bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable Marine Aquaponics: Effects of Shrimp to Plant Ratios and C/N Ratios
Authors: Chu Yu-Ting , Brown Paul B.
Published: December 2021

Integrated aquaponic food production systems are capable of producing more food on less land using less water than conventional food systems, and marine systems offer the potential of conserving freshwater resources. However, there have been few evaluations of species combinations or operational parameters in marine aquaponics. The goal of this experiment was evaluation of stocking density ratio of Pacific whiteleg shrimp (Litopenaeus vannamei) to three edible halophytes (Atriplex hortensis, Salsola komarovii, and Plantago coronopus) with two C/N ratios in a 3 × 2 factorial design. There were three stocking density ratios (shrimp: plant), 2:1, 3:1, and 5:1; and two C/N ratios, 12 and 15. The results indicated that stocking density ratio exerted a significant impact on shrimp growth. Shrimp reared in 2:1 and 3:1 treatments had better growth performance. In contrast, plants were affected by both stocking density ratio and C/N ratio. Halophytes grown in stocking density ratios of 3:1 and 5:1 with a C/N ratio of 15 had better growth performance and nutrient content. The concentrations of TAN and NO2– were below 0.2 mg/L throughout the experiment, including the higher stocking density ratio treatments. In conclusion, the stocking density ratio of 3:1 with a C/N ratio of 15 was suggested as the optimal condition for the operation of marine aquaponics in which whiteleg shrimp and the three halophytes are target crops.
Propagation of the 2014–2016 Northeast Pacific Marine Heatwave Through the Salish Sea
Authors: Khangaonkar Tarang , Nugraha Adi , Yun Su Kyong , Premathilake Lakshitha , Keister Julie E. , Bos Julia
Published: December 2021

Effects and impacts of the Northeast Pacific marine heatwave of 2014–2016 on the inner coastal estuarine waters of the Salish Sea were examined using a combination of monitoring data and an established three-dimensional hydrodynamic and biogeochemical model of the region. The anomalous high temperatures reached the U.S. Pacific Northwest continental shelf toward the end of 2014 and primarily entered the Salish Sea waters through an existing strong estuarine exchange. Elevated temperatures up to + 2.3°C were observed at the monitoring stations throughout 2015 and 2016 relative to 2013 before dissipating in 2017. The hydrodynamic and biogeochemical responses to this circulating high-temperature event were examined using the Salish Sea Model over a 5-year window from 2013 to 2017. Responses of conventional water-quality indicator variables, such as temperature and salinity, nutrients and phytoplankton, zooplankton, dissolved oxygen, and pH, were evaluated relative to a baseline without the marine heatwave forcing. The simulation results relative to 2014 show an increase in biological activity (+14%, and 6% Δ phytoplankton biomass, respectively) during the peak heatwave year 2015 and 2016 propagating toward higher zooplankton biomass (+14%, +18% Δ mesozooplankton biomass). However, sensitivity tests show that this increase was a direct result of higher freshwater and associated nutrient loads accompanied by stronger estuarine exchange with the Pacific Ocean rather than warming due to the heatwave. Strong vertical circulation and mixing provided mitigation with only ≈+0.6°C domain-wide annual average temperature increase within Salish Sea, and served as a physical buffer to keep waters cooler relative to the continental shelf during the marine heatwave.
Cefiderocol: An Overview of Its in-vitro and in-vivo Activity and Underlying Resistant Mechanisms
Authors: Yao Jiahui , Wang Jin , Chen Mengli , Cai Yun
Published: December 2021

Treatment of multidrug-resistant (MDR) Gram-negative bacteria (GNB) infections has led to a global public health challenging due to the bacterial resistance and limited choices of antibiotics. Cefiderocol (CFDC), a novel siderophore cephalosporin possessed unique drug delivery systems and stability to β-lactamases, has the potential to become first-line therapy for most aggressive MDR Gram-negative pathogens infection. However, there have been reports of drug resistance in the course of using CFDC. This study provides an overview of the in-vitro and in-vivo activity of CFDC and potential resistance mechanism was also summarized. In general, CFDC shows excellent activity against a broad range of MDR GNB pathogens including Enterobacteriaceae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. The expressions of metallo-β-lactamases such as inosine 5'-monophosphate (IMP), Verona integron-mediated metallo-β-lactamase (VIM), and New Delhi metallo-β-lactamase (NDM) are associated with a higher resistance rate of CFDC. Carbapenem-resistant phenotype has little effect on the resistance rate, although the acquisition of a particular carbapenemase may affect the susceptibility of the pathogens to CFDC. For potential resistance mechanism, mutations in β-lactamases and TonB-dependent receptors, which assist CFDC entering bacteria, would increase a minimum inhibitory concentration (MIC)90 value of CFDC against MDR pathogens. Since the development of CFDC, resistance during its utilization has been reported thus, prudent clinical applications are still necessary to preserve the activity of CFDC.
Pyramid-Net: Intra-layer Pyramid-Scale Feature Aggregation Network for Retinal Vessel Segmentation
Authors: Zhang Jiawei , Zhang Yanchun , Qiu Hailong , Xie Wen , Yao Zeyang , Yuan Haiyun , Jia Qianjun , Wang Tianchen , Shi Yiyu , Huang Meiping , Zhuang Jian , Xu Xiaowei
Published: December 2021

Retinal vessel segmentation plays an important role in the diagnosis of eye-related diseases and biomarkers discovery. Existing works perform multi-scale feature aggregation in an inter-layer manner, namely inter-layer feature aggregation. However, such an approach only fuses features at either a lower scale or a higher scale, which may result in a limited segmentation performance, especially on thin vessels. This discovery motivates us to fuse multi-scale features in each layer, intra-layer feature aggregation, to mitigate the problem. Therefore, in this paper, we propose Pyramid-Net for accurate retinal vessel segmentation, which features intra-layer pyramid-scale aggregation blocks (IPABs). At each layer, IPABs generate two associated branches at a higher scale and a lower scale, respectively, and the two with the main branch at the current scale operate in a pyramid-scale manner. Three further enhancements including pyramid inputs enhancement, deep pyramid supervision, and pyramid skip connections are proposed to boost the performance. We have evaluated Pyramid-Net on three public retinal fundus photography datasets (DRIVE, STARE, and CHASE-DB1). The experimental results show that Pyramid-Net can effectively improve the segmentation performance especially on thin vessels, and outperforms the current state-of-the-art methods on all the adopted three datasets. In addition, our method is more efficient than existing methods with a large reduction in computational cost. We have released the source code at https://github.com/JerRuy/Pyramid-Net.
Structural Lesion Progression of the Sacroiliac Joint and Clinical Features in axSpA During TNFi Reduction: A Retrospective Cohort Study
Authors: Mo Qian , Dong Yuanji , Ye Cong , Zhong Jixin , Cai Shaozhe , Wang Min , Dong Lingli
Published: December 2021

Objective: In the clinic, some patients with axial spondyloarthritis (axSpA) have to reduce tumor necrosis factor inhibitor (TNFi) for various reasons. However, there are few studies about how to balance the relapse and TNFi reduction. Here we retrospectively analyzed the structural progression of the sacroiliac joint (SIJ) and clinical features in axSpA during TNFi reduction.

Methods: A total of 108 patients with axSpA who followed up for 2 years and completed at least baseline, 12-month, and 24-month MRI scans of SIJ were divided into the tapering group (n = 63) and withdrawal group (n = 45) according to whether TNFi was stopped. We divided 2 years into five intervals, calculating the average dose quotient (DQ) for each of 540 intervals from 108 patients. By using generalized estimation equations with inverse probability of treatment weighting, we investigated the unbiased effects of average DQ on structural progression and treatment response.

Results: The disease activity (such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, and ASDAS-ESR) and relapse rate were lower in the tapering group at 12 and 24 months (p < 0.05). Δerosion (β = −0.0100, p = 0.00026) and Δthe Spondyloarthritis Research Consortium of Canada (SPARCC; β = −0.0959, p < 0.0001) were negatively correlated with average DQ. The average DQ 30 (74.8%, 80.0%) or 41.6 (76.5%, 83%) was best to discriminate the status of treatment response or the status of bone marrow edema, but considering operability, the average DQ 25 (78.0%, 63.3%) was also acceptable especially for patients with HLA-B27 negative and non-severe fat metaplasia.

Conclusion: Complete TNFi withdrawal was not recommended. Our study provided a referable strategy (tapering then maintained the average DQ over 30 or even 25) for patients who need TNFi reduction. Higher dose usage of TNFi was associated with a slower erosion progression of SIJ.
Comparative Study of Intestinal Microbiota Composition of Six Edible Fish Species
Authors: Ofek Tamir , Lalzar Maya , Laviad-Shitrit Sivan , Izhaki Ido , Halpern Malka
Published: December 2021

Intensive freshwater aquaculture in the Spring Valley, Israel, is implemented mainly in earthen fishponds and reservoirs that are stocked with a variety of edible fish species. Here we sampled six different healthy fish species from these intensive aquacultures. The fish were hybrid striped bass, European bass, red drum (all carnivores), hybrid tilapia, flathead grey mullet (both herbivores), and common carp (an omnivore). Significant differences were found among the intestinal microbiota of the six studied fish species. The microbiota composition diversity was strongly related to the trophic level of the fish, such that there was a significant difference between the carnivore and the herbivore species, while the omnivore species was not significantly different from either group. The most abundant genus in the majority of the fishes’ intestinal microbiota was Cetobacterium. Furthermore, we found that beside Cetobacterium, a unique combination of taxa with relative abundance >10% characterized the intestine microbiota of each fish species: unclassified Mycoplasmataceae, Aeromonas, and Vibrio (hybrid striped bass); Turicibacter and Clostridiaceae 1 (European bass); Vibrio (red drum); ZOR0006—Firmicutes (hybrid tilapia); unclassified Mycoplasmataceae and unclassified Vibrionaceae (flathead grey mullet); and Aeromonas (common carp). We conclude that each fish species has a specific bacterial genera combination that characterizes it. Moreover, diet and the trophic level of the fish have a major influence on the gut microbiota of healthy fish that grow in intensive freshwater aquaculture.
Characteristics of Microbial Community and Function With the Succession of Mangroves
Authors: Mai Zhimao , Ye Mai , Wang Youshao , Foong Swee Yeok , Wang Lin , Sun Fulin , Cheng Hao
Published: December 2021

In this study, 16S high-throughput and metagenomic sequencing analyses were employed to explore the changes in microbial community and function with the succession of mangroves (Sonneratia alba, Rhizophora apiculata, and Bruguiera parviflora) along the Merbok river estuary in Malaysia. The sediments of the three mangroves harbored their own unique dominant microbial taxa, whereas R. apiculata exhibited the highest microbial diversity. In general, Gammaproteobacteria, Actinobacteria, Alphaproteobacteria, Deltaproteobacteria, and Anaerolineae were the dominant microbial classes, but their abundances varied significantly among the three mangroves. Principal coordinates and redundancy analyses revealed that the specificity of the microbial community was highly correlated with mangrove populations and environmental factors. The results further showed that R. apiculata exhibited the highest carbon-related metabolism, coinciding with the highest organic carbon and microbial diversity. In addition, specific microbial taxa, such as Desulfobacterales and Rhizobiales, contributed the highest functional activities related to carbon metabolism, prokaryote carbon fixation, and methane metabolism. The present results provide a comprehensive understanding of the adaptations and functions of microbes in relation to environmental transition and mangrove succession in intertidal regions. High microbial diversity and carbon metabolism in R. apiculata might in turn facilitate and maintain the formation of climax mangroves in the middle region of the Merbok river estuary.
Recent Advances in Bunyavirus Reverse Genetics Research: Systems Development, Applications, and Future Perspectives
Authors: Ren Fuli , Shen Shu , Wang Qiongya , Wei Gang , Huang Chaolin , Wang Hualin , Ning Yun-Jia , Zhang Ding-Yu , Deng Fei
Published: December 2021

Bunyaviruses are members of the Bunyavirales order, which is the largest group of RNA viruses, comprising 12 families, including a large group of emerging and re-emerging viruses. These viruses can infect a wide variety of species worldwide, such as arthropods, protozoans, plants, animals, and humans, and pose substantial threats to the public. In view of the fact that a better understanding of the life cycle of a highly pathogenic virus is often a precondition for developing vaccines and antivirals, it is urgent to develop powerful tools to unravel the molecular basis of the pathogenesis. However, biosafety level −3 or even −4 containment laboratory is considered as a necessary condition for working with a number of bunyaviruses, which has hampered various studies. Reverse genetics systems, including minigenome (MG), infectious virus-like particle (iVLP), and infectious full-length clone (IFLC) systems, are capable of recapitulating some or all steps of the viral replication cycle; among these, the MG and iVLP systems have been very convenient and effective tools, allowing researchers to manipulate the genome segments of pathogenic viruses at lower biocontainment to investigate the viral genome transcription, replication, virus entry, and budding. The IFLC system is generally developed based on the MG or iVLP systems, which have facilitated the generation of recombinant infectious viruses. The MG, iVLP, and IFLC systems have been successfully developed for some important bunyaviruses and have been widely employed as powerful tools to investigate the viral replication cycle, virus–host interactions, virus pathogenesis, and virus evolutionary process. The majority of bunyaviruses is generally enveloped negative-strand RNA viruses with two to six genome segments, of which the viruses with bipartite and tripartite genome segments have mostly been characterized. This review aimed to summarize current knowledge on reverse genetic studies of representative bunyaviruses causing severe diseases in humans and animals, which will contribute to the better understanding of the bunyavirus replication cycle and provide some hints for developing designed antivirals.
Bacterial Lipoprotein Posttranslational Modifications. New Insights and Opportunities for Antibiotic and Vaccine Development
Authors: Smithers Luke , Olatunji Samir , Caffrey Martin
Published: December 2021

Lipoproteins are some of the most abundant proteins in bacteria. With a lipid anchor to the cell membrane, they function as enzymes, inhibitors, transporters, structural proteins, and as virulence factors. Lipoproteins activate the innate immune system and have biotechnological applications. The first lipoprotein was described by Braun and Rehn in 1969. Up until recently, however, work on lipoproteins has been sluggish, in part due to the challenges of handling proteins that are anchored to membranes by covalently linked lipids or are membrane integral. Activity in the area has quickened of late. In the past 5 years, high-resolution structures of the membrane enzymes of the canonical lipoprotein synthesis pathway have been determined, new lipoprotein types have been discovered and the enzymes responsible for their synthesis have been characterized biochemically. This has led to a flurry of activity aimed at developing novel antibiotics targeting these enzymes. In addition, surface exposed bacterial lipoproteins have been utilized as candidate vaccine antigens, and their potential to act as self-adjuvanting antigens is increasingly recognized. A summary of the latest developments in lipoproteins and their synthesis, as well as how this information is being exploited for therapeutic purposes is presented here.
Experimental Treatment of Hazardous Ash Waste by Microbial Consortium Aspergillus niger and Chlorella sp.: Decrease of the Ni Content and Identification of Adsorption Sites by Fourier-Transform Infrared Spectroscopy
Authors: Šimonovičová Alexandra , Takáčová Alžbeta , Šimkovic Ivan , Nosalj Sanja
Published: December 2021

Despite the negative impact on the environment, incineration is one of the most commonly used methods for dealing with waste. Besides emissions, the production of ash, which usually shows several negative properties, such as a higher content of hazardous elements or strongly alkaline pH, is problematic from an environmental viewpoint as well. The subject of our paper was the assessment of biosorption of Ni from ash material by a microbial consortium of Chlorella sp. and Aspergillus niger. The solid substrate represented a fraction of particles of size <0.63 mm with a Ni content of 417 mg kg–1. We used a biomass consisting of two different organisms as the sorbent: a non-living algae culture of Chlorella sp. (an autotrophic organism) and the microscopic filamentous fungus A. niger (a heterotrophic organism) in the form of pellets. The experiments were conducted under static conditions as well as with the use of shaker (170 rpm) with different modifications: solid substrate, Chlorella sp. and pellets of A. niger; solid substrate and pellets of A. niger. The humidity-temperature conditions were also changed. Sorption took place under dry and also wet conditions (with distilled water in a volume of 30–50 ml), partially under laboratory conditions at a temperature of 25°C as well as in the exterior. The determination of the Ni content was done using inductively coupled plasma optical emission spectrometry (ICP-OES). The removal of Ni ranged from 13.61% efficiency (Chlorella sp., A. niger with the addition of 30 ml of distilled water, outdoors under static conditions after 48 h of the experiment) to 46.28% (Chlorella sp., A. niger with the addition of 30 ml of distilled water, on a shaker under laboratory conditions after 48 h of the experiment). For the purpose of analyzing the representation of functional groups in the microbial biomass and studying their interaction with the ash material, we used Fourier-transform infrared (FTIR) spectroscopy. We observed that the amount of Ni adsorbed positively correlates with absorbance in the spectral bands where we detect the vibrations of several organic functional groups. These groups include hydroxyl, aliphatic, carbonyl, carboxyl and amide structural units. The observed correlations indicate that, aside from polar and negatively charged groups, aliphatic or aromatic structures may also be involved in sorption processes due to electrostatic attraction. The correlation between absorbance and the Ni content reached a maximum in amide II band (r = 0.9; P < 0.001), where vibrations of the C=O, C–N, and N–H groups are detected. The presented results suggest that the simultaneous use of both microorganisms in biosorption represents an effective method for reducing Ni content in a solid substrate, which may be useful as a partial process for waste disposal.
Developments in Vaccination for Herpes Simplex Virus
Authors: Krishnan Rohini , Stuart Patrick M.
Published: December 2021

Herpes simplex virus (HSV) is an alpha herpes virus, with two subtypes: HSV-1 and HSV-2. HSV is one of the most prevalent sexually transmitted infections. It is the cause of severe neonatal infections and a leading cause of infectious blindness in the Western world. As of 2016, 13.2% of the global population ages 15–49 were existing with HSV-2 infection and 66.6% with HSV-1. This high prevalence of disease and the fact that resistance to current therapies is on the rise makes it imperative to develop and discover new methods of HSV prevention and management. Among the arsenal of therapies/treatments for this virus has been the development of a prophylactic or therapeutic vaccine to prevent the complications of HSV reactivation. Our current understanding of the immune responses involved in latency and reactivation provides a unique challenge to the development of vaccines. There are no approved vaccines currently available for either prophylaxis or therapy. However, there are various promising candidates in the pre-clinical and clinical phases of study. Vaccines are being developed with two broad focuses: preventative and therapeutic, some with a dual use as both immunotherapeutic and prophylactic. Within this article, we will review the current guidelines for the treatment of herpes simplex infections, our understanding of the immunological pathways involved, and novel vaccine candidates in development.
Early Life Stress Promotes Heroin Seeking But Does Not Alter the Excitability of Insular Pyramidal Cells Targeting the Nucleus Accumbens
Authors: Leyrer-Jackson Jonna M. , Overby Paula F. , Nagy Erin K. , Olive M. Foster
Published: December 2021

A number of retrospective studies have demonstrated adverse childhood experiences are associated with increased vulnerability to substance use disorders, including opioid use disorders (OUDs). These adverse childhood experiences, also referred to as early life stress (ELS), can be modeled in laboratory animals by various paradigms including limited bedding and nesting (LBN) procedures. Studies using rodent models of ELS have been shown to recapitulate various aspects of OUDs, including relapse propensity and perseverance of drug-seeking behavior. In the current study, we utilized the LBN paradigm to explore potential effects on heroin self-administration, extinction, and relapse-like behaviors in male and female rats. We also utilized in vitro whole-cell electrophysiology to examine the effects of LBN and repeated heroin administration on the excitability of pyramidal neurons in the anterior insular cortex (AIC) projecting to the nucleus accumbens core (NAc), as recent studies suggest that this circuit may mediate various aspects of OUDs and may be compromised as a result of either ELS or OUDs. We observed that compared to control animals, rats exposed to LBN conditions during postnatal days 2–9 showed increased breakpoints for heroin self-administration under a progressive ratio schedule of reinforcement, impaired extinction of heroin-seeking behavior, and increased reinstatement of heroin-seeking behavior induced by heroin-associated cues. No effect of LBN rearing conditions were observed on the acquisition and maintenance of heroin self-administration, and no sex differences in heroin intake were observed. LBN and control reared animals showed no differences in the excitability of AIC-NAc pyramidal neurons, but animals treated with repeated heroin showed decreased excitability of these neurons through a significant increase in rheobase and reduction in action potentials induced by depolarizing currents. Together, these results suggest that ELS exposure produces exacerbations of heroin seeking behavior without parallel effects on AIC-NAc excitability, although heroin itself reduces the excitability of these neurons.
Laminar Organization of the Entorhinal Cortex in Macaque Monkeys Based on Cell-Type-Specific Markers and Connectivity
Authors: Ohara Shinya , Yoshino Rintaro , Kimura Kei , Kawamura Taichi , Tanabe Soshi , Zheng Andi , Nakamura Shinya , Inoue Ken-ichi , Takada Masahiko , Tsutsui Ken-Ichiro , Witter Menno P.
Published: December 2021

The entorhinal cortex (EC) is a major gateway between the hippocampus and telencephalic structures, and plays a critical role in memory and navigation. Through the use of various molecular markers and genetic tools, neuron types constituting EC are well studied in rodents, and their layer-dependent distributions, connections, and functions have also been characterized. In primates, however, such cell-type-specific understandings are lagging. To bridge the gap between rodents and primates, here we provide the first cell-type-based global map of EC in macaque monkeys. The laminar organization of the monkey EC was systematically examined and compared with that of the rodent EC by using immunohistochemistry for molecular markers which have been well characterized in the rodent EC: reelin, calbindin, and Purkinje cell protein 4 (PCP4). We further employed retrograde neuron labeling from the nucleus accumbens and amygdala to identify the EC output layer. This cell-type-based approach enabled us to apply the latest laminar definition of rodent EC to monkeys. Based on the similarity of the laminar organization, the monkey EC can be divided into two subdivisions: rostral and caudal EC. These subdivisions likely correspond to the lateral and medial EC in rodents, respectively. In addition, we found an overall absence of a clear laminar arrangement of layer V neurons in the rostral EC, unlike rodents. The cell-type-based architectural map provided in this study will accelerate the application of genetic tools in monkeys for better understanding of the role of EC in memory and navigation.
New Trends and Most Promising Therapeutic Strategies for Epilepsy Treatment
Authors: Riva Antonella , Golda Alice , Balagura Ganna , Amadori Elisabetta , Vari Maria Stella , Piccolo Gianluca , Iacomino Michele , Lattanzi Simona , Salpietro Vincenzo , Minetti Carlo , Striano Pasquale
Published: December 2021

Background: Despite the wide availability of novel anti-seizure medications (ASMs), 30% of patients with epilepsy retain persistent seizures with a significant burden in comorbidity and an increased risk of premature death. This review aims to discuss the therapeutic strategies, both pharmacological and non-, which are currently in the pipeline.

Methods: PubMed, Scopus, and EMBASE databases were screened for experimental and clinical studies, meta-analysis, and structured reviews published between January 2018 and September 2021. The terms “epilepsy,” “treatment” or “therapy,” and “novel” were used to filter the results.

Conclusions: The common feature linking all the novel therapeutic approaches is the spasmodic rush toward precision medicine, aiming at holistically evaluating patients, and treating them accordingly as a whole. Toward this goal, different forms of intervention may be embraced, starting from the choice of the most suitable drug according to the type of epilepsy of an individual or expected adverse effects, to the outstanding field of gene therapy. Moreover, innovative insights come from in-vitro and in-vivo studies on the role of inflammation and stem cells in the brain. Further studies on both efficacy and safety are needed, with the challenge to mature evidence into reliable assets, ameliorating the symptoms of patients, and answering the challenges of this disease.
Distinctive Mediating Effects of Subcortical Structure Changes on the Relationships Between Amyloid or Vascular Changes and Cognitive Decline
Authors: Jung Na-Yeon , Shin Jeong-Hyeon , Kim Hee Jin , Jang Hyemin , Moon Seung Hwan , Kim Seung Joo , Kim Yeshin , Cho Soo Hyun , Kim Ko Woon , Kim Jun Pyo , Jung Young Hee , Kim Sung Tae , Kim Eun-Joo , Na Duk L. , Vogel Jacob W. , Lee Sangjin , Seong Joon-Kyung , Seo Sang Won
Published: December 2021

Objective: We investigated the mediation effects of subcortical volume change in the relationship of amyloid beta (Aβ) and lacune with cognitive function in patients with mild cognitive impairment (MCI).

Methods: We prospectively recruited 101 patients with MCI who were followed up with neuropsychological tests, MRI, or Pittsburgh compound B (PiB) PET for 3 years. The mediation effect of subcortical structure on the association of PiB or lacunes with cognitive function was analyzed using mixed effects models.

Results: Volume changes in the amygdala and hippocampus partially mediated the effect of PiB changes on memory function (direct effect = −0.168/−0.175, indirect effect = −0.081/−0.077 for amygdala/hippocampus) and completely mediated the effect of PiB changes on clinical dementia rating scale sum of the box (CDR-SOB) (indirect effect = 0.082/0.116 for amygdala/hippocampus). Volume changes in the thalamus completely mediated the effect of lacune on memory, frontal executive functions, and CDR-SOB (indirect effect = −0.037, −0.056, and 0.047, respectively).

Conclusions: Our findings provide a better understanding of the distinct role of subcortical structures in the mediation of the relationships of amyloid or vascular changes with a decline in specific cognitive domains.
MS-MDA: Multisource Marginal Distribution Adaptation for Cross-Subject and Cross-Session EEG Emotion Recognition
Authors: Chen Hao , Jin Ming , Li Zhunan , Fan Cunhang , Li Jinpeng , He Huiguang
Published: December 2021

As an essential element for the diagnosis and rehabilitation of psychiatric disorders, the electroencephalogram (EEG) based emotion recognition has achieved significant progress due to its high precision and reliability. However, one obstacle to practicality lies in the variability between subjects and sessions. Although several studies have adopted domain adaptation (DA) approaches to tackle this problem, most of them treat multiple EEG data from different subjects and sessions together as a single source domain for transfer, which either fails to satisfy the assumption of domain adaptation that the source has a certain marginal distribution, or increases the difficulty of adaptation. We therefore propose the multi-source marginal distribution adaptation (MS-MDA) for EEG emotion recognition, which takes both domain-invariant and domain-specific features into consideration. First, we assume that different EEG data share the same low-level features, then we construct independent branches for multiple EEG data source domains to adopt one-to-one domain adaptation and extract domain-specific features. Finally, the inference is made by multiple branches. We evaluate our method on SEED and SEED-IV for recognizing three and four emotions, respectively. Experimental results show that the MS-MDA outperforms the comparison methods and state-of-the-art models in cross-session and cross-subject transfer scenarios in our settings. Codes athttps://github.com/VoiceBeer/MS-MDA.
Acute Response and Neuroprotective Role of Myo/Nog Cells Assessed in a Rat Model of Focal Brain Injury
Authors: Joseph-Pauline Sahlia , Morrison Nathan , Braccia Michael , Payne Alana , Gugerty Lindsay , Mostoller Jesse , Lecker Paul , Tsai E-jine , Kim Jessica , Martin Mark , Brahmbhatt Rushil , Gorski Grzegorz , Gerhart Jacquelyn , George-Weinstein Mindy , Stone Jonathan , Purushothuman Sivaraman , Bravo-Nuevo Arturo
Published: December 2021

Focal brain injury in the form of a needlestick (NS) results in cell death and induces a self-protective response flanking the lesion. Myo/Nog cells are identified by their expression of bone morphogenetic protein inhibitor Noggin, brain-specific angiogenesis inhibitor 1 (BAI1) and the skeletal muscle specific transcription factor MyoD. Myo/Nog cells limit cell death in two forms of retinopathy. In this study, we examined the acute response of Myo/Nog cells to a NS lesion that extended from the rat posterior parietal cortex to the hippocampus. Myo/Nog cells were identified with antibodies to Noggin and BAI1. These cells were the primary source of both molecules in the uninjured and injured brain. One day after the NS, the normally small population of Myo/Nog cells expanded approximately eightfold within a 1 mm area surrounding the lesion. Myo/Nog cells were reduced by approximately 50% along the lesion with an injection of the BAI1 monoclonal antibody and complement. The number of dying cells, identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), was unchanged at this early time point in response to the decrease in Myo/Nog cells. However, increasing the number of Myo/Nog cells within the lesion by injecting BAI1-positive (+) cells isolated from the brains of other animals, significantly reduced cell death and increased the number of NeuN+ neurons compared to brains injected with phosphate buffered saline or exogenous BAI1-negative cells. These findings demonstrate that Myo/Nog cells rapidly react to injury within the brain and increasing their number within the lesion is neuroprotective.
Unpleasant Odors Affect Alerting Attention in Young Men: An Event-Related Potential Study Using the Attention Network Test
Authors: Zhang Minggang , Gong Xinyu , Jia Jiafeng , Wang Xiaochun
Published: December 2021

Attention to unpleasant odors is crucial for human safety because they may signal danger; however, whether odor concentration also plays a role remains debated. Here, we explored the effects of two concentrations of pleasant and unpleasant odors on the attention network, comprising the alerting, orienting, and executive control networks. Behavioral responses were examined using the Attention Network Test, while electrophysiological responses were examined by assessing N1 and N2 amplitudes in 30 young men. We found that irrespective of odor concentration, an unpleasant odor induced larger cue-related N1 and N2 amplitudes in the alerting and executive control networks at occipital and frontal electrode sites and that was only paralleled by a reduced behavioral response time of cue-related trails in the alerting network. Thus, our results do not provide supporting evidence for a concentration-dependent effect, but they do suggest that more attentional resources are allocated to alerting-relevant stimuli to improve behavioral response times to a potential threat in young men.
Failure to Upregulate the RNA Binding Protein ZBP After Injury Leads to Impaired Regeneration in a Rodent Model of Diabetic Peripheral Neuropathy
Authors: Jones James I. , Costa Christopher J. , Cooney Caitlin , Goldberg David C. , Ponticiello Matthew , Cohen Melanie W. , Mellado Wilfredo , Ma Thong C. , Willis Dianna E.
Published: December 2021

Most diabetes patients eventually suffer from peripheral nerve degeneration. Unfortunately, there is no treatment for the condition and its mechanisms are not well understood. There is, however, an emerging consensus that the inability of peripheral nerves to regenerate normally after injury contributes to the pathophysiology. We have previously shown that regeneration of peripheral axons requires local axonal translation of a pool of axonal mRNAs and that the levels and members of this axonal mRNA pool are altered in response to injury. Here, we show that following sciatic nerve injury in a streptozotocin rodent model of type I diabetes, this mobilization of RNAs into the injured axons is attenuated and correlates with decreased axonal regeneration. This failure of axonal RNA localization results from decreased levels of the RNA binding protein ZBP1. Over-expression of ZBP1 rescues the in vitro growth defect in injured dorsal root ganglion neurons from diabetic rodents. These results provide evidence that decreased neuronal responsiveness to injury in diabetes is due to a decreased ability to alter the pool of axonal mRNAs available for local translation, and may open new therapeutic opportunities for diabetic peripheral neuropathy.
Pregnancy and Lactation in Sprague-Dawley Rats Result in Permanent Reductions of Tibia Trabecular Bone Mineral Density and Structure but Consumption of Red Rooibos Herbal Tea Supports the Partial Recovery
Authors: McAlpine Michael D. , Yumol Jenalyn L. , Ward Wendy E.
Published: December 2021

During pregnancy and lactation, maternal bone mineral density (BMD) is reduced as calcium is mobilized to support offspring bone development. In humans, BMD returns to pre-pregnancy levels shortly after delivery, shifting from a high rate of bone resorption during pregnancy and lactation, into a rapid phase of bone formation post-lactation. This rapid change in bone turnover may provide an opportunity to stimulate a greater gain in BMD and stronger trabecular and cortical structure than present pre-pregnancy. Providing polyphenols present in red rooibos herbal tea may promote such an effect. In vitro, red rooibos polyphenols stimulate osteoblast activity, reduce osteoclastic resorption, and increase mineral production. The study objective was to determine if consuming red rooibos from pre-pregnancy through to 4 months post-lactation resulted in a higher BMD and improved trabecular and cortical bone structure in a commonly used rat model. Female Sprague-Dawley rats (n = 42) were randomized to one of the following groups: PREG TEA (pregnant, received supplemental level of red rooibos in water: ~2.6 g /kg body weight/day in water), PREG WATER (pregnant, received water), or NONPREG CON (age-matched, non-pregnant control, received water) from 2 weeks pre-pregnancy (age 8 weeks) through to 4 months post-lactation. Rats were fed AIN-93G (pre-pregnancy through to the end of lactation) and AIN-93M (post-lactation onwards). BMD and trabecular structure (bone volume fraction, trabecular number, trabecular separation) were improved (p < 0.05) by 1- or 2-months post-lactation when comparing PREG TEA to PREG CON, though neither group recovered to the level of NONPREG CON. Cortical outcomes (cortical area fraction, cortical thickness, tissue mineral density) for PREG TEA and PREG CON were reduced (p < 0.05) following lactation but returned to the level of NONPREG CON by 2-months post-lactation, with the exception of cortical thickness. The lack of recovery of BMD and key outcomes of trabecular bone structure was unexpected. While consumption of red rooibos did not result in stronger bone post-lactation, red rooibos did support the partial recovery of trabecular BMD and bone structure following pregnancy and lactation. The findings also provide insight into the timing and dose of polyphenols to study in future interventions.
Fast DNA Vaccination Strategy Elicits a Stronger Immune Response Dependent on CD8+CD11c+ Cell Accumulation
Authors: Liu Chenlu , Cong Xianling , Wang Yuqian , Guo Qianqian , Xie Yu , Geng Fei , Guo Jie , Dong Ling , Zhou Yi , Wu Hui , Yu Bin , Wu Jiaxin , Zhang Haihong , Yu Xianghui , Kong Wei
Published: December 2021

Conventional DNA vaccine strategies usually employ a regimen of immunizations at 2-week or longer intervals to induce effective memory cell-dependent immune responses. Clinical cancer treatment requires a faster immunization strategy to contend with tumor progression. In this study, a novel fast immunization strategy was established, wherein a DNA vaccine was intramuscularly administered on days 0, 2, and 5 in a murine lung cancer model. Effector cells peaked 7 to 10 days after the last vaccination. Compared with traditional 2-week-interval immunization strategies, antigen-specific cytolysis and INF-γ secretion were significantly enhanced under the fast vaccination approach. As a result, the rapidly administered DNA vaccine elicited stronger and more prompt antitumor effects. The probable underlying mechanism of fast immunization was the accumulation of CD8+CD11c+ antigen-presenting cells at the injection site, which enhanced subsequent antigen presentation. In conclusion, the fast DNA vaccination strategy shortened vaccination time to 5 days and elicited a stronger antitumor immune response.
Golgi Phosphoprotein 73: The Driver of Epithelial-Mesenchymal Transition in Cancer
Authors: Liu Yiming , Hu Xinyang , Liu Shiyao , Zhou Sining , Chen Zhi , Jin Hongchuan
Published: December 2021

Golgi phosphoprotein 73 (GP73, also termed as GOLM1 or GOLPH2) is a glycosylated protein residing on cis-Golgi cisternae and highly expressed in various types of cancer tissues. Since GP73 is a secretory protein and detectable in serum derived from cancer patients, it has been regarded as a novel serum biomarker for the diagnosis of different cancers, especially hepatocellular carcinoma (HCC). However, the functional roles of GP73 in cancer development are still poorly understood. In recent years, it has been discovered that GP73 acts as a multifunctional protein-facilitating cancer progression, and strikingly, it has been identified as a leading factor promoting epithelial-mesenchymal transition (EMT) of cancer cells and causing cancer metastasis. In this review, we have overviewed the latest findings of the functional roles of GP73 in elevating cancer progression, especially in facilitating EMT and cancer metastasis through modulating expression, transactivation, and trafficking of EMT-related proteins. In addition, unsolved research fields of GP73 have been lightened, which might be helpful to elucidate the regulatory mechanisms of GP73 on EMT and provide potential approaches in therapeutics against cancer metastasis.
Pre-conceptional Maternal Vitamin B12 Supplementation Improves Offspring Neurodevelopment at 2 Years of Age: PRIYA Trial
Authors: D'souza Naomi , Behere Rishikesh V. , Patni Bindu , Deshpande Madhavi , Bhat Dattatray , Bhalerao Aboli , Sonawane Swapnali , Shah Rohan , Ladkat Rasika , Yajnik Pallavi , Bandyopadhyay Souvik K. , Kumaran Kalyanaraman , Fall Caroline , Yajnik Chittaranjan S.
Published: December 2021

Background: The first thousand days window does not include the pre-conceptional period. Maternal pre-conceptional health has a profound influence on early embryonic development (implantation, gastrulation, placentation etc). Nutrition provided by B-complex vitamins is important for fetal growth, especially neural development. We report effects of a maternal pre-conceptional vitamin B12 and multi micronutrient (MMN) supplementation on offspring neurodevelopmental performance.

Methods: In the Pune Rural Intervention in Young Adolescents trial (PRIYA), adolescents (N = 557, 266 females) were provided with vitamin B12 (2 μg/day) with or without multiple micronutrients, or a placebo, from preconception until delivery. All groups received mandatory iron and folic acid. We used the Bayley's Scale of Infant Development (BSID-III) at 24–42 months of age to investigate effects on offspring neurodevelopment.

Results: Participants had similar baseline B12 levels. The levels improved in the B12 supplemented groups during pre-conception and pregnancy (28 weeks gestation), and were reflected in higher cord blood holotranscobalamin (holo-TC) levels compared to the placebo group. Neurodevelopmental outcomes in the B12 alone group (n = 21) were better than the placebo (n = 27) in cognition (p = 0.044) and language (p = 0.020) domains (adjusted for maternal baseline B12 levels). There was no difference in neurodevelopmental outcomes between the B12 + MMN (n = 26) and placebo group. Cord blood Brain Derived Neurotrophic Factor (BDNF) levels were highest in the B12 alone group, though not significant.

Conclusion: Pre-conceptional vitamin B12 supplementation improved maternal B12 status and offspring neurodevelopment at 2 years of age. The usefulness of cord BDNF as a marker of brain development needs further investigation. Our results highlight the importance of intervening during pre-conception.
Comparison of Multivariable Logistic Regression and Machine Learning Models for Predicting Bronchopulmonary Dysplasia or Death in Very Preterm Infants
Authors: Khurshid Faiza , Coo Helen , Khalil Amal , Messiha Jonathan , Ting Joseph Y. , Wong Jonathan , Shah Prakesh S.
Published: December 2021

Bronchopulmonary dysplasia (BPD) is the most prevalent and clinically significant complication of prematurity. Accurate identification of at-risk infants would enable ongoing intervention to improve outcomes. Although postnatal exposures are known to affect an infant's likelihood of developing BPD, most existing BPD prediction models do not allow risk to be evaluated at different time points, and/or are not suitable for use in ethno-diverse populations. A comprehensive approach to developing clinical prediction models avoids assumptions as to which method will yield the optimal results by testing multiple algorithms/models. We compared the performance of machine learning and logistic regression models in predicting BPD/death. Our main cohort included infants <33 weeks' gestational age (GA) admitted to a Canadian Neonatal Network site from 2016 to 2018 (n = 9,006) with all analyses repeated for the <29 weeks' GA subcohort (n = 4,246). Models were developed to predict, on days 1, 7, and 14 of admission to neonatal intensive care, the composite outcome of BPD/death prior to discharge. Ten-fold cross-validation and a 20% hold-out sample were used to measure area under the curve (AUC). Calibration intercepts and slopes were estimated by regressing the outcome on the log-odds of the predicted probabilities. The model AUCs ranged from 0.811 to 0.886. Model discrimination was lower in the <29 weeks' GA subcohort (AUCs 0.699–0.790). Several machine learning models had a suboptimal calibration intercept and/or slope (k-nearest neighbor, random forest, artificial neural network, stacking neural network ensemble). The top-performing algorithms will be used to develop multinomial models and an online risk estimator for predicting BPD severity and death that does not require information on ethnicity.
Application of B-Type Natriuretic Peptide in Neonatal Diseases
Authors: Xie Haotai , Huo Yixuan , Chen Qinzheng , Hou Xinlin
Published: December 2021

Numerous congenital or secondary diseases, including, heart disease, respiratory disease, sepsis and many others, can lead to neonatal death. B-type natriuretic peptide (BNP) is a peptide hormone secreted by ventricular cells following an increase in ventricular wall tension. BNP functions to promote vasodilation, diuresis, and sodium release to regulate blood pressure. BNP is a sensitive index reflecting ventricular function, which may aid the diagnosis and monitoring of various neonatal diseases. In neonates, there is currently no consensus on a reference BNP level, as the plasma BNP concentration of healthy newborns varies with age, peaks in the first week after birth, and then gradually decreased to a stable level. In disease states, the correlation between the plasma BNP concentration and the results of echocardiography is good, which is of great significance in the screening, monitoring, and prognosis evaluation of neonatal cardiovascular diseases, including congenital heart disease, patent ductus arteriosus, etcetera. It also facilitates the judgment of the efficacy of treatment and perioperative management. Moreover, the monitoring of plasma BNP concentration provides guidance for the diagnosis, evaluation, and treatment selection of certain neonatal respiratory diseases and neonatal sepsis. This review summarizes the normal BNP values and discusses the application value of BNP in relation to physiological and pathological aspects in neonates.