceptibility test showed that 35.5% of the S. aureus isolates were resistant to at least one antimicrobial agent, with resistance to penicillin being the highest (32.3%, 95% CI: 20.6–43.9%) followed by tetracycline (24.2%, 95% CI: 13.5–34.9%), ciprofloxacin (16.1%, 95% CI: 7.0–25.3%) and chloramphenicol (16.1%, 95% CI: 7.0–25.3%). Moreover, five isolates (8.1%, 95% CI: 1.3–14.8%) were identified as methicillin-resistant S. aureus (MRSA, cefoxitin resistant). Regarding virulence/resistance genes, 46,8% (95% CI: 34.4–59.2%) isolates harbored at least one enterotoxin-encoding gene, and the seg gene was the most frequently detected (41.9%, 95% CI: 29.7–54.2%) followed by the sei (40.3%, 95% CI: 28.1–52.5%), sec (6.5%, 95% CI: 0.3–12.6%), seh (4.8%, 95% CI: 0.0–10.2%), and sea (1.6%, 95% CI: 0.0–4.7%) genes. Five (8.1%, 95% CI: 1.3–14.8%) non-enterotoxigenic isolates carried the mecA gene (corresponding to isolates phenotypically classified as MRSA), and 4.8% (95% CI: 0.0–10.2%) enterotoxigenic strains also had the tsst-1 gene. Our study confirm that raw milk can be a zoonotic source of S. aureus, including enterotoxigenic and MRSA strains. Furthermore, the majority of enterotoxigenic isolates were found to contain genes encoding SEs (SEG, SEH and SEI) not routinely screened. This shows the need for a broader SE screening in food safety control, as well as the relevance of risk mitigation measures to control S. aureus transmission along the food chain in Portugal.
Gold-Derived Molecules as New Antimicrobial Agents
Authors: Ratia Carlos , Soengas Raquel G. , Soto Sara M.
Published: March 2022

Antimicrobial resistance is considered one of the three most important health problems by the World Health Organization. The emergence and spread of an increasing number of antimicrobial-resistant microorganisms make this a worldwide problem. Antibiotic-resistant bacteria are estimated to be the cause of 33,000 deaths in Europe and 700,000 worldwide each year. It is estimated that in 2050 bacterial infections will cause 10 million deaths across the globe. This problem is concomitant with a decrease in the investment and, therefore, the discovery and marketing of new antibiotics. Recently, there have been tremendous efforts to find new effective antimicrobial agents. Gold complexes, with their broad-spectrum antimicrobial activities and unique modes of action, are particularly relevant among several families of derivatives that have been investigated. This mini review revises the role of gold-derived molecules as antibacterial agents.
Mechanical Wiping Increases the Efficacy of Liquid Disinfectants on SARS-CoV-2
Authors: Sloan Angela , Kasloff Samantha B. , Cutts Todd
Published: March 2022

High-touch environmental surfaces are acknowledged as potential sources of pathogen transmission, particularly in health care settings where infectious agents may be readily abundant. Methods of disinfecting these surfaces often include direct application of a chemical disinfectant or simply wiping the surface with a disinfectant pre-soaked wipe (DPW). In this study, we examine the ability of four disinfectants, ethanol (EtOH), sodium hypochlorite (NaOCl), chlorine dioxide (ClO2), and potassium monopersulfate (KMPS), to inactivate SARS-CoV-2 on a hard, non-porous surface, assessing the effects of concentration and contact time. The efficacy of DPWs to decontaminate carriers spiked with SARS-CoV-2, as well as the transferability of the virus from used DPWs to clean surfaces, is also assessed. Stainless steel carriers inoculated with approximately 6 logs of SARS-CoV-2 prepared in a soil load were disinfected within 5 min through exposure to 66.5% EtOH, 0.5% NaOCl, and 1% KMPS. The addition of mechanical wiping using DPWs impregnated with these biocides rendered the virus inactive almost immediately, with no viral transfer from the used DPW to adjacent surfaces. Carriers treated with 100 ppm of ClO2 showed a significant amount of viable virus remaining after 10 min of biocide exposure, while the virus was only completely inactivated after 10 min of treatment with 500 ppm of ClO2. Wiping SARS-CoV-2-spiked carriers with DPWs containing either concentration of ClO2 for 5 s left significant amounts of viable virus on the carriers. Furthermore, higher titers of infectious virus retained on the ClO2-infused DPWs were transferred to uninoculated carriers immediately after wiping. Overall, 66.5% EtOH, 0.5% NaOCl, and 1% KMPS appear to be highly effective biocidal agents against SARS-CoV-2, while ClO2 formulations are much less efficacious.
Inflammatory Bowel Disease and COVID-19: How Microbiomics and Metabolomics Depict Two Sides of the Same Coin
Authors: Cortes Gian Mario , Marcialis Maria Antonietta , Bardanzellu Flaminia , Corrias Angelica , Fanos Vassilios , Mussap Michele
Published: March 2022

The integrity of the gastrointestinal tract structure and function is seriously compromised by two pathological conditions sharing, at least in part, several pathogenetic mechanisms: inflammatory bowel diseases (IBD) and coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. IBD and COVID-19 are marked by gut inflammation, intestinal barrier breakdown, resulting in mucosal hyperpermeability, gut bacterial overgrowth, and dysbiosis together with perturbations in microbial and human metabolic pathways originating changes in the blood and fecal metabolome. This review compared the most relevant metabolic and microbial alterations reported from the literature in patients with IBD with those in patients with COVID-19. In both diseases, gut dysbiosis is marked by the prevalence of pro-inflammatory bacterial species and the shortfall of anti-inflammatory species; most studies reported the decrease in Firmicutes, with a specific decrease in obligately anaerobic producers short-chain fatty acids (SCFAs), such as Faecalibacterium prausnitzii. In addition, Escherichia coli overgrowth has been observed in IBD and COVID-19, while Akkermansia muciniphila is depleted in IBD and overexpressed in COVID-19. In patients with COVID-19, gut dysbiosis continues after the clearance of the viral RNA from the upper respiratory tract and the resolution of clinical symptoms. Finally, we presented and discussed the impact of gut dysbiosis, inflammation, oxidative stress, and increased energy demand on metabolic pathways involving key metabolites, such as tryptophan, phenylalanine, histidine, glutamine, succinate, citrate, and lipids.
Vaccines as a Strategy to Control Trichinellosis
Authors: Tang Bin , Li Jian , Li Tingting , Xie Yiting , Guan Wei , Zhao Yanqing , Yang Shuguo , Liu Mingyuan , Xu Daoxiu
Published: March 2022

Trichinellosis caused by Trichinella spiralis is a worldwide food-borne parasitic zoonosis. Several approaches have been performed to control T. spiralis infection, including veterinary vaccines, which contribute to improving animal health and increasing public health by preventing the transmission of trichinellosis from animals to humans. In the past several decades, many vaccine studies have been performed in effort to control T. spiralis infection by reducing the muscle larvae and adult worms burden. Various candidate antigens, selected from excretory-secretory (ES) products and different functional proteins involved in the process of establishing infection have been investigated in rodent or swine models to explore their protective effect against T. spiralis infection. Moreover, different types of vaccines have been developed to improve the protective effect against T. spiralis infection in rodent or swine models, such as live attenuated vaccines, natural antigen vaccines, recombinant protein vaccines, DNA vaccines, and synthesized epitope vaccines. However, few studies of T. spiralis vaccines have been performed in pigs, and future research should focus on exploring the protective effect of different types of vaccines in swine models. Here, we present an overview of the strategies for the development of effective T. spiralis vaccines and summarize the factors of influencing the effectiveness of vaccines. We also discuss several propositions in improving the effectiveness of vaccines and may provide a route map for future T. spiralis vaccines development.
Comprehensive Analysis of Pyroptosis-Related Genes and Tumor Microenvironment Infiltration Characterization in Papillary Renal Cell Carcinoma
Authors: Zhang Chiyu , Huang Ruizhen , Xi Xiaoqing
Published: March 2022

Background: Immunotherapy has emerged as an important technique for treating a variety of cancers. The dynamic interplay between tumor cells and invading lymphocytes in the tumor microenvironment is responsible for the good response to immunotherapy (TME). Pyroptosis, or inflammation-induced cell death, is closely linked to a number of cancers. However, in papillary renal cell carcinoma (KIRP), the association between pyroptosis and clinical prognosis, immune cell infiltration, and immunotherapy impact remains unknown.

Methods: We carefully investigated the link between pyroptosis and tumor growth, prognosis, and immune cell infiltration by evaluating 52 pyroptosis-related genes. The PRG score was utilized to measure a single tumor patient’s pyroptosis pattern. After that, we looked at how well these values predicted prognoses and therapy responses in KIRP.

Results: We discovered that PRG differences between subgroups were linked to clinical and pathological aspects, prognosis, and TME in two separate genetic subtypes. After that, a PRG score for estimating overall survival (OS) was developed, and its predictive potential in KIRP patients was confirmed. As a result, we developed a very precise nomogram to improve the PRG score’s clinical usefulness. A low PRG score, which is determined by mutation load and immune activation, suggests a good chance of survival. Furthermore, the PRG score was linked to chemotherapeutic drug sensitivity in a substantial way.

Conclusions: The possible functions of PRGs in the TME, clinical and pathological characteristics, and prognosis were established in our thorough investigation of PRGs in KIRP. These results might help us better understand PRGs in KIRP and offer a new avenue for prognostic evaluation and the development of more effective immunotherapy treatments.