bluuebunny/crossref_metadata_2025 huggingface dataset:
New β-Propellers Are Continuously Amplified From Single Blades in all Major Lineages of the β-Propeller Superfamily
Authors: Pereira Joana , Lupas Andrei N.
Published: June 2022

β-Propellers are toroidal folds, in which consecutive supersecondary structure units of four anti-parallel β-strands–called blades–are arranged radially around a central axis. Uniquely among toroidal folds, blades span the full range of sequence symmetry, from near identity to complete divergence, indicating an ongoing process of amplification and differentiation. We have proposed that the major lineages of β-propellers arose through this mechanism and that therefore their last common ancestor was a single blade, not a fully formed β-propeller. Here we show that this process of amplification and differentiation is also widespread within individual lineages, yielding β-propellers with blades of more than 60% pairwise sequence identity in most major β-propeller families. In some cases, the blades are nearly identical, indicating a very recent amplification event, but even in cases where such recently amplified β-propellers have more than 80% overall sequence identity to each other, comparison of their DNA sequence shows that the amplification occurred independently.
Increased Voluntary Alcohol Consumption in Mice Lacking GABAB(1) Is Associated With Functional Changes in Hippocampal GABAA Receptors
Authors: Floris Gabriele , Asuni Gino Paolo , Talani Giuseppe , Biggio Francesca , Pisu Maria Giuseppina , Zanda Mary Tresa , Contu Liliana , Maciocco Elisabetta , Serra Mariangela , Follesa Paolo
Published: June 2022

Gamma-aminobutyric acid type B receptor (GABABR) has been extensively involved in alcohol use disorders; however, the mechanisms by which this receptor modulates alcohol drinking behavior remain murky. In this study, we investigate alcohol consumption and preference in mice lacking functional GABABR using the 2-bottle choice paradigm. We found that GABAB(1), knockout (KO), and heterozygous (HZ) mice drank higher amounts of an alcoholic solution, preferred alcohol to water, and reached higher blood alcohol concentrations (BACs) compared to wild-type (WT) littermates. The GABABR agonist GHB significantly reduced alcohol consumption in the GABAB(1) HZ and WT but not in the KO mice. Next, because of a functional crosstalk between GABABR and δ-containing GABAA receptor (δ-GABAAR), we profiled δ subunit mRNA expression levels in brain regions in which the crosstalk was characterized. We found a loss of the alcohol-sensitive GABAAR δ subunit in the hippocampus of the GABAB(1) KO alcohol-naïve mice that was associated with increased ɣ2 subunit abundance. Electrophysiological recordings revealed that these molecular changes were associated with increased phasic inhibition, suggesting a potential gain of synaptic GABAAR responsiveness to alcohol that has been previously described in an animal model of excessive alcohol drinking. Interestingly, voluntary alcohol consumption did not revert the dramatic loss of hippocampal δ-GABAAR occurring in the GABAB(1) KO mice but rather exacerbated this condition. Finally, we profiled hippocampal neuroactive steroids levels following acute alcohols administration in the GABAB(1) KO and WT mice because of previous involvement of GABABR in the regulation of cerebral levels of these compounds. We found that systemic administration of alcohol (1.5 g/kg) did not produce alcohol-induced neurosteroid response in the GABAB(1) KO mice but elicited an expected increase in the hippocampal level of progesterone and 3α,5α-THP in the WT controls. In conclusion, we show that genetic ablation of the GABAB(1) subunit results in increased alcohol consumption and preference that were associated with functional changes in hippocampal GABAAR, suggesting a potential mechanism by which preference for alcohol consumption is maintained in the GABAB(1) KO mice. In addition, we documented that GABAB(1) deficiency results in lack of alcohol-induced neurosteroids, and we discussed the potential implications of this finding in the context of alcohol drinking and dependence.
Real-Time Path Planning for Robot Using OP-PRM in Complex Dynamic Environment
Authors: Ye Lingjian , Chen Jinbao , Zhou Yimin
Published: June 2022

During task execution, the autonomous robots would likely pass through many narrow corridors along with mobile obstacles in dynamically complex environments. In this case, the off-line path planning algorithm is rather difficult to be directly implemented to acquire the available path in real-time. Hence, this article proposes a probabilistic roadmap algorithm based on the obstacle potential field sampling strategy to tackle the online path planning, called Obstacle Potential field-Probabilistic Roadmap Method (OP-PRM). The obstacle potential field is introduced to determine the obstacle area so as to construct the potential linked roadmap. Then the specific range around the obstacle boundary is justified as the target sampling area. Based on this obstacle localization, the effectiveness of the sampling points falling into the narrow corridors can be increased greatly for feasible roadmap construction. Furthermore, an incremental heuristic D* Lite algorithm is applied to search the shortest paths between the starting point and the target point on the roadmap. Simulation experiments demonstrate that the OP-PRM path planning algorithm can enable robots to search the optimal path fast from the starting point to the destination and effectively cross narrow corridors in complex dynamic environments.
Roles of Micro Ribonucleic Acids in Astrocytes After Cerebral Stroke
Authors: Zhang Yuansheng , Lei Li , Zhou Hu , Lu Xiaoyang , Cai Feifei , Li Tao
Published: June 2022

Cerebral stroke is one of the highest-ranking causes of death and the leading cause of disability globally, particularly with an increasing incidence and prevalence in developing countries. Steadily more evidence has indicated that micro ribonucleic acids (miRNAs) have important regulatory functions in gene transcription and translation in the course of cerebral stroke. It is beyond arduous to understand the pathophysiology of cerebral stroke, due in part to the perplexity of influencing the network of the inflammatory response, brain edema, autophagy and neuronal apoptosis. The recent research shows miRNA plays a key role in regulating aquaporin 4 (AQP4), and many essential pathological processes after cerebral stroke. This article reviews the recent knowledge on how miRNA influences the inflammatory response, brain edema, infarction size, and neuronal injury after cerebral stroke. In addition, some miRNAs may serve as potential biomarkers in stroke diagnosis and therapy since the expression of some miRNAs in the blood is stable after cerebral stroke.
PD-1/PD-L Axis in Neuroinflammation: New Insights
Authors: Manenti Susanna , Orrico Mario , Masciocchi Stefano , Mandelli Alessandra , Finardi Annamaria , Furlan Roberto
Published: June 2022

The approval of immune checkpoint inhibitors (ICIs) by the Food and Drug Administration (FDA) led to an improvement in the treatment of several types of cancer. The main targets of these drugs are cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein-1/programmed death-ligand 1 pathway (PD-1/PD-L1), which are important inhibitory molecules for the immune system. Besides being generally safer than common chemotherapy, the use of ICIs has been associated with several immune-related adverse effects (irAEs). Although rare, neurological adverse effects are reported within the irAEs in clinical trials, particularly in patients treated with anti-PD-1 antibodies or a combination of both anti-CTLA-4 and PD-1 drugs. The observations obtained from clinical trials suggest that the PD-1 axis may play a remarkable role in the regulation of neuroinflammation. Moreover, numerous studies in preclinical models have demonstrated the involvement of PD-1 in several neurological disorders. However, a comprehensive understanding of these cellular mechanisms remains elusive. Our review aims to summarize the most recent evidence concerning the regulation of neuroinflammation through PD-1/PD-L signaling, focusing on cell populations that are involved in this pathway.
Long Term Performance of a Bi-Directional Neural Interface for Deep Brain Stimulation and Recording
Authors: Stanslaski Scott R. , Case Michelle A. , Giftakis Jonathon E. , Raike Robert S. , Stypulkowski Paul H.
Published: June 2022

Background: In prior reports, we described the design and initial performance of a fully implantable, bi-directional neural interface system for use in deep brain and other neurostimulation applications. Here we provide an update on the chronic, long-term neural sensing performance of the system using traditional 4-contact leads and extend those results to include directional 8-contact leads.

Methods: Seven ovine subjects were implanted with deep brain stimulation (DBS) leads at different nodes within the Circuit of Papez: four with unilateral leads in the anterior nucleus of the thalamus and hippocampus; two with bilateral fornix leads, and one with bilateral hippocampal leads. The leads were connected to either an Activa PC+S® (Medtronic) or Percept PC°ledR (Medtronic) deep brain stimulation and recording device. Spontaneous local field potentials (LFPs), evoked potentials (EPs), LFP response to stimulation, and electrode impedances were monitored chronically for periods of up to five years in these subjects.

Results: The morphology, amplitude, and latencies of chronic hippocampal EPs evoked by thalamic stimulation remained stable over the duration of the study. Similarly, LFPs showed consistent spectral peaks with expected variation in absolute magnitude dependent upon behavioral state and other factors, but no systematic degradation of signal quality over time. Electrode impedances remained within expected ranges with little variation following an initial stabilization period. Coupled neural activity between the two nodes within the Papez circuit could be observed in synchronized recordings up to 5 years post-implant. The magnitude of passive LFP power recorded from directional electrode segments was indicative of the contacts that produced the greatest stimulation-induced changes in LFP power within the Papez network.

Conclusion: The implanted device performed as designed, providing the ability to chronically stimulate and record neural activity within this network for up to 5 years of follow-up.
Interoception: A Multi-Sensory Foundation of Participation in Daily Life
Authors: Schmitt Carolyn M. , Schoen Sarah
Published: June 2022

The purpose of this article is to examine evidence that broadens the clinical perspective on interoception as an imperative consideration for individuals with mental health and sensory processing challenges. The central supposition is that interoception is broader than just signals from the viscera. Rather, interoception refers to perceptions of bodily signals and bodily states that construct a subjective representation of the experience. These representations are then utilized for categorizing the sensory attributes and constructing meaning. Thus, this updated conceptualization presents interoception as a complex multidimensional system, with bidirectional features. The interplay between the brain and the body is necessary to maintain homeostasis as well as respond adaptively to the changes in one’s internal and external environment. As a sensory capacity, interoceptive information must be processed and interpreted before it can be integrated into a personal experiential history. Interoception supports both body and mental functions and as such, interoceptive processes support health and wellness by establishing a felt sense of psychological and physiological safety that is foundational to meaningful participation in life. The information presented in this article is central to the pursuit of evidence-based best practices for any professional wishing to integrate consideration of interoception into their clinical practice.
Genetic Variability of Incretin Receptors and Alcohol Dependence: A Pilot Study
Authors: Tsermpini Evangelia Eirini , Goričar Katja , Kores Plesničar Blanka , Plemenitaš Ilješ Anja , Dolžan Vita
Published: June 2022

Alcohol dependence is a chronic mental disorder that leads to decreased quality of life for patients and their relatives and presents a considerable burden to society. Incretin hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are endogenous gut-brain peptides, which can travel across the blood-brain barrier and access the nervous system. Their respective receptors, GIPR and GLP-1R, are expressed in the reward-related brain areas and are involved in memory formation and neurogenesis, which results in behavioral changes in rodent models. The current study investigated the potential association of genetic variability of incretin receptors with alcohol dependence and alcohol-related psychosymptomatology. Alcohol dependence and comorbid psychosymptomatology were assessed in a cohort of Slovenian male participants, comprised of 89 hospitalized alcohol-dependent patients, 98 abstinent alcohol-dependent patients, and 93 healthy blood donors. All participants were genotyped for GIPR rs1800437 and GLP1R rs10305420 and rs6923761 polymorphisms. For the statistical analysis Kruskal–Wall and Mann–Whitney tests were used in additive and dominant genetic models. Our findings indicated that GIPR rs1800437 genotypes were associated with an increased risk of alcohol dependence. Statistically significant association between GIPR rs1800437 GG genotype and Brief Social Phobia Scale scores were observed in the abstinent alcohol-dependent patients, while GLP1R rs6923761 GG genotype was associated with Zung anxiety scores in healthy controls. Our pilot study indicates that GIPR rs1800437 may play some role in susceptibility to alcohol dependence, as well as in alcohol-related psychosymptomatology symptoms. To our knowledge, this is the first study that indicates the involvement of GIPR in alcohol dependence. However, studies with larger cohorts are needed to confirm these preliminary findings.
Role Medium-Chain Fatty Acids in the Lipid Metabolism of Infants
Authors: Yuan Tinglan , Wang Lei , Jin Jun , Mi Lijuan , Pang Jinzhu , Liu Zhengdong , Gong Jinyan , Sun Cong , Li Jufang , Wei Wei , Jin Qingzhe , Wang Xingguo
Published: June 2022

Human breastmilk, the ideal food for healthy infants, naturally contains a high concentration of medium-chain fatty acids (MCFAs, about 15% of total fatty acids). MCFAs are an important energy source for infants due to their unique digestive and metabolic properties. MCFA-enriched oils are widely used in an infant formula, especially the formula produced for preterm infants. Recently, there has been a growing interest in the triglyceride structure of MCFAs in human milk, their metabolism, and their effects on infant health. This study summarized the MCFA composition and structure in both human milk and infant formula. Recent studies on the nutritional effects of MCFAs on infant gut microbiota have been reviewed. Special attention was given to the MCFAs digestion and metabolism in the infants. This paper aims to provide insights into the optimization of formulations to fulfill infant nutritional requirements.
The Relationship Between Vitamin D and Postoperative Atrial Fibrillation: A Prospective Cohort Study
Authors: Ohlrogge Amelie H. , Brederecke Jan , Ojeda Francisco M. , Pecha Simon , Börschel Christin S. , Conradi Lenard , Rimkus Vanessa , Blankenberg Stefan , Zeller Tanja , Schnabel Renate B.
Published: June 2022

Background and Aims

The relationship between postoperative atrial fibrillation (POAF) and 25-hydroxyvitamin D [25(OH)D] concentration as well as vitamin D supplementation has been discussed controversially. The relation of pre-operative vitamin D status and POAF remains unclear.

Methods and Results

We analysed the risk of POAF in a prospective, observational cohort study of n = 201 patients undergoing coronary artery bypass graft surgery (CABG) with 25(OH)D concentration. The median age was 66.6 years, 15.4% were women. The median (25th/75th percentile) vitamin D concentration at baseline was 17.7 (12.6/23.7) ng/ml. During follow-up we observed 48 cases of POAF. In age, sex, and creatinine-adjusted analyses, 25(OH)D was associated with an increased risk of POAF, though with borderline statistical significance [odds ratio (OR) 1.85, 95% confidence interval (CI) 0.87–3.92, p-value 0.107], in further risk factor-adjusted analyses the results remained stable (OR 1.99, 95% CI 0.90–4.39, p-value 0.087). The subgroup with vitamin D supplementation at baseline showed an increased risk of POAF (OR 5.03, 95% CI 1.13–22.33, p-value 0.034).

Conclusion

In our contemporary mid-European cohort, higher 25(OH)D concentration did not show a benefit for POAF in CABG patients and may even be harmful, though with borderline statistical significance. Our data are in line with a recent randomised study in community-based adults and call for further research to determine both, the clinical impact of elevated 25(OH)D concentration and vitamin D supplementation as well as the possible underlying pathophysiological mechanisms.
Assessing Adherence to Healthy Dietary Habits Through the Urinary Food Metabolome: Results From a European Two-Center Study
Authors: Castellano-Escuder Pol , González-Domínguez Raúl , Vaillant Marie-France , Casas-Agustench Patricia , Hidalgo-Liberona Nicole , Estanyol-Torres Núria , Wilson Thomas , Beckmann Manfred , Lloyd Amanda J. , Oberli Marion , Moinard Christophe , Pison Christophe , Borel Jean-Christian , Joyeux-Faure Marie , Sicard Mariette , Artemova Svetlana , Terrisse Hugo , Dancer Paul , Draper John , Sánchez-Pla Alex , Andres-Lacueva Cristina
Published: June 2022

Background

Diet is one of the most important modifiable lifestyle factors in human health and in chronic disease prevention. Thus, accurate dietary assessment is essential for reliably evaluating adherence to healthy habits.

Objectives

The aim of this study was to identify urinary metabolites that could serve as robust biomarkers of diet quality, as assessed through the Alternative Healthy Eating Index (AHEI-2010).

Design

We set up two-center samples of 160 healthy volunteers, aged between 25 and 50, living as a couple or family, with repeated urine sampling and dietary assessment at baseline, and 6 and 12 months over a year. Urine samples were subjected to large-scale metabolomics analysis for comprehensive quantitative characterization of the food-related metabolome. Then, lasso regularized regression analysis and limma univariate analysis were applied to identify those metabolites associated with the AHEI-2010, and to investigate the reproducibility of these associations over time.

Results

Several polyphenol microbial metabolites were found to be positively associated with the AHEI-2010 score; urinary enterolactone glucuronide showed a reproducible association at the three study time points [false discovery rate (FDR): 0.016, 0.014, 0.016]. Furthermore, other associations were found between the AHEI-2010 and various metabolites related to the intake of coffee, red meat and fish, whereas other polyphenol phase II metabolites were associated with higher AHEI-2010 scores at one of the three time points investigated (FDR < 0.05 or β ≠ 0).

Conclusion

We have demonstrated that urinary metabolites, and particularly microbiota-derived metabolites, could serve as reliable indicators of adherence to healthy dietary habits.

Clinical Trail Registration

www.ClinicalTrials.gov, Identifier: NCT03169088.
Correlation of Gut Microbiota, Vitamin D Status, and Pulmonary Function Tests in Children With Cystic Fibrosis
Authors: Albedewi Hadeel , Bindayel Iman , Albarrag Ahmed , Banjar Hanaa
Published: June 2022

Background

Children with cystic fibrosis (CF) are expected to have suboptimal serum vitamin D status and altered gut microbiota. The altered gut microbiota is hypothesized to have a pro-inflammatory effect that further complicates the existing respiratory inflammation. Emerging evidence suggests an association between vitamin D and gut microbiota. The aim of this study was to assess the relationships between 25-hydroxyvitamin D [25(OH)D] status, pulmonary function, and fecal bacteria in children with CF.

Methods

In this cross-sectional study, a total of 35 children with CF (8.7 ± 2.83 years) and 24 controls without CF (9 ± 2.7 years) were included in this study. Serum 25(OH)D status was measured using the Elecsys vitamin D total II assay. In the CF group, gut microbiota composition was assessed using real-time PCR analysis. Pulmonary function tests (PFTs) were measured using spirometry. Comparisons between the CF and non-CF controls were conducted using the independent sample t-test. In the CF group, one-way analysis of variance (ANOVA) was used to assess differences in PFTs and gut microbiota composition across the three vitamin D subgroups. The correlations between 25(OH)D status and PFTs, or gut microbiota composition, and PFTs with gut microbiota composition were analyzed using the Pearson's correlation coefficient test.

Results

Children with CF had significantly lower serum 25(OH)D levels compared with children without CF (44.3 ± 22.4 vs. 59 ± 25.5, respectively, P = 0.026). Children with CF with optimal serum 25(OH)D level had significantly higher levels of Bacteroidetes, Firmicutes, and total bacteria (P = 0.007, P = 0.007, and P = 0.022, respectively). The level of Firmicutes was found to be significantly higher in mild forced expiratory volume in 1 s (FEV1) compared with moderate FEV1 (P = 0.032), whereas the level of the other bacteria species was comparable across FEV1 severity groups.

Conclusion

Our findings may encourage studies that target and modify gut microbiota to potentially achieve better outcomes in terms of respiratory function in CF.
Curcuminoids for Metabolic Syndrome: Meta-Analysis Evidences Toward Personalized Prevention and Treatment Management
Authors: Nurcahyanti Agustina Dwi Retno , Cokro Fonny , Wulanjati Martha P. , Mahmoud Mona F. , Wink Michael , Sobeh Mansour
Published: June 2022

The metabolic syndrome (MS) is a multifactorial syndrome associated with a significant economic burden and healthcare costs. MS management often requires multiple treatments (polydrug) to ameliorate conditions such as diabetes mellitus, insulin resistance, obesity, cardiovascular diseases, hypertension, and non-alcoholic fatty liver disease (NAFLD). However, various therapeutics and possible drug-drug interactions may also increase the risk of MS by altering lipid and glucose metabolism and promoting weight gain. In addition, the medications cause side effects such as nausea, flatulence, bloating, insomnia, restlessness, asthenia, palpitations, cardiac arrhythmias, dizziness, and blurred vision. Therefore, is important to identify and develop new safe and effective agents based on a multi-target approach to treat and manage MS. Natural products, such as curcumin, have multi-modalities to simultaneously target several factors involved in the development of MS. This review discusses the recent preclinical and clinical findings, and up-to-date meta-analysis from Randomized Controlled Trials regarding the effects of curcumin on MS, as well as the metabonomics and a pharma-metabolomics outlook considering curcumin metabolites, the gut microbiome, and environment for a complementary personalized prevention and treatment for MS management.
University Students' Knowledge and Perceptions About Concepts, Recommendations, and Health Effects of Added Sugars
Authors: Santana Isabela Paz , Scapin Tailane , Rodrigues Vanessa Mello , Bernardo Greyce Luci , Uggioni Paula Lazzarin , Fernandes Ana Carolina , Proença Rossana Pacheco da Costa
Published: June 2022

It is recommended to limit added sugars to below 10% of the daily energy intake, as excessive consumption has been associated with several chronic non-communicable diseases. This exploratory qualitative study used focus groups to investigate the knowledge and perception of Brazilian university students about added sugars concepts, consumption recommendations, and health effects. Focus groups were led by a moderator using a semi-structured discussion guide. The focus groups were recorded, transcribed verbatim, and subjected to thematic analysis. Five focus groups were conducted with a total of 32 participants (50% women, mean age 23 years). Participants could not distinguish added sugars from sugars naturally present in foods and were unaware of the health impacts associated with excessive added sugar consumption, except for the risk of diabetes. Although most participants reported limiting sugar consumption, they had no knowledge of official consumption recommendations. Given that current public policy agendas aim to reduce added sugar intake, there is a need to strengthen strategies for disseminating information on added sugar concepts, recommendations, health effects and how to identify them in the foods products.
Maternal Consumption of Milk or Dairy Products During Pregnancy and Birth Outcomes: A Systematic Review and Dose-Response Meta-Analysis
Authors: Huang Donghui , Wu Qijun , Xu Xin , Ji Chao , Xia Yang , Zhao Zhiying , Dai Huixu , Li Hang , Gao Shanyan , Chang Qing , Zhao Yuhong
Published: June 2022

Purpose

This study aimed to systematically review current evidence and quantitatively evaluate the associations between milk or dairy consumption during pregnancy and birth outcomes.

Methods

This systematic review had been reported in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A supplementary literature search in PubMed, Web of Science, Cochrane Library, and Embase was conducted on 30 March 2021. Studies that assessed the association of maternal consumption of milk or dairy with birth-related outcomes were identified. The dose-response meta-analyses of continuous data and categorical data were applied. One-stage approach and two-stage approach were used where appropriate.

Results

In total, 42 studies were eligible for the present systematic review, and 18 of them were included in the outcome-specific meta-analyses. The dose-response meta-analysis [Number of studies (N) = 9] predicted a maximum mean change in birthweight of 63.38 g [95% Confidence Interval (CI) = 0.08, 126.67] at 5.00 servings per day. Intake of dairy products had the greatest protective effect on small for gestational age at a maximum of 7.2 servings per day [Relative risk (RR) = 0.69, 95% CI = 0.56, 0.85] (N = 7). The risk of large for gestational age was predicted to be maximum at 7.20 servings per day of dairy consumption, with the RR and 95% CI of 1.30 (1.15, 1.46; N = 4). In addition, the relationship between dairy consumption and low birth weight (RR = 0.70, 95% CI = 0.33, 1.50; N = 5) and pre-mature birth (RR = 1.13, 95% CI = 0.87, 1.47; N = 5) was not significant, respectively.

Conclusions

Maternal consumption of dairy during pregnancy has a potential effect on fetal growth. Further well-designed studies are warranted to clarify the specific roles of individual dairy products.

Systematic Review Registration

identifier: PROSPERO 2020 CRD42020150608
Spontaneous Riboflavin-Overproducing Limosilactobacillus reuteri for Biofortification of Fermented Foods
Authors: Spacova Irina , Ahannach Sarah , Breynaert Annelies , Erreygers Isabel , Wittouck Stijn , Bron Peter A. , Van Beeck Wannes , Eilers Tom , Alloul Abbas , Blansaer Naïm , Vlaeminck Siegfried E. , Hermans Nina , Lebeer Sarah
Published: June 2022

Riboflavin-producing lactic acid bacteria represent a promising and cost-effective strategy for food biofortification, but production levels are typically insufficient to support daily human requirements. In this study, we describe the novel human isolate Limosilactobacillus reuteri AMBV339 as a strong food biofortification candidate. This strain shows a high natural riboflavin (vitamin B2) overproduction of 18.36 μg/ml, biomass production up to 6 × 1010 colony-forming units/ml (in the typical range of model lactobacilli), and pH-lowering capacities to a pH as low as 4.03 in common plant-based (coconut, soy, and oat) and cow milk beverages when cultured up to 72 h at 37°C. These properties were especially pronounced in coconut beverage and butter milk fermentations, and were sustained in co-culture with the model starter Streptococcus thermophilus. Furthermore, L. reuteri AMBV339 grown in laboratory media or in a coconut beverage survived in gastric juice and in a simulated gastrointestinal dialysis model with colon phase (GIDM-colon system) inoculated with fecal material from a healthy volunteer. Passive transport of L. reuteri AMBV339-produced riboflavin occurred in the small intestinal and colon stage of the GIDM system, and active transport via intestinal epithelial Caco-2 monolayers was also demonstrated. L. reuteri AMBV339 did not cause fecal microbiome perturbations in the GIDM-colon system and inhibited enteric bacterial pathogens in vitro. Taken together, our data suggests that L. reuteri AMBV339 represents a promising candidate to provide riboflavin fortification of plant-based and dairy foods, and has a high application potential in the human gastrointestinal tract.
Structural Characterization and Anti-inflammatory Activity of a Galactorhamnan Polysaccharide From Citrus medica L. var. sarcodactylis
Authors: Luo Bi , Lv Jia , Li Kejie , Liao Peiran , Chen Peng
Published: June 2022

This study aimed to extract polysaccharides from Citrus medica L. var. sarcodactylis (finger citron fruits) and analyze their structures and potential bioactivities. A new polysaccharide named K-CMLP was isolated and purified by Diethylaminoethylcellulose (DEAE)-Sepharose Fast Flow and DEAE-52 cellulose column chromatography with an average molecular weight of 3.76 × 103 kDa. Monosaccharide composition analysis revealed that K-CLMP consisted of rhamnose, galactose, and glucose, with a molar ratio of 6.75:5.87:1.00. Co-resolved by methylation and two-dimensional nuclear magnetic resonance (NMR), K-CLMP was alternately connected with 1, 2-Rha and 1, 4-Gal to form the backbone, and a small number of glucose residues was connected to O-4 of rhamnose. The results of DPPH⋅ and ABTS+⋅ radical scavenging assays indicated that both crude polysaccharide Citrus medica L. var. polysaccharide (CMLP) and K-CLMP exhibited strong free-radical-scavenging properties in a dose-dependent manner. In addition, K-CMLP significantly inhibited the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species (ROS) in RAW 264.7 cells treated with LPS. These results provide a basis for further use as one of the potential functions of food or natural medicine.
Cooked Adzuki Bean Reduces High-Fat Diet-Induced Body Weight Gain, Ameliorates Inflammation, and Modulates Intestinal Homeostasis in Mice
Authors: Zhao Qingyu , Liu Zhenyu , Zhu Yiqing , Wang Han , Dai Zijian , Yang Xuehao , Ren Xin , Xue Yong , Shen Qun
Published: June 2022

Adzuki bean is widely consumed in East Asia. Although the positive effects of its biologically active ingredients on obesity have been confirmed, the role of whole cooked adzuki bean in preventing obesity and the relationship between the effects and gut microbiota remain unclear. Mice were fed either a low-fat diet (LFD) or high-fat diet (HFD) with or without 15% cooked adzuki bean for 12 weeks. Cooked adzuki bean significantly inhibited weight gain and hepatic steatosis, reduced high levels of serum triacylglycerol (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), and alleviated systemic inflammation and metabolic endotoxemia in mice fed a HFD. Importantly, cooked adzuki bean regulated gut microbiota composition, decreased the abundance of lipopolysaccharide (LPS)-producing bacteria (Desulfovibrionaceae,Helicobacter,and Bilophila), and HFD-dependent taxa (Deferribacteraceae, Ruminiclostridium_9, Ruminiclostridium, Mucispirillum, Oscillibacter, Enterorhabdus, Tyzzerella, Anaerotruncus, Intestinimonas, unclassified_f_Ruminococcaceae, Ruminiclostridium_5, and Ruminococcaceae), and enriched Muribaculaceae, norank_f_Muribaculaceae, Anaeroplasma, Lachnospiraceae_NK4A136_group, and Lachnospiraceae to alleviate inflammation and metabolic disorders induced by HFD. These findings provide new evidence for understanding the anti-obesity effect of cooked adzuki bean.
Role of Adenoviruses in Cancer Therapy
Authors: Tseha Sintayehu Tsegaye
Published: June 2022

Cancer is one of the leading causes of death in the world, which is the second after heart diseases. Adenoviruses (Ads) have become the promise of new therapeutic strategy for cancer treatment. The objective of this review is to discuss current advances in the applications of adenoviral vectors in cancer therapy. Adenoviral vectors can be engineered in different ways so as to change the tumor microenvironment from cold tumor to hot tumor, including; 1. by modifying Ads to deliver transgenes that codes for tumor suppressor gene (p53) and other proteins whose expression result in cell cycle arrest 2. Ads can also be modified to express tumor specific antigens, cytokines, and other immune-modulatory molecules. The other strategy to use Ads in cancer therapy is to use oncolytic adenoviruses, which directly kills tumor cells. Gendicine and Advexin are replication-defective recombinant human p53 adenoviral vectors that have been shown to be effective against several types of cancer. Gendicine was approved for treatment of squamous cell carcinoma of the head and neck by the Chinese Food and Drug Administration (FDA) agency in 2003 as a first-ever gene therapy product. Oncorine and ONYX-015 are oncolytic adenoviral vectors that have been shown to be effective against some types of cancer. The Chiness FDA agency has also approved Oncorin for the treatment of head and neck cancer. Ads that were engineered to express immune-stimulatory cytokines and other immune-modulatory molecules such as TNF-α, IL-2, BiTE, CD40L, 4-1BBL, GM-CSF, and IFN have shown promising outcome in treatment of cancer. Ads can also improve therapeutic efficacy of immune checkpoint inhibitors and adoptive cell therapy (Chimeric Antigen Receptor T Cells). In addition, different replication-deficient adenoviral vectors (Ad5-CEA, Ad5-PSA, Ad-E6E7, ChAdOx1–MVA and Ad-transduced Dendritic cells) that were tested as anticancer vaccines have been demonstrated to induce strong antitumor immune response. However, the use of adenoviral vectors in gene therapy is limited by several factors such as pre-existing immunity to adenoviral vectors and high immunogenicity of the viruses. Thus, innovative strategies must be continually developed so as to overcome the obstacles of using adenoviral vectors in gene therapy.
High Expression Levels of SIGLEC9 Indicate Poor Outcomes of Glioma and Correlate With Immune Cell Infiltration
Authors: Xu Heng , Feng Yanyan , Kong Weijia , Wang Hesong , Feng Yuyin , Zhen Jianhua , Tian Lichun , Yuan Kai
Published: June 2022

Objective

This study aimed to investigate the diagnostic value and underlying mechanisms of sialic acid-binding Ig-like lectin 9 (SIGLEC9) in gliomas.

Patients and Methods

The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to analyze the association of SIGLEC9 expression levels with tumor stages and survival probability. Immunohistochemical staining of SIGLEC9 and survival analysis were performed in 177 glioma patients. Furthermore, related mechanisms were discovered about SIGLEC9 in glioma tumorigenesis, and we reveal how SIGLEC9 functions in macrophages through single-cell analysis.

Results

TCGA and CGGA databases indicated that patients with high SIGLEC9 expression manifested a significantly shorter survival probability than those with low SIGLEC9 expression. SIGLEC9 was upregulated significantly in malignant pathological types, such as grade III, grade IV, mesenchymal subtype, and isocitrate dehydrogenase wild-type gliomas. The immunohistochemical staining of tissue sections from 177 glioma patients showed that high-SIGLEC9-expression patients manifested a significantly shorter survival probability than low-SIGLEC9-expression patients with age ≧60 years, grade IV, glioblastoma multiforme, alpha thalassemia/intellectual disability syndrome X-linked loss, and without radiotherapy or chemotherapy. Furthermore, the SIGLEC9 expression level was positively correlated with myeloid-derived suppressor cell infiltration and neutrophil activation. The SIGLEC9 expression was also positively correlated with major immune checkpoints, such as LAIR1, HAVCR2, CD86, and LGALS9. Through single-cell analysis, we found that the SIGLEC9 gene is related to the ability of macrophages to process antigens and the proliferation of macrophages.

Conclusion

These findings suggested that SIGLEC9 is a diagnostic marker of poor outcomes in glioma and might serve as a potential immunotherapy target for glioma patients in the future.
Case Report: Fanconi-Bickel Syndrome in a Chinese Girl With Diabetes and Severe Hypokalemia
Authors: Chen Hongbo , Lyu Juan-juan , Huang Zhuo , Sun Xiao-mei , Liu Ying , Yuan Chuan-jie , Ye Li , Yu Dan , Wu Jin
Published: June 2022

Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive carbohydrate metabolism disorder. The main symptoms of FBS are hepatomegaly, nephropathy, postprandial hyperglycemia, fasting hypoglycemia, and growth retardation. Hypokalemia is a rare clinical feature in patients with FBS. In this study, we present a neonate suffering from FBS. She presented with hypokalemia, dysglycaemia, glycosuria, hepatomegaly, abnormality of liver function, and brain MRI. Trio whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants. A compound heterozygous mutation (NM_000340.2; p. Trp420*) of SLC2A2 was identified. Here, we report a patient with FBS in a consanguineous family with diabetes, severe hypokalemia, and other typical FBS symptoms. Patients with common clinical features may be difficult to diagnose just by phenotypes in the early stage of life, but WES could be an important tool. We also discuss the use of insulin in patients with FBS and highlight the importance of a continuous glucose monitoring system (CGMS), not only in diagnosis but also to avoid hypoglycemic events.
Cardiac Manifestations of Myotonic Dystrophy in a Pediatric Cohort
Authors: Brunet Garcia Laia , Hajra Ankita , Field Ella , Wacher Joseph , Walsh Helen , Norrish Gabrielle , Manzur Adnan , Muntoni Francesco , Munot Pinki , Robb Stephanie , Quinlivan Rosaline , Scoto Mariacristina , Baranello Giovanni , Sarkozy Anna , Starling Luke , Kaski Juan Pablo , Cervi Elena
Published: June 2022

Myotonic dystrophy type 1 (DM1) is the most prevalent inherited neuromuscular dystrophy in adults. It is a multisystem disease with cardiac manifestations. Whilst these are well-defined in adults, there are scarce published data in the pediatric population. This study aimed to investigate the yield and progression of cardiac disease in pediatric DM1 patients, focusing on congenital DM1 (cDM1).

Methods

A retrospective observational study of all pediatric DM1 patients referred to our center (December 2000-November 2020) was conducted. Patients were classified into DM1 forms according to age of symptom onset and disease severity. Patients underwent clinical and cardiac evaluation with 12-lead ECG, transthoracic echocardiography and 24-h ECG Holter monitoring.

Results

67 DM1 pediatric patients were included: 56 (83.6%) cDM1 and 11 (16.4%) non-cDM1. Median follow-up time of cDM1 patients was 8.0 [3.25–11.0] years. 49 (87.5%) cDM1 patients had baseline 12-lead ECG and 44 (78.6%) had a follow-up 12-lead-ECG, with a median follow-up time from diagnosis to baseline ECG of 2.8 [1.0–8.5] years and to follow-up ECG of 10.9 [5.7–14.2] years. Overall, 43 (87.8%) presented ECG abnormalities, most commonly in the form of asymptomatic conduction disease (n = 23, 46.9%), of which 21 (42.9%) had first degree atrioventricular block (1st AVB). There was an increase of prevalence from baseline to follow-up ECG in low QRS voltage (16.7%), poor R wave progression (13.9%), abnormal repolarisation (11.9%) and 1st AVB (7.6%). one patient (1.8%) underwent pacemaker implantation for syncope in the context of progressive conduction disease. No patients developed left ventricular systolic dysfunction. 4 (7.1%) cDM1 patients died during follow up, including three who died suddenly with no clear cause of death.

Conclusions

This study is the first to analyse the prevalence and progression of ECG abnormalities in cDM1 pediatric patients. The high prevalence of abnormal findings, progressive changes and number of potentially associated events (1 pacemaker implantation and 3 unexplained sudden deaths) stresses the importance of systematic and continued cardiac evaluation of these patients.
Severe Outcomes Associated With SARS-CoV-2 Infection in Children: A Systematic Review and Meta-Analysis
Authors: Sumner Madeleine W. , Kanngiesser Alicia , Lotfali-Khani Kosar , Lodha Nidhi , Lorenzetti Diane , Funk Anna L. , Freedman Stephen B.
Published: June 2022

Objective

To estimate the proportion of SARS-CoV-2 infected children experiencing hospitalization, intensive care unit (ICU) admission, severe outcomes, and death.

Data Sources

PubMed, Embase, and MedRxiv were searched for studies published between December 1, 2019 and May 28, 2021. References of relevant systematic reviews were also screened.

Study Selection

We included cohort or cross-sectional studies reporting on at least one outcome measure (i.e., hospitalization, ICU admission, severe outcomes, death) for ≥100 children ≤21 years old within 28 days of SARS-CoV-2 positivity; no language restrictions were applied.

Data Extraction and Synthesis

Two independent reviewers performed data extraction and risk of bias assessment. Estimates were pooled using random effects models. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

Main Outcomes and Measures

Percentage of SARS-CoV-2 positive children experiencing hospitalization, ICU admission, severe outcome, and death.

Results

118 studies representing 3,324,851 SARS-CoV-2 infected children from 68 countries were included. Community-based studies (N = 48) reported that 3.3% (95%CI: 2.7–4.0%) of children were hospitalized, 0.3% (95%CI: 0.2–0.6%) were admitted to the ICU, 0.1% (95%CI: 0.0–2.2%) experienced a “severe” outcome and 0.02% (95%CI: 0.001–0.05%) died. Hospital-based screening studies (N = 39) reported that 23.9% (95%CI: 19.0–29.2%) of children were hospitalized, 2.9% (95%CI: 2.1–3.8%) were admitted to the ICU, 1.3% (95%CI: 0.5–2.3%) experienced a severe outcome, and 0.2% (95%CI: 0.02–0.5%) died. Studies of hospitalized children (N = 31) reported that 10.1% (95%CI: 6.1–14.9%) of children required ICU admission, 4.2% (95%CI: 0.0–13.8%) had a severe outcome and 1.1% (95%CI: 0.2–2.3%) died. Low risk of bias studies, those from high-income countries, and those reporting outcomes later in the pandemic presented lower estimates. However, studies reporting outcomes after May 31, 2020, compared to earlier publications, had higher proportions of hospitalized patients requiring ICU admission and experiencing severe outcomes.

Conclusion and Relevance

Among children tested positive for SARS-CoV-2, 3.3% were hospitalized, with rates being higher early in the pandemic. Severe outcomes, ICU admission and death were uncommon, however estimates vary by study population, pandemic timing, study risk of bias, and economic status of the country.

Systematic Review Registration

PROSPERO, identifier [CRD42021260164].
The Therapeutic Potential of Ethnomedicinally Important Anatolian Thyme Species: A Phytochemical and Biological Assessment
Authors: Eroglu Ozkan Esra , Ersoy Ezgi , Yesil Canturk Yeter , Mataraci Kara Emel , Cinar Ercan , Sahin Hasan , Karahan Selim , Karaca Sancaktepe Kubra , Yilmaz Mustafa Abdullah , Boga Mehmet
Published: June 2022

Thyme has been used for various therapeutic purposes in many different cultures, which makes it one of the most riveting medicinal plants throughout history. From its beneficial effects on the respiratory tract or the gastrointestinal system, to its unique skin-related activities, the investigation of the medicinal properties of thyme has always been an alluring topic for researchers aiming to develop conventional medications from this traditional herb. With an incentive to contribute to the extensive thyme research, threeThymusL. species namelyThymus cariensisHub-Mor. & Jalas (endemic),Thymus praceoxsubsp.grossheimii(Ronniger) Jalas, andThymus pubescensBoiss. et Kotschy ex Celak from Turkey were deeply investigated within this study. The analysis of the phytochemical constituents of the extracts was conducted by LC-MS/MS. 12 biologically important secondary metabolites (p-coumaric acid, caffeic acid, salicylic acid, quinic acid, fumaric acid, vanillin, malic acid, rutin, apigenin, naringenin, and nicotiflorin) were detected in all extracts. Their total phenolic and flavonoid contents were calculated (11.15 ± 0.17—61.12 ± 2.59 μg PEs/mg extract, 2.53 ± 0.04—40.28 ± 0.92 μg QEs/mg extract, respectively), and the antioxidant potential of the extracts was evaluated by DPPH and ABTS radical scavenging and CUPRAC activity methods, accordingly, the extracts were shown to possess significant antioxidant activity. Among them,Thymus cariensisHub-Mor. & Jalas was the most active with IC50values of 34.97 ± 1.00 μg/ml and 9.98 ± 0.04 μg/ml regarding the DPPH and ABTS radical scavenging assays, respectively, and an A0.5value of 5.80 ± 0.02 μg/ml according to CUPRAC activity method. Their anticholinesterase, antityrosinase, and antiurease activities were also tested,Thymus cariensisHub-Mor. & Jalas (35.61 ± 1.20%) andThymus pubescensBoiss. et Kotschy ex Celak aerial part extract (33.49 ± 1.39%) exhibited moderate antibutyrylcholinesterase activity at 200 μg/ml concentration. The results of the cell viability assay indicated that the extracts demonstrated moderate-to-low cytotoxicity on A498 human renal cell lines. Furthermore, all studied extracts exerted noteworthy antimicrobial activity, especially againstCandida tropicalis(MIC values: 19.53—78.12 μg/ml). The presented data substantiates the use of thyme extracts as therapeutic agents in both ethnomedicine and conventional therapies.
Future Circular Collider: Integrated Programme and Feasibility Study
Authors: Benedikt Michael , Zimmermann Frank
Published: June 2022

The Future Circular Collider (FCC) Integrated Project foresees, in a first stage, a high-luminosity high-energy electron-positron collider, serving as Higgs, top and electroweak factory, and, in a second stage, an energy frontier hadron collider, with a centre-of-mass energy of at least 100 TeV. This programme well matches the highest priority future requests issued by the 2020 Update of the European Strategy for Particle Physics. In 2021, with the support of the CERN Council, a five-year FCC Feasibility Study was launched. In this article, we present the FCC integrated project and the preparations for the FCC Feasibility Study.