bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative OMICS Data-Driven Procedure Using a Derivatized Meta-Analysis Approach
Authors: Cervantes-Gracia Karla , Chahwan Richard , Husi Holger
Published: February 2022

The wealth of high-throughput data has opened up new opportunities to analyze and describe biological processes at higher resolution, ultimately leading to a significant acceleration of scientific output using high-throughput data from the different omics layers and the generation of databases to store and report raw datasets. The great variability among the techniques and the heterogeneous methodologies used to produce this data have placed meta-analysis methods as one of the approaches of choice to correlate the resultant large-scale datasets from different research groups. Through multi-study meta-analyses, it is possible to generate results with greater statistical power compared to individual analyses. Gene signatures, biomarkers and pathways that provide new insights of a phenotype of interest have been identified by the analysis of large-scale datasets in several fields of science. However, despite all the efforts, a standardized regulation to report large-scale data and to identify the molecular targets and signaling networks is still lacking. Integrative analyses have also been introduced as complementation and augmentation for meta-analysis methodologies to generate novel hypotheses. Currently, there is no universal method established and the different methods available follow different purposes. Herein we describe a new unifying, scalable and straightforward methodology to meta-analyze different omics outputs, but also to integrate the significant outcomes into novel pathways describing biological processes of interest. The significance of using proper molecular identifiers is highlighted as well as the potential to further correlate molecules from different regulatory levels. To show the methodology’s potential, a set of transcriptomic datasets are meta-analyzed as an example.
Characterization of Interplay Between Autophagy and Ferroptosis and Their Synergistical Roles on Manipulating Immunological Tumor Microenvironment in Squamous Cell Carcinomas
Authors: Chen Lijie , Niu Xing , Qiao Xue , Liu Sai , Ma Hongmei , Shi Xueqing , He Xuemei , Zhong Ming
Published: February 2022

Objective

Squamous cell carcinomas (SCCs) with shared etiology, histological characteristics, and certain risk factors represent the most common solid cancers. This study reports the crosstalk between autophagy and ferroptosis at the molecular level in SCCs, and their roles on the immunological tumor microenvironment (TME) of SCCs.

Methods

In this study, the connections between autophagy and ferroptosis were characterized in SCCs by analyzing the associations between autophagy- and ferroptosis-related genes in mRNA expression and prognosis, protein-protein interactions and shared signaling pathways. Autophagy potential index (API) and ferroptosis potential index (FPI) of each tumor were quantified for reflecting autophagy and ferroptosis levels via principal-component analysis algorithm. Their synergistical roles on TME, immunity, drug resistance and survival were systematically analyzed in SCCs.

Results

There were close connections between autophagy and ferroptosis at the mRNA and protein levels and prognosis. Both shared cancer-related pathways. The API and FPI were separately developed based on prognostic autophagy- and ferroptosis-related genes. A high correlation between API and FPI was found in SCCs. Their interplay was distinctly associated with favorable prognosis, enhanced sensitivity to chemotherapy drugs (Sunitinib, Gefitinib, Vinblastine and Vorinostat), an inflamed TME and higher likelihood of response to immunotherapy in SCCs.

Conclusion

This study is the first to ﻿provide a comprehensive analysis of the interplay between autophagy and ferroptosis and their synergistical roles on manipulating the immunological TME in SCCs. These findings indicated that the induction of autophagy and ferroptosis combined with immunotherapy might produce synergistically enhanced anti-SCCs activity.
Utilization of Treg Cells in Solid Organ Transplantation
Authors: Juneja Tanya , Kazmi Maria , Mellace Michael , Saidi Reza F.
Published: February 2022

Organ transplants have been a life-saving form of treatment for many patients who are facing end stage organ failure due to conditions such as diabetes, hypertension, various congenital diseases, idiopathic diseases, traumas, and other end-organ failure. While organ transplants have been monumental in treatment for these conditions, the ten year survival and long-term outcome for these patients is poor. After receiving the transplant, patients receive a multi-drug regimen of immunosuppressants. These drugs include cyclosporine, mTOR inhibitors, corticosteroids, and antibodies. Polyclonal antibodies, which inhibit the recipient’s B lymphocytes, and antibodies targeting host cytokine inhibitors which prevent activation of B cells by T cells. Use of these drugs suppresses the immune system and increases the risk of opportunistic pathogen infections, tumors, and further damage to the transplanted organs and vasculature. Many regulatory mechanisms are present in organs to prevent the development of autoimmune disease, and Tregs are central to these mechanisms. Tregs secrete suppressive cytokines such as IL-10, TGF-B, and IL-35 to suppress T cells. Additionally, Tregs can bind to target cells to induce cell cycle arrest and apoptosis and can inhibit induction of IL-2 mRNA in target T cells. Tregs also interact with CTLA-4 and CD80/CD86 on antigen presenting cells (APCs) to prevent their binding to CD28 present on T cells. Due to their various immunosuppressive capabilities, Tregs are being examined as a possible treatment for patients that receive organ transplants to minimize rejection and prevent the negative outcomes. Several studies in which participants were given Tregs after undergoing organ transplantations were reviewed to determine the efficacy and safety of using Tregs in solid organ transplantation to prevent adverse outcomes.
Pegylation Reduces the Uptake of Certolizumab Pegol by Dendritic Cells and Epitope Presentation to T-Cells
Authors: de Bourayne Marie , Meunier Sylvain , Bitoun Samuel , Correia Evelyne , Mariette Xavier , Nozach Hervé , Maillère Bernard
Published: February 2022

Pegylation of biopharmaceuticals is the most common strategy to increase their half-life in the blood and is associated with a reduced immunogenicity. As antigen presentation is a primary event in the activation of CD4 T-cells and initiation of Anti-Drug Antibody (ADA) response, we investigated the role of the PEG molecule on the T-cell reactivity of certolizumab pegol (CZP), a pegylated anti-TNFα Fab. We generated T-cell lines raised against CZP and its non-pegylated form (CZNP) and demonstrated CZP primed few T-cells in comparison to CZNP. CZP-primed lines from 3 donors responded to a total of 5 epitopes, while CZNP-primed lines from 3 donors responded to a total of 7 epitopes, 4 epitopes were recognized by both CZP- and CZNP-primed lines. In line with this difference of T-cell reactivity, CZP is less internalized by the dendritic cells than CZNP. In vitro digestion assay of CZP by Cathepsin B showed a rapid removal of the PEG moiety, suggesting a limited influence of PEG on CZP proteolysis. We therefore demonstrate that pegylation diminishes antigen capture by dendritic cells, peptide presentation to T-cells and T-cell priming. This mechanism might reduce immunogenicity and contribute to the long half-life of CZP and possibly of other pegylated molecules.
Pathogenic and Potential Therapeutic Roles of Exosomes Derived From Immune Cells in Liver Diseases
Authors: Zhou Leyu , Shen Mengyi , Fan Xiaoli , Liu Yifeng , Yang Li
Published: February 2022

Liver diseases, such as viral hepatitis, alcoholic hepatitis and cirrhosis, nonalcoholic steatohepatitis, and hepatocellular carcinoma place a heavy burden on many patients worldwide. However, the treatment of many liver diseases is currently insufficient, and the treatment may be associated with strong side effects. Therapies for liver diseases targeting the molecular and cellular levels that minimize adverse reactions and maximize therapeutic effects are in high demand. Immune cells are intimately involved in the occurrence, development, and prognosis of liver diseases. The immune response in the liver can be suppressed, leading to tolerance in homeostasis. When infection or tissue damage occurs, immunity in the liver is activated rapidly. As small membrane vesicles derived from diverse cells, exosomes carry multiple cargoes to exert their regulatory effects on recipient cells under physiological or pathological conditions. Exosomes from different immune cells exert different effects on liver diseases. This review describes the biology of exosomes and focuses on the effects of exosomes from different immune cells on pathogenesis, diagnosis, and prognosis and their therapeutic potential in liver diseases.
LLT1-CD161 Interaction in Cancer: Promises and Challenges
Authors: Braud Veronique M. , Meghraoui-Kheddar Aïda , Elaldi Roxane , Petti Luciana , Germain Claire , Anjuère Fabienne
Published: February 2022

The success of immune checkpoint therapy in cancer has changed our way of thinking, promoting the design of future cancer treatments that places the immune system at the center stage. The knowledge gained on immune regulation and tolerance helped the identification of promising new clinical immune targets. Among them, the lectin-like transcript 1 (LLT1) is the ligand of CD161 (NKR-P1A) receptor expressed on natural killer cells and T cells. LLT1/CD161 interaction modulates immune responses but the exact nature of the signals delivered is still partially resolved. Investigation on the role of LLT1/CD161 interaction has been hampered by the lack of functional homologues in animal models. Also, some studies have been misled by the use of non-specific reagents. Recent studies and meta-analyses of single cell data are bringing new insights into the function of LLT1 and CD161 in human pathology and notably in cancer. The advances made on the characterization of the tumor microenvironment prompt us to integrate LLT1/CD161 interaction into the equation. This review recapitulates the key findings on the expression profile of LLT1 and CD161, their regulation, the role of their interaction in cancer development, and the relevance of targeting LLT1/CD161 interaction.
Allicin Improves Intestinal Epithelial Barrier Function and Prevents LPS-Induced Barrier Damages of Intestinal Epithelial Cell Monolayers
Authors: Gao Jingxia , Song Guanzhong , Shen Haibo , Wu Yiming , Zhao Chongqi , Zhang Zhuo , Jiang Qian , Li Xilong , Ma Xiaokang , Tan Bie , Yin Yulong
Published: February 2022

Gut barrier disruption is the initial pathogenesis of various diseases. We previously reported that dietary allicin improves tight junction proteins in the endoplasmic reticulum stressed jejunum. However, whether the allicin benefits the gut barrier within mycotoxin or endotoxin exposure is unknown. In the present study, IPEC-J2 cell monolayers within or without deoxynivalenol (DON) or lipopolysaccharide (LPS) challenges were employed to investigate the effects of allicin on intestinal barrier function and explore the potential mechanisms. Results clarified that allicin at 2 μg/mL increased the viability, whereas the allicin higher than 10 μg/mL lowered the viability of IPEC-J2 cells via inhibiting cell proliferation. Besides, allicin increased trans-epithelial electric resistance (TEER), decreased paracellular permeability, and enhanced ZO-1 integrity of the IPEC-J2 cell monolayers. Finally, allicin supplementation prevented the LPS-induced barrier damages via activating Nrf2/HO-1 pathway-dependent antioxidant system. In conclusion, the present study strongly confirmed allicin as an effective nutrient to improve intestinal barrier function and prevent bacterial endotoxin-induced barrier damages.
Incidence and All-Cause Mortality Rates in Neonates Infected With Carbapenem Resistant Organisms
Authors: Thomas Reenu , Ondongo-Ezhet Claude , Motsoaledi Nini , Sharland Mike , Clements Michelle , Velaphi Sithembiso
Published: February 2022

Introduction

Multidrug-resistant, Gram-negative infections, particularly due to carbapenem resistant organisms (CRO), have increased globally. Few studies have reported on the burden of CRO in neonates from low-middle income countries (LMIC). This study aimed to determine the incidence and mortality rates of culture-confirmed Gram-negative infections, with a special focus on CRO in a neonatal unit from a LMIC.

Materials and Methods

Positive bacterial cultures from sterile sites of infants admitted in the neonatal unit from the 1st January 2018 to 31st December 2019, were reviewed retrospectively. Type of organism, susceptibility and outcomes were recorded. Data on Gram-negative isolates, including the CRO, were extracted. Rates and outcomes were analysed.

Results

There were 2219 neonates with organisms isolated from sterile sites (blood and cerebrospinal fluid), accounting for 30% of all admissions, giving a neonatal sepsis incidence of 17.9/1000 patient-days. There was a total of 1746 positive isolates (excluding coagulase negative Staphyloccocus). Of these, 1706 (98%) were isolated from blood, and 40 (2%) from cerebrospinal fluid. Overall, 1188 (68%) were Gram-negative, 371 (21%) Gram-positive and 187 (10.7%) fungal isolates. The common Gram-negatives were Acinetobacter baumannii (526/1188;44%) and Klebsiella pneumoniae (469/1188;40%). Carbapenem resistance was observed in 359 (68%) of the Acinetobacter baumannii (CRAB) and in 103 (18%) of the Enterobacterales (CRE) isolates, with 98% of CRE being Klebsiella pneumoniae (CR-Klebs). Twenty-four (41%) of Pseudomonas species were carbapenem resistant. Overall, carbapenem resistance was seen in 42% of all Gram-negative organisms. The rate of CRAB and CRE were 2.9 and 0.8/1000 patient-days respectively. The overall, all-cause in-hospital mortality rate in infants with Gram-negative isolates was 22%, with higher mortality rate in those infected with CRO compared to non-CRO (34% vs 13%; OR 3.44; 95% CI 2.58–4.60; p < 0.001). The mortality rate in infants with CRE was higher than those with CRAB (48% vs 33%; OR 1.85; 95% CI 1.18–2.89; p = 0.007).

Conclusion

We observed a high incidence of positive cultures from sterile sites. The common organisms isolated were Gram-negatives, and among these carbapenem resistance was high and was associated with high mortality. Mortality was higher in infants with CRE compared to those with CRAB.
Global Mass Spectrometric Analysis Reveals Chemical Diversity of Secondary Metabolites and 44-Methylgambierone Production in Philippine Gambierdiscus Strains
Authors: Malto Zabrina Bernice L. , Benico Garry A. , Batucan Jeremiah D. , Dela Cruz James , Romero Marc Lawrence J. , Azanza Rhodora V. , Salvador-Reyes Lilibeth A.
Published: February 2022

Surveillance and characterization of emerging marine toxins and toxigenic dinoflagellates are warranted to evaluate their associated health risks. Here, we report the occurrence of the ciguatera poisoning-causative dinoflagellate Gambierdiscus balechii in the Philippines. Toxin production and chemical diversity of secondary metabolites in G. balechii GtoxSAM092414, G. balechii Gtox112513, and the recently reported Gambierdiscus carpenteri Gam1BOL080513 were assessed using targeted and untargeted UPLC-MS/MS analysis and radioligand receptor-binding assay (RBA). 44-methylgambierone was produced by all three strains, albeit with different levels based on RBA and UPLC-HRMS/MS analysis. The fatty acid composition was similar in all strains, while subtle differences in monosaccharide content were observed, related to the collection site rather than the species. Molecular networking using the GNPS database identified 45 clusters belonging to at least ten compound classes, with terpene glycosides, carbohydrate conjugates, polyketides, and macrolides as major convergence points. Species-specific peptides and polyhydroxylated compounds were identified in G. balechii GtoxSAM092414 and G. carpenteri Gam1BOL080513, respectively. These provide a glimpse of the uncharacterized biosynthetic potential of benthic dinoflagellates and highlight the intricate and prolific machinery for secondary metabolites production in these organisms.
Movement Shapes the Structure of Fish Communities Along a Cross-Shore Section in the California Current
Authors: Guiet Jérôme , Bianchi Daniele , Maury Olivier , Barrier Nicolas , Kessouri Fayçal
Published: February 2022

Pelagic fish communities are shaped by bottom-up and top-down processes, transport by currents, and active swimming. However, the interaction of these processes remains poorly understood. Here, we use a regional implementation of the APex ECOSystem Model (APECOSM), a mechanistic model of the pelagic food web, to investigate these processes in the California Current, a highly productive upwelling system characterized by vigorous mesoscale circulation. The model is coupled with an eddy-resolving representation of ocean currents and lower trophic levels, and is tuned to reproduce observed fish biomass from fisheries independent trawls. Several emergent properties of the model compare realistically with observations. First, the epipelagic community accounts for one order of magnitude less biomass than the vertically migratory community, and is composed by smaller species. Second, the abundance of small fish decreases from the coast to the open ocean, while the abundance of large fish remains relatively uniform. This in turn leads to flattening of biomass size-spectra away from the coast for both communities. Third, the model reproduces a cross-shore succession of small to large sizes moving offshore, consistent with observations of species occurrence. These cross-shore variations emerge in the model from a combination of: (1) passive offshore advection by the mean current, (2) active swimming toward coastal productive regions to counterbalance this transport, and (3) mesoscale heterogeneity that reduces the ability of organisms to return to coastal waters. Our results highlight the importance of passive and active movement in structuring the pelagic food web, and suggest that a representation of these processes can help to improve the realism in simulations with marine ecosystem models.
Functional Stability of a Coastal Mediterranean Plankton Community During an Experimental Marine Heatwave
Authors: Soulié Tanguy , Vidussi Francesca , Mas Sébastien , Mostajir Behzad
Published: February 2022

As heatwaves are expected to increase in frequency and intensity in the Mediterranean Sea due to global warming, we conducted an in situ mesocosm experiment for 20 days during the late spring and early summer of 2019 in a coastal Mediterranean lagoon to investigate the effects of heatwaves on the composition and function of coastal plankton communities. A heatwave was simulated by elevating the water temperature of three mesocosms to +3°C while three control mesocosms had natural lagoon water temperature, for 10 days. Further, the heating procedure was halted for 10 days to study the resilience and recovery of the system. Automated high frequency monitoring of dissolved oxygen concentration and saturation, chlorophyll-a fluorescence, photosynthetic active radiation, salinity, and water temperature was completed with manual sampling for nutrient and phytoplankton pigment analyses. High-frequency data were used to estimate different functional processes: gross primary production (GPP), community respiration (R), and phytoplankton growth (μ), and loss (l) rates. Ecosystem stability was assessed by calculating resistance, resilience, recovery, and temporal stability in terms of the key functions (GPP, R, μ, and l). Meanwhile, the composition of phytoplankton functional types (PFT) was assessed through chemotaxonomic pigment composition. During the heatwave, GPP, R, μ, and l increased by 31, 49, 16, and 21%, respectively, compared to the control treatment. These positive effects persisted several days after the offset of the heatwave, resulting in low resilience in these key functions. However, GPP and R recovered almost completely at the end of the experiment, suggesting that the effect of the heatwave on these two rates was reversible. The heatwave also affected the PFT composition, as diatoms, prymnesiophytes, and cyanobacteria were favored, whereas dinoflagellates were negatively affected. By highlighting important effects of a simulated marine heatwave on the metabolism and functioning of a coastal Mediterranean plankton community, this study points out the importance to extend this type of experiments to different sites and conditions to improve our understanding of the impacts of this climate-change related stressor that will grow in frequency and intensity in the future.
The Chemical Structure Properties and Promoting Biofilm Activity of Exopolysaccharide Produced by Shigella flexneri
Authors: Song Yinglong , Ma Fenglian , Sun Mengying , Mu Guangqing , Tuo Yanfeng
Published: February 2022

Shigella flexneri is a waterborne and foodborne pathogen that can damage human health. The exopolysaccharides (S-EPS) produced by S. flexneri CMCC51574 were found to promote biofilm formation and virulence. In this research, the crude S-EPS produced by S. flexneri CMCC51574 were separated into three main different fractions, S-EPS 1-1, S-EPS 2-1, and S-EPS 3-1. The structure of the S-ESP 2-1 was identified by FT-IR, ion chromatography analysis, methylation analysis, and NMR analysis. The main chain of S-EPS 2-1 was α-Manp-(1 → 3)-α-Manp-[(1 → 2,6)-α-Manp]15-[(1 → 2)-Manf-(1→]8; there were two branched-chain R1 and R2 with a ratio of 4:1, R1: α-Manp-(1 → 6)- and R2: α-Manp-(1 → 6)- Glc-(1 → 6)- were linked with (1 → 2,6)-α-Manp. It was found that S-EPS 2-1 exhibited the highest promoting effect on biofilm formation of S. flexneri. The S-EPS 2-1 was identified to interact with extracellular DNA (eDNA) of S. flexneri, indicating that the S-EPS 2-1 was the specific polysaccharide in the spatial structure of biofilm formation. Our research found the important role of S-EPS in S. flexneri biofilm formation, which will help us to understand the underlining mechanisms of the biofilm formation and find effective ways to prevent S. flexneri biofilm infection.
Mapping of Brain Activity in the Analgesia Induced by Phα1β and Morphine
Authors: Diniz Danuza Montijo , Malamut Carlos , Araújo Marina Rios , Ferreira Andrea Vidal , Silva Juliana Figueira , Cordeiro Marta do Nascimento , Borges Marcia Helena , Romano Silva Marco Aurélio , Gomez Marcus Vinicius , Castro Junior Célio Jose
Published: February 2022

Preclinical evidence suggests the potential of Phα1β, a toxin obtained from the venom of spider Phoneutria nigriventer, as a new analgesic drug. Molecular brain imaging techniques have afforded exciting opportunities to examine brain processes in clinical pain conditions. This paper aims to study the brain regions involved in the analgesic effects of Phα1β compared with Morphine, in a model of acute pain induced by formalin in Sprague Dawley rats. We used 18F-fluorodeoxyglucose as a metabolic radiotracer to perform brain imaging of rats pretreated with Phα1β or Morphine in a model of acute inflammatory pain caused by intraplantar injection of formalin. The rats’ hind paw’s formalin stimulation resulted in a brain metabolic increase at the bilateral motor cortex, visual cortex, somatosensory cortex, thalamus, and cingulate cortex.In rats treated with Phα1β, selective inhibition of unilateral motor cortex and cingulate cortex was observed. Morphine treatment leads to small and selective inhibition at the bilateral amygdala striatum and accumbens. Our results indicate that the analgesic effect of Phα1β and Morphine possesses a differential profile of central processing in the pain state.
Major Bleeding Risk in Patients With Non-valvular Atrial Fibrillation Concurrently Taking Direct Oral Anticoagulants and Antidepressants
Authors: Chang Kuo-Hsuan , Chen Chiung-Mei , Wang Chun-Li , Tu Hui-Tzu , Huang Yu-Tung , Wu Hsiu-Chuan , Chang Chien-Hung , Chang Shang-Hung
Published: February 2022

Direct oral anticoagulants (DOACs) are commonly prescribed with antidepressants that may increase bleeding risk. Here we assessed the association between DOACs with and without concurrent antidepressants and major bleeding risk in patients with atrial fibrillation (AF) by a retrospective cohort study included patients with AF who received prescriptions of DOACs in Taiwan’s National Health Insurance database between 2012 and 2017. Adjusted rate ratio (ARR) of major bleeding was calculated by comparing incidence rate adjusted with Poisson regression and inverse probability of treatment weighting using the propensity score between patient-times with and without antidepressants. Among 98863 patients with AF, concurrent use of bupropion with DOACs increased the risks of all major bleeding (ARR: 1.49, 95% CI: 1.02–2.16) and gastrointestinal hemorrhage (ARR: 1.57, 95% CI: 1.04–2.33). An increased risk of intracerebral hemorrhage (ICH) was associated with the combinations of DOACs with selective serotonin reuptake inhibitors (SSRIs, ARR: 1.38, 95% CI: 1.08–1.76), particularly in paroxetine (ARR: 2.11, 95% CI: 1.17–3.81), and tetracyclic antidepressants (TeCAs, ARR: 1.34, 95% CI: 1.01–1.78). In subgroup analyses stratified by individual NOACs, SSRIs increased the risk of ICH in the dabigatran-treated patients (ARR: 1.55, 95% CI: 1.04–2.33). The combinations of apixaban and serotonin-norepinephrine reuptake inhibitors (SNRIs) were associated with a higher risk of all major bleeding (ARR: 1.63, 95% CI: 1.04–2.55). These results clearly indicate the drug–drug interactions between DOACs and antidepressants, which should be carefully considered when prescribing DOACs in adult patients. Careful monitoring for bleeding should be performed while concurrently prescribing DOACs with bupropion, SSRI, SNRI, and TeCA. Concomitant use of DOACs and TCAs may be a relatively safe strategy for patients with AF.
Blind Face Restoration via Multi-Prior Collaboration and Adaptive Feature Fusion
Authors: Teng Zi , Yu Xiaosheng , Wu Chengdong
Published: February 2022

Blind face restoration (BFR) from severely degraded face images is important in face image processing and has attracted increasing attention due to its wide applications. However, due to the complex unknown degradations in real-world scenarios, existing priors-based methods tend to restore faces with unstable quality. In this article, we propose a multi-prior collaboration network (MPCNet) to seamlessly integrate the advantages of generative priors and face-specific geometry priors. Specifically, we pretrain a high-quality (HQ) face synthesis generative adversarial network (GAN) and a parsing mask prediction network, and then embed them into a U-shaped deep neural network (DNN) as decoder priors to guide face restoration, during which the generative priors can provide adequate details and the parsing map priors provide geometry and semantic information. Furthermore, we design adaptive priors feature fusion (APFF) blocks to incorporate the prior features from pretrained face synthesis GAN and face parsing network in an adaptive and progressive manner, making our MPCNet exhibits good generalization in a real-world application. Experiments demonstrate the superiority of our MPCNet in comparison to state-of-the-arts and also show its potential in handling real-world low-quality (LQ) images from several practical applications.
Alterations of the Hippocampal Networks in Valproic Acid-Induced Rat Autism Model
Authors: Bódi Veronika , Májer Tímea , Kelemen Viktor , Világi Ildikó , Szűcs Attila , Varró Petra
Published: February 2022

Autism Spectrum Disorder (ASD) is one of the most frequently diagnosed neurodevelopmental disorders, characterized among others by impairments in social interactions and repetitive behavior. According to one of the leading hypotheses about its origin, ASD is caused by the imbalance of excitatory and inhibitory circuit activity. ASD-related morphological and functional changes can be observed in several brain regions i.e., in the prefrontal cortex and the hippocampus. It is well-established that prenatal valproic-acid (VPA) exposure of rats on day 12.5 leads to neurodevelopmental alterations with autism-like clinical and behavioral symptoms. The aim of this study was to investigate potential changes in the excitability of neuronal networks and individual neurons of the hippocampus elicited by prenatal VPA treatment. As there are marked sex differences in ASD, offspring of both sexes were systematically tested, using two different age groups, to elucidate eventual differences in neurodevelopment after VPA treatment. Excitatory connections and long-term synaptic plasticity as well as intrinsic excitability of CA1 pyramidal cells were examined. Pregnant female Wistar rats received saline or 500 mg/kg VPA i. p. on gestation day 12.5. Brain slices of 6-week-old and 3-month-old offspring were investigated using extra- and intracellular electrophysiological techniques. Field potential- and whole-cell patch clamp recordings were carried out to measure network excitability and single cell activity in the CA1 region hippocampus. Enhanced excitability of hippocampal networks was detected in the 6-week-old VPA-treated male rats; however, this change could not be observed in 3-month-old males. Intrinsic excitability of single neurons, however, was increased in 3-month-old males. In 6-week-old treated females, the most prominent effect of VPA was an increase in voltage sag, to a similar degree to the neurons of the older age group. In 3-month-old females, a network excitability increase could be demonstrated, in a lesser degree than in younger males. It can be concluded, that VPA treatment had diverse effects on hippocampal excitability depending on the sex and the age of the animals. We found that certain alterations manifested in 6-week-old rats were compensated later, on the other hand, other changes persisted until the age of 3 months.
Analytic Model for Feature Maps in the Primary Visual Cortex
Authors: Liu Xiaochen , Robinson Peter A.
Published: February 2022

A compact analytic model is proposed to describe the combined orientation preference (OP) and ocular dominance (OD) features of simple cells and their mutual constraints on the spatial layout of the combined OP-OD map in the primary visual cortex (V1). This model consists of three parts: (i) an anisotropic Laplacian (AL) operator that represents the local neural sensitivity to the orientation of visual inputs; and (ii) obtain a receptive field (RF) operator that models the anisotropic spatial projection from nearby neurons to a given V1 cell over scales of a few tenths of a millimeter and combines with the AL operator to give an overall OP operator; and (iii) a map that describes how the parameters of these operators vary approximately periodically across V1. The parameters of the proposed model maximize the neural response at a given OP with an OP tuning curve fitted to experimental results. It is found that the anisotropy of the AL operator does not significantly affect OP selectivity, which is dominated by the RF anisotropy, consistent with Hubel and Wiesel's original conclusions that orientation tuning width of V1 simple cell is inversely related to the elongation of its RF. A simplified and idealized OP-OD map is then constructed to describe the approximately periodic local OP-OD structure of V1 in a compact form. It is shown explicitly that the OP map can be approximated by retaining its dominant spatial Fourier coefficients, which are shown to suffice to reconstruct its basic spatial structure. Moreover, this representation is a suitable form to analyze observed OP maps compactly and to be used in neural field theory (NFT) for analyzing activity modulated by the OP-OD structure of V1. Application to independently simulated V1 OP structure shows that observed irregularities in the map correspond to a spread of dominant coefficients in a circle in Fourier space. In addition, there is a strong bias toward two perpendicular directions when only a small patch of local map is included. The bias is decreased as the amount of V1 included in the Fourier transform is increased.
The Triglyceride Glucose Index Is a Risk Factor for Enlarged Perivascular Space
Authors: Cai Yazhen , Chen Binxiong , Zeng Xiaoyi , Xie Meirong , Wei Xiaolan , Cai Jiangping
Published: February 2022

The triglyceride glucose (TyG) index is considered a simple surrogate marker for insulin resistance and has been associated with cerebrovascular diseases. However, limited information is available regarding its association with the subclinical cerebral small vessel disease (CSVD). Here, we investigated the association of TyG index with the burden and distribution of enlarged perivascular space (EPVS) in the non-diabetic population. The data of 531 non-diabetic patients from 2017 to 2020 were assessed. Participants were grouped according to the burden of EPVS. TyG index was calculated using the log scale of fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2. The association of TyG index with EPVS burden and distribution was evaluated. In the multivariable logistic regression analysis, the TyG index was associated with moderate to severe EPVS [odds ratio (OR): 2.077; 95% CI = 1.268–3.403]. The TyG index was significantly associated with an increased risk of moderate to severe EPVS in subgroups of age <65 years, male, diastolic blood pressure (DBP) <90 mmHg, low-density lipoprotein cholesterol (LDL-C) ≥2.85 mmol/L, serum homocysteine <10 μmol/L, and estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2, as well as those without smoking. Further analysis of EPVS distribution, the TyG index was found to be associated with moderate to severe EPVS in the centrum semiovale (CSO), not in the basal ganglia (BG). Conclusively, the TyG index was independently and positively associated with moderate to severe CSO EPVS. TyG index may serve as an independent risk factor for CSVD in clinical practice.
A Study of Word Complexity Under Conditions of Non-experimental, Natural Overt Speech Production Using ECoG
Authors: Glanz Olga , Hader Marina , Schulze-Bonhage Andreas , Auer Peter , Ball Tonio
Published: February 2022

The linguistic complexity of words has largely been studied on the behavioral level and in experimental settings. Only little is known about the neural processes underlying it in uninstructed, spontaneous conversations. We built up a multimodal neurolinguistic corpus composed of synchronized audio, video, and electrocorticographic (ECoG) recordings from the fronto-temporo-parietal cortex to address this phenomenon based on uninstructed, spontaneous speech production. We performed extensive linguistic annotations of the language material and calculated word complexity using several numeric parameters. We orthogonalized the parameters with the help of a linear regression model. Then, we correlated the spectral components of neural activity with the individual linguistic parameters and with the residuals of the linear regression model, and compared the results. The proportional relation between the number of consonants and vowels, which was the most informative parameter with regard to the neural representation of word complexity, showed effects in two areas: the frontal one was at the junction of the premotor cortex, the prefrontal cortex, and Brodmann area 44. The postcentral one lay directly above the lateral sulcus and comprised the ventral central sulcus, the parietal operculum and the adjacent inferior parietal cortex. Beyond the physiological findings summarized here, our methods may be useful for those interested in ways of studying neural effects related to natural language production and in surmounting the intrinsic problem of collinearity between multiple features of spontaneously spoken material.
Regional Haemodynamic and Metabolic Coupling in Infants
Authors: Siddiqui Maheen F. , Pinti Paola , Lloyd-Fox Sarah , Jones Emily J. H. , Brigadoi Sabrina , Collins-Jones Liam , Tachtsidis Ilias , Johnson Mark H. , Elwell Clare E.
Published: February 2022

Metabolic pathways underlying brain function remain largely unexplored during neurodevelopment, predominantly due to the lack of feasible techniques for use with awake infants. Broadband near-infrared spectroscopy (bNIRS) provides the opportunity to explore the relationship between cerebral energy metabolism and blood oxygenation/haemodynamics through the measurement of changes in the oxidation state of mitochondrial respiratory chain enzyme cytochrome-c-oxidase (ΔoxCCO) alongside haemodynamic changes. We used a bNIRS system to measure ΔoxCCO and haemodynamics during functional activation in a group of 42 typically developing infants aged between 4 and 7 months. bNIRS measurements were made over the right hemisphere over temporal, parietal and central cortical regions, in response to social and non-social visual and auditory stimuli. Both ΔoxCCO and Δ[HbO2] displayed larger activation for the social condition in comparison to the non-social condition. Integration of haemodynamic and metabolic signals revealed networks of stimulus-selective cortical regions that were not apparent from analysis of the individual bNIRS signals. These results provide the first spatially resolved measures of cerebral metabolic activity alongside haemodynamics during functional activation in infants. Measuring synchronised changes in metabolism and haemodynamics have the potential for uncovering the development of cortical specialisation in early infancy.
Magnitude Estimates Orchestrate Hierarchal Construction of Context-Dependent Representational Maps for Vestibular Space and Time: Theoretical Implications for Functional Dizziness
Authors: Arshad Qadeer , Saman Yougan , Sharif Mishaal , Kaski Diego , Staab Jeffrey P.
Published: February 2022

Maintaining balance necessitates an accurate perceptual map of the external world. Neuro-physiological mechanisms of locomotor control, sensory perception, and anxiety systems have been viewed as separate entities that can on occasion affect each other (i.e., walking on ice). Emerging models are more integrated, that envision sensory perception and threat assessment as a fundamental component of balance. Here we present an empirically based theoretical argument that vestibular cortical areas construct magnitude estimates of our environment via neural integration of incoming sensory signals. In turn, these cortically derived magnitude estimates, construct context-dependent vestibulo-spatial and vestibulo-temporal, representational maps of the external world, and ensure an appropriate online scaling factor for associated action-perceptual risk. Thus, threat signals are able to exert continuous influence on planning movements, predicting outcomes of motion of self and surrounding objects, and adjusting tolerances for discrepancies between predicted and actual estimates. Such a process affects the degree of conscious attention directed to spatial and temporal aspects of motion stimuli, implying that maintaining balance may follow a Bayesian approach in which the relative weighting of vestibulo-spatial and vestibulo-temporal signals and tolerance for discrepancies are adjusted in accordance with the level of threat assessment. Here, we seek to mechanistically explain this process with our novel empirical concept of a Brainstem Cortical Scaling Metric (BCSM), which we developed from a series of neurophysiological studies illustrating the central role of interhemispheric vestibulo-cortical asymmetries for balance control. We conclude by using the BCSM to derive theoretical predictions of how a dysfunctional BCSM can mechanistically account for functional dizziness.
Metabolomic Comparison of Patients With Colorectal Cancer at Different Anticancer Treatment Stages
Authors: Li Zhuofei , Deng Xingming , Luo Jun , Lei Yunpeng , Jin Xinghan , Zhu Jing , Lv Guoqing
Published: February 2022

Background

The difficulties of early diagnosis of colorectal cancer (CRC) result in a high mortality rate. The ability to predict the response of a patient to surgical resection or chemotherapy may be of great value for clinicians when planning CRC treatments. Metabolomics is an emerging tool for biomarker discovery in cancer research. Previous reports have indicated that the metabolic profile of individuals can be significantly altered between CRC patients and healthy controls. However, metabolic changes in CRC patients at different treatment stages have not been explored.

Methods

To this end, we performed nuclear magnetic resonance (NMR)-based metabolomic analysis to determine metabolite aberrations in CRC patients before and after surgical resection or chemotherapy. In general, a total of 106 urine samples from four clinical groups, namely, healthy volunteers (n = 31), presurgery CRC patients (n = 25), postsurgery CRC patients (n = 25), and postchemotherapy CRC patients (n = 25), were collected and subjected to further analysis.

Results

In the present study, we identified five candidate metabolites, namely, N-phenylacetylglycine, succinate, 4-hydroxyphenylacetate, acetate, and arabinose, in CRC patients compared with healthy individuals, three of which were reported for the first time. Furthermore, approximately ten metabolites were uniquely identified at each stage of CRC treatment, serving as good candidates for biomarker panel selection.

Conclusion

In summary, these potential metabolite candidates may provide promising early diagnostic and monitoring approaches for CRC patients at different anticancer treatment stages.
The Potential Diagnostic and Prognostic Value of Circulating MicroRNAs in the Assessment of Patients With Prostate Cancer: Rational and Progress
Authors: Samami Elham , Pourali Ghazaleh , Arabpour Mahla , Fanipakdel Azar , Shahidsales Soodabeh , Javadinia Seyed Alireza , Hassanian Seyed Mahdi , Mohammadparast Saeid , Avan Amir
Published: February 2022

Prostate cancer (P.C.) is one of the most frequent diagnosed cancers among men and the first leading cause of death with an annual incidence of 1.4 million worldwide. Prostate-specific antigen is being used for screening/diagnosis of prostate disease, although it is associated with several limitations. Thus, identification of novel biomarkers is warranted for diagnosis of patients at earlier stages. MicroRNAs (miRNAs) are recently being emerged as potential biomarkers. It has been shown that these small molecules can be circulated in body fluids and prognosticate the risk of developing P.C. Several miRNAs, including MiR-20a, MiR-21, miR-375, miR-378, and miR-141, have been proposed to be expressed in prostate cancer. This review summarizes the current knowledge about possible molecular mechanisms and potential application of tissue specific and circulating microRNAs as diagnosis, prognosis, and therapeutic targets in prostate cancer.
Altered Behavior in Encephalitis: Insights From the Australian Childhood Encephalitis Study, 2013–2018
Authors: Burrell Rebecca , Jones Cheryl A. , Britton Philip N. ,   The PAEDS Network
Published: February 2022

Altered mental status is a major criterion for a diagnosis of encephalitis to be made with alteration in behavior, a key manifestation of altered mental status. We reviewed all evaluated cases identified by the Australian Childhood Encephalitis study between May 2013 and June 2018, to review the frequency and features of altered behavior (ALB). ALB was reported in >72% of cases of childhood encephalitis in all three major etiologic groups (infectious, immune-mediated, and unknown). The duration of ALB was >7 days in a minority, but significantly more frequent in immune-mediated compared with infectious encephalitis (27 and 10%, respectively, p < 0.01). ALB was most frequently characterized as irritability/agitation (47%), which predominated in children aged <1 year, and among the leading infectious causes in this age group (enterovirus, parechovirus, and bacterial meningoencephalitis). ALB in the form of disorientation/confusion (25%) was most prominent in those aged >1 year and most frequent in immune-mediated encephalitis. Hallucinations, paranoia, and aggression were all infrequent; suicidality/self-harm was not observed. ALB was reported in 20 of 21 cases of anti-N-methyl-d-aspartate receptor (anti-NMDAr), 19% for >7 days, and disorientation/confusion was the most frequent feature. Only one case was reported as presenting with “psychosis” and was diagnosed with anti-NMDAr encephalitis. Clinician-reported ALB is frequent but most often non-specific in childhood encephalitis. A longer duration of ALB is associated with an immune-mediated cause. More specific psychiatric symptoms (hallucinations, paranoia) are very infrequent. ALB is a hallmark of anti-NMDAr encephalitis, but psychosis is uncommon in contrast to the disorder in adults.
THRIVE Conceptual Framework and Study Protocol: A Community-Partnered Longitudinal Multi-Cohort Study to Promote Child and Youth Thriving, Health Equity, and Community Strength
Authors: Ettinger Anna K. , Landsittel Doug , Abebe Kaleab Z. , Bey Jamil , Chavis Val , Navratil Judith D. , Savage Friedman Felicia , Dermody Terence S. , Miller Elizabeth ,   the Pittsburgh Study Committee Co-Leads
Published: February 2022

Background

Given the profound inequities in maternal and child health along racial, ethnic, and socioeconomic lines, strength-based, community-partnered research is required to foster thriving children, families, and communities, where thriving is defined as optimal development across physical, mental, cognitive, and social domains. The Pittsburgh Study (TPS) is a community-partnered, multi-cohort study designed to understand and promote child and youth thriving, build health equity, and strengthen communities by integrating community partners in study design, implementation, and dissemination. TPS launched the Tracking Health, Relationships, Identity, EnVironment, and Equity (THRIVE) Study to evaluate children's developmental stages and contexts from birth through completion of high school and to inform a child health data hub accessible to advocates, community members, educators, health professionals, and policymakers.

Methods and Analysis

TPS is rooted in community-partnered participatory research (CPPR), health equity, antiracism, and developmental science. Using our community-informed conceptual framework of child thriving, the THRIVE Study will assess cross-cutting measures of place, environment, health service use, and other social determinants of health to provide longitudinal associations with developmentally appropriate child and youth thriving outcomes across participants in six cohorts spanning from pregnancy through adolescence (child ages 0-18 years). Data from electronic health records, school records, and health and human services use are integrated to assess biological and social influences of thriving. We will examine changes over time using paired t-tests and adjusted linear regression models for continuous thriving scores and McNemar tests and adjusted logistic regression models for categorical outcomes (thriving/not thriving). Data analyses will include mixed models with a random intercept (in combination with the previously-specified types of regression models) to account for within-subject correlation.

Discussion

By enhancing assessment of child and youth well-being, TPS will fill critical gaps in our understanding of the development of child and youth thriving over time and test strategies to support thriving in diverse communities and populations. Through CPPR and co-design, the study aims to improve child health inequities across multiple socioecological levels and developmental domains.