bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetics and Early Life Stress: Experimental Brood Size Affects DNA Methylation in Great Tits (Parus major)
Authors: Sepers Bernice , Erven Jolijn A. M. , Gawehns Fleur , Laine Veronika N. , van Oers Kees
Published: March 2021

Early developmental conditions are known to have life-long effects on an individual’s behavior, physiology and fitness. In altricial birds, a majority of these conditions, such as the number of siblings and the amount of food provisioned, are controlled by the parents. This opens up the potential for parents to adjust the behavior and physiology of their offspring according to local post-natal circumstances. However, the mechanisms underlying such intergenerational regulation remain largely unknown. A mechanism often proposed to possibly explain how parental effects mediate consistent phenotypic change is DNA methylation. To investigate whether early life effects on offspring phenotypes are mediated by DNA methylation, we cross-fostered great tit (Parus major) nestlings and manipulated their brood size in a natural study population. We assessed genome-wide DNA methylation levels of CpG sites in erythrocyte DNA, using Reduced Representation Bisulfite Sequencing (RRBS). By comparing DNA methylation levels between biological siblings raised in enlarged and reduced broods and between biological siblings of control broods, we assessed which CpG sites were differentially methylated due to brood size. We found 32 differentially methylated sites (DMS) between siblings from enlarged and reduced broods, a larger number than in the comparison between siblings from control broods. A considerable number of these DMS were located in or near genes involved in development, growth, metabolism, behavior and cognition. Since the biological functions of these genes line up with previously found effects of brood size and food availability, it is likely that the nestlings in the enlarged broods suffered from nutritional stress. We therefore conclude that early life stress might directly affect epigenetic regulation of genes related to early life conditions. Future studies should link such experimentally induced DNA methylation changes to expression of phenotypic traits and assess whether these effects affect parental fitness to determine if such changes are also adaptive.
Comparative Transcriptome Analysis of Early- and Late-Bolting Traits in Chinese Cabbage (Brassica rapa)
Authors: Wei Xiaochun , Rahim Md. Abdur , Zhao Yanyan , Yang Shuangjuan , Wang Zhiyong , Su Henan , Li Lin , Niu Liujing , Harun-Ur-Rashid Md. , Yuan Yuxiang , Zhang Xiaowei
Published: March 2021

Chinese cabbage is one of the most important and widely consumed vegetables in China. The developmental transition from the vegetative to reproductive phase is a crucial process in the life cycle of flowering plants. In spring-sown Chinese cabbage, late bolting is desirable over early bolting. In this study, we analyzed double haploid (DH) lines of late bolting (“Y410-1” and “SY2004”) heading Chinese cabbage (Brassica rapavar.pekinensis) and early-bolting Chinese cabbage (“CX14-1”) (B. rapassp.chinensisvar.parachinensis) by comparative transcriptome profiling using the Illumina RNA-seq platform. We assembled 721.49 million clean high-quality paired-end reads into 47,363 transcripts and 47,363 genes, including 3,144 novel unigenes. There were 12,932, 4,732, and 4,732 differentially expressed genes (DEGs) in pairwise comparisons of Y410-1 vs. CX14-1, SY2004 vs. CX14-1, and Y410-1 vs. SY2004, respectively. The RNA-seq results were confirmed by reverse transcription quantitative real-time PCR (RT-qPCR). A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs revealed significant enrichment for plant hormone and signal transduction as well as starch and sucrose metabolism pathways. Among DEGs related to plant hormone and signal transduction, six unigenes encoding the indole-3-acetic acid-induced protein ARG7 (BraA02g009130), auxin-responsive protein SAUR41 (BraA09g058230), serine/threonine-protein kinase BSK11 (BraA07g032960), auxin-induced protein 15A (BraA10g019860), and abscisic acid receptor PYR1 (BraA08g012630 and BraA01g009450), were upregulated in both late bolting Chinese cabbage lines (Y410-1 and SY2004) and were identified as putative candidates for the trait. These results improve our understanding of the molecular mechanisms underlying flowering in Chinese cabbage and provide a foundation for studies of this key trait in related species.
A Stacking Ensemble Learning Framework for Genomic Prediction
Authors: Liang Mang , Chang Tianpeng , An Bingxing , Duan Xinghai , Du Lili , Wang Xiaoqiao , Miao Jian , Xu Lingyang , Gao Xue , Zhang Lupei , Li Junya , Gao Huijiang
Published: March 2021

Machine learning (ML) is perhaps the most useful tool for the interpretation of large genomic datasets. However, the performance of a single machine learning method in genomic selection (GS) is currently unsatisfactory. To improve the genomic predictions, we constructed a stacking ensemble learning framework (SELF), integrating three machine learning methods, to predict genomic estimated breeding values (GEBVs). The present study evaluated the prediction ability of SELF by analyzing three real datasets, with different genetic architecture; comparing the prediction accuracy of SELF, base learners, genomic best linear unbiased prediction (GBLUP) and BayesB. For each trait, SELF performed better than base learners, which included support vector regression (SVR), kernel ridge regression (KRR) and elastic net (ENET). The prediction accuracy of SELF was, on average, 7.70% higher than GBLUP in three datasets. Except for the milk fat percentage (MFP) traits, of the German Holstein dairy cattle dataset, SELF was more robust than BayesB in all remaining traits. Therefore, we believed that SEFL has the potential to be promoted to estimate GEBVs in other animals and plants.
Transcriptome and Comparative Chloroplast Genome Analysis of Vincetoxicum versicolor: Insights Into Molecular Evolution and Phylogenetic Implication
Authors: Yu Xiaolei , Wang Wenxiu , Yang Hongxia , Zhang Xiaoying , Wang Dan , Tian Xiaoxuan
Published: March 2021

Vincetoxicum versicolor(Bunge) Decne is the original plant species of the Chinese herbal medicine Cynanchi Atrati Radix et Rhizoma. The lack of information on the transcriptome and chloroplast genome ofV. versicolorhinders its evolutionary and taxonomic studies. Here, theV. versicolortranscriptome and chloroplast genome were assembled and functionally annotated. In addition, the comparative chloroplast genome analysis was conducted between the generaVincetoxicumandCynanchum. A total of 49,801 transcripts were generated, and 20,943 unigenes were obtained fromV. versicolor. One thousand thirty-two unigenes fromV. versicolorwere classified into 73 functional transcription factor families. The transcription factors bHLH and AP2/ERF were the most significantly abundant, indicating that they should be analyzed carefully in theV. versicolorecological adaptation studies. The chloroplast genomes ofVincetoxicumandCynanchumexhibited a typical quadripartite structure with highly conserved gene order and gene content. They shared an analogous codon bias pattern in which the codons of protein-coding genes had a preference for A/U endings. The natural selection pressure predominantly influenced the chloroplast genes. A total of 35 RNA editing sites were detected in theV. versicolorchloroplast genome by RNA sequencing (RNA-Seq) data, and one of them restored the start codon in the chloroplastndhDofV. versicolor. Phylogenetic trees constructed with protein-coding genes supported the view thatVincetoxicumandCynanchumwere two distinct genera.
STATegra: Multi-Omics Data Integration – A Conceptual Scheme With a Bioinformatics Pipeline
Authors: Planell Nuria , Lagani Vincenzo , Sebastian-Leon Patricia , van der Kloet Frans , Ewing Ewoud , Karathanasis Nestoras , Urdangarin Arantxa , Arozarena Imanol , Jagodic Maja , Tsamardinos Ioannis , Tarazona Sonia , Conesa Ana , Tegner Jesper , Gomez-Cabrero David
Published: March 2021

Technologies for profiling samples using different omics platforms have been at the forefront since the human genome project. Large-scale multi-omics data hold the promise of deciphering different regulatory layers. Yet, while there is a myriad of bioinformatics tools, each multi-omics analysis appears to start from scratch with an arbitrary decision over which tools to use and how to combine them. Therefore, it is an unmet need to conceptualize how to integrate such data and implement and validate pipelines in different cases. We have designed a conceptual framework (STATegra), aiming it to be as generic as possible for multi-omics analysis, combining available multi-omic anlaysis tools (machine learning component analysis, non-parametric data combination, and a multi-omics exploratory analysis) in a step-wise manner. While in several studies, we have previously combined those integrative tools, here, we provide a systematic description of the STATegra framework and its validation using two The Cancer Genome Atlas (TCGA) case studies. For both, the Glioblastoma and the Skin Cutaneous Melanoma (SKCM) cases, we demonstrate an enhanced capacity of the framework (and beyond the individual tools) to identify features and pathways compared to single-omics analysis. Such an integrative multi-omics analysis framework for identifying features and components facilitates the discovery of new biology. Finally, we provide several options for applying the STATegra framework when parametric assumptions are fulfilled and for the case when not all the samples are profiled for all omics. The STATegra framework is built using several tools, which are being integrated step-by-step as OpenSource in the STATegRa Bioconductor package.1
Variation, Variegation and Heritable Gene Repression in S. cerevisiae
Authors: Shaban Kholoud , Sauty Safia Mahabub , Yankulov Krassimir
Published: March 2021

Phenotypic heterogeneity provides growth advantages for a population upon changes of the environment. InS. cerevisiae, such heterogeneity has been observed as “on/off” states in the expression of individual genes in individual cells. These variations can persist for a limited or extended number of mitotic divisions. Such traits are known to be mediated by heritable chromatin structures, by the mitotic transmission of transcription factors involved in gene regulatory circuits or by the cytoplasmic partition of prions or other unstructured proteins. The significance of such epigenetic diversity is obvious, however, we have limited insight into the mechanisms that generate it. In this review, we summarize the current knowledge of epigenetically maintained heterogeneity of gene expression and point out similarities and converging points between different mechanisms. We discuss how the sharing of limiting repression or activation factors can contribute to cell-to-cell variations in gene expression and to the coordination between short- and long- term epigenetic strategies. Finally, we discuss the implications of such variations and strategies in adaptation and aging.
Zika Virus Envelope Domain III Recombinant Protein Delivered With Saponin-Based Nanoadjuvant From Quillaja brasiliensis Enhances Anti-Zika Immune Responses, Including Neutralizing Antibodies and Splenocyte Proliferation
Authors: Cibulski Samuel , Varela Ana Paula Muterle , Teixeira Thais Fumaco , Cancela Martín Pablo , Sesterheim Patrícia , Souza Diogo Onofre , Roehe Paulo Michel , Silveira Fernando
Published: March 2021

Nanoadjuvants that combine immunostimulatory properties and delivery systems reportedly bestow major improvements on the efficacy of recombinant, protein-based vaccines. Among these, self-assembled micellar formulations named ISCOMs (immune stimulating complexes) show a great ability to trigger powerful immunological responses against infectious pathogens. Here, a nanoadjuvant preparation, based on saponins fromQuillaja brasiliensis, was evaluated together with an experimental Zika virus (ZIKV) vaccine (IQB80-zEDIII) and compared to an equivalent vaccine with alum as the standard adjuvant. The preparations were administered to mice in two doses (on days zero and 14) and immune responses were evaluated on day 28 post-priming. Serum levels of anti-Zika virus IgG, IgG1, IgG2b, IgG2c, IgG3 were significantly increased by the nanoadjuvant vaccine, compared to the mice that received the alum-adjuvanted vaccine or the unadjuvanted vaccine. In addition, a robust production of neutralizing antibodies andin vitrosplenocyte proliferative responses were observed in mice immunized with IQB80-zEDIII nanoformulated vaccine. Therefore, the IQB80-zEDIII recombinant preparation seems to be a suitable candidate vaccine for ZIKV. Overall, this study identified saponin-based delivery systems as an adequate adjuvant for recombinant ZIKV vaccines and has important implications for recombinant protein-based vaccine formulations against other flaviviruses and possibly enveloped viruses.
Cell-Mediated Immunological Biomarkers and Their Diagnostic Application in Livestock and Wildlife Infected With Mycobacterium bovis
Authors: Smith Katrin , Kleynhans Léanie , Warren Robin M. , Goosen Wynand J. , Miller Michele A.
Published: March 2021

Mycobacterium bovis has the largest host range of the Mycobacterium tuberculosis complex and infects domestic animal species, wildlife, and humans. The presence of global wildlife maintenance hosts complicates bovine tuberculosis (bTB) control efforts and further threatens livestock and wildlife-related industries. Thus, it is imperative that early and accurate detection of M. bovis in all affected animal species is achieved. Further, an improved understanding of the complex species-specific host immune responses to M. bovis could enable the development of diagnostic tests that not only identify infected animals but distinguish between infection and active disease. The primary bTB screening standard worldwide remains the tuberculin skin test (TST) that presents several test performance and logistical limitations. Hence additional tests are used, most commonly an interferon-gamma (IFN-γ) release assay (IGRA) that, similar to the TST, measures a cell-mediated immune (CMI) response to M. bovis. There are various cytokines and chemokines, in addition to IFN-γ, involved in the CMI component of host adaptive immunity. Due to the dominance of CMI-based responses to mycobacterial infection, cytokine and chemokine biomarkers have become a focus for diagnostic tests in livestock and wildlife. Therefore, this review describes the current understanding of host immune responses to M. bovis as it pertains to the development of diagnostic tools using CMI-based biomarkers in both gene expression and protein release assays, and their limitations. Although the study of CMI biomarkers has advanced fundamental understanding of the complex host-M. bovis interplay and bTB progression, resulting in development of several promising diagnostic assays, most of this research remains limited to cattle. Considering differences in host susceptibility, transmission and immune responses, and the wide variety of M. bovis-affected animal species, knowledge gaps continue to pose some of the biggest challenges to the improvement of M. bovis and bTB diagnosis.
Dynamic Changes in Microbial Composition During Necrotizing Soft-Tissue Infections in ICU Patients
Authors: Thy Michael , Tanaka Sébastien , Tran-Dinh Alexy , Ribeiro Lara , Lortat-Jacob Brice , Donadio Julia , Zappella Nathalie , Ben-Rehouma Mouna , Tashk Parvine , Snauwaert Aurelie , Atchade Enora , Grall Nathalie , Montravers Philippe
Published: March 2021

Introduction: Recent studies described the threat of emerging multidrug-resistant (MDR) bacteria in intensive care unit (ICU) patients, but few data are available for necrotizing skin and soft tissue infections (NSTI). In a cohort of ICU patients admitted for NSTI, we describe the dynamic changes of microbial population during repeated surgeries.

Materials and Methods: This retrospective study compiled consecutive cases admitted for the management of severe NSTI. Clinical characteristics, NSTI features, morbidity and mortality data were collected. The microbiological characteristics of surgical samples obtained during initial surgery were compared with those obtained during the first reoperation, including persistence of initial pathogens and/or emergence of microorganisms. Risk factors for emergence of microorganisms and MDR bacteria were assessed by univariable and multivariable analyses.

Results: Among 100 patients {63% male, 58 years old [interquartile ratio (IQR) 50–68]} admitted for NSTI, 54 underwent reoperation with a median [IQR] delay of 3 (1–7) days. Decreased proportions of susceptible strains and emergence of Gram-negative bacteria, including Pseudomonas aeruginosa, staphylococci and enterococci strains, were reported based on the cultures of surgical specimen collected on reoperation. On reoperation, 22 (27%) of the isolated strains were MDR (p < 0.0001 vs. MDR bacteria cultured from the first samples). Broad-spectrum antibiotic therapy as first-line therapy was significantly associated with a decreased emergence of microorganisms. Adequate antibiotic therapy from the initial surgery did not modify the frequency of emergence of microorganisms (p = 0.79) and MDR bacteria (p = 1.0) or the 1-year survival rate.

Conclusion: The emergence of microorganisms, including MDR bacteria, is frequently noted in NSTI without affecting mortality.
In vitro Optimization of Ceftazidime/Avibactam for KPC-Producing Klebsiella pneumoniae
Authors: Huang Yanqin , Wu Tiffany , Perez Omar , Rana Amisha P. , Chen Liang , Kreiswirth Barry N. , Satlin Michael J. , Bulman Zackery P.
Published: March 2021

Ceftazidime/avibactam is an important treatment option for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp), however, resistance can emerge during treatment. The objective of the study was to define the ceftazidime/avibactam concentrations required to suppress bacterial regrowth in ceftazidime/avibactam susceptible isolates and identify active therapies against ceftazidime/avibactam-resistant KPC-Kp. Time-kill assays were performed against twelve ST258 KPC-Kp isolates that harbored blaKPC–2 or blaKPC–3. Nine KPC-Kp isolates (KPC-Kp 5A, 6A, 7A, 8A, 9A, 24A, 25A, 26A, and 27A) were susceptible to ceftazidime/avibactam, two (KPC-Kp 6B and 7B) were ceftazidime/avibactam resistant and meropenem susceptible, and one (KPC-Kp 1244) was resistant to both ceftazidime/avibactam and meropenem. Sequencing of the blaKPC genes revealed mutations in KPC-Kp 6B (D179Y substitution) and 7B (novel 21 base pair deletion) that both affected the Ω-loop encoding portion of the gene. Time-kill assays showed that against ceftazidime/avibactam-susceptible KPC-Kp, ceftazidime/avibactam concentrations ≥40/7.5 mg/L caused mean 5.42 log10CFU/mL killing and suppressed regrowth. However, regrowth occurred for some KPC-Kp isolates with a ceftazidime/avibactam concentration of 20/3.75 mg/L. Against ceftazidime/avibactam-resistant and meropenem-susceptible KPC-Kp 6B and 7B, bactericidal activity and synergy was observed for ceftazidime/avibactam in combination with meropenem ≤3.125 mg/L, while meropenem concentrations ≥50 mg/L were bactericidal as monotherapy. In contrast, clinically achievable concentrations of ceftazidime/avibactam were bactericidal against KPC-Kp 1244, which was ceftazidime/avibactam-resistant and meropenem-resistant due to outer membrane porin mutations and elevated blaKPC expression. Achieving high ceftazidime/avibactam concentrations may help to suppress bacterial regrowth in the presence of ceftazidime/avibactam. The optimal treatment approach for ceftazidime/avibactam-resistant KPC-Kp likely depends on the mechanism of resistance. Additional studies are warranted to confirm these findings.
Synaptic Function and Dysfunction in Lysosomal Storage Diseases
Authors: Rebiai Rima , Givogri Maria I. , Gowrishankar Swetha , Cologna Stephania M. , Alford Simon T. , Bongarzone Ernesto R.
Published: March 2021

Lysosomal storage diseases (LSDs) with neurological involvement are inherited genetic diseases of the metabolism characterized by lysosomal dysfunction and the accumulation of undegraded substrates altering glial and neuronal function. Often, patients with neurological manifestations present with damage to the gray and white matter and irreversible neuronal decline. The use of animal models of LSDs has greatly facilitated studying and identifying potential mechanisms of neuronal dysfunction, including alterations in availability and function of synaptic proteins, modifications of membrane structure, deficits in docking, exocytosis, recycling of synaptic vesicles, and inflammation-mediated remodeling of synapses. Although some extrapolations from findings in adult-onset conditions such as Alzheimer’s disease or Parkinson’s disease have been reported, the pathogenetic mechanisms underpinning cognitive deficits in LSDs are still largely unclear. Without being fully inclusive, the goal of this mini-review is to present a discussion on possible mechanisms leading to synaptic dysfunction in LSDs.
The Theta Rhythm of the Hippocampus: From Neuronal and Circuit Mechanisms to Behavior
Authors: Nuñez Angel , Buño Washington
Published: March 2021

This review focuses on the neuronal and circuit mechanisms involved in the generation of the theta (θ) rhythm and of its participation in behavior. Data have accumulated indicating that θ arises from interactions between medial septum-diagonal band of Broca (MS-DbB) and intra-hippocampal circuits. The intrinsic properties of MS-DbB and hippocampal neurons have also been shown to play a key role in θ generation. A growing number of studies suggest that θ may represent a timing mechanism to temporally organize movement sequences, memory encoding, or planned trajectories for spatial navigation. To accomplish those functions, θ and gamma (γ) oscillations interact during the awake state and REM sleep, which are considered to be critical for learning and memory processes. Further, we discuss that the loss of this interaction is at the base of various neurophatological conditions.
Impacts on Thrombus and Chordae Willisii During Mechanical Thrombectomy in the Superior Sagittal Sinus
Authors: Ye Yuanliang , Ding Jiuyang , Liu Shoutang , Huang Shaoming , Li Zhu , Yang Jianqing , Huang Jiang
Published: March 2021

The anatomical structures of the superior sagittal sinus (SSS) are usually damaged during mechanical thrombectomy (MT), and MT procedure could lead to new thrombosis in the sinuses. However, the mechanism remains unclear. We aimed to investigate the risks of embolism and assess the damage to chordae willisii (CW)-associated MT using a stent passing across the thrombus. A contrast-enhanced in vitro model was used to mimick MT in the SSS. The thrombus was removed with a stent. The emboli generated during the procedure were collected and measured. The residual thrombus area after the MT was measured by J Image software. The damage of CW was evaluated by an endoscope. Three procedural experiments were carried out on each cadaveric sample. The average numbers of visible emboli particles in experiments 1, 2, and 3 were 11.17 ± 2.17, 9.00 ± 2.07, and 5.00 ± 2.96, respectively. The number of large size particles produced by experiment 1 was significantly higher than that of the other experiments. The thrombus area measured after experiment 3 was larger than that of experiments 1 and 2. The number of minor damage cases to CW was 55 (90.16%), and there were six serious damage cases (9.84%). The use of stent resulted in no significant increase in damage to CW after the three experimental procedures. A large amount of thrombi particles was produced during MT, and multiple MT procedures on the same sample can increase residual thrombus area. Moreover, the stent caused minor damages to the CW in SSS.
Adrenergic Mechanisms of Audiogenic Seizure-Induced Death in a Mouse Model of SCN8A Encephalopathy
Authors: Wengert Eric R. , Wenker Ian C. , Wagner Elizabeth L. , Wagley Pravin K. , Gaykema Ronald P. , Shin Jung-Bum , Patel Manoj K.
Published: March 2021

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death amongst patients whose seizures are not adequately controlled by current therapies. Patients with SCN8A encephalopathy have an elevated risk for SUDEP. While transgenic mouse models have provided insight into the molecular mechanisms of SCN8A encephalopathy etiology, our understanding of seizure-induced death has been hampered by the inability to reliably trigger both seizures and seizure-induced death in these mice. Here, we demonstrate that mice harboring an Scn8a allele with the patient-derived mutation N1768D (D/+) are susceptible to audiogenic seizures and seizure-induced death. In adult D/+ mice, audiogenic seizures are non-fatal and have nearly identical behavioral, electrographical, and cardiorespiratory characteristics as spontaneous seizures. In contrast, at postnatal days 20–21, D/+ mice exhibit the same seizure behavior, but have a significantly higher incidence of seizure-induced death following an audiogenic seizure. Seizure-induced death was prevented by either stimulating breathing via mechanical ventilation or by acute activation of adrenergic receptors. Conversely, in adult D/+ mice inhibition of adrenergic receptors converted normally non-fatal audiogenic seizures into fatal seizures. Taken together, our studies show that in our novel audiogenic seizure-induced death model adrenergic receptor activation is necessary and sufficient for recovery of breathing and prevention of seizure-induced death.
Novel Graphene Electrode for Retinal Implants: An in vivo Biocompatibility Study
Authors: Nguyen Diep , Valet Manon , Dégardin Julie , Boucherit Leyna , Illa Xavi , de la Cruz Jose , del Corro Elena , Bousquet Jessica , Garrido Jose A. , Hébert Clément , Picaud Serge
Published: March 2021

Evaluating biocompatibility is a core essential step to introducing a new material as a candidate for brain-machine interfaces. Foreign body reactions often result in glial scars that can impede the performance of the interface. Having a high conductivity and large electrochemical window, graphene is a candidate material for electrical stimulation with retinal prosthesis. In this study, non-functional devices consisting of chemical vapor deposition (CVD) graphene embedded onto polyimide/SU-8 substrates were fabricated for a biocompatibility study. The devices were implanted beneath the retina of blind P23H rats. Implants were monitored by optical coherence tomography (OCT) and eye fundus which indicated a high stability in vivo up to 3 months before histology studies were done. Microglial reconstruction through confocal imaging illustrates that the presence of graphene on polyimide reduced the number of microglial cells in the retina compared to polyimide alone, thereby indicating a high biocompatibility. This study highlights an interesting approach to assess material biocompatibility in a tissue model of central nervous system, the retina, which is easily accessed optically and surgically.
Neural Coding in Spiking Neural Networks: A Comparative Study for Robust Neuromorphic Systems
Authors: Guo Wenzhe , Fouda Mohammed E. , Eltawil Ahmed M. , Salama Khaled Nabil
Published: March 2021

Various hypotheses of information representation in brain, referred to as neural codes, have been proposed to explain the information transmission between neurons. Neural coding plays an essential role in enabling the brain-inspired spiking neural networks (SNNs) to perform different tasks. To search for the best coding scheme, we performed an extensive comparative study on the impact and performance of four important neural coding schemes, namely, rate coding, time-to-first spike (TTFS) coding, phase coding, and burst coding. The comparative study was carried out using a biological 2-layer SNN trained with an unsupervised spike-timing-dependent plasticity (STDP) algorithm. Various aspects of network performance were considered, including classification accuracy, processing latency, synaptic operations (SOPs), hardware implementation, network compression efficacy, input and synaptic noise resilience, and synaptic fault tolerance. The classification tasks on Modified National Institute of Standards and Technology (MNIST) and Fashion-MNIST datasets were applied in our study. For hardware implementation, area and power consumption were estimated for these coding schemes, and the network compression efficacy was analyzed using pruning and quantization techniques. Different types of input noise and noise variations in the datasets were considered and applied. Furthermore, the robustness of each coding scheme to the non-ideality-induced synaptic noise and fault in analog neuromorphic systems was studied and compared. Our results show that TTFS coding is the best choice in achieving the highest computational performance with very low hardware implementation overhead. TTFS coding requires 4x/7.5x lower processing latency and 3.5x/6.5x fewer SOPs than rate coding during the training/inference process. Phase coding is the most resilient scheme to input noise. Burst coding offers the highest network compression efficacy and the best overall robustness to hardware non-idealities for both training and inference processes. The study presented in this paper reveals the design space created by the choice of each coding scheme, allowing designers to frame each scheme in terms of its strength and weakness given a designs’ constraints and considerations in neuromorphic systems.
Vitamin D and Acute Kidney Injury: A Two-Way Causality Relation and a Predictive, Prognostic, and Therapeutic Role of Vitamin D
Authors: Graidis Spyridon , Papavramidis Theodosios S. , Papaioannou Maria
Published: March 2021

Background: Acute kidney injury (AKI) constitutes a multi-factorially caused condition, which significantly affects kidney function and can lead to elevated risk of morbidity and mortality. Given the rising scientific evidence regarding vitamin D's (VitD's) multisystemic role, the connection between AKI and VitD is currently being studied, and the complex relation between them has started to be unraveled.

Methods: A systematic review had been conducted to identify the pathogenetic relation of VitD and AKI and the potential role of VitD as a biomarker and therapeutic–renoprotective factor.

Results: From 792 articles, 74 articles were identified that fulfilled the inclusion criteria. Based on these articles, it has been found that not only can VitD disorders (VitD deficiency or toxicity) cause AKI but, also, AKI can lead to great disruption in the metabolism of VitD. Moreover, it has been found that VitD serves as a novel biomarker for prediction of the risk of developing AKI and for the prognosis of AKI's severity. Finally, animal models showed that VitD can both ameliorate AKI and prevent its onset, suggesting its renoprotective effect.

Conclusion: There is a complex two-way pathogenetic relation between VitD disorders and AKI, while, concomitantly, VitD serves as a potential novel predictive–prognostic biomarker and a treatment agent in AKI therapy.
Chlorine Solutions for a Safe Method of Decontamination of Breast Pump Milk Collection Kits Before and After the Coronavirus Disease 2019 Pandemic
Authors: Rigourd Virginie , Mouadh Benali , Poupon Joel , Langrand Jerome , Goutard Arnaud , Droguet Christine , Bille Emmanuel , Frange Pierre , Bahri Yasmina , Pasquier David , Lapillonne Alexandre , Skurnik David
Published: March 2021

To promote breast feeding and breast pumping is essential for the most vulnerable infants even if the current coronavirus disease 2019 (COVID-19) pandemic sanitary crisis imposes more stringent hygienic measures. As recommended by the Centers for Disease Control and Prevention, World Health Organization, and Milk Bank Association, “after each pumping session, all pump part that come into contact with breast milk should be appropriately disinfected.” The present study proposed different methods than can be used and focus on the safety analysis of chlorine solution (CS) in terms of residual hypochlorous acid (HCA) and total trihalomethanes (THM). We also performed an efficacy testing of the CS approach to decontaminate the devices used to collect the milk (breast pumps and bottles). The bacteriologic results of 1,982 breast pump milk samples collected in three different settings showed a major decrease of the microbial contamination using either sterile device or decontamination with CS compared to a simple soap washing. The main messages from our study are to propose a guideline for the safe use of CS and to define situations when breast pump decontamination might be necessary: vulnerable babies for which sterile device is recommended; special circumstances, for example the current COVID-19 pandemic; special situations, for example women living in precarious conditions; or women pumping their milk at work but that would have low or no access to boiled water. Overall, cold decontamination reduced losses of milk for bacteriological reasons in human milk banks and may also be interesting to prevent horizontal contamination by virus like COVID-19.
The Nutritional Issue of Older People Receiving Home-Delivered Meals: A Systematic Review
Authors: Fleury Ségolène , Tronchon Paul , Rota Juliane , Meunier Charlotte , Mardiros Oliver , Van Wymelbeke-Delannoy Virginie , Sulmont-Rossé Claire
Published: March 2021

Background:Setting up a home-delivered meal service often allows older people suffering from physical and/or cognitive disabilities to stay at home. However, older people who delegate their food activities (food purchasing, cooking…) have been reported to have a worse nutritional status than people who take care of their food activities. In this context, we will conduct a systematic review of all studies related to the nutritional issue in home-delivered meal older recipients.

Methods:In June 2020, we searched 3 databases (Pubmed, Web of Science, EMBASE) to identify studies from all years on older adults at home and receiving home-delivered meal services (population). The followingoutcomeswere considered: nutritional status (Body Mass Index, weight, undernutrition) and nutritional intake. Any nutritionalintervention, comparator, andstudy designwere relevant for inclusion.

Results:Forty-eight original studies met the inclusion criteria, most of them being published after the year 2000 (n= 34) and undertaken in the USA (n= 32). The selection includes 30 cross-sectional and 18 longitudinal studies. The main findings of this review are the following: (1) home-delivery meal older recipients are at high risk of undernutrition; (2) providing home-delivery meals may improve the nutritional status and nutrient intake; (3) this improvement is even higher when the home-delivery meal service is improved, for instance by providing dietetic counseling or adding supplementary snacks/meals or enriched food. However, even an improved service does not allow all the older recipients meeting their recommended nutritional allowance.

Conclusion:This review reveals a need to further develop strategies allowing home-delivery meal older recipients to fulfill their nutritional needs. From a methodological point of view, there is a need to describe in more detail the home-delivered services provided to studies' participants to better consider meal frequency and meal content in the results.
Morphological Subtypes of Tumor Spread Through Air Spaces in Non-Small Cell Lung Cancer: Prognostic Heterogeneity and Its Underlying Mechanism
Authors: Xie Huikang , Su Hang , Zhu Erjia , Gu Chang , Zhao Shengnan , She Yunlang , Ren Yijiu , Xie Dong , Zheng Hui , Wu Chunyan , Dai Chenyang , Chen Chang
Published: March 2021

Background

Tumor spread through air spaces (STAS) has three morphologic subtypes: single cells, micropapillary clusters, and solid nests. However, whether their respective clinical significance is similar remains unclear.

Methods

We retrospectively reviewed 803 patients with resected non-small cell lung cancer (NSCLC) from January to December 2009. Recurrence-free survival (RFS) and overall survival (OS) were compared among patients stratified by STAS subtypes. We also performed a prospective study of NSCLC resection specimens to evaluate the influence of a prosecting knife on the presence of STAS subtypes during specimen handling (83 cases).

Results

STAS was found in 370 NSCLCs (46%), including 47 single cell STAS (13%), 187 micropapillary cluster STAS (50%), and 136 solid nest STAS (37%). STAS-negative patients had significantly better survival than patients with micropapillary cluster STAS (RFS: P < 0.001; OS: P < 0.001) and solid nest STAS (RFS: P < 0.001; OS: P < 0.001), but similar survival compared with those with single cell STAS (RFS: P = 0.995; OS: P = 0.71). Multivariate analysis revealed micropapillary cluster (RFS: P < 0.001; OS: P < 0.001) and solid nest STAS (RFS: P = 0.001; OS: P = 0.003) to be an independent prognostic indicator, but not for single cell STAS (RFS: P = 0.989; OS: P = 0.68). Similar results were obtained in subgroup analysis of patients with adenocarcinoma. The prospective study of NSCLC specimens suggested that 18 cases were considered as STAS false-positive, and most were singe cell pattern (13/18, 72%).

Conclusions

Single cell STAS was the common morphologic type of artifacts produced by a prosecting knife. A precise protocol of surgical specimen handling is required to minimize artifacts as much as possible.
Evaluation of an Ultrasound-Based Navigation System for Spine Neurosurgery: A Porcine Cadaver Study
Authors: Gueziri Houssem-Eddine , Rabau Oded , Santaguida Carlo , Collins D. Louis
Published: March 2021

Background

With the growing incidence of patients receiving surgical treatment for spinal metastatic tumours, there is a need for developing cost-efficient and radiation-free alternatives for spinal interventions. In this paper, we evaluate the capabilities and limitations of an image-guided neurosurgery (IGNS) system that uses intraoperative ultrasound (iUS) imaging for guidance.

Methods

Using a lumbosacral section of a porcine cadaver, we explored the impact of CT image resolution, ultrasound depth and ultrasound frequency on system accuracy, robustness and effectiveness. Preoperative CT images with an isotropic resolution of , and were acquired. During surgery, vertebrae L1 to L6 were exposed. For each vertebra, five iUS scans were acquired using two depth parameters (5 cm and 7 cm) and two frequencies (6 MHz and 12 MHz). A total of 120 acquisition trials were evaluated. Ultrasound-based registration performance is compared to the standard alignment procedure using intraoperative CT. We report target registration error (TRE) and computation time. In addition, the scans’ trajectories were analyzed to identify vertebral regions that provide the most relevant features for the alignment.

Results

For all acquisitions, the median TRE ranged from 1.42 mm to 1.58 mm and the overall computation time was 9.04 s ± 1.58 s. Fourteen out of 120 iUS acquisitions (11.66%) yielded a level-to-level mismatch (and these are included in the accuracy measurements reported). No significant effect on accuracy was found with CT resolution (F(2,10) = 1.70, p = 0.232), depth (F(1,5) = 0.22, p= 0.659) nor frequency (F(1,5) = 1.02, p = 0.359). While misalignment increases linearly with the distance from the imaged vertebra, accuracy was satisfactory for directly adjacent levels. A significant relationship was found between iUS scan coverage of laminae and articular processes, and accuracy.

Conclusion

Intraoperative ultrasound can be used for spine surgery neuronavigation. We demonstrated that the IGNS system yield acceptable accuracy and high efficiency compared to the standard CT-based navigation procedure. The flexibility of the iUS acquisitions can have repercussions on the system performance, which are not fully identified. Further investigation is needed to understand the relationship between iUS acquisition and alignment performance.
Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy
Authors: Carrano Anna , Zarco Natanael , Phillipps Jordan , Lara-Velazquez Montserrat , Suarez-Meade Paola , Norton Emily S. , Chaichana Kaisorn L. , Quiñones-Hinojosa Alfredo , Asmann Yan W. , Guerrero-Cázares Hugo
Published: March 2021

Glioblastoma (GBM) is the most common and devastating primary cancer of the central nervous system in adults. High grade gliomas are able to modify and respond to the brain microenvironment. When GBM tumors infiltrate the Subventricular zone (SVZ) they have a more aggressive clinical presentation than SVZ-distal tumors. We suggest that cerebrospinal fluid (CSF) contact contributes to enhance GBM malignant characteristics in these tumors. We evaluated the impact of human CSF on GBM, performing a transcriptome analysis on human primary GBM cells exposed to CSF to measure changes in gene expression profile and their clinical relevance on disease outcome. In addition we evaluated the proliferation and migration changes of CSF-exposed GBM cells in vitro and in vivo. CSF induced transcriptomic changes in pathways promoting cell malignancy, such as apoptosis, survival, cell motility, angiogenesis, inflammation, and glucose metabolism. A genetic signature extracted from the identified transcriptional changes in response to CSF proved to be predictive of GBM patient survival using the TCGA database. Furthermore, CSF induced an increase in viability, proliferation rate, and self-renewing capacity, as well as the migratory capabilities of GBM cells in vitro. In vivo, GBM cells co-injected with human CSF generated larger and more proliferative tumors compared to controls. Taken together, these results provide direct evidence that CSF is a key player in determining tumor growth and invasion through the activation of complex gene expression patterns characteristic of a malignant phenotype. These findings have diagnostic and therapeutic implications for GBM patients. The changes induced by CSF contact might play a role in the increased malignancy of SVZ-proximal GBM.
A Radiomic Nomogram for the Ultrasound-Based Evaluation of Extrathyroidal Extension in Papillary Thyroid Carcinoma
Authors: Wang Xian , Agyekum Enock Adjei , Ren Yongzhen , Zhang Jin , Zhang Qing , Sun Hui , Zhang Guoliang , Xu Feiju , Bo Xiangshu , Lv Wenzhi , Hu Shudong , Qian Xiaoqin
Published: March 2021

Purpose

To construct a sequence diagram based on radiological and clinical factors for the evaluation of extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC).

Materials and Methods

Between January 2016 and January 2020, 161 patients with PTC who underwent preoperative ultrasound examination in the Affiliated People’s Hospital of Jiangsu University were enrolled in this retrospective study. According to the pathology results, the enrolled patients were divided into a non-ETE group and an ETE group. All patients were randomly divided into a training cohort (n = 97) and a validation cohort (n = 64). A total of 479 image features of lesion areas in ultrasonic images were extracted. The radiomic signature was developed using least absolute shrinkage and selection operator algorithms after feature selection using the minimum redundancy maximum relevance method. The radiomic nomogram model was established by multivariable logistic regression analysis based on the radiomic signature and clinical risk factors. The discrimination, calibration, and clinical usefulness of the nomogram model were evaluated in the training and validation cohorts.

Results

The radiomic signature consisted of six radiomic features determined in ultrasound images. The radiomic nomogram included the parameters tumor location, radiological ETE diagnosis, and the radiomic signature. Area under the curve (AUC) values confirmed good discrimination of this nomogram in the training cohort [AUC, 0.837; 95% confidence interval (CI), 0.756–0.919] and the validation cohort (AUC, 0.824; 95% CI, 0.723–0.925). The decision curve analysis showed that the radiomic nomogram has good clinical application value.

Conclusion

The newly developed radiomic nomogram model is a noninvasive and reliable tool with high accuracy to predict ETE in patients with PTC.
Effect of Metabolic Syndrome and Individual Components on Colon Cancer Characteristics and Prognosis
Authors: Silva Ana , Pereira Sofia S. , Monteiro Mariana P. , Araújo António , Faria Gil
Published: March 2021

Metabolic syndrome (MS) is recognized as a risk factor for colon cancer (CC). However, whether the cluster of metabolic changes that define MS also influence CC prognosis remains unclear. Thus, our aim was to investigate whether the presence of MS or any of the MS individual components could provide prognostic information on tumor phenotype and survival outcomes. Clinical and pathological data from patients with CC (n = 300) who underwent surgical resection at a single tertiary hospital were retrospectively collected to evaluate presence of MS components and diagnostic criteria, CC phenotype and disease outcomes. Patients were allocated into two groups according to the presence or absence of MS (n = 85 MS vs n = 83 non-MS). The overall prevalence of MS individual components was 82.7% for increased waist-circumference (WC), 61.3% for high blood pressure (BP), 48.8% for low HDL-cholesterol, 39.9% for high fasting glucose, and 33.9% for hypertriglyceridemia. Patients in the MS group presented smaller tumors (p = 0.006) with lower T-stage (p = 0.002). High BP (p = 0.029) and hypertriglyceridemia (p = 0.044) were associated with a smaller tumor size, while low-HDL (p = 0.008) was associated with lower T-stage. After propensity score matching using age, tumor size and staging as covariates high-BP (p = 0.020) and WC (p = 0.003) were found to influence disease-free survival, but not overall survival. In conclusion, despite MS being an established risk factor for CC, our data does not support the hypothesis that MS components have a negative impact on disease extension or prognosis. Nevertheless, a protective role of BP and lipid lowering drugs cannot be excluded.
CXCL12 and CD3E as Indicators for Tumor Microenvironment Modulation in Bladder Cancer and Their Correlations With Immune Infiltration and Molecular Subtypes
Authors: Liu Yi , Wu YuCai , Zhang PeiPei , Xu ChaoJie , Liu ZeSen , He ChaoJie , Liu YiMing , Kang ZhengJun
Published: March 2021

Bladder cancer (BLCA) represents the ninth most common malignant tumor in the world and is characterized by high recurrence risk. Tumor microenvironment (TME) plays an important role in regulating the progression of BLCA. Immunotherapy, including Bacillus Calmette-Guerin (BCG) and programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1), is closely associated with TME and is widely used for treating BLCA. But parts of BLCA patients have no response to these treatment ways, thus a better understanding of the complex TME of BLCA is still needed. We downloaded the gene expression profile and corresponding clinical information of 414 BLCA patients from the TCGA database. Via the ESTIMATE and CIBERSORT algorithm, we identified the two hub genes (CXCL12 and CD3E) and explored their correlations with immune infiltration. We found that BLCA patients with higher expression of CXCL12 and lower expression of CD3E had prolonged survival. Gene set enrichment analysis (GSEA) revealed that both CXCL12 and CD3E were enriched in immune-related pathways. We also discovered that stromal score and the level of CXCL12 were higher in luminal subtype, and immune score and the level of CD3E were higher in the basal subtype. Furtherly, we found that CXCL12 was associated with naive B cells, resting mast cell, M2 macrophages, follicular helper T cells, and dendritic cells. CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), and macrophages were correlated with CD3E. In conclusions, we found that CXCL12 and CD3E might serve as indicators of TME modulation in BLCA. Therapy targeting CXCL12 and CD3E had the potential as novel therapeutic strategy.