bluuebunny/crossref_metadata_2025 huggingface dataset:
Socializing Models During Lactation Alter Colonic Mucosal Gene Expression and Fecal Microbiota of Growing Piglets
Authors: Bi Yanju , Wei Haidong , Nian Haoyang , Liu Runze , Ji Wenbo , Liu Honggui , Bao Jun
Published: July 2022

The enrichment of the social environment during lactation alleviates the stress of weaned piglets. It is significant to understand how the enriched social environment improves the weaning stress of piglets. RNA sequencing (RNA-seq) of colonic mucosa, 16S rRNA sequencing of feces, and short-chain fatty acids (SCFAs) of colonic content were used to determine the effects of social contact during lactation. In this study, thirty litter lactating piglets were divided into intermittent social contact (ISC) group that contacted with neighbors intermittently, continuous social contact (CSC) group that contacted with neighbors starting at day (D) 14 after birth, and control (CON) group in which piglets were kept in their original litter. The piglets were weaned at D35 and regrouped at D36. The colonic mucosal RNA-seq, fecal microbes, and SCFAs of colonic contents of 63-day-old piglets were analyzed. The results of RNA-seq showed that compared with the CON group, the pathways of digestion and absorption of minerals, protein, and vitamins of piglets were changed in the ISC group, whereas the pathways of retinol metabolism and nitrogen metabolism in the colonic mucosal were affected and stimulated the immune response in the CSC group. Compared with the CON group, the abundances of pernicious microorganisms (Desulfovibrio, Pseudomonas, Brevundimonas, etc.) in the CSC group and pernicious microorganisms (Desulfovibrio, Neisseria, Sutterella, etc.) and beneficial bacteria (Bifidobacterium, Megamonas, and Prevotella_9) in the ISC group were significantly higher (p < 0.05). The abundances of proinflammatory bacteria (Coriobacteriaceae_unclassified, Coprococcus_3, and Ruminococcus_2) in the CSC group were significantly increased (p < 0.05), but the abundances of SCFAs producing bacteria (Lachnospiraceae_UCG-010, Parabacteroides, Anaerotruncus, etc.) and those of anti-inflammatory bacteria (Eubacterium, Parabacteroides, Ruminiclostridium_9, and Alloprevotella) were significantly reduced (p < 0.05) in the CSC group. Compared with the CON group, the concentrations of microbial metabolites, acetate, and propionate in the colonic contents were reduced (p < 0.05) in the ISC group, whereas the concentration of acetate was reduced (p < 0.05) in the CSC group. Therefore, both ISC and CSC during lactation affected the composition of fecal microbes and changed the expression of intestinal mucosal genes related to nutrient metabolism and absorption of piglets.
Auxiliary Metabolic Gene Functions in Pelagic and Benthic Viruses of the Baltic Sea
Authors: Heyerhoff Benedikt , Engelen Bert , Bunse Carina
Published: July 2022

Marine microbial communities are facing various ecosystem fluctuations (e.g., temperature, organic matter concentration, salinity, or redox regimes) and thus have to be highly adaptive. This might be supported by the acquisition of auxiliary metabolic genes (AMGs) originating from virus infections. Marine bacteriophages frequently contain AMGs, which allow them to augment their host’s metabolism or enhance virus fitness. These genes encode proteins for the same metabolic functions as their highly similar host homologs. In the present study, we analyzed the diversity, distribution, and composition of marine viruses, focusing on AMGs to identify their putative ecologic role. We analyzed viruses and assemblies of 212 publicly available metagenomes obtained from sediment and water samples across the Baltic Sea. In general, the virus composition in both compartments differed compositionally. While the predominant viral lifestyle was found to be lytic, lysogeny was more prevalent in sediments than in the pelagic samples. The highest proportion of AMGs was identified in the genomes of Myoviridae. Overall, the most abundantly occurring AMGs are encoded for functions that protect viruses from degradation by their hosts, such as methylases. Additionally, some detected AMGs are known to be involved in photosynthesis, 7-cyano-7-deazaguanine synthesis, and cobalamin biosynthesis among other functions. Several AMGs that were identified in this study were previously detected in a large-scale analysis including metagenomes from various origins, i.e., different marine sites, wastewater, and the human gut. This supports the theory of globally conserved core AMGs that are spread over virus genomes, regardless of host or environment.
Temporal Changes in Fecal Unabsorbed Carbohydrates Relative to Perturbations in Gut Microbiome of Neonatal Calves: Emerging of Diarrhea Induced by Extended-Spectrum β-lactamase-Producing Enteroaggregative Escherichia coli
Authors: He Zhiyuan , Ma Yulin , Chen Xu , Yang Sirui , Zhang Shuyuan , Liu Shuai , Xiao Jianxin , Wang Yajing , Wang Wei , Yang Hongjian , Li Shengli , Cao Zhijun
Published: July 2022

Early gut microbiota development and colonization are crucial for the long-term health and performance of ruminants. However, cognition among these microbiota is still vague, particularly among the neonatal dairy calves. Here, extended-spectrum β-lactamase-producing enteroaggregative E. coli (ESBL-EAEC)-induced temporal changes in diversity, stability, and composition of gut microbiota were investigated among the neonatal female calves, with the view of discerning potential biomarkers of this arising diarrhea cases in local pastures. Nearly, 116 newborn calves were enrolled in this time period study during their first 2 weeks of life, and a total of 40 selected fecal samples from corresponding calves were used in this study. The results revealed that differentiated gut microbiome and metabolome discerned from neonatal calves were accompanied by bacterial infections over time. Commensal organisms like Butyricicoccus, Faecalibacterium, Ruminococcus, Collinsella, and Coriobacterium, as key microbial markers, mainly distinguish “healthy” and “diarrheic” gut microbiome. Random forest machine learning algorithm indicated that enriched fecal carbohydrates, including rhamnose and N-acetyl-D-glucosamine, and abundant short-chain fatty acids (SCFAs) existed in healthy ones. In addition, Spearman correlation results suggested that the presence of Butyricicoccus, Faecalibacterium, Collinsella, and Coriobacterium, key commensal bacteria of healthy calves, is positively related to high production of unabsorbed carbohydrates, SCFAs, and other prebiotics, and negatively correlated to increased concentrations of lactic acid, hippuric acid, and α-linolenic acid. Our data suggested that ESBL-EAEC-induced diarrhea in female calves could be forecasted by alterations in the gut microbiome and markedly changed unabsorbed carbohydrates in feces during early lives, which might be conducive to conduct early interventions to ameliorate clinical symptoms of diarrhea induced by the rising prevalence of ESBL-EAEC.
Resistome Analysis of Global Livestock and Soil Microbiomes
Authors: Lawther Katie , Santos Fernanda Godoy , Oyama Linda Boniface , Rubino Francesco , Morrison Steven , Creevey Chris J. , McGrath John W. , Huws Sharon Ann
Published: July 2022

Antimicrobial resistance (AMR) is a serious threat to public health globally; it is estimated that AMR bacteria caused 1.27 million deaths in 2019, and this is set to rise to 10 million deaths annually. Agricultural and soil environments act as antimicrobial resistance gene (ARG) reservoirs, operating as a link between different ecosystems and enabling the mixing and dissemination of resistance genes. Due to the close interactions between humans and agricultural environments, these AMR gene reservoirs are a major risk to both human and animal health. In this study, we aimed to identify the resistance gene reservoirs present in four microbiomes: poultry, ruminant, swine gastrointestinal (GI) tracts coupled with those from soil. This large study brings together every poultry, swine, ruminant, and soil shotgun metagenomic sequence available on the NCBI sequence read archive for the first time. We use the ResFinder database to identify acquired antimicrobial resistance genes in over 5,800 metagenomes. ARGs were diverse and widespread within the metagenomes, with 235, 101, 167, and 182 different resistance genes identified in the poultry, ruminant, swine, and soil microbiomes, respectively. The tetracycline resistance genes were the most widespread in the livestock GI microbiomes, including tet(W)_1, tet(Q)_1, tet(O)_1, and tet(44)_1. The tet(W)_1 resistance gene was found in 99% of livestock GI tract microbiomes, while tet(Q)_1 was identified in 93%, tet(O)_1 in 82%, and finally tet(44)_1 in 69%. Metatranscriptomic analysis confirmed these genes were “real” and expressed in one or more of the livestock GI tract microbiomes, with tet(40)_1 and tet(O)_1 expressed in all three livestock microbiomes. In soil, the most abundant ARG was the oleandomycin resistance gene, ole(B)_1. A total of 55 resistance genes were shared by the four microbiomes, with 11 ARGs actively expressed in two or more microbiomes. By using all available metagenomes we were able to mine a large number of samples and describe resistomes in 37 countries. This study provides a global insight into the diverse and abundant antimicrobial resistance gene reservoirs present in both livestock and soil microbiomes.
The Mutational Landscape of SARS-CoV-2 Variants of Concern Recovered From Egyptian Patients in 2021
Authors: Seadawy Mohamed G. , Binsuwaidan Reem , Alotaibi Badriyah , El-Masry Thanaa A. , El-Harty Bassem E. , Gad Ahmed F. , Elkhatib Walid F. , El-Bouseary Maisra M.
Published: July 2022

In December 2019, a mysterious viral pneumonia first developed in Wuhan, China, resulting in a huge number of fatal cases. This pneumonia, which was named COVID-19, was attributed to a novel coronavirus, SARS-CoV-2. The emerging SARS-CoV-2 mutations pose the greatest risk to human health because they could result in an increase in the COVID-19 severity or the failure of current vaccines. One of these notable mutations is the SARS-CoV-2 Delta variant (B.1.617) that was first detected in India and has rapidly expanded to 115 countries worldwide. Consequently, in this study, we performed next-generation sequencing and phylogenetic analysis of SARS-CoV-2 during the third wave of the pandemic to determine the SARS-CoV-2 variants of concern (VOC) prevalence in Egypt. We observed several mutational patterns, revealing that SARS-CoV-2 evolution has expanded in Egypt with a considerable increase in the number of VOC. Therefore, the Egyptian authorities should take an appropriate approach to investigate the compatibility of already employed vaccines with this VOC and to examine the efficacy of the existing therapeutic regimen against new SARS-CoV-2 variants.
Denitrification Performance in Packed-Bed Reactors Using Novel Carbon-Sulfur-Based Composite Filters for Treatment of Synthetic Wastewater and Anaerobic Ammonia Oxidation Effluent
Authors: Wang Yao , Liang Baorui , Kang Fei , Wang Youzhao , Yuan Zhihong , Lyu Zhenning , Zhu Tong , Zhang Zhijun
Published: July 2022

To avoid nitrate pollution in water bodies, two low-cost and abundant natural organic carbon sources were added to make up the solid-phase denitrification filters. This study compared four novel solid-phase carbon-sulfur-based composite filters, and their denitrification abilities were investigated in laboratory-scale bioreactors. The filter F4 (mixture of elemental sulfur powder, shell powder, and peanut hull powder with a mass ratio of 6:2.5:1.5) achieved the highest denitrification ability, with an optimal nitrate removal rate (NRR) of 723 ± 14.2 mg NO3–-N⋅L–1⋅d–1 when the hydraulic retention time (HRT) was 1 h. The HRT considerably impacted effluent quality after coupling of anaerobic ammonium oxidation (ANAMMOX) and solid-phase-based mixotrophic denitrification process (SMDP). The concentration of suspended solids (SS) of the ANAMMOX effluent may affect the performance of the coupled system. Autotrophs and heterotrophs were abundant and co-existed in all reactors; over time, the abundance of heterotrophs decreased while that of autotrophs increased. Overall, the SMDP process showed good denitrification performance and reduced the sulfate productivity in effluent compared to the sulfur-based autotrophic denitrification (SAD) process.
Indole Diketopiperazine Alkaloids Isolated From the Marine-Derived Fungus Aspergillus chevalieri MCCC M23426
Authors: Lv Dongli , Xia Jinmei , Guan Xiaoqing , Lai Qiliang , Zhang Beibei , Lin Jianhui , Shao Zongze , Luo Sulan , Zhangsun Dongting , Qin Jiang-Jiang , Wang Weiyi
Published: July 2022

Two new indole diketopiperazines (1–2) obtained from the fermentation culture of a deep-sea-derived fungus Aspergillus chevalieri MCCC M23426, were characterized, together with nine biogenetic related compounds (3–11). The structures of 1–2 were assigned based on NMR, MS, NMR calculation, DP4+ analysis, and ECD calculation. The bioactive assay showed that compounds 1, 5–7 significantly inhibited the growth of Staphylococcus aureus. Meanwhile, compound 8 potently reduced the cell viability of gastric cancer cell MKN1 with an IC50 value of 4.6 μM.
Development and Validation of a Website to Guide Decision-Making for Disorders of Consciousness
Authors: Kang Junwei , Zhong Yuan , Chen Gengfa , Huang Lianghua , Tang Yunliang , Ye Wen , Feng Zhen
Published: July 2022

Background

This study aimed to develop and validate a nomogram and present it on a website to be used to predict the overall survival at 16, 32, and 48 months in patients with prolonged disorder of consciousness (pDOC).

Methods

We retrospectively analyzed the data of 381 patients with pDOC at two centers. The data were randomly divided into training and validation sets using a ratio of 6:4. On the training set, Cox proportional hazard analyses were used to identify the predictive variables. In the training set, two models were screened by COX regression analysis, and based on clinical evidence, model 2 was eventually selected in the nomogram after comparing the receiver operating characteristic (ROC) of the two models. In the training and validation sets, ROC curves, calibration curves, and decision curve analysis (DCA) curves were utilized to measure discrimination, calibration, and clinical efficacy, respectively.

Results

The final model included age, Glasgow coma scale (GCS) score, serum albumin level, and computed tomography (CT) midline shift, all of which had a significant effect on survival after DOCs. For the 16-, 32-, and 48-month survival on the training set, the model had good discriminative power, with areas under the curve (AUCs) of 0.791, 0.760, and 0.886, respectively. For the validation set, the AUCs for the 16-, 32-, and 48-month survival predictions were 0.806, 0.789, and 0.867, respectively. Model performance was good for both the training and validation sets according to calibration plots and DCA.

Conclusion

We developed an accurate, efficient nomogram, and a corresponding website based on four correlated factors to help clinicians improve their assessment of patient outcomes and help personalize the treatment process and clinical decisions.
Aβ/Amyloid Precursor Protein-Induced Hyperexcitability and Dysregulation of Homeostatic Synaptic Plasticity in Neuron Models of Alzheimer’s Disease
Authors: Martinsson Isak , Quintino Luis , Garcia Megg G. , Konings Sabine C. , Torres-Garcia Laura , Svanbergsson Alexander , Stange Oliver , England Rebecca , Deierborg Tomas , Li Jia-Yi , Lundberg Cecilia , Gouras Gunnar K.
Published: July 2022

Alzheimer’s disease (AD) is increasingly seen as a disease of synapses and diverse evidence has implicated the amyloid-β peptide (Aβ) in synapse damage. The molecular and cellular mechanism(s) by which Aβ and/or its precursor protein, the amyloid precursor protein (APP) can affect synapses remains unclear. Interestingly, early hyperexcitability has been described in human AD and mouse models of AD, which precedes later hypoactivity. Here we show that neurons in culture with either elevated levels of Aβ or with human APP mutated to prevent Aβ generation can both induce hyperactivity as detected by elevated calcium transient frequency and amplitude. Since homeostatic synaptic plasticity (HSP) mechanisms normally maintain a setpoint of activity, we examined whether HSP was altered in AD transgenic neurons. Using methods known to induce HSP, we demonstrate that APP protein levels are regulated by chronic modulation of activity and that AD transgenic neurons have an impaired adaptation of calcium transients to global changes in activity. Further, AD transgenic compared to WT neurons failed to adjust the length of their axon initial segments (AIS), an adaptation known to alter excitability. Thus, we show that both APP and Aβ influence neuronal activity and that mechanisms of HSP are disrupted in primary neuron models of AD.
Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease
Authors: Gu Xuefeng , Lai Donglin , Liu Shuang , Chen Kaijie , Zhang Peng , Chen Bing , Huang Gang , Cheng Xiaoqin , Lu Changlian
Published: July 2022

Alzheimer's disease (AD), the most common neurodegenerative disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. Meanwhile, abnormalities in iron metabolism have been demonstrated in patients and mouse models with AD. Therefore, this study sought to find hub genes based on iron metabolism that can influence the diagnosis and treatment of AD. First, gene expression profiles were downloaded from the GEO database, including non-demented (ND) controls and AD samples. Fourteen iron metabolism-related gene sets were downloaded from the MSigDB database, yielding 520 iron metabolism-related genes. The final nine hub genes associated with iron metabolism and AD were obtained by differential analysis and WGCNA in brain tissue samples from GSE132903. GO analysis revealed that these genes were mainly involved in two major biological processes, autophagy and iron metabolism. Through stepwise regression and logistic regression analyses, we selected four of these genes to construct a diagnostic model of AD. The model was validated in blood samples from GSE63061 and GSE85426, and the AUC values showed that the model had a relatively good diagnostic performance. In addition, the immune cell infiltration of the samples and the correlation of different immune factors with these hub genes were further explored. The results suggested that these genes may also play an important role in immunity to AD. Finally, eight drugs targeting these nine hub genes were retrieved from the DrugBank database, some of which were shown to be useful for the treatment of AD or other concomitant conditions, such as insomnia and agitation. In conclusion, this model is expected to guide the diagnosis of patients with AD by detecting the expression of several genes in the blood. These hub genes may also assist in understanding the development and drug treatment of AD.
Research Progress on MRI for White Matter Hyperintensity of Presumed Vascular Origin and Cognitive Impairment
Authors: Meng Fanhua , Yang Ying , Jin Guangwei
Published: July 2022

White matter hyperintensity of presumed vascular origin (WMH) is a common medical imaging manifestation in the brains of middle-aged and elderly individuals. WMH can lead to cognitive decline and an increased risk of cognitive impairment and dementia. However, the pathogenesis of cognitive impairment in patients with WMH remains unclear. WMH increases the risk of cognitive impairment, the nature and severity of which depend on lesion volume and location and the patient's cognitive reserve. Abnormal changes in microstructure, cerebral blood flow, metabolites, and resting brain function are observed in patients with WMH with cognitive impairment. Magnetic resonance imaging (MRI) is an indispensable tool for detecting WMH, and novel MRI techniques have emerged as the key approaches for exploring WMH and cognitive impairment. This article provides an overview of the association between WMH and cognitive impairment and the application of dynamic contrast-enhanced MRI, structural MRI, diffusion tensor imaging, 3D-arterial spin labeling, intravoxel incoherent motion, magnetic resonance spectroscopy, and resting-state functional MRI for examining WMH and cognitive impairment.
Functional MRI Correlates of Carbon Dioxide Chemosensing in Persons With Epilepsy
Authors: Hampson Johnson P. , Lacuey Nuria , Rani MR Sandhya , Hampson Jaison S. , Simeone Kristina A. , Simeone Timothy A. , Narayana Ponnada A. , Lemieux Louis , Lhatoo Samden D.
Published: July 2022

Objectives

Sudden unexpected death in epilepsy (SUDEP) is a catastrophic epilepsy outcome for which there are no reliable premortem imaging biomarkers of risk. Percival respiratory depression is seen in monitored SUDEP and near SUDEP cases, and abnormal chemosensing of raised blood carbon dioxide (CO2) is thought to contribute. Damage to brainstem respiratory control and chemosensing structures has been demonstrated in structural imaging and neuropathological studies of SUDEP. We hypothesized that functional MRI (fMRI) correlates of abnormal chemosensing are detectable in brainstems of persons with epilepsy (PWE) and are different from healthy controls (HC).

Methods

We analyzed fMRI BOLD activation and brain connectivity in 10 PWE and 10 age- and sex-matched HCs during precisely metered iso-oxic, hypercapnic breathing challenges. Segmented brainstem responses were of particular interest, along with characterization of functional connectivity metrics between these structures. Regional BOLD activations during hypercapnic challenges were convolved with hemodynamic responses, and the resulting activation maps were passed on to group-level analyses. For the functional connectivity analysis, significant clusters from BOLD results were used as seeds. Each individual seed time-series activation map was extracted for bivariate correlation coefficient analyses to study changes in brain connectivity between PWE and HCs.

Results

(1) Greater brainstem BOLD activations in PWE were observed compared to HC during hypercapnic challenges in several structures with respiratory/chemosensing properties. Group comparison between PWE vs. HC showed significantly greater activation in the dorsal raphe among PWE (p < 0.05) compared to HCs. (2) PWE had significantly greater seed-seed connectivity and recruited more structures during hypercapnia compared to HC.

Significance

The results of this study show that BOLD responses to hypercapnia in human brainstem are detectable and different in PWE compared to HC. Increased dorsal raphe BOLD activation in PWE and increased seed-seed connectivity between brainstem and adjacent subcortical areas may indicate abnormal chemosensing in these individuals. Imaging investigation of brainstem respiratory centers involved in respiratory regulation in PWE is an important step toward identifying suspected dysfunction of brainstem breathing control that culminates in SUDEP and deserve further study as potential imaging SUDEP biomarkers.
The Predictive Role of Hand Section of Fugl–Meyer Assessment and Motor Activity Log in Action Research Arm Test in People With Stroke
Authors: Chen Peiming , Liu Tai-Wa , Tse Mimi M. Y. , Lai Claudia K. Y. , Tsoh Joshua , Ng Shamay S. M.
Published: July 2022

Background:

Recent findings of clinical studies have demonstrated a significant positive relationship between Fugl–Meyer Assessment of upper extremity score and the action research arm test (ARAT) score in people with stroke. Although the motor activity log (MAL) can assess the self-perception of motor performance, which can affect the performance of the upper limb, the relationship between MAL score and ARAT score still remains unclear. The objective of this study is to quantify the independent contribution of MAL score and FMA-hand score on the ARAT score in people with stroke.

Methods

This is a cross-sectional study. There were a total of 87 subjects (50 males, 37 females; mean age = 61.12 ± 6.88 years, post-stroke duration=6.31 ± 2.84 years) included in this study. Self-perceived performance in using the paretic limb was measured by MAL, including subscale of the amount of usage (MAL-AOU) and quality of movement (MAL-QOM). Functional performance of the upper limb was measured by action research arm test (ARAT). Upper limb motor control of the hand was measured by hand section of Fugl–Meyer assessment (FMA-hand).

Results

The result showed that MAL-QOM (r = 0.648, p < 0.001), MAL-AOU (r = 0.606, p < 0.001), FMA-hand scores (r = 0.663, p < 0.001), and the use of a walking aid (r = −0.422, p < 0.001) were significantly correlated with the ARAT scores. A total 66.9% of the variance in the ARAT scores was predicted by the final regression model including MAL-QOM, MAL-AOU, FMA-hand scores, and walking aid. The FMA-hand score was the best predictor of ARAT scores, which can predict a 36.4% variance of ARAT scores in people with stroke, which controlled the effect of using a walking aid. After controlling for use of a walking aid and FMA-hand scores, the multiple linear regression modeling showed that MAL-QOM and MAL-AOU scores could also independently predict an additional 10.4% of the variance in ARAT scores.

Conclusion

In addition to the FMA-hand score, the MAL score was significantly correlated with the ARAT score. Improving self-perceived performance should be one goal of rehabilitation in people with stroke. Further work developing and testing techniques to do so is clearly warranted.
Quantitative Analysis of Diffusion-Restricted Lesions in a Differential Diagnosis of Status Epilepticus and Acute Ischemic Stroke
Authors: Machegger Lukas , Bosque Varela Pilar , Kuchukhidze Giorgi , Steinbacher Jürgen , Öllerer Andreas , Prüwasser Tanja , Zimmermann Georg , Pikija Slaven , Pfaff Johannes , Trinka Eugen , Mc Coy Mark
Published: July 2022

Background and Purpose

Distinction between acute ischemic stroke (AIS) and status epilepticus (SE) on MRI can be challenging as restricted diffusion may occur in both conditions. In this study, we aimed to test a tool, which could help in differentiating AIS from SE when restricted diffusion was present on MRI.

Materials and Methods

In diffusion weighted imaging (DWI) with a b-value of 1,000 and apparent diffusion coefficient (ADC) maps, we compared the ratios of intensities of gray values of diffusion-restricted lesions to the healthy mirror side in patients with AIS and SE. Patients were recruited prospectively between February 2019 and October 2021. All patients underwent MRI and EEG within the first 48 h of symptom onset.

Results

We identified 26 patients with SE and 164 patients with AIS. All patients had diffusion-restricted lesions with a hyperintensity in DWI and ADC signal decrease. Diffusion restriction was significantly more intense in patients with AIS as compared to patients with SE. The median ratios of intensities of gray values of diffusion-restricted lesions to the healthy mirror side for DWI were 1.42 (interquartile range [IQR] 1.32–1.47) in SE and 1.67 (IQR 1.49–1.90) in AIS (p < 0.001). ADC decrease was more significant in AIS as compared to SE with median ratios of 0.80 (IQR 0.72–0.89) vs. 0.61 (IQR 0.50–0.71), respectively (p < 0.001). A cutoff value for ratios of DWI signal was 1.495 with a sensitivity of 75% and a specificity of 85%. Values lower than 1.495 were more likely to be associated with SE and higher values were with AIS. A cutoff value for ADC ratios was 0.735 with a sensitivity of 73% and a specificity of 84%. Values lower than 0.735 were more likely to be associated with AIS and higher values were with SE.

Conclusion

Diffusion restriction and ADC decrease were significantly more intense in patients with AIS as compared to SE. Therefore, quantitative analysis of diffusion restriction may be a helpful tool for differentiating between AIS and SE when restricted diffusion is present on MRI.
Concentration of Serum Biomarkers of Brain Injury in Neonates With a Low Cord pH With or Without Mild Hypoxic-Ischemic Encephalopathy
Authors: Gaulee Pratima , Yang Zhihui , Sura Livia , Xu Haiyan , Rossignol Candace , Weiss Michael D. , Bliznyuk Nikolay
Published: July 2022

Objective

To determine the concentrations of four neuroprotein biomarkers and 68 miRNAs in neonates with low cord pH and/or mild hypoxic-ischemic encephalopathy (HIE).

Study Design

A prospective cohort study enrolled neonates with low cord pH (n = 18), moderate-severe HIE (n = 40), and healthy controls (n = 38). Groups provided serum samples at 0–6 h of life. The concentrations of biomarkers and miRNAs were compared between cohorts.

Result

The low cord pH and moderate-severe HIE groups had increased concentrations of GFAP, NFL and Tau compared to controls (P < 0.05, P < 0.001, respectively). NFL concentrations in mild HIE was higher than controls (P < 0.05) but less than moderate-severe HIE (P < 0.001). Of 68 miRNAs, 36 in low cord pH group and 40 in moderate-severe HIE were upregulated compared to controls (P < 0.05). Five miRNAs in low cord pH group (P < 0.05) and 3 in moderate-severe HIE were downregulated compared to controls (P < 0.05).

Conclusion

A biomarker panel in neonates with low cord pH may help clinicians make real-time decisions.
Vascular Cognitive Impairment After Mild Stroke: Connectomic Insights, Neuroimaging, and Knowledge Translation
Authors: Holguin Jess A. , Margetis John L. , Narayan Anisha , Yoneoka Grant M. , Irimia Andrei
Published: July 2022

Contemporary stroke assessment protocols have a limited ability to detect vascular cognitive impairment (VCI), especially among those with subtle deficits. This lesser-involved categorization, termed mild stroke (MiS), can manifest compromised processing speed that negatively impacts cognition. From a neurorehabilitation perspective, research spanning neuroimaging, neuroinformatics, and cognitive neuroscience supports that processing speed is a valuable proxy for complex neurocognitive operations, insofar as inefficient neural network computation significantly affects daily task performance. This impact is particularly evident when high cognitive loads compromise network efficiency by challenging task speed, complexity, and duration. Screening for VCI using processing speed metrics can be more sensitive and specific. Further, they can inform rehabilitation approaches that enhance patient recovery, clarify the construct of MiS, support clinician-researcher symbiosis, and further clarify the occupational therapy role in targeting functional cognition. To this end, we review relationships between insult-derived connectome alterations and VCI, and discuss novel clinical approaches for identifying disruptions of neural networks and white matter connectivity. Furthermore, we will frame knowledge translation efforts to leverage insights from cutting-edge structural and functional connectomics research. Lastly, we highlight how occupational therapists can provide expertise as knowledge brokers acting within their established scope of practice to drive substantive clinical innovation.
Sparse Hierarchical Representation Learning on Functional Brain Networks for Prediction of Autism Severity Levels
Authors: Kwon Hyeokjin , Kim Johanna Inhyang , Son Seung-Yeon , Jang Yong Hun , Kim Bung-Nyun , Lee Hyun Ju , Lee Jong-Min
Published: July 2022

Machine learning algorithms have been widely applied in diagnostic tools for autism spectrum disorder (ASD), revealing an altered brain connectivity. However, little is known about whether an magnetic resonance imaging (MRI)-based brain network is related to the severity of ASD symptoms in a large-scale cohort. We propose a graph convolution neural network-based framework that can generate sparse hierarchical graph representations for functional brain connectivity. Instead of assigning initial features for each node, we utilized a feature extractor to derive node features and the extracted representations can be fed to a hierarchical graph self-attention framework to effectively represent the entire graph. By incorporating connectivity embeddings in the feature extractor, we propose adjacency embedding networks to characterize the heterogeneous representations of the brain connectivity. Our proposed model variants outperform the benchmarking model with different configurations of adjacency embedding networks and types of functional connectivity matrices. Using this approach with the best configuration (SHEN atlas for node definition, Tikhonov correlation for connectivity estimation, and identity-adjacency embedding), we were able to predict individual ASD severity levels with a meaningful accuracy: the mean absolute error (MAE) and correlation between predicted and observed ASD severity scores resulted in 0.96, and r = 0.61 (P < 0.0001), respectively. To obtain a better understanding on how to generate better representations, we investigate the relationships between the extracted feature embeddings and the graph theory-based nodal measurements using canonical correlation analysis. Finally, we visualized the model to identify the most contributive functional connections for predicting ASD severity scores.
Identification of Candidate Genes Associated With Prognosis in Glioblastoma
Authors: Li Rongjie , Jiang Qiulan , Tang Chunhai , Chen Liechun , Kong Deyan , Zou Chun , Lin Yan , Luo Jiefeng , Zou Donghua
Published: July 2022

Background

Glioblastoma (GBM) is the most common malignant primary brain tumor, which associated with extremely poor prognosis.

Methods

Data from datasets GSE16011, GSE7696, GSE50161, GSE90598 and The Cancer Genome Atlas (TCGA) were analyzed to identify differentially expressed genes (DEGs) between patients and controls. DEGs common to all five datasets were analyzed for functional enrichment and for association with overall survival using Cox regression. Candidate genes were further screened using least absolute shrinkage and selection operator (LASSO) and random forest algorithms, and the effects of candidate genes on prognosis were explored using a Gaussian mixed model, a risk model, and concordance cluster analysis. We also characterized the GBM landscape of immune cell infiltration, methylation, and somatic mutations.

Results

We identified 3,139 common DEGs, which were associated mainly with PI3K-Akt signaling, focal adhesion, and Hippo signaling. Cox regression identified 106 common DEGs that were significantly associated with overall survival. LASSO and random forest algorithms identified six candidate genes (AEBP1, ANXA2R, MAP1LC3A, TMEM60, PRRG3 and RPS4X) that predicted overall survival and GBM recurrence. AEBP1 showed the best prognostic performance. We found that GBM tissues were heavily infiltrated by T helper cells and macrophages, which correlated with higher AEBP1 expression. Stratifying patients based on the six candidate genes led to two groups with significantly different overall survival. Somatic mutations in AEBP1 and modified methylation of MAP1LC3A were associated with GBM.

Conclusion

We have identified candidate genes, particularly AEBP1, strongly associated with GBM prognosis, which may help in efforts to understand and treat the disease.
Combined Exposure to 33 Trace Elements and Associations With the Risk of Oral Cancer: A Large-Scale Case-Control Study
Authors: Wang Huiying , Wang Jing , Cao Yujie , Chen Jinfa , Deng Qingrong , Chen Yujia , Qiu Yu , Lin Lisong , Shi Bin , Liu Fengqiong , He Baochang , Chen Fa
Published: July 2022

Background

Trace elements exist widely in the natural environment and mostly enter the human body through drinking water or various types of food, which has raised increasing health concerns. Exposure to a single or a few trace elements has been previously reported to be associated with oral cancer risk, but studies on other elements and combined effects are limited. This study aimed to comprehensively evaluate the independent and joint effects of 33 trace elements on oral cancer risk.

Methods

The concentrations of 33 trace elements from the serum samples of 463 cases and 1,343 controls were measured using inductively coupled plasma mass spectrometry (ICP-MS). Propensity score matching was used to minimize the impact of potential confounders. Conditional logistic regression was utilized to evaluate the association of each element individually with oral cancer risk. Quantile g-computation and Bayesian kernel machine regression (BKMR) models were used to assess the joint effect of the overall element mixture and interactions.

Results

In single-element models, essential elements (Cu, Se, Zn, Sr, and Cr) and non-essential elements (As, Li, Th, Ce, Ti, and Sc) showed significant association with oral cancer risk. In multiple-element models, a quartile increase in overall non-essential elements was observed for a significant inverse association with oral cancer risk (β = −3.36, 95% CI: −4.22 to −2.51). The BKMR analysis revealed a potential beneficial joint effect of essential metals on the risk of oral cancer. Among these, higher levels of serum Zn and V exhibited an adverse effect, while serum Sr, Se, and Cu displayed favorable effects when all other essential elements were fixed at 25th or 50th percentiles. Of note, Se performed complex interactions among essential metals. As for non-essential elements, there were greater effect estimates for serum Th, Li, and Y when all other elements were held at the 75th percentile.

Conclusion

This study provides supportive evidence that the overall mixture effect of essential and non-essential elements might be associated with oral cancer risk, especially for serum Zn, V, Cu, Sr, Se, Th, Li, and Y. Extensive prospective studies and other experiments are warranted to confirm our findings.
Nutrition Transition in Europe: East-West Dimensions in the Last 30 Years—A Narrative Review
Authors: Dokova Klara G. , Pancheva Rouzha Z. , Usheva Natalya V. , Haralanova Galina A. , Nikolova Silviya P. , Kostadinova Todorka I. , Egea Rodrigues Caue , Singh Jessica , Illner Anne-Kathrin , Aleksandrova Krasimira
Published: July 2022

The current review aims to summarize published research on nutrition transition patterns (depicting changes in dietary consumption) in European populations over the last three decades (1990–2020), with a focus on East-West regional comparisons. Pubmed and Google-Scholar databases were searched for articles providing information on repeated dietary intakes in populations living in countries across Europe, published between January 1990 and July 2021. From the identified 18,031 articles, 62 were found eligible for review (17 from Eastern and 45 from Western European populations). Overall, both in Eastern and Western Europe, there have been pronounced changes in dietary consumption patterns over the last three decades characterized by reductions in average reported intakes of sugar, carbohydrates and saturated fats and increases in reported fruit and vegetable consumption. There has also been a tendency toward a reduction in traditional foods, such as fish, observed in some Mediterranean countries. Overall, these data suggests that European countries have undergone a nutrition transition toward adopting healthier dietary behaviors. These processes occurred already in the period 1990–2000 in many Western European, and in the last decades have been also spreading throughout Eastern European countries. Firm conclusions are hampered by the lack of standardized methodologies depicting changes in dietary intakes over time and the limited coverage of the full variety of European populations. Future studies based on standardized dietary assessment methods and representative for the whole range of populations across Europe are warranted to allow monitoring trends in nutrition transition within and among European countries.
Infant Formula With a Specific Blend of Five Human Milk Oligosaccharides Drives the Gut Microbiota Development and Improves Gut Maturation Markers: A Randomized Controlled Trial
Authors: Bosheva Miroslava , Tokodi Istvan , Krasnow Aleksander , Pedersen Helle Krogh , Lukjancenko Oksana , Eklund Aron C. , Grathwohl Dominik , Sprenger Norbert , Berger Bernard , Cercamondi Colin I. ,   5 HMO Study Investigator Consortium
Published: July 2022

Background

Human milk oligosaccharides (HMOs) have important biological functions for a healthy development in early life.

Objective

This study aimed to investigate gut maturation effects of an infant formula containing five HMOs (2′-fucosyllactose, 2′,3-di-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose, and 6′-sialyllactose).

Methods

In a multicenter study, healthy infants (7–21 days old) were randomly assigned to a standard cow’s milk-based infant formula (control group, CG); the same formula with 1.5 g/L HMOs (test group 1, TG1); or with 2.5 g/L HMOs (test group 2, TG2). A human milk-fed group (HMG) was enrolled as a reference. Fecal samples collected at baseline (n∼150/formula group; HMG n = 60), age 3 (n∼140/formula group; HMG n = 65) and 6 (n∼115/formula group; HMG n = 60) months were analyzed for microbiome (shotgun metagenomics), metabolism, and biomarkers.

Results

At both post-baseline visits, weighted UniFrac analysis indicated different microbiota compositions in the two test groups (TGs) compared to CG (P < 0.01) with coordinates closer to that of HMG. The relative abundance of Bifidobacterium longum subsp. infantis (B. infantis) was higher in TGs vs. CG (P < 0.05; except at 6 months: TG2 vs. CG P = 0.083). Bifidobacterium abundance was higher by ∼45% in TGs vs. CG at 6-month approaching HMG. At both post-baseline visits, toxigenic Clostridioides difficile abundance was 75–85% lower in TGs vs. CG (P < 0.05) and comparable with HMG. Fecal pH was significantly lower in TGs vs. CG, and the overall organic acid profile was different in TGs vs. CG, approaching HMG. At 3 months, TGs (vs. CG) had higher secretory immunoglobulin A (sIgA) and lower alpha-1-antitrypsin (P < 0.05). At 6 months, sIgA in TG2 vs. CG remained higher (P < 0.05), and calprotectin was lower in TG1 (P < 0.05) vs. CG.

Conclusion

Infant formula with a specific blend of five HMOs supports the development of the intestinal immune system and gut barrier function and shifts the gut microbiome closer to that of breastfed infants with higher bifidobacteria, particularly B. infantis, and lower toxigenic Clostridioides difficile.

Clinical Trial Registration

[https://clinicaltrials.gov/ct2/show/], identifier [NCT03722550].
Stress and Diet Quality Among Ecuadorian Adults During the COVID-19 Pandemic. A Cross-Sectional Study
Authors: Abril-Ulloa Victoria , Santos Sueny Paloma Lima-dos , Morejón-Terán Yadira Alejandra , Carpio-Arias Tannia Valeria , Espinoza-Fajardo Ana Cristina , Vinueza-Veloz María Fernanda
Published: July 2022

Background

Stress has been associated with food habits. Stress changes eating patterns and the salience and consumption of hyperpalatable foods. During the lock-down due to the COVID-19 pandemic, stress was very common.

Objective

We investigated the association between stress and diet quality in Ecuadorian adults during the COVID-19 pandemic.

Design

A cross-sectional study.

Setting

Data was collected using a self-administered online survey. Stress was measured using the Perceived Stress Scale (PSS-14), and diet quality was evaluated using the Global Diet Index (GDI). A linear regression model with restrictive cubic splines was used to investigate the association between stress and diet quality.

Participants

Participants were recruited by convenience sampling, including a total of 2602 individuals. Most participants were female (68.57%) and had university education (78.52%), with a median age of 25 (IQR: 25, 37).

Results

Stress was reported by 26.06% of participants. The majority of individuals (75.79%) reported having a diet that needed changes or an unhealthy diet. Independently from biological sex, age, level of education, people/room ratio, economic allowance, and expenses for food, stress was statistically significantly associated with diet quality (p = 0.035). The association between stress and diet quality was inverse and non-linear; higher stress levels were associated with poorer diet quality. The consumption of palatable foods was not statistically significant associated with stress.

Conclusions

Stress is associated with poorer diet quality. Public health measures to improve the mental health and lifestyle of the population are needed during the lock-down of the pandemic.
Circulatory Level of Inflammatory Cytoskeleton Signaling Regime Proteins in Cancer Invasion and Metastasis
Authors: Singh Abhinay Kumar , Batra Atul , Upadhaya Ashish Datt , Gupta Subhash , K P Haresh , Dey Sharmistha
Published: July 2022

Early detection of metastatic breast cancer (MBC) is a serious issue for the healthcare system. It is essential to develop potential non-invasive, low-cost molecular biomarkers. The present study explored specific serum proteins of inflammatory, MAPK, and cytoskeletal signaling pathways involved in the progression of MBC to establish a panel of blood-based diagnostic and prognostic biomarkers. Healthy-control (HC), non-metastatic (NM), and metastatic (M) (pre- and post-therapy) breast cancer (BC) patients were recruited. LOX5, Rac1, Rac1b, p38α, phospho-p38α (Y182), LIMK1, phospho-LIMK1 (T508), cofilin1, and phospho-cofilin1 (S3) were quantified in the serum of the study group by real-time label-free surface plasmon resonance technology and verified by Western blot. Proteins were found to be significantly elevated in the serum of BC patients compared to HC and also higher in M compared to NM, which further downregulated in post-therapy M patients. Elevation of phospho-LIMK1 and phospho-cofilin1, which are critical for M, was also indicated in the serum level and can differentiate from NM. Receiver operating characteristics (ROC) derived area under the curve (AUC) (0.9) is very strong to differentiate between HC and BC. Moreover, the combined ROC of 3 molecules phospho-LIMK, p38α, and phospho-p38α were found to be a potent predictive panel of biomarkers between M and NM with AUC0.95. The panel of inflammatory cytoskeleton signaling regime proteins specified in this study can have significant clinical utility for diagnosis as well as prognosis of MBC at an early stage. The study may have a high translational value in a simple and cost-effective way by avoiding frequent CT/PET scans.