bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of stigma maydis polysaccharide on the gut microbiota and transcriptome of VPA induced autism model rats
Authors: Yang Xiaolei , Li Jiyuan , Zhou Yang , Zhang Ning , Liu Jicheng
Published: November 2022

Stigma maydis polysaccharide (SMPS) is a plant polysaccharide that participates in immune regulation and gastrointestinal motility. Autism spectrum disorder (ASD) refers to a group of neurodevelopmental disorders, and ASD patients often present intestinal microflora imbalance problems; however, there is no effective treatment method. This study explores the effect of SMPS intervention on the gut microbiota in autism model rats as well as the potential action pathways. Female Wistar rats were intraperitoneally injected with sodium valproic acid (VPA) or normal saline at embryonic day 12.5 to establish an autism model or normal control in their offspring. The offspring prenatally exposed to VPA were randomly assigned to the VPA and the SMPS groups. The SMPS group was administered SMPS from E0.5 to postnatal day (PND) 21. We performed 16S rRNA and transcriptomics analyses to reveal the gut microbiota (GM) and differentially expressed genes in the autism model rats in response to SMPS intervention. SMPS intervention significantly improved the diversity and structure of the GM in autism model rats compared with the VPA rats. Moreover, the relative abundance of Prevotellaceae and Lachnospiraceae_NK4A136_group was increased after SMPS intervention. Transcriptome sequencing showed that 496 differentially expressed genes (DEGs) were identified after SMPS administration compared with the VPA group. Meanwhile, gene ontology (GO) enrichment analysis of DEGs was showed that the SMPS group had significant 653 GO terms. SMPS intervention had a major influence on oxidative phosphorylation, retrograde endocannabinoid signaling, thermogenesis, ribosome, protein digestion and absorption, renin-angiotensin system, calcium signaling pathway, glycosphingolipid biosynthesis-ganglio series, and propanoate metabolism pathways. Overall, this study suggests that SMPS interventions in early life may have an impact on gut microbiota, and then affect the transcriptomics levels of the hippocampal tissue in the VPA-induced autism model rats. It provides scientific evidence for the role of the microbe-gut-brain axis in ASD research.
Commensal bacteria contribute to the growth of multidrug-resistant Avibacterium paragallinarum in chickens
Authors: Zhu Jiajia , Chen Yunsheng , Wu Yifan , Wang Yongqiang , Zhu Kui
Published: November 2022

Avibacterium paragallinarum-associated infectious coryza (IC) is an important threat in commercial poultry. Previous studies about the characteristics of A. paragallinarum are succeeded in revealing the course of IC disease, but whether and how resident microbes contribute to the infection remains unclear. To understand the role of commensal bacteria, we isolated 467 commensal bacteria, including 38 A. paragallinarum, from the respiratory tract of IC chicken. The predominant commensal isolates were Gram-positive bacteria belonging to Staphylococcus spp. [33.19%, 95% confidence interval (CI): 28.93–37.66%], Enterococcus spp. (16.49%, 95% CI: 13.23–20.17%), and Bacillus spp. (16.27%, 95% CI: 13.04–19.94%). These isolates were closely correlated with the survival of A. paragallinarum. We examined and found that commensal bacteria aggravate A. paragallinarum-associated infections because certain commensal species (28.57%, 95% CI: 15.72–44.58%) induced hemolysis and promoted the growth of A. paragallinarum in vitro. Notably, A. paragallinarum showed high resistance to routine antibiotics such as erythromycin (84.21%, 95% CI: 68.75–93.98%), tetracycline (73.68%, 95% CI: 56.90–86.60%) and carried diverse mobile resistance gene clusters. Overall, we found commensal bacteria especially Gram-positive bacteria facilitate the survival of multidrug-resistant A. paragallinarum to exacerbate infections, suggesting that novel strategies may diminish A. paragallinarum-associated infections by modulating the population dynamics of commensal bacteria.
A deep ensemble learning-based automated detection of COVID-19 using lung CT images and Vision Transformer and ConvNeXt
Authors: Tian Geng , Wang Ziwei , Wang Chang , Chen Jianhua , Liu Guangyi , Xu He , Lu Yuankang , Han Zhuoran , Zhao Yubo , Li Zejun , Luo Xueming , Peng Lihong
Published: November 2022

Since the outbreak of COVID-19, hundreds of millions of people have been infected, causing millions of deaths, and resulting in a heavy impact on the daily life of countless people. Accurately identifying patients and taking timely isolation measures are necessary ways to stop the spread of COVID-19. Besides the nucleic acid test, lung CT image detection is also a path to quickly identify COVID-19 patients. In this context, deep learning technology can help radiologists identify COVID-19 patients from CT images rapidly. In this paper, we propose a deep learning ensemble framework called VitCNX which combines Vision Transformer and ConvNeXt for COVID-19 CT image identification. We compared our proposed model VitCNX with EfficientNetV2, DenseNet, ResNet-50, and Swin-Transformer which are state-of-the-art deep learning models in the field of image classification, and two individual models which we used for the ensemble (Vision Transformer and ConvNeXt) in binary and three-classification experiments. In the binary classification experiment, VitCNX achieves the best recall of 0.9907, accuracy of 0.9821, F1-score of 0.9855, AUC of 0.9985, and AUPR of 0.9991, which outperforms the other six models. Equally, in the three-classification experiment, VitCNX computes the best precision of 0.9668, an accuracy of 0.9696, and an F1-score of 0.9631, further demonstrating its excellent image classification capability. We hope our proposed VitCNX model could contribute to the recognition of COVID-19 patients.
Microbial community succession during crude oil-degrading bacterial enrichment cultivation and construction of a degrading consortium
Authors: Yu Tianfei , Liu Xiaodong , Ai Jiamin , Wang Jiamin , Guo Yidan , Liu Xinhui , He Xiaolong , Deng Zhenshan , Jiang Yingying
Published: November 2022

Microbial community succession during the enrichment of crude-oil-degrading bacteria was analyzed using Illumina high-throughput sequencing to guide bacterial isolation and construction of a bacterial consortium. Community change occurred in 6 days; the most abundant phylum changed from Proteobacteria to Actinobacteria; the most abundant genera were Dietzia and unspecified_Idiomarinaceae. Two crude oil-degrading strains, Rhodococcus sp. OS62-1 and Dietzia sp. OS33, and one weak-crude-oil-degrading strain, Pseudomonas sp. P35, were isolated. A consortium comprising Rhodococcus sp. OS62-1 and Pseudomonas sp. P35 showed the highest crude-oil-degrading efficiency, reaching 85.72 ± 3.21% within 7 days, over a wide pH range (5–11) and salinity (0–80 g·L−1). Consumption of saturated hydrocarbons, aromatic hydrocarbons, and resins was greater by the consortium than by a single strain, as was degradation of short-chain-alkanes (C13–C17) according to gas-chromatography. The bacterial consortium provides technical support for bioremediation of crude oil pollution.
Micro-PET imaging of hepatitis C virus NS3/4A protease activity using a protease-activatable retention probe
Authors: Chuang Chih-Hung , Cheng Tian-Lu , Chen Wei-Chun , Huang Yi-Jung , Wang Hsin-Ell , Lo Yen-Chen , Hsieh Yuan-Chin , Lin Wen-Wei , Hsieh Ya-Ju , Ke Chien-Chih , Huang Kang-Chieh , Lee Jin-Ching , Huang Ming-Yii
Published: November 2022

Hepatitis C virus (HCV) NS3/4A protease is an attractive target for direct-acting antiviral agents. Real-time tracking of the NS3/4A protease distribution and activity is useful for clinical diagnosis and disease management. However, no approach has been developed that can systemically detect NS3/4A protease activity or distribution. We designed a protease-activatable retention probe for tracking HCV NS3/4A protease activity via positron emission topography (PET) imaging. A cell-penetrating probe was designed that consisted of a cell-penetrating Tat peptide, HCV NS3/4A protease substrate, and a hydrophilic domain. The probe was labeled by fluorescein isothiocyanate (FITC) and 124I in the hydrophilic domain to form a TAT-ΔNS3/4A-124I-FITC probe. Upon cleavage at NS3/4A substrate, the non-penetrating hydrophilic domain is released and accumulated in the cytoplasm allowing PET or optical imaging. The TAT-ΔNS3/4A-FITC probe selectively accumulated in NS3/4A-expressing HCC36 (NS3/4A-HCC36) cells/tumors and HCV-infected HCC36 cells. PET imaging showed that the TAT-ΔNS3/4A-124I-FITC probe selectively accumulated in the NS3/4A-HCC36 xenograft tumors and liver-implanted NS3/4A-HCC36 tumors, but not in the control HCC36 tumors. The TAT-ΔNS3/4A-124I-FITC probe can be used to represent NS3/4 protease activity and distribution via a clinical PET imaging system allowing. This strategy may be extended to detect any cellular protease activity for optimization the protease-based therapies.
Implementation of a combined bioinformatics and experimental approach to address lncRNA mechanism of action: The example of NRIR
Authors: Mariotti Barbara , Di Blas Costanza , Bazzoni Flavia
Published: November 2022

In this study, we demonstrate the benefit of applying combined strategies to analyze lncRNA action based on bioinformatics and experimental information. This strategy was developed to identify the molecular function of negative regulator of interferon response (NRIR), a type I interferon-stimulated gene (ISG), that we have previously demonstrated to be involved in the upregulation of a subset of ISGs in LPS-stimulated human monocytes. In this study, we provide experimental evidence that NRIR is localized in cellular nuclei, enriched on the chromatin fraction, and upregulates ISGs acting at the transcriptional level. In silico analysis of secondary structures identified distinct NRIR structural domains, comprising putative DNA- and protein-binding regions. In parallel, the presence of a putative DNA-binding domain in NRIR and the five putative NRIR-binding sites in the promoter of NRIR-target genes support the function of NRIR as a transcriptional regulator of its target genes. By use of integrated experimental/bioinformatics approaches, comprising database and literature mining together with in silico analysis of putative NRIR-binding proteins, we identified a list of eight transcription factors (TFs) shared by the majority of NRIR-target genes and simultaneously able to bind TF binding sites enriched in the NRIR-target gene promoters. Among these TFs, the predicted NRIR:STAT interactions were experimentally validated by RIP assay.
Disinhibitory circuit mediated by connections from vasoactive intestinal polypeptide to somatostatin interneurons underlies the paradoxical decrease in spike synchrony with increased border ownership selective neuron firing rate
Authors: Wagatsuma Nobuhiko , Shimomura Haruka , Nobukawa Sou
Published: November 2022

The activity of border ownership selective (BOS) neurons in intermediate-level visual areas indicates which side of a contour owns a border relative to its classical receptive field and provides a fundamental component of figure-ground segregation. A physiological study reported that selective attention facilitates the activity of BOS neurons with a consistent border ownership preference, defined as two neurons tuned to respond to the same visual object. However, spike synchrony between this pair is significantly suppressed by selective attention. These neurophysiological findings are derived from a biologically-plausible microcircuit model consisting of spiking neurons including two subtypes of inhibitory interneurons, somatostatin (SOM) and vasoactive intestinal polypeptide (VIP) interneurons, and excitatory BOS model neurons. In our proposed model, BOS neurons and SOM interneurons cooperate and interact with each other. VIP interneurons not only suppress SOM interneuron responses but also are activated by feedback signals mediating selective attention, which leads to disinhibition of BOS neurons when they are directing selective attention toward an object. Our results suggest that disinhibition arising from the synaptic connections from VIP to SOM interneurons plays a critical role in attentional modulation of neurons in intermediate-level visual areas.
Researches on cognitive sequelae of burn injury: Current status and advances
Authors: Xie Chenchen , Hu Jun , Cheng Yong , Yao Zhongxiang
Published: November 2022

Burn injury is a devastating disease with high incidence of disability and mortality. The cognitive dysfunctions, such as memory defect, are the main neurological sequelae influencing the life quality of burn-injured patients. The post-burn cognitive dysfunctions are related to the primary peripheral factors and the secondary cerebral inflammation, resulting in the destruction of blood-brain barrier (BBB), as is shown on Computed Tomography (CT) and magnetic resonance imaging examinations. As part of the neurovascular unit, BBB is vital to the nutrition and homeostasis of the central nervous system (CNS) and undergoes myriad alterations after burn injury, causing post-burn cognitive defects. The diagnosis and treatment of cognitive dysfunctions as burn injury sequelae are of great importance. In this review, we address the major manifestations and interventions of post-burn cognitive defects, as well as the mechanisms involved in memory defect, including neuroinflammation, destruction of BBB, and hormone imbalance.
Slow, deep breathing intervention improved symptoms and altered rectal sensitivity in patients with constipation-predominant irritable bowel syndrome
Authors: Liu Jie , Lv Chaolan , Wang Wei , Huang Yizhou , Wang Bo , Tian Jiashuang , Sun Chenyu , Yu Yue
Published: November 2022

Background and aim

Limited treatment options have been shown to alter the natural course of irritable bowel syndrome (IBS). Slow, deep breathing (SDB) is a common pain self-management intervention. This pilot study aimed to explore the impact of SDB on measures of autonomic and anorectal functions as well as patient-reported symptoms in constipation-predominant IBS (IBS-C).

Methods

Eighty-five IBS-C patients were enrolled in this study and randomly assigned to the experimental group (Group A, n = 42) and the control group (Group B, n = 43). SDB was conducted at six breathing cycles per minute with an inhalation for 4 s and exhalation for 6 s at a ratio of 2:3 and repeated for 30 min during the intervention. All subjects underwent high-resolution anorectal manometry (HRAM) and completed the standardized IBS symptom severity system (IBS-SSS) questionnaire. Meanwhile, changes in stool consistency, weekly frequency of complete spontaneous bowel movements (CSBMs), and weekly frequency of spontaneous bowel movements (SBMs) were recorded. All IBS-C patients received electrocardiogram (ECG) recordings for heart rate variability (HRV) analysis at baseline, weeks 3, 6.

Results

At baseline, no differences were found between Groups A and B. The IBS-SSS score and its five sub-scores of Group B patients were significantly higher at week 6 than those of Group A patients (all p < 0.001). Furthermore, compared with Group B patients, Group A patients had a significantly higher threshold volume for the first sensation (p < 0.001), desire to defecate (p = 0.017), and maximum tolerable volume (p = 0.018) at week 6 of the SDB treatment. We also noted significant improvements in stool consistency (p = 0.002), weekly SBM frequencies (p < 0.001), and weekly CSBM frequencies (p = 0.018) of Group A patients at week 6 when compared with Group B patients. Finally, the corrected high frequency (HF) of Group A patients was significantly higher than the HF of Group B patients at week 3 (p < 0.001) and at week 6 (p < 0.001). Likewise, patients in Group A had a significantly higher root mean square of the successive differences (RMSSD) than that of patients in Group B at week 3 (p < 0.001) and at week 6 (p < 0.001).

Conclusion

We found that a 6-week SDB intervention improved symptoms and altered rectal sensation in IBS-C patients. Moreover, SDB enhanced vagal activity. These findings suggest that the effect of SDB on IBS-C may be due to mechanisms involving autonomic responses.
Manipulation of the diet–microbiota–brain axis in Alzheimer’s disease
Authors: Lee Daniel , Lee Virginia M-Y. , Hur Seong Kwon
Published: November 2022

Several studies investigating the pathogenesis of Alzheimer’s disease have identified various interdependent constituents contributing to the exacerbation of the disease, including Aβ plaque formation, tau protein hyperphosphorylation, neurofibrillary tangle accumulation, glial inflammation, and the eventual loss of proper neural plasticity. Recently, using various models and human patients, another key factor has been established as an influential determinant in brain homeostasis: the gut–brain axis. The implications of a rapidly aging population and the absence of a definitive cure for Alzheimer’s disease have prompted a search for non-pharmaceutical tools, of which gut-modulatory therapies targeting the gut–brain axis have shown promise. Yet multiple recent studies examining changes in human gut flora in response to various probiotics and environmental factors are limited and difficult to generalize; whether the state of the gut microbiota in Alzheimer’s disease is a cause of the disease, a result of the disease, or both through numerous feedback loops in the gut–brain axis, remains unclear. However, preliminary findings of longitudinal studies conducted over the past decades have highlighted dietary interventions, especially Mediterranean diets, as preventative measures for Alzheimer’s disease by reversing neuroinflammation, modifying the intestinal and blood–brain barrier (BBB), and addressing gut dysbiosis. Conversely, the consumption of Western diets intensifies the progression of Alzheimer’s disease through genetic alterations, impaired barrier function, and chronic inflammation. This review aims to support the growing body of experimental and clinical data highlighting specific probiotic strains and particular dietary components in preventing Alzheimer’s disease via the gut–brain axis.
Validation of GOAL questionnaire as screening tool for clinical obstructive sleep apnea: A large sample study in China
Authors: Zheng Zhenzhen , Zhu Jinru , Liang Hongwei , Wang Chaoyu , Chen Mingdi , Li Chunhe , Zhang Zhiping , Chen Riken , Wu Kang , Liu Wang
Published: November 2022

Background

Obstructive sleep apnea (OSA) is a serious disease with a high prevalence in the general population. The purpose of this study is to explore the effectiveness of the GOAL questionnaire in the clinical screening of OSA and compare it with other existing screening tools.

Materials and methods

Outpatients and inpatients who underwent polysomnography (PSG) examination at the Sleep Medicine Center of the First Affiliated Hospital of Guangzhou Medical University from January 2013 to November 2016 were analyzed retrospectively. The basic data such as demographic, medical history, etc., and PSG data of the patients were collected, and the sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of GOAL and five other screening scales (the NoSAS score, Epworth Sleepiness Scale, the Berlin questionnaire, STOP, and STOP-Bang questionnaire) were calculated.

Results

Data from 2,171 participants (1,644 male; 78%) were analyzed there were 1,507 OSA patients [Apnea Hypopnea Index (AHI) ≥ 5 events/h] among them, accounting for about 69.415%. No matter which cut-off point (AHI ≥ 5, 15 and 30 events/h), the AUC score reveals that GOAL questionnaire had comparable screening ability to the NoSAS and STOP-BANG, and performed better than the ESS, and the AUC scores of the STOP questionnaire and Epworth Sleepiness Scale (ESS) were both lower than 0.7. When the cut-off point of the AHI was 5 events/h, the AUC of GOAL was the highest at 0.799 (0.781–0.816), and its sensitivity was the highest at 89.1%. The sensitivity levels of the NoSAS score and STOP-Bang questionnaire were 67.4 and 78.8% respectively, while ESS and the Berlin questionnaire have higher specificity (70.2 and 72.3% respectively) but lower sensitivity (49.3 and 60.0% respectively).

Conclusion

GOAL is a free, efficient and easy to manage tool with a screening ability comparable to NoSAS and STOP-Bang, and better than that of ESS.
Perceptions of persons who wear face coverings are modulated by the perceivers’ attitude
Authors: Leder Johannes , Koßmann Lisa , Carbon Claus-Christian
Published: November 2022

We examined if the effect of facial coverings on person perception is influenced by the perceiver’s attitudes. We used two online experiments in which participants saw the same human target persons repeatedly appearing with and without a specific piece of clothing and had to judge the target persons’ character. In Experiment 1 (N = 101), we investigated how the wearing of a facial mask influences a person’s perception depending on the perceiver’s attitude toward measures against the COVID-19 pandemic. In Experiment 2 (N = 114), we examined the effect of wearing a head cover associated with Arabic culture on a person’s perception depending on the perceiver’s attitude toward Islam. Both studies were preregistered; both found evidence that a person’s perception is a process shaped by the personal attitudes of the perceiver as well as merely the target person’s outward appearance. Integrating previous findings, we demonstrate that facial covers, as well as head covers, operate as cues which are used by the perceivers to infer the target persons’ underlying attitudes. The judgment of the target person is shaped by the perceived attitude toward what the facial covering stereotypically symbolizes.
Vicinal glutamates are better phosphomimetics: Phosphorylation is required for allosteric activation of guanylyl cyclase-A
Authors: Otto Neil M. , Potter Lincoln R.
Published: November 2022

Multisite phosphorylation of guanylyl cyclase (GC)-A, also known as NPR-A or NPR1, is required for receptor activation by natriuretic peptides (NPs) because alanine substitutions for the first four GC-A phosphorylation sites produce an enzyme that cannot be stimulated by NPs. In contrast, single Glu substitutions for the first six chemically identified GC-A phosphorylation sites to mimic the negative charge of phosphate produced an enzyme that is activated by NPs but had an elevated Michaelis constant (Km), resulting in low activity. Here, we show that vicinal (double adjacent) Glu substitutions for the same sites to mimic the two negative charges of phosphate produced a near wild type (WT) enzyme with a low Km. Unlike the enzyme with single glutamate substitutions, the vicinally substituted enzyme did not require the functionally identified Ser-473-Glu substitution to achieve WT-like activity. Importantly, the negative charge associated with either phosphorylation or glutamate substitutions was required for allosteric activation of GC-A by ATP. We conclude that vicinal Glu substitutions are better phosphomimetics than single Glu substitutions and that phosphorylation is required for allosteric activation of GC-A in the absence and presence of NP. Finally, we suggest that the putative functionally identified phosphorylation sites, Ser-473 in GC-A and Ser-489 in GC-B, are not phosphorylation sites at all.
Identification of tryptophan metabolic gene-related subtypes, development of prognostic models, and characterization of tumor microenvironment infiltration in gliomas
Authors: Liu Yi , Xiang Juan , Liao Yiwei , Peng Gang , Shen Chenfu
Published: November 2022

Background

Epigenetic regulation and immunotherapy of tumor microenvironment (TME) is a hot topic in recent years. However, the potential value of tryptophan metabolism genes in regulating TME and immunotherapy is still unclear.

Materials and methods

A comprehensive study of glioma patients was carried out based on 40 tryptophan metabolic genes. Subsequently, these prognostic tryptophan metabolic genes are systematically associated with immunological characteristics and immunotherapy. A risk score model was constructed and verified in the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) cohorts to provide guidance for prognosis prediction and immunotherapy of glioma patients.

Results

We described the changes of tryptophan metabolism genes in 966 glioma samples from genetic and transcriptional fields and evaluated their expression patterns from two independent data sets. We identified two different molecular subtypes and found that two subtypes were associated with clinicopathological features, prognosis, TME cell infiltration, and immune checkpoint blockers (ICBs). Then, four genes (IL4I1, CYP1A1, OGDHL, and ASMT) were screened out by univariate and multivariate cox regression analysis of tryptophan metabolism genes, and a risk score model for predicting the overall survival (OS) of glioma patients was constructed. And its predictive ability is verified using the CGGA database. At the same time, we verified the expression of IL4I1, CYP1A1, OGDHL, and ASMT four genes in glioma specimens and cell lines in GES4260 and GES15824. Therefore, we constructed a nomogram to improve the clinical applicability of the risk assessment model. The high risk score group, characterized by increased TMB and immune cell infiltration, was also sensitive to temozolomide immunotherapy. Our comprehensive analysis of tryptophan metabolic genes in gliomas shows that they play a potential role in tumor immune stromal microenvironment, clinicopathological features, and prognosis.

Conclusion

Tryptophan metabolism genes play an indispensable role in the complexity, diversity, and prognosis of TME. This risk score model based on tryptophan metabolism gene is a new predictor of clinical prognosis and immunotherapy response of glioma, and guides a more appropriate immunotherapy strategy for glioma patients.
Tannic acid attenuates intestinal oxidative damage by improving antioxidant capacity and intestinal barrier in weaned piglets and IPEC-J2 cells
Authors: Wang Meiwei , Huang Huijun , Wang Lei , Yin Lanmei , Yang Huansheng , Chen Chiqing , Zheng Qiankun , He Shanping
Published: November 2022

Tannic acid (TA) has received widespread attention for its beneficial biological function with antioxidant capacity. This study investigated the protective role of TA on the intestinal antioxidant capacity and intestinal barrier in weaned piglets and porcine intestinal epithelial cells (IPEC-J2). A total of 18 weaned piglets were randomly allocated into two groups (n = 9) and fed with a basal diet (control, CON) and a basal diet containing 1,000 mg/kg TA for two weeks. The in vivo results showed that treatment with TA increased both glutathione peroxidase (GSH-PX) activity and the protein expression of ZO-1 in the jejunum of weaned piglets, and reduced the level of malondialdehyde (MDA) in the serum and the mRNA and protein expression of Keap1 in the jejunum of weaned piglets. Furthermore, in vitro results indicated that TA treatment effectively alleviated tert-butyl hydroperoxide (TBH)-induced oxidative stress in IPEC-J2 cells, improved the antioxidant capacity by elevating the cell redox state and activating the Nrf2 pathway, and improved the intestinal barrier by upregulating the mRNA and protein expression of intestinal tight junction proteins and increasing the transepithelial electrical resistance (TEER) value. In conclusion, these results confirmed that TA relieves oxidative injury and improves intestinal barrier function and intestinal antioxidant capacity by activating the Nrf2 signaling pathway. These findings suggest that TA has the potential application in alleviating oxidative stress in the intestine of weaned piglets.
Intraoperative indocyanine green fluorescence cholangiography can rule out biliary atresia: A preliminary report
Authors: Shirota Chiyoe , Hinoki Akinari , Togawa Takao , Ito Shogo , Sumida Wataru , Makita Satoshi , Amano Hizuru , Takimoto Aitaro , Takada Shunya , Okamoto Masamune , Nakagawa Yoichi , Kato Daiki , Uchida Hiroo
Published: November 2022

Background

The prognosis of BA is known to be poor if definitive surgery is performed too late. Therefore, excluding BA as a diagnosis at an early stage is crucial. Conventional cholangiography requiring cannulation through the gallbladder may be unnecessarily invasive for patients, especially when ruling out BA. Therefore, a less invasive alternative such as indocyanine green (ICG) cholangiography, which does not require cannulation, should be established. In this study, we focused on excluding BA and confirmed the usefulness of intravenous ICG fluorescence cholangiography. To the best of our knowledge, this is the first preliminary study to report the use of intravenous ICG cholangiography for BA exclusion.

Methods

The study participants were patients who underwent liver biopsy and intraoperative cholangiography after they were suspected to have BA, between 2013 and 2022. ICG fluorescence cholangiography was performed on all patients who provided informed consent.

Results

During the study period, 88 patients underwent a laparoscopic liver biopsy and cholangiography. Among them, 65 (74%) were diagnosed with BA and underwent a subsequent laparoscopic Kasai portoenterostomy. BA was ruled out intraoperatively in 23 patients. Of the 23 patients in whom BA was ruled out, 14 underwent ICG cholangiography, 11 had gallbladder (GB) fluorescence, and 9 had both GB and common bile duct (CBD) fluorescence. Conventional cholangiography was very difficult in 2 of 23 cases: in 1 case, cannulation of the atrophic gallbladder was impossible, and cholecystectomy was indicated after multiple attempts; in 1 case, upstream cholangiography was not possible. In both cases, ICG fluorescence cholangiography successfully imaged the CBD and the GB.

Conclusions

In conclusion, intravenous ICG fluorescence cholangiography might be a useful and less invasive diagnostic procedure that can rule out BA in infants.
A survey of registered pharmacological clinical trials on rare neurological diseases in children in 2010–2020
Authors: Chang Xuting , Zhang Jie , Jiang Yuwu , Shang Meixia , Wu Ye
Published: November 2022

Objective

To clarify the current state of methodology of clinical trials for rare neurological diseases in children, and to provide a basis for the further optimization of the trial design.

Methods

Data of clinical trials for the rare neurological diseases with childhood onset (searched through https://rarediseases.info.nih.gov/diseases and www.Orpha.net) registered on the Clinicaltrils.gov from January 2010 to June 2020 was collected. Analysis on the methodology of the clinical trials were performed, focusing on initiator of the studies, multi or single research center, study design, sample size, and the endpoint using in the trial.

Results

A total of 162 clinical trials were included, covering only 7.3% (61/835) of rare neurological diseases in children. 101 (62.3%) were initiated by pharmaceutical companies, and 61 (37.7%) by investigators. Most (95.4%) of global multicenter studies were initiated by pharmaceutical companies, whereas most (70.0%) of single-center studies were initiated by investigators (χ2 = 61.635, P < 0.001). Of the 162 trials, 74 (45.7%) were open-label single-arm trials, 68 (42.0%) were randomized double-blind parallel controlled trials (RCT), 12 (7.4%) were randomized crossover trials. Most of RCTs (73.5%) and 54.1% of open-label single-arm trials were initiated by pharmaceutical companies. The proportion of RCTs in clinical trials for diseases with a prevalence of ≥1/10,000 (62.5%) was higher than that in diseases with prevalence ≤1/1,000,000 (12.0%) or 1/1,000,000~1/10,000 (43.1%) (χ2 = 14.790, P = 0.001). The median expected sample size of the studies was 34 (4–500). 132 (132/162, 81.5%) studies enrolled fewer than 100 cases. Diseases with a prevalence of ≥1/10,000 had significantly larger sample sizes than other prevalence classes (P < 0.001, P = 0.003).

Conclusions

There were few clinical trials targeting on treatment of rare neurological diseases in children. Trials on rare diseases used fewer participants, and high-quality randomized controlled trials were less common. It is necessary to conduct global multicenter recruitment and choose optimal study designs to improve the level of evidence in clinical trials on rare diseases.
Correlations between gastrointestinal and oral microbiota in children with cerebral palsy and epilepsy
Authors: Huang Congfu , Chu Chunuo , Peng Yuanping , Zhang Nong , Yang Zhenyu , You Jia , Wei Fengxiang
Published: November 2022

We here studied the correlation between gut and oral microbiota in children with cerebral palsy and Epilepsy (CPE). We enrolled 27 children with this condition from the social welfare center of Longgang District, collected their oral plaque and stool samples, and analyzed their gut microbiota (GM) and oral microbiota (OM) through 16S rRNA gene sequencing. Taxonomical annotation revealed that the levels of Firmicutes and Bacteroides in the oral cavity were significantly lower in CPE children than in healthy children, whereas the abundance of Actinomycetes increased significantly in CPE children. In addition, Prevotella, Fusobacterium, and Neisseria were the top three abundant genera, representing 15.49%, 9.34%, and 7.68% of the OM and suggesting potential correlations with caries, periodontitis, and malnutrition. For the GM, Bifidobacterium, Bacteroides, and Prevotella were the top three abundant genera in CPE children and probably contributed to the development of chronic inflammation and malnutrition. Furthermore, the OM and GM correlated with each other closely, and the bacterial components of these microbiota in CPE children were remarkably different from those in healthy children, such as Bifidobacterium, Fusobacterium, Bacteroides, and Neisseria. Conclusively, dysbiotic OM can translocate to the intestinal tract and induce GM dysbiosis, suggesting the consistency between OM and GM variations. Altered oral and gut microbial structures have potential impacts on the occurrence of clinical diseases such as periodontitis, caries, and malnutrition.
Cardiac arrhythmias associated with immune checkpoint inhibitors: A comprehensive disproportionality analysis of the FDA adverse event reporting system
Authors: Wang Feifei , Wei Qi , Wu Xinan
Published: November 2022

Introduction: With the widespread application of Immune checkpoint inhibitors (ICIs), it is important to explore the association between ICIs and cardiac arrhythmias and to characterize the clinical features of ICI-associated cardiac arrhythmias in real-world studies.

Objective: The purpose of this study was to characterize the main features of ICI-related cardiac arrhythmias.

Methods: From January 2017 to June 2021, data in the Food and Drug Administration Adverse Event Reporting System (FAERS) database were retrieved to conduct the disproportionality analysis. For the ICI-related cardiac arrhythmia detection, signals were detected by reporting odds ratio (ROR) and information component (IC), calculated using two-by-two contingency tables The clinical characteristics of patients reported with ICI-related cardiac arrhythmias were compared between fatal and non-fatal groups, and the time to onset (TTO) following different ICI regimens was further investigated. Multivariate logistic regression was used to evaluate the association between concurrent cardiotoxicities and ICI-associated arrhythmias.

Results: We identified a total of 1957 ICI–associated cardiac arrhythmias reports which appeared to influence more men (64.44%) than women (30.76%), with a median age of 68 [interquartile range (IQR) 60–75] years. Cardiac arrhythmias were reported most often in patients with lung, pleura, thymus and heart cancers (38.02% of 1957 patients). Compared with the full database, ICIs were detected with pharmacovigilance of cardiac arrhythmias (ROR025 = 1.16, IC025 = 0.19). Anti-PD-1 and anti-PD-L1 monotherapies were found to be related to higher reporting of arrhythmias, corresponding to ROR025 = 1.03, IC025 = 0.06 and ROR025 = 1.27, IC025 = 0.29, respectively, with the exception of anti-CTLA-4 monotherapies (ROR025 = 0.57, IC025 = −1.21). The spectrum of arrhythmias induced by ICIs differed among therapeutic regimens. There was no significant difference in the onset time between monotherapy and combination regimen. Moreover, reports of ICI-associated arrhythmias were associated with other concurrent cardiotoxicity, including cardiac failure [ROR 2.61 (2.20–3.09)], coronary artery disorders [ROR 2.28 (1.83–2.85)], myocardial disorders [ROR 5.25 (4.44–6.22)], pericardial disorders [ROR 2.76 (2.09–3.64)] and cardiac valve disorders [ROR 3.21 (1.34–7.68)].

Conclusion: ICI monotherapy and combination therapy can lead to cardiac arrhythmias that can result in serious outcomes and tend to occur early. Our findings underscore the importance of early recognition and management of ICI-related cardiac arrhythmias.
Assessment of walkability and walkable routes of a 15-min city for heat adaptation: Development of a dynamic attenuation model of heat stress
Authors: Wang Yu , He Bao-Jie , Kang Chong , Yan Li , Chen Xueke , Yin Mingqiang , Liu Xiao , Zhou Tiejun
Published: November 2022

Actively addressing urban heat challenges is an urgent task for numerous cities. Existing studies have primarily developed heat mitigation strategies and analyzed their cooling performance, while the adaptation strategies are far from comprehensive to protect citizens from heat-related illnesses and deaths. To address this research gap, this paper aims to enhance people's adaptation capacity by investigating walkability within fifteen-minute cities (FMC). Taking cognizance of thermal comfort, health, and safety, this paper developed a dynamic attenuation model (DAM) of heat stress, along with heat stress aggravation, continuance, and alleviation. An indicator of remaining tolerant heat discomfort (Rt) was proposed with the integration of the Universal Thermal Climate Index (UTCI) to assess heat-related walkability. Following an empirical study among 128 residents in Mianyang, China, and assessing four levels of heat stress, the maximum tolerant heat discomfort was determined to be 60 min. Furthermore, the DAM was applied to an FMC with 12 neighborhoods in Fucheng, Mianyang, China. The results indicate that for each neighborhood, the street was generally walkable with anRtranging between 15 and 30 min, after walking for 900 m. A population-based FMC walkability was further determined, finding that the core area of the FMC was favorable for walking with anRtof 45–46 min, and the perpetual areas were also walkable with anRtof 15–30 min. Based on these results, suggestions on the frequency of public services (frequently used, often used, and occasionally used) planning were presented. Overall, this paper provides a theoretical model for analyzing walkability and outlines meaningful implications for planning heat adaptation in resilient, safe, comfortable, and livable FMCs.
Recent developments on psychological factors in medically unexplained symptoms and somatoform disorders
Authors: Mewes Ricarda
Published: November 2022

Somatic symptoms which are not fully explained by a medical condition (medically unexplained symptoms) have a high relevance for the public health. They are very common both in the general population and in patients in health care, and may develop into chronic impairing conditions such as somatoform disorders. In recent years, the relevance of specific negative psychological factors for the diagnosis and the stability of somatoform disorders and for the impairment by medically unexplained symptoms gained more and more attention. This resulted—among others- in core changes in the diagnostic classification criteria of somatoform disorders. Against this background, the present “Perspective” will outline recent developments and findings in the area of medically unexplained somatic symptoms and somatoform disorders. Moreover, it will lay a special focus on evidence on specific negative psychological factors that may influence the course of unexplained somatic symptoms and disorders and the impairment caused by these symptoms.
Physical activity programs for cardiovascular outcomes in community wheelchair users: A systematic review
Authors: Andrabi Mudasir Saleem , Mumba Mercy , Key Betty , Motl Robert
Published: November 2022

Purpose

Physical inactivity is one of the important factors leading to chronic diseases including cardiovascular disease (CVD) in individuals with disabilities. However, not many Physical Activity (PA) interventions are available for improving the efficacy of PA and cardiovascular outcomes among community wheelchair users. Therefore, this systematic review will appraise the existing PA interventions for the community dwelling wheelchair users; we especially examined features of the PA programs that showed the improvements in PA and the CVD outcomes compared to the interventions that did not show any improvements in these outcomes among these population. The study also aimed to provide some recommendations for future research.

Materials and Methods

A comprehensive and systematic search of literature published between 2015 and 2020 using the databases Scopus, Pubmed, Embase, and Cochrane CENTRAL was conducted. This review has followed the Preferred Reporting Items for Systematic Review (PRISMA) guidelines. The quality of the evidence was assessed by Using Joanna Briggs Institute's critical appraisal tool. Studies that tested the efficacy of PA interventions for community-dwelling adult wheelchair users and published in English were involved. Two reviewers reviewed the literature and any disagreements among these reviewers were resolved by a third reviewer.

Results

Fourteen articles were selected for this review. Most of the studies reported improvements in PA. A few studies followed up the participants and majority of the studies have looked at the CVD outcomes.

Conclusion

Large-scale studies with follow-ups, and community participatory research that evaluates the effect of PA interventions on PA and CVD outcomes among wheelchair users are needed.
A new paradigm in management of frequent attenders to emergency departments with severe alcohol use disorder—A pilot study for assertive community treatment in Singapore
Authors: Mak Charles Chia Meng , Mao Desmond Ren Hao , Siddiqui Fahad Javaid , Lim Alex , Davamoni-Thomas Jayson , Tang June Peiwen , Bachik Rozinah , Ng Charis Wei Ling , Kandasami Gomathinayagam , Lee Cheng
Published: November 2022

Introduction

A majority of frequent users of emergency medical services in Singapore present with alcohol-related problems. These patients are known to engage poorly with traditional addiction services and frequently attend Emergency Departments (EDs) instead, resulting in high healthcare burden. Assertive Community Treatment (ACT) is an alternative intervention to traditional addiction management. ACT involves community visits with focus on holistic care and harm-reduction.

Materials and methods

We conducted a prospective before-and-after cohort study at the major tertiary center for addiction disorders in Singapore. The main objective was to evaluate effectiveness of ACT in reducing alcohol-related attendances at EDs nationwide. Socio-demographics, alcohol-related ED attendances, and the Christo Inventory for Substance-misuse Services (CISS) scores were collected for the patients recruited from April 2018 to March 2019. Descriptive analyses and the Wilcoxon Signed-Rank Test were performed.

Results

All 14 patients were male with a mean age of 55 years. There was a significant 45.3% reduction in average alcohol-related ED attendances from 6.8 (range 3–22, median 5.5) in the pre-intervention 6-month period, to 3.7 (range 0–28, median 1.5) in the post-intervention 6-month period (Z= −2.244,p= 0.025). CISS scores showed significant improvement from a pre-intervention median of 13.5 (range 9–16) to a post-intervention median of 6.5 (range 1–10,p= 0.001), corresponding to reduction in alcohol-related problem severity.

Conclusion

This pilot study suggests that ACT can be effective in reducing alcohol-related ED attendances and alcohol-related problem severity in patients with AUD who frequently attend ED. A multicenter, prospective study using ACT for such patients across four hospitals in Singapore is currently underway.
Perceived factors that influence adoption, implementation and sustainability of an evidence-based intervention promoting healthful eating and physical activity in childcare centers in an urban area in the United States serving children from low-income, racially/ethnically diverse families
Authors: Siegel Leilah , Asada Yuka , Lin Shuhao , Fitzgibbon Marian L. , Kong Angela
Published: November 2022

Introduction

Early childcare centers offer optimal settings to provide healthy built environments where preschool age children spend a majority of their week. Many evidence-based interventions (EBIs) promoting healthful eating and physical activity for early childcare settings exist, but there is a limited understanding of how best to support adoption, implementation and sustainability in community settings. This study examined how early childcare teachers and administrators from Chicago-area childcare centers serving children from low-income, racially/ethnically diverse communities viewed an EBI called Hip to Health (H3), and the factors they perceived as relevant for EBI adoption, implementation, and sustainability.

Methods

A multiple methods study including key informant interviews and a brief survey was conducted. Key informant interviews with teachers and administrators from childcare centers located in Chicago, IL were completed between December 2020 and May 2021. An interview guide and coding guide based on the Consolidated Framework for Implementation Research (CFIR) was developed. Interview transcripts were team coded in MAXQDA Qualitative Data Analysis software. Thematic analysis was used to identify findings specific to adoption, implementation, and sustainability. Participants were also asked to respond to survey measures about the acceptability, feasibility, and appropriateness of H3.

Results

Overall, teachers (n = 20) and administrators (n = 16) agreed that H3 was acceptable, appropriate, and feasible. Low start-up costs, ease-of-use, adaptability, trialability, compatibility, and leadership engagement were important to EBI adoption. Timely and flexible training was critical to implementation. Participants noted sustainability was tied to low ongoing costs, access to ongoing support, and positive observable benefits for children and positive feedback from parents.

Conclusions

These findings suggest that EBIs suitable for adoption, implementation, and sustainment in childcare centers serving racially/ethnically diverse, low-income families should be adaptable, easy to use, and low-cost (initial and ongoing). There is also some evidence from these findings of the heterogeneity that exists among childcare centers serving low-income families in that smaller, less resourced centers are often less aware of EBIs, and the preparation needed to implement EBIs. Future research should examine how to better support EBI dissemination and implementation to these settings.