bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncoupling hepatic insulin resistance – hepatic inflammation to improve insulin sensitivity and to prevent impaired metabolism-associated fatty liver disease in type 2 diabetes
Authors: Niranjan Sitara , Phillips Brett E. , Giannoukakis Nick
Published: June 2023

Diabetes mellitus is a metabolic disease clinically-characterized as acute and chronic hyperglycemia. It is emerging as one of the common conditions associated with incident liver disease in the US. The mechanism by which diabetes drives liver disease has become an intense topic of discussion and a highly sought-after therapeutic target. Insulin resistance (IR) appears early in the progression of type 2 diabetes (T2D), particularly in obese individuals. One of the co-morbid conditions of obesity-associated diabetes that is on the rise globally is referred to as non-alcoholic fatty liver disease (NAFLD). IR is one of a number of known and suspected mechanism that underlie the progression of NAFLD which concurrently exhibits hepatic inflammation, particularly enriched in cells of the innate arm of the immune system. In this review we focus on the known mechanisms that are suspected to play a role in the cause-effect relationship between hepatic IR and hepatic inflammation and its role in the progression of T2D-associated NAFLD. Uncoupling hepatic IR/hepatic inflammation may break an intra-hepatic vicious cycle, facilitating the attenuation or prevention of NAFLD with a concurrent restoration of physiologic glycemic control. As part of this review, we therefore also assess the potential of a number of existing and emerging therapeutic interventions that can target both conditions simultaneously as treatment options to break this cycle.
Combining iCn3D and NextStrain to create a novel undergraduate research experience around SARS-CoV-2 variants and commercial antibodies
Authors: Porter Sandra G. , Smith Todd M.
Published: June 2023

Undergraduate research experiences are increasingly important in biology education with efforts underway to provide more projects by embedded them in a course. The shift to online learning at the beginning of the pandemic presented a challenge. How could biology instructors provide research experiences to students who were unable to attend in-person labs? During the 2021 ISMB (Intelligent Systems for Molecular Biology) iCn3D Hackathon–Collaborative Tools for Protein Analysis–we learned about new capabilities in iCn3D for analyzing the interactions between amino acids in the paratopes of antibodies with amino acids in the epitopes of antigens and predicting the effects of mutations on binding. Additionally, new sequence alignment tools in iCn3D support aligning protein sequences with sequences in structure models. We used these methods to create a new undergraduate research project, that students could perform online as part of a course, by combining the use of new features in iCn3D with analysis tools in NextStrain, and a data set of anti-SARS-CoV-2 antibodies. We present results from an example project to illustrate how students would investigate the likelihood of SARS-CoV-2 variants escaping from commercial antibodies and use chemical interaction data to support their hypotheses. We also demonstrate that online tools (iCn3D, NextStrain, and the NCBI databases) can be used to carry out the necessary steps and that this work satisfies the requirements for course-based undergraduate research. This project reinforces major concepts in undergraduate biology–evolution and the relationship between the sequence of a protein, its three-dimensional structure, and its function.
Placental microRNA methylome signatures may serve as biomarkers and therapeutic targets for prenatally opioid-exposed infants with neonatal opioid withdrawal syndrome
Authors: Radhakrishna Uppala , Nath Swapan K. , Uppala Lavanya V. , Veerappa Avinash , Forray Ariadna , Muvvala Srinivas B. , Metpally Raghu P. , Crist Richard C. , Berrettini Wade H. , Mausi Lori M. , Vishweswaraiah Sangeetha , Bahado-Singh Ray O.
Published: June 2023

Introduction: The neonate exposed to opioids in utero faces a constellation of withdrawal symptoms postpartum commonly called neonatal opioid withdrawal syndrome (NOWS). The incidence of NOWS has increased in recent years due to the opioid epidemic. MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. Epigenetic variations in microRNAs (miRNAs) and their impact on addiction-related processes is a rapidly evolving area of research.

Methods: The Illumina Infinium Methylation EPIC BeadChip was used to analyze DNA methylation levels of miRNA-encoding genes in 96 human placental tissues to identify miRNA gene methylation profiles as-sociated with NOWS: 32 from mothers whose prenatally opioid-exposed infants required pharmacologic management for NOWS, 32 from mothers whose prenatally opioid-exposed infants did not require treat-ment for NOWS, and 32 unexposed controls.

Results: The study identified 46 significantly differentially methylated (FDR p-value ≤ 0.05) CpGs associated with 47 unique miRNAs, with a receiver operating characteristic (ROC) area under the curve (AUC) ≥0.75 including 28 hypomethylated and 18 hypermethylated CpGs as potentially associated with NOWS. These dysregulated microRNA methylation patterns may be a contributing factor to NOWS pathogenesis.

Conclusion: This is the first study to analyze miRNA methylation profiles in NOWS infants and illustrates the unique role miRNAs might have in diagnosing and treating the disease. Furthermore, these data may provide a step toward feasible precision medicine for NOWS babies as well.
Durability of immune response after SARS-CoV-2 vaccination in patients with chronic liver disease
Authors: Song Ruixin , Yang Chao , Li Qianqian , Wang Jiayin , Chen Jing , Sun Kai , Lv Hongmin , Yang Yankai , Liang Jing , Ye Qing , Gao YanYing , Li Jun , Li Ying , Yan Junqing , Liu Ying , Wang Tao , Liu Changen , Zhu Ping , Wang Fei , Yin Weili , Xiang Huiling
Published: June 2023

Aim

The present study aimed to evaluate the durability of immune response after basic and booster immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with chronic liver disease (CLD).

Methods

Patients with CLD and complete basic or booster immunization with SARS-CoV-2 vaccines were included in this study. Based on the vaccination situation, they were divided into the basic immunity group (Basic) and the booster immunity group (Booster), which were then subdivided into four groups according to the time interval from completion of basic immunization or booster immunization to serological specimen collection. The positive rates and antibody titers of novel coronavirus neutralizing antibody (nCoV NTAb) and novel coronavirus spike receptor-binding domain antibody (nCoV S-RBD) were analyzed.

Results

A total of 313 patients with CLD were enrolled in this study, including 201 in Basic and 112 in Booster. The positive rates of nCoV NTAb and nCoV S-RBD within 30 days of completing basic immunization were 80.4% and 84.8%, respectively, but decreased rapidly with the extension of vaccination time, and only 29% and 48.4% of patients with CLD remained positive for nCoV NTAb and nCoV S-RBD, respectively, after 120 days of completing basic immunization. Within 30 days of booster immunization, the positive rates of nCoV NTAb and nCoV S-RBD in patients with CLD rapidly increased from 29.0% and 48.4% at the end of basic immunization to 95.2% and 90.5%, and maintained a high level (defined as the positive rate >50%) until 120 days when the positive rates of nCoV NTAb and nCoV S-RBD were still high at 79.5% and 87.2%, respectively. After basic immunization, the time for nCoV NTAb and nCoV S-RBD to turn negative was 120 and 169 days, respectively, and the negative time of nCoV NTAb and nCoV S-RBD was significantly prolonged to 266 days and 329 days, respectively.

Conclusion

It is safe and effective for patients with CLD to complete basic and booster immunization with SARS-CoV-2 vaccines. After booster immunization, the immune response of patients with CLD was further improved and the durability of the SARS-CoV-2 antibody was significantly prolonged.
The influence of environmental regulation on high-quality development of marine economy from different subjects’ perspectives
Authors: Wu Fan , Cui Fengxiang , Liu Tao
Published: June 2023

As the high-quality development of marine economy cannot be separated from the improvement of marine ecological environment quality, it is of great importance to clarify the relationship between environmental regulation and the high-quality development of marine economy. In this paper, firstly, an aggregative indicator system of high-quality development of marine economy was constructed to dynamically describe and analyze the overall and provincial trends of high-quality development indicators of marine economy from two dimensions: time trend and spatial pattern. Then, a theoretical analysis framework of environmental regulation affecting the high-quality development of marine economy was constructed, and the theoretical explanation and hypotheses were put forward and tested from the action mechanism of different types of environmental regulation affecting the high-quality development of marine economy, such as command control, market incentive and public participation. At last, the paths and countermeasures of environmental regulation to promote the high-quality development of marine economy were put forward combined with the theoretical analysis and empirical test results.
Pathophysiology and management of liver cirrhosis: from portal hypertension to acute-on-chronic liver failure
Authors: Jagdish Rakesh Kumar , Roy Akash , Kumar Karan , Premkumar Madhumita , Sharma Mithun , Rao Padaki Nagaraja , Reddy Duvvur Nageshwar , Kulkarni Anand V.
Published: June 2023

Cirrhosis transcends various progressive stages from compensation to decompensation driven by the severity of portal hypertension. The downstream effect of increasing portal hypertension severity leads to various pathophysiological pathways, which result in the cardinal complications of cirrhosis, including ascites, variceal hemorrhage, and hepatic encephalopathy. Additionally, the severity of portal hypertension is the central driver for further advanced complications of hyperdynamic circulation, hepatorenal syndrome, and cirrhotic cardiomyopathy. The management of these individual complications has specific nuances which have undergone significant developments. In contrast to the classical natural history of cirrhosis and its complications which follows an insidious trajectory, acute-on-chronic failure (ACLF) leads to a rapidly downhill course with high short-term mortality unless intervened at the early stages. The management of ACLF involves specific interventions, which have quickly evolved in recent years. In this review, we focus on complications of portal hypertension and delve into an approach toward ACLF.
Predictors for early cardiac death after discharge from successfully treated acute myocardial infarction
Authors: Choi Young , Lee Kwan Yong , Kim Sang Hyun , Kim Kyung An , Hwang Byung-Hee , Choo Eun Ho , Lim Sungmin , Kim Chan Jun , Kim Jin-Jin , Byeon Jaeho , Oh Gyu Chul , Jeon Doo Soo , Yoo Ki Dong , Park Ha-Wook , Kim Min Chul , Ahn Youngkeun , Ho Jeong Myung , Hwang Youngdeok , Chang Kiyuk
Published: June 2023

Background

The use of a cardioverter defibrillator for the primary prevention of sudden cardiac death is not recommended within 40 days after acute myocardial infarction (AMI). We investigated the predictors for early cardiac death among patients who were admitted for AMI and successfully discharged.

Methods

Consecutive patients with AMI were enrolled in a multicenter prospective registry. Among 10,719 patients with AMI, 554 patients with in-hospital death and 62 patients with early non-cardiac death were excluded. Early cardiac death was defined as a cardiac death within 90 days after index AMI.

Results

Early cardiac death after discharge occurred in 168/10,103 (1.7%) patients. A defibrillator was not implanted in all patients with early cardiac death. Killip class ≥3, chronic kidney disease stage ≥4, severe anemia, cardiopulmonary support usage, no dual antiplatelet therapy at discharge, and left ventricular ejection fraction (LVEF) ≤35% were independent predictors for early cardiac death. The incidence of early cardiac death according to the number of factors added to LVEF criteria in each patient was 3.03% for 0 factor, 8.11% for 1 factor, and 9.16% for ≥2 factors. Each model that sequentially added the factors in the presence of LVEF criteria showed a significant gradual increase in predictive accuracy and an improvement in reclassification capability. A model with all factors showed C-index 0.742 [95% CI 0.702–0.781], p < 0.001; IDI 0.024 [95% CI 0.015–0.033], p < 0.001; and NRI 0.644 [95% CI 0.492–0.795], p < 0.001.

Conclusion

We identified six predictors for early cardiac death after discharge from AMI. These predictors would help to discriminate high-risk patients over current LVEF criteria and to provide an individualized therapeutic approach in the subacute stage of AMI.
Long-term functional and structural outcomes in X-linked retinoschisis: implications for clinical trials
Authors: Fenner Beau J. , Russell Jonathan F. , Drack Arlene V. , Dumitrescu Alina V. , Sohn Elliott H. , Russell Stephen R. , Boldt H. Culver , Affatigato Louisa M. , Hoffmann Jeremy M. , Andorf Jeaneen L. , Stone Edwin M. , Han Ian C.
Published: June 2023

Introduction

X-linked retinoschisis (XLRS) is an inherited retinal disease (IRD) caused by pathogenic mutations in the retinoschisin gene, RS1. Affected individuals develop retinal layer separation, leading to loss of visual acuity (VA). Several XLRS gene therapy trials have been attempted but none have met their primary endpoints. An improved understanding of XLRS natural history and clinical outcomes may better inform future trials. Here, we report the long-term functional and structural outcomes of XLRS and the relevance of RS1 genotypes to the visual prognosis of affected individuals.

Methods

A retrospective chart review of patients with molecularly confirmed X-linked retinoschisis was performed. Functional and structural outcomes, and RS1 genotype data, were included for analysis.

Results

Fifty-two patients with XLRS from 33 families were included in the study. Median age at symptom onset was 5 years (range 0–49) and median follow-up was 5.7 years (range 0.1–56.8). Macular retinoschisis occurred in 103 of 104 eyes (99.0%), while peripheral retinoschisis occurred in 48 of 104 eyes (46.2%), most often in the inferotemporal quadrant (40.4%). Initial and final VA were similar (logMAR 0.498 vs. 0.521; p = 0.203). Fifty of 54 eyes (92.6%) developed detectable outer retinal loss by age 20, and 29 of 66 eyes (43.9%) had focal or diffuse outer retinal atrophy (ORA) by age 40. ORA but not central subfield thickness (CST) was associated with reduced VA. Inter-eye correlation was modest for VA (r-squared = 0.03; p = 0.08) and CST (r-squared = 0.15; p = 0.001). Carbonic anhydrase inhibitors (CAIs) improved CST (p = 0.026), but not VA (p = 0.380). Eight of 104 eyes (7.7%) had XLRS-related retinal detachment (RD), which was associated with poorer outcomes compared to eyes without RD (median final VA 0.875 vs. 0.487; p <0.0001). RS1 null genotypes had greater odds of at least moderate visual impairment at final follow-up (OR 7.81; 95% CI 2.17, 28.10; p = 0.002) which was independent of age at onset, initial CST, initial ORA, or previous RD.

Discussion

Overall, long-term follow-up of XLRS patients demonstrated relatively stable VA, with presenting CST, development of ORA, and null RS1 mutations associated with poorer long-term visual outcomes, indicating a clinically relevant genotype-phenotype correlation in XLRS.
Comparative genomic analysis of Cohnella hashimotonis sp. nov. isolated from the International Space Station
Authors: Simpson Anna C. , Eedara V. V. Ramprasad , Singh Nitin K. , Damle Namita , Parker Ceth W. , Karouia Fathi , Mason Christopher E. , Venkateswaran Kasthuri
Published: June 2023

A single strain from the family Paenibacillaceae was isolated from the wall behind the Waste Hygiene Compartment aboard the International Space Station (ISS) in April 2018, as part of the Microbial Tracking mission series. This strain was identified as a gram-positive, rod-shaped, oxidase-positive, catalase-negative motile bacterium in the genus Cohnella, designated as F6_2S_P_1T. The 16S sequence of the F6_2S_P_1T strain places it in a clade with C. rhizosphaerae and C. ginsengisoli, which were originally isolated from plant tissue or rhizosphere environments. The closest 16S and gyrB matches to strain F6_2S_P_1T are to C. rhizosphaerae with 98.84 and 93.99% sequence similarity, while a core single-copy gene phylogeny from all publicly available Cohnella genomes places it as more closely related to C. ginsengisoli. Average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values to any described Cohnella species are <89 and <22%, respectively. The major fatty acids for strain F6_2S_P_1T are anteiso-C15:0 (51.7%), iso-C16:0 (23.1%), and iso-C15:0 (10.5%), and it is able to metabolize a wide range of carbon compounds. Given the results of the ANI and dDDH analyses, this ISS strain is a novel species within the genus Cohnella for which we propose the name Cohnella hashimotonis, with the type strain F6_2S_P_1T (=NRRL B-65657T and DSMZ 115098T). Because no closely related Cohnella genomes were available, this study generated the whole-genome sequences (WGSs) of the type strains for C. rhizosphaerae and C. ginsengisoli. Phylogenetic and pangenomic analysis reveals that F6_2S_P_1T, C. rhizosphaerae, and C. ginsengisoli, along with two uncharacterized Cohnella strains, possess a shared set of 332 gene clusters which are not shared with any other WGS of Cohnella species, and form a distinct clade branching off from C. nanjingensis. Functional traits were predicted for the genomes of strain F6_2S_P_1T and other members of this clade.
Probiotic lactic acid bacteria alleviate pediatric IBD and remodel gut microbiota by modulating macrophage polarization and suppressing epithelial apoptosis
Authors: Hua Huiying , Pan Chun , Chen Xixi , Jing Mengxia , Xie Jinfang , Gao Yuanqi , Huang Jiebin , Chen Xuehua , Gao Yujing , Xu Chundi , Li Pu
Published: June 2023

Introduction

The incidence of pediatric inflammatory bowel disease (PIBD) continues to rise. It was reported that the probiotic lactic acid bacteria Pediococcus pentosaceus (P. pentosaceus) can interfere with intestinal immunity, but it is still unknown whether it can alleviate PIBD and the concrete mechanism of immune regulation is unclear.

Methods

For this study, 3-week-old juvenile mice were selected for modeling the development of PIBD. The mice treated with 2% DSS were randomly divided into two groups, which were given P. pentosaceus CECT8330 and equal amounts of solvent, respectively. The feces and intestinal tissue were collected for the mechanism exploration in vivo. THP-1 and NCM460 cells were used to investigate the effects of P. pentosaceus CECT8330 on macrophage polarization, epithelial cell apoptosis, and their crosstalk in vitro.

Results

P. pentosaceus CECT8330 obviously alleviated colitis symptoms of juvenile mice, including weight loss, colon length shortening, spleen swelling, and intestinal barrier function. Mechanistically, P. pentosaceus CECT8330 could inhibit intestinal epithelial apoptosis by suppressing the NF-κB signaling pathway. Meanwhile, it reprogramed macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, leading to a decreased secretion of IL-1β which contributes to the reduction in ROS production and epithelial apoptosis. Additionally, the 16S rRNA sequence analysis revealed that P. pentosaceus CECT8330 could recover the balance of gut microbiota, and a significantly increased content of Akkermansia muciniphila was particularly observed.

Conclusion

P. pentosaceus CECT8330 shifts macrophage polarization toward an anti-inflammatory M2 phenotype. The decreased production of IL-1β leads to a reduction in ROS, NF-κB activation, and apoptosis in the intestinal epithelium, all of which help to repair the intestinal barrier and adjust gut microbiota in juvenile colitis mice.
Isolation, identification, and antibacterial evaluation of endophytic fungi from Gannan navel orange
Authors: Wang Huan , Liu Ziyue , Duan Fangfang , Chen Yan , Qiu Kaidi , Xiong Qin , Lin Huiting , Zhang Jun , Tan Haibo
Published: June 2023

Gannan navel orange is a famous brand in China but the isolation of its endophytic fungi was rarely reported. In this study, a total of 54 strains of endophytic fungi were successfully isolated from the pulp, peel, twig, and leaf of Gannan navel orange; they were successfully identified to belong to 17 species of 12 genera. All these strains were fermented using potato-dextrose agar (PDA) medium, and their secondary metabolites were then extracted with ethyl acetate (EtOAc). The antibacterial assays of Escherichia coli (E. coli), methicillin-resistant Staphylococcus aureus (MRSA), and Xanthomonas citri subsp. citri (Xcc) were also performed for the EtOAc extracts of these strains. As a result, the extracts of both Geotrichum sp. (gc-1-127-30) and Diaporthe biconispora (gc-1-128-79) demonstrated significant antibacterial activities against Xcc, and the MIC value for the extract of Colletotrichum gloeosporioides against MRSA was low to 62.5 μg/mL. Moreover, the chemical components of the extracts of Colletotrichum sp., Diaporthe biconispora, and Annulohypoxylon atroroseum were primarily investigated, and they successfully led to the isolation of 24 compounds involving a new botryane sesquiterpene. Among the isolated products, compound 2 showed significant inhibitory activities toward SA, MRSA, E. coli, and Xcc with MIC values of 12.5, 3.1, 125, and 12.5 μg/mL, respectively. This study revealed that the endophytic fungi of Gannan navel orange showed high potency to produce secondary metabolites with significant antibacterial effects.
Could oral hygiene prevent cases of at-home-acquired Legionnaires’ disease? – Results of a comprehensive case–control study on infection sources, risk, and protective behaviors
Authors: Lehfeld Ann-Sophie , Reber Franziska , Lewandowsky Marina M. , Jahn Heiko J. , Lück Christian , Petzold Markus , Schaefer Benedikt , Germelmann Anna-Rachel , Lorenz Katrin , Buchholz Udo
Published: June 2023

Introduction

The “LeTriWa study” on community-acquired cases of Legionnaires’ disease (LD) found that most cases likely acquired their infection at home (AHALD). However, which sources confer the infection is largely unknown. We therefore analyzed the data set from the LeTriWa study to find out if individual sources were associated with AHALD and if specific behavioral habits may increase or lower the risk for AHALD.

Methods

During the study we had used two comparison groups: (i) controls matched for age group and hospital (“controls”), (ii) household members of cases with AHALD (“AHALD-HHM”). We inquired about exposure to water sources, such as showering or wearing dentures, as well as behavioral factors and habits related to oral hygiene. We took standardized household bathroom water and biofilm samples of both cases with AHALD and controls, and in addition from households of cases with AHALD only samples from suspect residential (non-)drinking water sources. We first conducted bivariate analyses for infection sources and behaviors, followed by multivariable analyses.

Results

There were 124 cases with AHALD, 217 controls and 59 AHALD-HHM. In bivariate analyses using controls for comparison, wearing dentures was the only variable significantly positively associated (odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.1–2.7, p-value = 0.02). Behavioral factors such as showering, letting water run before use and not being alcohol abstinent were significantly negatively associated, smoking was significantly positively associated. In a multivariable analysis, we identified good oral hygiene as a preventive factor for both denture wearers (OR = 0.33, 95% CI = 0.13–0.83, p-value = 0.02) and non-denture wearers (OR = 0.32, 95% CI = 0.10–1.04, p-value = 0.06). Analyses of comparisons with AHALD-HHM showed similar effects but lacked statistical power. We identified Legionella in 16 residential (non-)drinking water sources, one of which was a PCR-positive scratch sample of dentures.

Discussion

Wearing (inadequately cleaned) dentures or poor oral hygiene might confer an increased risk for AHALD, and oral hygiene may prevent AHALD. The hypothesis that Legionella in oral biofilm or dental plaque may be the cause of cases with AHALD should be examined further. If confirmed this may open new and simple avenues for the prevention of LD.
Effect of oxic and anoxic conditions on intracellular storage of polyhydroxyalkanoate and polyphosphate in Magnetospirillum magneticum strain AMB-1
Authors: Su Qingxian , Andersen Henrik Rasmus , Bazylinski Dennis A. , Jensen Marlene Mark
Published: June 2023

Magnetotactic bacteria (MTB) are microorganisms widely inhabiting the oxic-anoxic interface of aquatic environments. Beside biomineralizing magnetic nanocrystals, MTBs are able to sequester various chemical elements (e.g., carbon and phosphorus) for the biogenesis of intracellular granules, like polyhydroxyalkanoate (PHA) and polyphosphate (polyP), making them potentially important in biogeochemical cycling. Yet, the environmental controls of intracellular storage of carbon and phosphorus in MTB remain poorly understood. Here, we investigated the influence of oxic, anoxic and transient oxic-anoxic conditions on intracellular storage of PHA and polyP in Magnetospirillum magneticum strain AMB-1. In the incubations with oxygen, transmission electron microscopy revealed intercellular granules highly rich in carbon and phosphorus, which were further interpreted as PHA and polyP based on chemical and Energy-Dispersive X-ray spectroscopy analysis. Oxygen had a strong effect on PHA and polyP storage in AMB-1 cells, as PHA and polyP granules accounted for up to 47 ± 23% and 5.1 ± 1.7% of the cytoplasmic space, respectively, during continuous oxic conditions, while granules disappeared in anoxic incubations. Poly 3-hydroxybutyrate (PHB) and poly 3-hydroxyvalerate (PHV) accounted for 0.59 ± 0.66% and 0.0033 ± 0.0088% of dry cell weight, respectively, in anoxic incubations, while the values increased by a factor of 7 and 37 after oxygen was introduced. The results highlight a tight link between oxygen, carbon and phosphorus metabolisms in MTB, where favorable oxic growth conditions can lead to metabolic induction of polyP and PHA granule biogenesis.
Identification and genetic characteristics of tusavirus in fecal samples of patients with chronic diseases in Guangzhou, China
Authors: He Huan , Li Yongzhi , Chen Jiaqi , Xian Juxian , Zheng Liting , Sun Hengbiao , Fan Shunchang , Fu Jiaqi , Li Qiushuang , Chen Caiyun , Liang Minyi , Zhang Minyi , Wu Ruojun , Xiao Gang , Chen Qing
Published: June 2023

Purpose

The Tunisian stool-associated parvovirus [Tusavirus (TuV)] is a novel member of the genus Protoparvovirus, which may be linked to diarrhea. Herein, we investigated the prevalence of TuV in different populations and analyzed its genetic and bioinformatic characteristics.

Methods

This study was conducted in a tertiary hospital in Guangzhou (China) from February 2018 to July 2022. Demographic and clinical information and stool samples were collected from individuals who visited the hospital. ProtScale, SwissModel, Datamonkey, and other tools were used to analyze and predict the physicochemical parameters, tertiary structure, selection pressure, and B-cell epitopes of capsid viral protein 2 of TuV (VP2-TuV).

Results

A total of 3,837 participants were enrolled, among which two stool samples from patients with chronic illnesses were tested positive for TuV DNA. However, no positive sample was detected among patients with diarrhea. Two near-complete genome sequences were amplified. The genetic analysis revealed the presence of diversity among TuVs isolated from distinct host species. Bioinformatics analysis revealed that VP2-TuV exhibited hydrophilic properties and lacked transmembrane domains and signal peptides. The secondary structure of VP2-TuV was composed mainly of random coils and β-strands. Selective-pressure analysis of the VP2 region suggested that TuV primarily underwent negative selection during evolution. Negatively selected codon sites coincided with residues comprising of B-cell epitopes, suggesting minimal changes in the immunogenicity of TuV over time.

Conclusion

TuV was detected in patients with chronic diseases but not in patients with diarrhea. The putative roles of TuV in the pathogenicity of human diseases and zoonotic viruses must be determined by additional studies.
Deciphering psychobiotics’ mechanism of action: bacterial extracellular vesicles in the spotlight
Authors: Bleibel Layla , Dziomba Szymon , Waleron Krzysztof Franciszek , Kowalczyk Edward , Karbownik Michał Seweryn
Published: June 2023

The intake of psychobiotic bacteria appears to be a promising adjunct to neuropsychiatric treatment, and their consumption may even be beneficial for healthy people in terms of mental functioning. The psychobiotics’ mechanism of action is largely outlined by the gut-brain axis; however, it is not fully understood. Based on very recent studies, we provide compelling evidence to suggest a novel understanding of this mechanism: bacterial extracellular vesicles appear to mediate many known effects that psychobiotic bacteria exert on the brain. In this mini-review paper, we characterize the extracellular vesicles derived from psychobiotic bacteria to demonstrate that they can be absorbed from the gastrointestinal tract, penetrate to the brain, and carry the intracellular content to exert beneficial multidirectional action. Specifically, by regulating epigenetic factors, extracellular vesicles from psychobiotics appear to enhance expression of neurotrophic molecules, improve serotonergic neurotransmission, and likely supply astrocytes with glycolytic enzymes to favor neuroprotective mechanisms. As a result, some data suggest an antidepressant action of extracellular vesicles that originate even from taxonomically remote psychobiotic bacteria. As such, these extracellular vesicles may be regarded as postbiotics of potentially therapeutic application. The mini-review is enriched with illustrations to better introduce the complex nature of brain signaling mediated by bacterial extracellular vesicles and indicates knowledge gaps that require scientific exploration before further progress is made. In conclusion, bacterial extracellular vesicles appear to represent the missing piece of the puzzle in the mechanism of action of psychobiotics.
Prevalence of comorbidities post mild traumatic brain injuries: a traumatic brain injury model systems study
Authors: Sudhakar Shyam Kumar , Sridhar Shreya , Char Satvika , Pandya Kathan , Mehta Kaustav
Published: June 2023

Traumatic brain injury (TBI) is associated with an increased risk of long-lasting health-related complications. Survivors of brain trauma often experience comorbidities which could further dampen functional recovery and severely interfere with their day-to-day functioning after injury. Of the three TBI severity types, mild TBI constitutes a significant proportion of total TBI cases, yet a comprehensive study on medical and psychiatric complications experienced by mild TBI subjects at a particular time point is missing in the field. In this study, we aim to quantify the prevalence of psychiatric and medical comorbidities post mild TBI and understand how these comorbidities are influenced by demographic factors (age, and sex) through secondary analysis of patient data from the TBI Model Systems (TBIMS) national database. Utilizing self-reported information from National Health and Nutrition Examination Survey (NHANES), we have performed this analysis on subjects who received inpatient rehabilitation at 5 years post mild TBI. Our analysis revealed that psychiatric comorbidities (anxiety, depression, and post-traumatic stress disorder (PTSD)), chronic pain, and cardiovascular comorbidities were common among survivors with mild TBI. Furthermore, depression exhibits an increased prevalence in the younger compared to an older cohort of subjects whereas the prevalence of rheumatologic, ophthalmological, and cardiovascular comorbidities was higher in the older cohort. Lastly, female survivors of mild TBI demonstrated increased odds of developing PTSD compared to male subjects. The findings of this study would motivate additional analysis and research in the field and could have broader implications for the management of comorbidities after mild TBI.
Identifying languages in a novel dataset: ASMR-whispered speech
Authors: Song Meishu , Yang Zijiang , Parada-Cabaleiro Emilia , Jing Xin , Yamamoto Yoshiharu , Schuller Björn
Published: June 2023

Introduction

The Autonomous Sensory Meridian Response (ASMR) is a combination of sensory phenomena involving electrostatic-like tingling sensations, which emerge in response to certain stimuli. Despite the overwhelming popularity of ASMR in the social media, no open source databases on ASMR related stimuli are yet available, which makes this phenomenon mostly inaccessible to the research community; thus, almost completely unexplored. In this regard, we present the ASMR Whispered-Speech (ASMR-WS) database.

Methods

ASWR-WS is a novel database on whispered speech, specifically tailored to promote the development of ASMR-like unvoiced Language Identification (unvoiced-LID) systems. The ASMR-WS database encompasses 38 videos-for a total duration of 10 h and 36 min-and includes seven target languages (Chinese, English, French, Italian, Japanese, Korean, and Spanish). Along with the database, we present baseline results for unvoiced-LID on the ASMR-WS database.

Results

Our best results on the seven-class problem, based on segments of 2s length, and on a CNN classifier and MFCC acoustic features, achieved 85.74% of unweighted average recall and 90.83% of accuracy.

Discussion

For future work, we would like to focus more deeply on the duration of speech samples, as we see varied results with the combinations applied herein. To enable further research in this area, the ASMR-WS database, as well as the partitioning considered in the presented baseline, is made accessible to the research community.
Eye movement changes as an indicator of mild cognitive impairment
Authors: Opwonya Julius , Ku Boncho , Lee Kun Ho , Kim Joong Il , Kim Jaeuk U.
Published: June 2023

Background

Early identification of patients at risk of dementia, alongside timely medical intervention, can prevent disease progression. Despite their potential clinical utility, the application of diagnostic tools, such as neuropsychological assessments and neuroimaging biomarkers, is hindered by their high cost and time-consuming administration, rendering them impractical for widespread implementation in the general population. We aimed to develop non-invasive and cost-effective classification models for predicting mild cognitive impairment (MCI) using eye movement (EM) data.

Methods

We collected eye-tracking (ET) data from 594 subjects, 428 cognitively normal controls, and 166 patients with MCI while they performed prosaccade/antisaccade and go/no-go tasks. Logistic regression (LR) was used to calculate the EM metrics’ odds ratios (ORs). We then used machine learning models to construct classification models using EM metrics, demographic characteristics, and brief cognitive screening test scores. Model performance was evaluated based on the area under the receiver operating characteristic curve (AUROC).

Results

LR models revealed that several EM metrics are significantly associated with increased odds of MCI, with odds ratios ranging from 1.213 to 1.621. The AUROC scores for models utilizing demographic information and either EM metrics or MMSE were 0.752 and 0.767, respectively. Combining all features, including demographic, MMSE, and EM, notably resulted in the best-performing model, which achieved an AUROC of 0.840.

Conclusion

Changes in EM metrics linked with MCI are associated with attentional and executive function deficits. EM metrics combined with demographics and cognitive test scores enhance MCI prediction, making it a non-invasive, cost-effective method to identify early stages of cognitive decline.
Neuropharmacology of human TERA2.cl.SP12 stem cell-derived neurons in ultra-long-term culture for antiseizure drug discovery
Authors: Salmanzadeh Hamed , Poojari Ankita , Rabiee Atefeh , Zeitlin Benjamin D. , Halliwell Robert F.
Published: June 2023

Modeling the complex and prolonged development of the mammalian central nervous system in vitro remains a profound challenge. Most studies of human stem cell derived neurons are conducted over days to weeks and may or may not include glia. Here we have utilized a single human pluripotent stem cell line, TERA2.cl.SP12 to derive both neurons and glial cells and determined their differentiation and functional maturation over 1 year in culture together with their ability to display epileptiform activity in response to pro-convulsant agents and to detect antiseizure drug actions. Our experiments show that these human stem cells differentiate in vitro into mature neurons and glia cells and form inhibitory and excitatory synapses and integrated neural circuits over 6–8 months, paralleling early human neurogenesis in vivo; these neuroglia cultures display complex electrochemical signaling including high frequency trains of action potentials from single neurons, neural network bursts and highly synchronized, rhythmical firing patterns. Neural activity in our 2D neuron–glia circuits is modulated by a variety of voltage-gated and ligand-gated ion channel acting drugs and these actions were consistent in both young and highly mature neuron cultures. We also show for the first time that spontaneous and epileptiform activity is modulated by first, second and third generation antiseizure agents consistent with animal and human studies. Together, our observations strongly support the value of long-term human stem cell-derived neuroglial cultures in disease modeling and neuropsychiatric drug discovery.
Bibliometric analysis of acupuncture and moxibustion treatment for mild cognitive impairment
Authors: Yang Wei , Liu Xingfang , Zhang Xinyue , Li Cong , Li Zhenghong , Li Yiming , Li Mingquan
Published: June 2023

Objective

This study aims to analyze the current research status of acupuncture in the treatment of mild cognitive impairment (MCI) using bibliometric methods, explore current research hotspots, and predict future research trends.

Methods

Literature on acupuncture for MCI in China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) databases were searched from their inception to December 31, 2022. Articles were then filtered using inclusion and exclusion criteria and imported into VOSviewer 1.6.11 and CiteSpace 6.1.6msi software for descriptive analysis of publication numbers, network analysis of author/institution collaborations, and cluster analysis of keywords, as well as analysis of keyword emergence and linear relationships with time.

Results

The Chinese and English databases included 243 and 565 relevant articles, respectively. The overall volume of Chinese and English literature was stable, with the annual volume generally increasing. In terms of countries, institutions, and authors, China had the highest number of English-language publications; however, the number of joint publications among institutions/authors was low. Research institutions were independent and dispersed, with no collaborative teams formed around a single institution/author. The hotspots in Chinese literature were “needling, treatment, electric acupuncture, nimodipine, cognitive training” and other clinical research directions. The hotspots in English literature were “acupuncture, electro-acupuncture, Alzheimer’s disease, dementia, cognitive impairment, memory, vascular dementia, mild cognitive impairment, stroke, hippocampus, injury,” and other mechanisms of action.

Conclusion

The popularity of acupuncture for MCI is increasing year by year. Acupuncture for MCI, along with cognitive training, can help improve cognitive function. “Inflammation” is the frontier of acupuncture for MCI research. In the future, strengthening effective communication and cooperation among institutions, especially international cooperation, is essential for conducting high-quality research on acupuncture for MCI. This will help obtain high-level evidence and improve the output and translation of research results.
The effects and mechanisms of acupuncture for post-stroke cognitive impairment: progress and prospects
Authors: Li Ningcen , Wang Hui , Liu Hang , Zhu Lina , Lyu Zhongxi , Qiu Jiwen , Zhao Tianyi , Ren Haiyan , Huang Lihong , Chen Shuangli , Hu Xiuwu , Zhou Liang
Published: June 2023

Stroke is one of the important causes of both disability and death worldwide, which is very common in older adults. Post-stroke cognitive impairment (PSCI) is a common secondary damage of stroke, which is the main cause of long-term disability and decreased quality of life in stroke patients, which brings a heavy burden to society and families. Acupuncture, as one of the oldest and widely used worldwide techniques in Chinese medicine, is recommended by the World Health Organization (WHO) as an alternative and complementary strategy for improving stroke care. This review comprehensively summarizes literature from the last 25 years, showing that acupuncture can exert strong beneficial effect on PSCI. The mechanisms of acupuncture on PSCI involves anti-neuronal apoptosis, promoting synaptic plasticity, alleviating central and peripheral inflammatory reactions, and regulating brain energy metabolism disorders (including improving cerebral blood flow, glucose utilization and mitochondrial structure and function, etc.), etc. The effects and mechanisms of acupuncture on PSCI reviewed in this study provides scientific and reliable evidence for acupuncture application for PSCI.
Development and validation of an inflammatory response-related signature in triple negative breast cancer for predicting prognosis and immunotherapy
Authors: Guo Yangyang , Cen Kenan , Yang Shi , Mai Yifeng , Hong Kai
Published: June 2023

Background

Inflammation is one of the most important characteristics of tumor tissue. Signatures based on inflammatory response-related genes (IRGs) can predict prognosis and treatment response in a variety of tumors. However, the clear function of IRGs in the triple negative breast cancer (TNBC) still needs to be explored.

Methods

IRGs clusters were discovered via consensus clustering, and the prognostic differentially expressed genes (DEGs) across clusters were utilized to develop a signature using a least absolute shrinkage and selection operator (LASSO). Verification analyses were conducted to show the robustness of the signature. The expression of risk genes was identified by RT-qPCR. Lastly, we formulated a nomogram to improve the clinical efficacy of our predictive tool.

Results

The IRGs signature, comprised of four genes, was developed and was shown to be highly correlated with the prognoses of TNBC patients. In contrast with the performance of the other individual predictors, we discovered that the IRGs signature was remarkably superior. Also, the ImmuneScores were elevated in the low-risk group. The immune cell infiltration showed significant difference between the two groups, as did the expression of immune checkpoints.

Conclusion

The IRGs signature could act as a biomarker and provide a momentous reference for individual therapy of TNBC.
Unlocking the power of precision medicine for pediatric low-grade gliomas: molecular characterization for targeted therapies with enhanced safety and efficacy
Authors: Cipri Selene , Del Baldo Giada , Fabozzi Francesco , Boccuto Luigi , Carai Andrea , Mastronuzzi Angela
Published: June 2023

In the past decade significant advancements have been made in the discovery of targetable lesions in pediatric low-grade gliomas (pLGGs). These tumors account for 30-50% of all pediatric brain tumors with generally a favorable prognosis. The latest 2021 WHO classification of pLGGs places a strong emphasis on molecular characterization for significant implications on prognosis, diagnosis, management, and the potential target treatment. With the technological advances and new applications in molecular diagnostics, the molecular characterization of pLGGs has revealed that tumors that appear similar under a microscope can have different genetic and molecular characteristics. Therefore, the new classification system divides pLGGs into several distinct subtypes based on these characteristics, enabling a more accurate strategy for diagnosis and personalized therapy based on the specific genetic and molecular abnormalities present in each tumor. This approach holds great promise for improving outcomes for patients with pLGGs, highlighting the importance of the recent breakthroughs in the discovery of targetable lesions.
Allogenic platelet-rich plasma for treatment of knee and hip osteoarthritis
Authors: Gupta Ashim , Potty Anish G. , Maffulli Nicola
Published: June 2023

Osteoarthritis (OA) induces tremendous amounts of stress and financial burden on patients and healthcare systems worldwide. Current treatments have limitations and do not address the etiopathogenetic cause of OA. Regenerative medicine may circumvent limitations posed by traditional modalities and relies on the utilization of biologics including platelet-rich plasma (PRP). Several peer-reviewed studies have documented the safety and efficacy of autologous PRP in mitigating symptoms in knee and hip OA patients. Nonetheless, only few studies investigated the safety and efficacy of allogenic PRP. This mini review summarizes the outcomes of preclinical and clinical studies using allogenic PRP for treatment of knee or hip OA. We identified 3 preclinical and 1 clinical study using allogenic PRP for treatment of knee OA, and only 1 clinical study using allogenic PRP for treatment of hip OA. Administration of allogenic PRP is safe and probably efficacious in patients with knee or hip OA. However, more pre-clinical studies and high-powered, multi-center, non-randomized and randomized controlled trials with extended follow-up are warranted to further establish the safety and efficacy of allogenic PRP to justify its clinical use.
Autophagy in intestinal fibrosis: relevance in inflammatory bowel disease
Authors: Macias-Ceja Dulce C. , Barrachina María D. , Ortiz-Masià Dolores
Published: June 2023

Chronic inflammation is often associated with fibrotic disorders in which an excessive deposition of extracellular matrix is a hallmark. Long-term fibrosis starts with tissue hypofunction and finally ends in organ failure. Intestinal fibrosis is not an exception, and it is a frequent complication of inflammatory bowel disease (IBD). Several studies have confirmed the link between deregulated autophagy and fibrosis and the presence of common prognostic markers; indeed, both up- and downregulation of autophagy are presumed to be implicated in the progression of fibrosis. A better knowledge of the role of autophagy in fibrosis may lead to it becoming a potential target of antifibrotic therapy. In this review we explore novel advances in the field that highlight the relevance of autophagy in fibrosis, and give special focus to fibrosis in IBD patients.