bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil gelatinase-associated lipocalin as predictor of acute kidney injury requiring renal replacement therapy: A systematic review and meta-analysis
Authors: Xu Chunhua , Lin Shan , Mao Longyi , Li Zesong
Published: September 2022

Background

Patients with severe acute kidney injury (AKI) may require renal replacement therapy (RRT), such as hemodialysis and peritoneal dialysis. Neutrophil gelatinase-associated lipocalin (NGAL) is a sensitive indicator for early diagnosis and recognition of AKI; however, its predictive value of AKI-associated need for RRT needs further evaluation.

Methods

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, relevant articles were systematically searched and selected from seven databases. The random effects model was applied to evaluate the predictive performance of NGAL for AKI requiring RRT. The Newcastle–Ottawa Scale (NOS) was used to assess the quality of each included study.

Results

A total of 18 studies including 1,787 patients with AKI and having an average NOS score of 7.67 were included in the meta-analysis. For plasma/serum NGAL, the pooled sensitivity and specificity with corresponding 95% confidence interval (CI) were 0.75 (95% CI: 0.68–0.81) and 0.76 (95% CI: 0.70–0.81), respectively. The pooled positive likelihood ratio (PLR) was 2.9 (95% CI: 2.1–4.1), and the pooled negative likelihood ratio (NLR) was 0.34 (95% CI: 0.25–0.46). Subsequently, the pooled diagnostic odds ratio (DOR) was 9 (95% CI: 5–16) using a random effects model, and the area under the curve (AUC) of summary receiver operating characteristic to summarize predictive accuracy was 0.82 (95% CI: 0.79–0.85). For urine NGAL, the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC values were 0.78 (95% CI: 0.61–0.90), 0.77 (95% CI: 0.65–0.85), 3.4 (95% CI: 2.4–4.8), 0.28 (95% CI: 0.15–0.52), 12 (95% CI: 6–24), and 0.84 (95% CI: 0.80–0.87), respectively.

Conclusion

Plasma/serum and urine NGAL levels performed comparably well in predicting AKI requiring RRT. Our findings suggested that NGAL is an effective predictive biomarker for the AKI-associated need for RRT. Nevertheless, more pieces of high-quality evidence and future trials with larger sample sizes are needed for further improvement of patient outcomes.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022346595], identifier [CRD42022346595].
Clinical profile in KMT2A-SEPT6-positive acute myeloid leukemia: Does it often co-occur with NRAS mutations?
Authors: Chen Fang , Yang Ying , Fu Shuang
Published: September 2022

Background

The KMT2A-SEPT6 fusion gene is a relatively rare genetic event in leukemia. Its clinical characteristics and prognosis, especially the profile of co-occurring gene mutations remain unclear.

Methods

We retrospectively analyzed the characteristics of four cases carrying KMT2A-SEPT6 in our hospital, and provided a literature review.

Results

All the four patients were diagnosed with acute myeloid leukemia (AML) and harbored X chromosome and 11 chromosome rearrangements, they all manifested high levels of D-dimer. Three of four patients had NRAS mutations while one patient with congenital AML did not. Of the four cases, one developed drug resistance, one suffered relapse after bone marrow transplantation (BMT) and two died. Combined with other cases reported in the literature, we found that of all patients diagnosed with AML, 90.9% were children (≤9 years old). Patients with white blood cells ≥20.0 × 109/L or diagnosed with M4 had a shorter overall survival (P < 0.05). Age, whether to receive BMT, and the chromosome rearrangement patterns had no significant effect on overall survival (P > 0.05).

Conclusions

KMT2A-SEPT6 was more commonly observed in pediatric AML patients, some of which may co-occur with NRAS mutations. The prognosis was related to the white blood cell levels and the leukemia subtype, but was not related to age or BMT. More cases need to be accumulated to better understand the profile in KMT2A-SEPT6-positive AML.
Prevalence of emphysema in people living with human immunodeficiency virus in the current combined antiretroviral therapy era: A systematic review
Authors: Ringheim Hedda , Thudium Rebekka F. , Jensen Jens-Ulrik S. , Rezahosseini Omid , Nielsen Susanne D.
Published: September 2022

Before introducing combination antiretroviral therapy (cART), a higher prevalence of emphysema in people living with HIV (PLWH) than in the background population was reported. This systematic literature review aimed to investigate the prevalence of emphysema in PLWH and to compare the prevalence between PLWH and controls in the current cART era. A systematic literature search was conducted in PubMed, EMBASE, Scopus, and Web of Science (WOS), searching for “human immunodeficiency virus (HIV)” and “emphysema” from January 1, 2000 to March 10, 2021. Eligible studies were published after the introduction of cART, included PLWH, and reported the prevalence of emphysema. A total of 17 studies were included, and nine studies also included controls. The weighted average prevalence of emphysema in PLWH was 23% (95% CI: 16–30). In studies including both PLWH and controls the weighted average prevalence were 22% (95% CI: 10–33) and 9.7% (95% CI: 2.3–17), respectively (p = 0.052). The prevalence of emphysema in never-smoking PLWH and controls was just reported in one study and was 18 and 4%, respectively (p < 0.01). Thirteen of the studies had a moderate risk of bias, mainly due to selection of patients. A tendency to higher prevalence of emphysema was found in PLWH in comparison to controls in the current cART era. However, in the included studies, the definition of emphysema varied largely. Thus, to have a clear overview of the prevalence, further studies with well-designed cohorts of PLWH and controls are warranted.
On the use of wearable sensors as mobility biomarkers in the marketing authorization of new drugs: A regulatory perspective
Authors: Viceconti Marco , Tome Maria , Dartee Wilhelmus , Knezevic Igor , Hernandez Penna Sabina , Mazzà Claudia , Caulfield Brian , Garcia-Aymerich Judith , Becker Clemens , Maetzler Walter , Troosters Thierry , Sharrack Basil , Davico Giorgio , Corriol-Rohou Solange , Rochester Lynn ,   the Mobilise-D Consortium
Published: September 2022

The loss of mobility is a common trait in multiple health conditions (e.g., Parkinson's disease) and is associated with reduced quality of life. In this context, being able to monitor mobility in the real world, is important. Until recently, the technology was not mature enough for this; but today, miniaturized sensors and novel algorithms promise to monitor mobility accurately and continuously in the real world, also in pathological populations. However, before any such methodology can be employed to support the development and testing of new drugs in clinical trials, they need to be qualified by the competent regulatory agencies (e.g., European Medicines Agency). Nonetheless, to date, only very narrow scoped requests for regulatory qualification were successful. In this work, the Mobilise-D Consortium shares its positive experience with the European regulator, summarizing the two requests for Qualification Advice for the Mobilise-D methodologies submitted in October 2019 and June 2020, as well as the feedback received, which resulted in two Letters of Support publicly available for consultation on the website of the European Medicines Agency. Leveraging on this experience, we hereby propose a refined qualification strategy for the use of digital mobility outcome (DMO) measures as monitoring biomarkers for mobility in drug trials.
Genomic footprints related with adaptation and fumonisins production in Fusarium proliferatum
Authors: Wang Ling , Liu Qing , Ge Shuailing , Liang Wenhao , Liao Weiyang , Li Wen , Jiao Guiai , Wei Xiangjin , Shao Gaoneng , Xie Lihong , Sheng Zhonghua , Hu Shikai , Tang Shaoqing , Hu Peisong
Published: September 2022

Fusarium proliferatum is the principal etiological agent of rice spikelet rot disease (RSRD) in China, causing yield losses and fumonisins contamination in rice. The intraspecific variability and evolution pattern of the pathogen is poorly understood. Here, we performed whole-genome resequencing of 67 F. proliferatum strains collected from major rice-growing regions in China. Population structure indicated that eastern population of F. proliferatum located in Yangtze River with the high genetic diversity and recombinant mode that was predicted as the putative center of origin. Southern population and northeast population were likely been introduced into local populations through gene flow, and genetic differentiation between them might be shaped by rice-driven domestication. A total of 121 distinct genomic loci implicated 85 candidate genes were suggestively associated with variation of fumonisin B1 (FB1) production by genome-wide association study (GWAS). We subsequently tested the function of five candidate genes (gabap, chsD, palA, hxk1, and isw2) mapped in our association study by FB1 quantification of deletion strains, and mutants showed the impact on FB1 production as compared to the wide-type strain. Together, this is the first study to provide insights into the evolution and adaptation in natural populations of F. proliferatum on rice, as well as the complex genetic architecture for fumonisins biosynthesis.
The gas production, ruminal fermentation parameters, and microbiota in response to Clostridium butyricum supplementation on in vitro varying with media pH levels
Authors: Zhang Meimei , Liang Gege , Zhang Xinlong , Lu Xiaotan , Li Siyao , Wang Xu , Yang Wenzhu , Yuan Yuan , Jiao Peixin
Published: September 2022

The aim of this study was to investigate the gas production (GP), dry matter disappearance (DMD), fermentation parameters, and rumen microbiota in response to Clostridium butyricum (CB) supplementation in batch culture using a high forage substrate. The doses of CB were supplemented at 0 (Control), 0.5 × 106, 1 × 106, and 2 × 106  CFU/bottle, respectively, at either media pH 6.0 or pH 6.6. The 16S rRNA gene sequencing was used to detect the microbiota of fermentation culture in control and 1 × 106  CFU/bottle after 24 h of incubation. The results showed that the GP (p < 0.001), DMD (p = 0.008), total volatile fatty acid (VFA) concentration (p < 0.001), acetate to propionate ratio (p < 0.001), and NH3-N concentration (p < 0.001) were greater at media pH 6.6 than pH 6.0. Furthermore, the linearly increased DMD (pH 6.0, p = 0.002; pH 6.6, p < 0.001) and quadratically increased butyrate proportion (pH 6.0, p = 0.076; pH 6.6, p < 0.053) and NH3-N concentration (pH 6.0, p = 0.003; pH 6.6, p = 0.014) were observed with increasing doses of CB. The Alpha diversity indexes of OTU number and Chao1 were higher (p = 0.045) at media pH 6.6 than pH 6.0, but they were not affected by CB supplementation. The PCoA analysis (unweighted uniFrac) demonstrated that the clustering of the bacterial microbiota of control and CB were distinctly separated from each other at media pH 6.0. At the phylum level, the abundance of Bacteroidota (p < 0.001) decreased, whereas that of Firmicutes (p = 0.026) increased when the media pH was elevated from 6.0 to 6.6. Supplementation of CB increased relative abundances of Rikenellaceae_RC9_gut_group (p = 0.002), Christensenellaceae_R-7_group (p < 0.001), and NK4A214_group (p = 0.002) at genus level. Interactions between media pH and CB addition were observed for bacteria at both phylum and genus levels. These results indicated that increasing the media pH level and CB supplementation increased in vitro rumen digestibility, and altered the ruminal fermentation pattern (by media pH) and microbiota.
Sevoflurane exposure induces neurotoxicity by regulating mitochondrial function of microglia due to NAD insufficiency
Authors: Zhu Ruilou , Zeng Shuang , Li Ningning , Fu Ningning , Wang Yangyang , Miao Mengrong , Yang Yitian , Sun Mingyang , Zhang Jiaqiang
Published: September 2022

Developmental neurons received with sevoflurane, the commonly used inhalational anesthetic agent in clinical surgery, several times tend to be destroyed. Microglia, the resident immune cells of the central nervous system (CNS), are activated after sevoflurane exposure, accompanied by releasing proinflammatory cytokines that damage developing neurons. The sevoflurane-induced neurotoxicity could be attributed to activated microglia presenting proinflammatory and anti-inflammatory functions. Proinflammatory microglia release cytokines to impair the CNS, while anti-inflammatory microglia engulf damaged neurons to maintain CNS homeostasis. Sevoflurane exposure promotes the secretion of proinflammatory cytokines by microglia, inhibiting the microglial phagocytic function. Microglia with poor phagocytic function cannot engulf damaged neurons, leading to the accumulation of damaged neurons. The mechanism underlying poor phagocytic function may be attributed to mitochondrial dysfunction of microglia induced by sevoflurane exposure, in which affected mitochondria cannot generate adequate ATP and NAD to satisfy the energy demand. We discovered that sevoflurane treatment impaired the mitochondrial metabolism of microglia, which resulted in NAD deficiency and couldn’t produce sufficient energy to clear damaged neurons to maintain CNS development. Our findings provide an explanation of a new mechanism underlying sevoflurane-induced neurotoxicity.
Galectin-3 administration drives remyelination after hypoxic-ischemic induced perinatal white matter injury
Authors: Wang Qian , Diao Sihao , Qiu Han , Gao Ruiwei , Wang Minjie , Chen Qiufan , Xiao Mili , Li Zhihua , Chen Chao
Published: September 2022

Hypoxic-ischemic (HI) induced perinatal white matter injury (PWMI) is a major cause of neurologic disabilities characterized by selective oligodendroglial death and myelin disruption. Galectin-3 (Gal-3) modulates postnatal subventricular zone gliogenesis and attenuates ischemic injury. However, the association between Gal-3 and myelin formation still remains unclear. In this study, we first perform Gal-3 knockdown (KD) to identify the importance of Gal-3 on myelin formation. Our results show impeded myelin formation, manifested by Olig2/CC1 (+) mature oligodendrocytes number, expression of oligodendroglial maturation-associated markers (MBP and CNPase), and myelin thickness and integrity. Then we perform recombinant Gal-3 (rGal-3) administration by intracerebroventricular injection. Notably, although rGal-3 administration shows no beneficial effect on oligodendrogenesis and myelin formation under normal condition, our results show that rGal-3 administration attenuates cognitive deficits and drives remyelination after PWMI, which are coupled to signs of enhanced myelin resiliency and cognition. Also, our results indicates that the significant increases in substrates for remyelination of rGal-3 administration are accompanied by enhanced Iba-1 (microglia marker)/ Mrc1 (M2 marker) (+) microglia and decreased Iba-1/ iNOS (M1 marker) (+) microglia. Altogether, our data in this research confirm the association between Gal-3 and myelin formation, underscore its position for the capacity for remyelination and restoration of function, and unveils the efficacy of rGal-3 administration with anti-inflammatory phenotype microglia (M2 microglia) activation. Thus, the findings suggest that Gal-3 plays a significant role in myelin formation and remyelination restoration.
Altered brain functional activity and connectivity in bone metastasis pain of lung cancer patients: A preliminary resting-state fMRI study
Authors: Liu Daihong , Zhou Xiaoyu , Tan Yong , Yu Hong , Cao Ying , Tian Ling , Yang Liejun , Wang Sixiong , Liu Shihong , Chen Jiao , Liu Jiang , Wang Chengfang , Yu Huiqing , Zhang Jiuquan
Published: September 2022

Bone metastasis pain (BMP) is one of the most prevalent symptoms among cancer survivors. The present study aims to explore the brain functional activity and connectivity patterns in BMP of lung cancer patients preliminarily. Thirty BMP patients and 33 healthy controls (HCs) matched for age and sex were recruited from inpatients and communities, respectively. All participants underwent fMRI data acquisition and pain assessment. Low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were applied to evaluate brain functional activity. Then, functional connectivity (FC) was calculated for the ALFF- and ReHo-identified seed brain regions. A two-sample t-test or Manny–Whitney U-test was applied to compare demographic and neuropsychological data as well as the neuroimaging indices according to the data distribution. A correlation analysis was conducted to explore the potential relationships between neuroimaging indices and pain intensity. Receiver operating characteristic curve analysis was applied to assess the classification performance of neuroimaging indices in discriminating individual subjects between the BMP patients and HCs. No significant intergroup differences in demographic and neuropsychological data were noted. BMP patients showed reduced ALFF and ReHo largely in the prefrontal cortex and increased ReHo in the bilateral thalamus and left fusiform gyrus. The lower FC was found within the prefrontal cortex. No significant correlation between the neuroimaging indices and pain intensity was observed. The neuroimaging indices showed satisfactory classification performance between the BMP patients and HCs, and the combined ALFF and ReHo showed a better accuracy rate (93.7%) than individual indices. In conclusion, altered brain functional activity and connectivity in the prefrontal cortex, fusiform gyrus, and thalamus may be associated with the neuropathology of BMP and may represent a potential biomarker for classifying BMP patients and healthy controls.
Influence of pre-stroke dependency on safety and efficacy of endovascular therapy: A systematic review and meta-analysis
Authors: Zhao Hengxiao , Bai Xuesong , Li Wei , Tian Qiuyue , Wang Wenjiao , Guo Xiaofan , Feng Yao , Duan Linyan , Dmytriw Adam A. , Patel Aman B. , Yi Tingyu , Cao Wenbo , Min Xiaoli , Chen Wenhuo , Jiao Liqun
Published: September 2022

Background and purpose

In the landmark trials studying endovascular thrombectomy (EVT), pre-stroke dependent (PSD) patients were generally excluded. This systematic review and meta-analysis aimed to compare the safety and efficacy of EVT between PSD and pre-stroke independent (PSI) patients.

Methods

We searched CENTRAL, Embase, and Ovid MEDLINE up to 11 November 2021 for studies assessing PSD and PSI patients, which were separately defined as pre-stroke mRS score >2 or >1, and ≤2 or ≤1 accordingly. Two authors extracted data and assessed the risk of bias. A meta-analysis was carried out using the random-effects model. Adjusted OR and 95% CI were used to estimate adjusted pool effects. The main outcomes included favorable outcomes, successful recanalization, symptomatic intracranial hemorrhage, and 90-day mortality.

Results

A total of 8,004 records met the initial search strategy, and ten studies were included in the final decision. Compared with PSImRS≤2, PSDmRS>2 had a lower favorable outcome (OR 0.51; 95% CI, 0.33–0.79) and higher 90-day mortality (OR 3.32; 95% CI, 2.77–3.98). No significant difference was found in successful recanalization and sICH. After adjustment, only 90-day mortality (aOR 1.99; 95% CI, 1.58–2.49) remained significantly higher in PSDmRS>2. Compared with PSImRS≤1, PSDmRS>1 had lower 90-day mortality (OR, 3.10; 95% CI, 1.84–5.24). No significant difference was found regarding the favorable outcome, successful recanalization, and sICH. After adjustment, no significant difference was found in a favorable outcome, but a higher rate of 90-day mortality (aOR, 2.13; 95% CI, 1.66–2.72) remained in PSDmRS>1.

Conclusions

PSD does not innately influence the EVT outcomes regarding sICH and favorable outcomes but may increase the risk of 90-day mortality. Until further evidence is available, it is reasonable to suggest EVT for patients with PSD.
Infra-low frequency neurofeedback and insomnia as a model of CNS dysregulation
Authors: Moore Paul Terrence
Published: September 2022

This paper will review what is conventionally known of sleep homeostasis and focus on insomnia as a primary manifestation of brain dysregulation, whether as a solitary symptom or as part of a larger syndrome such as post-traumatic stress disorder, PTSD. It will discuss in brief behavioral/mindfulness treatments that have been used to treat neurologic diseases, as this is germane to the phenomenology of neurofeedback (NF). It will explore how neurofeedback may work at the subconscious level and cover the current clinical experience of the effectiveness of this technique in the treatment of insomnia. It will conclude with a case presentation.
Cellular loci involved in the development of brain arteriovenous malformations
Authors: Shabani Zahra , Schuerger Joana , Su Hua
Published: September 2022

Brain arteriovenous malformations (bAVMs) are abnormal vessels that are prone to rupture, causing life-threatening intracranial bleeding. The mechanism of bAVM formation is poorly understood. Nevertheless, animal studies revealed that gene mutation in endothelial cells (ECs) and angiogenic stimulation are necessary for bAVM initiation. Evidence collected through analyzing bAVM specimens of human and mouse models indicate that cells other than ECs also are involved in bAVM pathogenesis. Both human and mouse bAVMs vessels showed lower mural cell-coverage, suggesting a role of pericytes and vascular smooth muscle cells (vSMCs) in bAVM pathogenesis. Perivascular astrocytes also are important in maintaining cerebral vascular function and take part in bAVM development. Furthermore, higher inflammatory cytokines in bAVM tissue and blood demonstrate the contribution of inflammatory cells in bAVM progression, and rupture. The goal of this paper is to provide our current understanding of the roles of different cellular loci in bAVM pathogenesis.
Thalamo-cortical inter-subject functional correlation during movie watching across the adult lifespan
Authors: Niu Jinpeng , Zheng Zihao , Wang Ziqi , Xu Longchun , Meng Qingmin , Zhang Xiaotong , Kuang Liangfeng , Wang Shigang , Dong Li , Qiu Jianfeng , Jiao Qing , Cao Weifang
Published: September 2022

An increasing number of studies have shown that the functional interactions between the thalamus and cerebral cortices play an important role in cognitive function and are influenced by age. Previous studies have revealed age-related changes in the thalamo-cortical system within individuals, while neglecting differences between individuals. Here, we characterized inter-subject functional correlation (ISFC) between the thalamus and several cortical brain networks in 500 healthy participants aged 18–87 years old from the Cambridge Centre for Aging and Neuroscience (Cam-CAN) cohort using movie-watching state fMRI data. General linear models (GLM) were performed to assess age-related changes in ISFC of thalamo-cortical networks and the relationship between ISFC and fluid intelligence. We found significant age-related decreases in ISFC between the posterior thalamus (e.g., ventral posterior nucleus and pulvinar) and the attentional network, sensorimotor network, and visual network (FDR correction with p < 0.05). Meanwhile, the ISFC between the thalamus (mainly the mediodorsal nucleus and ventral thalamic nuclei) and higher-order cortical networks, including the default mode network, salience network and control network, showed complex changes with age. Furthermore, the altered ISFC of thalamo-cortical networks was positively correlated with decreased fluid intelligence (FDR correction with p < 0.05). Overall, our results provide further evidence that alterations in the functional integrity of the thalamo-cortical system might play an important role in cognitive decline during aging.
Selective deficits of S-cone in thyroid-associated ophthalmopathy patients without clinical signs of dysthyroid optic neuropathy
Authors: Jin Haochen , Yu Xi , Cao Suqi , Wang Mengting , Hu Xiaozhou , Ye Jie , Liu Weijie , Xu Mingna , Wu Wencan , Tu Yunhai
Published: September 2022

Purpose

We explored whether thyroid-associated ophthalmopathy (TAO) patients without clinical signs of dysthyroid optic neuropathy (DON) would have a selective deficit mediated by S-cone.

Methods

Thirty-two TAO patients without clinical signs of DON (non-DON, 42.03 ± 9.59 years old) and 27 healthy controls (41.46 ± 6.72 years old) participated in this prospective, cross-sectional study. All observers were tested psychophysically after passing color screening tests and a comprehensive ocular examination. Isolated L-, M-, and S-cone contrast thresholds were measured at 0.5 cyc/deg using Gabor patches. We calculated the area under the receiver operating characteristic (ROC) curve to quantify the ability of chromatic contrast sensitivity to detect the early visual function changes in non-DON patients.

Results

S-cone contrast sensitivity in non-DON patients was found to be lower than that of healthy controls (P < 0.001), whereas the sensitivities to L- and M-cone Gabor patches were similar between these two groups (P = 0.297, 0.666, respectively). Our analysis of the ROC curve revealed that the sensitivity to S-cone had the highest index to discriminate non-DON patients from healthy controls (AUC = 0.846, P < 0.001). The deficit of S-cone was significantly correlated with muscle index in non-DON patients (R = 0.576, P = 0.001).

Conclusion

There is a selective S-cone deficit in the early stage of TAO. S-cone contrast sensitivity could serve as a sensitive measure of visual impairments associated with early DON in patients with TAO.
Attention-deficit/hyperactive disorder updates
Authors: Kessi Miriam , Duan Haolin , Xiong Juan , Chen Baiyu , He Fang , Yang Lifen , Ma Yanli , Bamgbade Olumuyiwa A. , Peng Jing , Yin Fei
Published: September 2022

Background

Attention-deficit/hyperactive disorder (ADHD) is a neurodevelopmental disorder that commonly occurs in children with a prevalence ranging from 3.4 to 7.2%. It profoundly affects academic achievement, well-being, and social interactions. As a result, this disorder is of high cost to both individuals and society. Despite the availability of knowledge regarding the mechanisms of ADHD, the pathogenesis is not clear, hence, the existence of many challenges especially in making correct early diagnosis and provision of accurate management.

Objectives

We aimed to review the pathogenic pathways of ADHD in children. The major focus was to provide an update on the reported etiologies in humans, animal models, modulators, therapies, mechanisms, epigenetic changes, and the interaction between genetic and environmental factors.

Methods

References for this review were identified through a systematic search in PubMed by using special keywords for all years until January 2022.

Results

Several genes have been reported to associate with ADHD: DRD1, DRD2, DRD4, DAT1, TPH2, HTR1A, HTR1B, SLC6A4, HTR2A, DBH, NET1, ADRA2A, ADRA2C, CHRNA4, CHRNA7, GAD1, GRM1, GRM5, GRM7, GRM8, TARBP1, ADGRL3, FGF1, MAOA, BDNF, SNAP25, STX1A, ATXN7, and SORCS2. Some of these genes have evidence both from human beings and animal models, while others have evidence in either humans or animal models only. Notably, most of these animal models are knockout and do not generate the genetic alteration of the patients. Besides, some of the gene polymorphisms reported differ according to the ethnic groups. The majority of the available animal models are related to the dopaminergic pathway. Epigenetic changes including SUMOylation, methylation, and acetylation have been reported in genes related to the dopaminergic pathway.

Conclusion

The dopaminergic pathway remains to be crucial in the pathogenesis of ADHD. It can be affected by environmental factors and other pathways. Nevertheless, it is still unclear how environmental factors relate to all neurotransmitter pathways; thus, more studies are needed. Although several genes have been related to ADHD, there are few animal model studies on the majority of the genes, and they do not generate the genetic alteration of the patients. More animal models and epigenetic studies are required.
Visual analysis of the research trend and status on the association between vitamin D and immunity: From 2012 to 2021
Authors: Luo Xuemei , Deng Yali , He Wenfang
Published: September 2022

Objective

We conducted this study to visualize hot spots and trends in the correlation between vitamin D and immunity over the past decade with bibliometric analysis.

Methods

We collected relevant articles in the Web of Science Core Collection from 2012 to 2021 as the data source, and then used CiteSpace software to perform the data analysis. Some graphics were done with Graphpad software.

Results

A total of 1,656 articles were retrieved, with an average citation count of 25.2 times. The United States (439 articles, 26.51%) has the top number of published articles, followed by China (164 articles, 9.90%), England (135 articles, 8.15%), Italy (114 articles, 6.88%), and India (82 articles, 4.95%). The most literature is found in areas of Immunology (337 articles, 20.35%) and Biochemistry Molecular Biology (179 articles, 10.81%). In terms of institutions, the top five institutions with the highest number of publications all belong to Europe. Among them, the League of European Research Universities (LERU) (121, 7.31%) has a greater proportion of output articles. The United States Department of Health Human Services (225, 13.59%) and National Institutes of Health United States (223, 13.47%) funded most articles. The leading five authors with the largest number of publications were Hewison M (19, 1.15%), Bergman P (14, 0.85%), Agerberth B (13, 0.76%), Carlberg C (12, 0.73%), and White JH (12, 0.73%). The top five keywords with the highest co-occurrence frequency are “vitamin d” (367), “d deficiency” (217), “expression” (195), “association” (151), and “d receptor” (132). Among the 17 keyword clusters, the largest cluster is #0 “diet.” Despite cluster #13 “covid-19,” most of the clusters were conducted the studies before 2012.

Conclusion

The overall development of research in this field is promising. Western developed countries made outstanding contributions in this area and still take the leading role. But the participation of developing and low-income countries is also impressive. The potential therapeutic effects of vitamin D in immune-related diseases have been noted, especially in multiple sclerosis, COVID-19, etc. This is also the focus and frontier of current research. However, there is still no consensus conclusion in this field. Further research is needed in the future.
Combining mussel with fucoidan as a supplement for joint pain and prediabetes: Study protocol for a randomized, double-blinded, placebo-controlled trial
Authors: Tay Audrey , Jiang Yannan , Signal Nada , O'Brien Daniel , Chen Jinsong , Murphy Rinki , Lu Jun
Published: September 2022

Introduction

Pharmaceutical drugs are beneficial to inflammatory conditions but with side effects, which led to the search for alternative therapies. Perna canaliculus, the New Zealand green-lipped mussel, have shown promise in placebo-controlled trials for inflammatory conditions. Fucoidan, an extract from seaweed Undaria pinnatifida, has been found to have beneficial effects on joint pain and insulin resistance. However, green-lipped mussel and fucoidan have never been combined.

Methods and analysis

A parallel, two-arm, double-blind, randomized, placebo-controlled trial will be conducted in New Zealand to determine whether a food product supplemented with green-lipped mussel and fucoidan improves joint pain and/or insulin resistance. Those who are ethnically Chinese, are aged over 30 years, have prediabetes and hip or knee joint pain will be eligible to participate. They will be randomized at 1:1 ratio to consume either dark chocolate supplemented with 1000 mg mussel powder and 1000 mg fucoidan or dark chocolate with no active substances daily for 100 days. The primary endpoints are change in insulin resistance and patient-reported joint pain. Secondary endpoints include anthropometry, fasting glucose and insulin, HbA1c, inflammatory markers, satiety, quality of life, physical function, pain intensity, and analgesic medication use. A sample size of 150 (75 per arm) will provide 90% power at an overall significance level of 5% (two-sided) to detect a standardized effect size of 0.625 on either of the two co-primary outcomes allowing for 10% loss.

Ethics and dissemination

The study was approved by the Health and Disability Ethics Committee (number: 20/STH/153). Results will be made available to participants, funders, and other researchers.

Discussion

This trial will provide data on the potential utility of a mussel-fucoidan supplement in reducing joint pain and/or insulin resistance, to inform the development of a supplemented food product suitable for the Chinese market.

Clinical trial registration

https://trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12621000413820, ANZCTR Registration: ACTRN12621000413820, on 15 April 2021.
A novel nutritional score based on serum triglyceride and protein levels predicts outcomes of intrahepatic cholangiocarcinoma after curative hepatectomy: A multi-center study of 631 patients
Authors: Cai Yunshi , Xue Shuai , Li Jiaxin , Xiao Heng , Lan Tian , Wu Hong
Published: September 2022

Background

High serum triglyceride (STG) level is a well-established pathogenic factor for cardiovascular diseases and is associated with the risk of various malignancies. Nevertheless, the role of STG level in intrahepatic cholangiocarcinoma (ICC) remains uncertain.

Methods

A total of 631 ICC patients treated with curative hepatectomy in two centers (517 in the discovery set and 114 in the validation set) were retrospectively analyzed. Kaplan–Meier survival analysis was used to assess the outcomes of the patients with different STG levels. Time-dependent receiver operating characteristic (ROC) analysis was conducted to compare the prognostic value of STG with other established indexes. The Triglyceride-Albumin-Globulin (TAG) grade was introduced and evaluated using the time-dependent area under curves (AUC) analysis and decision curve analysis (DCA).

Results

Patients with increased STG levels and decreased albumin-globulin score (AGS) were correlated with improved overall survival (OS) and recurrence-free survival (RFS). STG level ≥ 1 mmol/L was an independent protective factor for surgically treated ICC patients. The predictive value of the TAG grade was superior to the STG or the AGS alone. In decision curve analysis, the net benefits of the TAG grade in the discovery and validation set were higher than STG and AGS.

Conclusion

The current study presented strong evidence that ICC patients with higher preoperative STG levels had preferred long-term surgical outcomes. The novel nutritional score based on serum triglyceride, albumin and globulin levels was inextricably linked to the prognosis of the surgically treated ICC patients. Evaluation of the TAG grade before curative hepatectomy may be beneficial for risk stratification and clinical decision support.
Can coffee silverskin be a useful tool to fight metabolic syndrome?
Authors: Andrade Nelson , Peixoto Juliana A. Barreto , Oliveira M. Beatriz P. P. , Martel Fátima , Alves Rita C.
Published: September 2022

Coffee is one of the most consumed products in the world, and its by-products are mainly discarded as waste. In order to solve this problem and in the context of a sustainable industrial attitude, coffee by-products have been studied concerning their chemical and nutritional features for a potential application in foodstuffs or dietary supplements. Under this perspective, coffee silverskin, the main by-product of coffee roasting, stands out as a noteworthy source of nutrients and remarkable bioactive compounds, such as chlorogenic acids, caffeine, and melanoidins, among others. Such compounds have been demonstrating beneficial health properties in the context of metabolic disorders. This mini-review compiles and discusses the potential health benefits of coffee silverskin and its main bioactive components on metabolic syndrome, highlighting the main biochemical mechanisms involved, namely their effects upon intestinal sugar uptake, glucose and lipids metabolism, oxidative stress, and gut microbiota. Even though additional research on this coffee by-product is needed, silverskin can be highlighted as an interesting source of compounds that could be used in the prevention or co-treatment of metabolic syndrome. Simultaneously, the valorization of this by-product also responds to the sustainability and circular economy needs of the coffee chain.
Natural sources and encapsulating materials for probiotics delivery systems: Recent applications and challenges in functional food development
Authors: Singh Shubhi , Gupta Rishibha , Chawla Sonam , Gauba Pammi , Singh Manisha , Tiwari Raj Kumar , Upadhyay Shuchi , Sharma Shalini , Chanda Silpi , Gaur Smriti
Published: September 2022

Probiotics are known as the live microorganisms which upon adequate administration elicit a health beneficial response inside the host by decreasing the luminal pH, eliminating the pathogenic bacteria in the gut as well as producing short chain fatty acids (SCFA). With advancements in research; probiotics have been explored as potential ingredients in foods. However, their use and applications in food industry have been limited due to restrictions of maintaining the viability of probiotic cells and targeting the successful delivery to gut. Encapsulation techniques have significant influence on increasing the viability rates of probiotic cells with the successful delivery of cells to the target site. Moreover, encapsulating techniques also prevent the live cells from harsh physiological conditions of gut. This review discusses several encapsulating techniques as well as materials derived from natural sources and nutraceutical compounds. In addition to this, this paper also comprehensively discusses the factors affecting the probiotics viability and evaluation of successful release and survival of probiotics under simulated gastric, intestinal conditions as well as bile, acid tolerant conditions. Lastly applications and challenges of using encapsulated bacteria in food industry for the development of novel functional foods have also been discussed in detail too. Future studies must include investigating the use of encapsulated bacterial formulations in in-vivo models for effective health beneficial properties as well as exploring the mechanisms behind the successful release of these formulations in gut, hence helping us to understand the encapsulation of probiotic cells in a meticulous manner.
Infant nutrition affects the microbiota-gut-brain axis: Comparison of human milk vs. infant formula feeding in the piglet model
Authors: Charton Elise , Bourgeois Alexandre , Bellanger Amandine , Le-Gouar Yann , Dahirel Patrice , Romé Véronique , Randuineau Gwenaelle , Cahu Armelle , Moughan Paul J. , Montoya Carlos A. , Blat Sophie , Dupont Didier , Deglaire Amélie , Le Huërou-Luron Isabelle
Published: September 2022

Early nutrition plays a dominant role in infant development and health. It is now understood that the infant diet impacts the gut microbiota and its relationship with gut function and brain development. However, its impact on the microbiota-gut-brain axis has not been studied in an integrative way. The objective here was to evaluate the effects of human milk (HM) or cow’s milk based infant formula (IF) on the relationships between gut microbiota and the collective host intestinal-brain axis. Eighteen 10-day-old Yucatan mini-piglets were fed with HM or IF. Intestinal and fecal microbiota composition, intestinal phenotypic parameters, and the expression of genes involved in several gut and brain functions were determined. Unidimensional analyses were performed, followed by multifactorial analyses to evaluate the relationships among all the variables across the microbiota-gut-brain axis. Compared to IF, HM decreased the α-diversity of colonic and fecal microbiota and modified their composition. Piglets fed HM had a significantly higher ileal and colonic paracellular permeability assessed by ex vivo analysis, a lower expression of genes encoding tight junction proteins, and a higher expression of genes encoding pro-inflammatory and anti-inflammatory immune activity. In addition, the expression of genes involved in endocrine function, tryptophan metabolism and nutrient transport was modified mostly in the colon. These diet-induced intestinal modifications were associated with changes in the brain tissue expression of genes encoding the blood-brain barrier, endocrine function and short chain fatty acid receptors, mostly in hypothalamic and striatal areas. The integrative approach underlined specific groups of bacteria (Veillonellaceae, Enterobacteriaceae, Lachnospiraceae, Rikenellaceae, and Prevotellaceae) associated with changes in the gut-brain axis. There is a clear influence of the infant diet, even over a short dietary intervention period, on establishment of the microbiota-gut-brain axis.
Research on food loss and waste in the Western Balkans: A systematic review
Authors: El Bilali Hamid , Berjan Sinisa , Ben Hassen Tarek , Memon Junaid Alam , Vaško Željko , Allahyari Mohammad S.
Published: September 2022

Food losses and waste (FLW) is considered a critical issue in the ongoing debate on the sustainability of agri-food systems. However, the scholarly literature on FLW is still geographically-biased, with more attention devoted to developed countries, even in Europe. In this context, this article analyses the state of research on FLW in the Western Balkan region (viz. Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, and Serbia). A search performed in October 2021 on the Web of Science database returned 34 documents, and 21 eligible ones were included in the systematic review. The topical analysis of the literature addressed causes of FLW, stages of the food supply chain, extent and magnitude of FLW, FLW and food security, economic and environmental impacts of FLW, and food waste (FW) management strategies. A central finding was the scarcity of data on FW in the Western Balkans. Moreover, the literature focused on FW at the consumer level, while food loss at other stages of the food chain was generally overlooked. There is a lack of comprehensive analyses of the economic and environmental impacts of FLW as well as its implications in terms of food and nutrition security. The quantification of FLW is generally inaccurate and based on estimates and self-reported data. The literature focuses on FW reuse and recycling (e.g., energy, compost) while other management strategies (e.g., reduction/prevention, redistribution) are rarely addressed. However, the results indicated that consumers in the Western Balkans pay attention to the FW issue, especially during the COVID-19 pandemic, which is an encouraging sign that can be exploited in awareness-raising campaigns and education activities. Meanwhile, research on FLW in the Western Balkans is highly needed to fill the identified knowledge gap and provide evidence to policies dealing with the transition to sustainable food systems in the region.
A major role for Nrf2 transcription factors in cell transformation by KSHV encoded oncogenes
Authors: Sapochnik Daiana , Raimondi Ana R. , Medina Victoria , Naipauer Julian , Mesri Enrique A. , Coso Omar
Published: September 2022

Kaposi’s sarcoma (KS) is the most common tumor in AIDS patients. The highly vascularized patient’s skin lesions are composed of cells derived from the endothelial tissue transformed by the KSHV virus. Heme oxygenase-1 (HO-1) is an enzyme upregulated by the Kaposi´s sarcoma-associated herpesvirus (KSHV) and highly expressed in human Kaposi Sarcoma (KS) lesions. The oncogenic G protein-coupled receptor (KSHV-GPCR or vGPCR) is expressed by the viral genome in infected cells. It is involved in KS development, HO-1 expression, and vascular endothelial growth factor (VEGF) expression. vGPCR induces HO-1 expression and HO-1 dependent transformation through the Ga13 subunit of heterotrimeric G proteins and the small GTPase RhoA. We have found several lines of evidence supporting a role for Nrf2 transcription factors and family members in the vGPCR-Ga13-RhoA signaling pathway that converges on the HO-1 gene promoter. Our current information assigns a major role to ERK1/2MAPK pathways as intermediates in signaling from vGPCR to Nrf2, influencing Nrf2 translocation to the cell nucleus, Nrf2 transactivation activity, and consequently HO-1 expression. Experiments in nude mice show that the tumorigenic effect of vGPCR is dependent on Nrf2. In the context of a complete KSHV genome, we show that the lack of vGPCR increased cytoplasmic localization of Nrf2 correlated with a downregulation of HO-1 expression. Moreover, we also found an increase in phospho-Nrf2 nuclear localization in mouse KS-like KSHV (positive) tumors compared to KSHV (negative) mouse KS-like tumors. Our data highlights the fundamental role of Nrf2 linking vGPCR signaling to the HO-1 promoter, acting upon not only HO-1 gene expression regulation but also in the tumorigenesis induced by vGPCR. Overall, these data pinpoint this transcription factor or its associated proteins as putative pharmacological or therapeutic targets in KS.
Potential methylation-regulated genes and pathways in hepatocellular neoplasm, not otherwise specified
Authors: Zhou Shengmei , Li Meng , Ostrow Dejerianne , Ruble David , Mascarenhas Leo , Pawel Bruce , Buckley Jonathan David , Triche Timothy J.
Published: September 2022

Background and Aims

The molecular basis of hepatocellular neoplasm, not otherwise specified (HCN-NOS) is unknown. We aimed to identify gene expression patterns, potential methylation-regulated genes and pathways that characterize the tumor, and its possible relationship to hepatoblastoma and hepatocellular carcinoma (HCC).

Approach & Results

Parallel genome-wide profiling of gene expression (RNAseq) and DNA methylation (EPIC850) was performed on 4 pairs of pre-treatment HCN-NOS tumors and adjacent non-tumor controls. 2530 significantly differentially expressed genes (DEGs) were identified between tumors and controls. Many of these DEGs were associated with hepatoblastoma and/or HCC. Analysis Match in Ingenuity Pathway Analysis determined that the gene expression profile of HCN-NOS was unique but significantly similar to that of both hepatoblastoma and HCC. A total of 27,195 CpG sites (CpGs) were significantly differentially methylated (DM) between tumors and controls, with a global hypomethylation pattern and predominant CpG island hypermethylation in promotor regions. Aberrant DNA methylation predominated in Developmental Process and Molecular Function Regulator pathways. Embryonic stem cell pathways were significantly enriched. In total, 1055 aberrantly methylated (at CpGs) and differentially expressed genes were identified, including 25 upstream regulators and sixty-one potential CpG island methylation-regulated genes. Eight methylation-regulated genes (TCF3, MYBL2, SRC, HMGA2, PPARGC1A, SLC22A1, COL2A1 and MYCN) had highly consistent gene expression patterns and prognostic value in patients with HCC, based on comparison to publicly available datasets.

Conclusions

HCN-NOS has a unique, stem-cell like gene expression and DNA methylation profile related to both hepatoblastoma and HCC but distinct therefrom. Further, 8 methylation-regulated genes associated with prognosis in HCC were identified.