bluuebunny/crossref_metadata_2025 huggingface dataset:
Does fasting plasma glucose values 5.1-5.6 mmol/l in the first trimester of gestation a matter?
Authors: Ramezani Tehrani Fahimeh , Farzadfar Farshad , Hosseinpanah Farhad , Rahmati Maryam , Firouzi Faegheh , Abedini Mehrandokht , Hadaegh Farzad , Valizadeh Majid , Torkestani Farahnaz , Khalili Davood , Solaymani-Dodaran Masoud , Bidhendi-Yarandi Razieh , Bakhshandeh Marzieh , Ostovar Afshin , Dovom Marzieh Rostami , Amiri Mina , Azizi Fereidoun , Behboudi-Gandevani Samira
Published: June 2023

Objectives

The aim of the study was to investigate the effect of treatment on pregnancy outcomes among women who had fasting plasma glucose (FPG) 5.1-5.6 mmol/l in the first trimester of pregnancy.

Methods

We performed a secondary-analysis of a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. All pregnant women with FPG values range 5.1-5.6 mmol/l in the first trimester of gestation were included in the present study (n=3297) and classified to either the (i) intervention group who received treatment for GDM along with usual prenatal care (n=1,198), (ii) control group who received usual-prenatal-care (n=2,099). Macrosomia/large for gestational age (LGA) and primary cesarean-section (C-S) were considered as primary-outcomes. A modified-Poisson-regression for binary outcome data with a log link function and robust error variance was used to RR (95%CI) for the associations between GDM status and incidence of pregnancy outcomes.

Results

The mean maternal age and BMI of pregnant women in both study groups were similar. There were no statistically significant differences in the adjusted risks of adverse pregnancy outcomes, including macrosomia, primary C-S, preterm birth, hyperbilirubinemia, preeclampsia, NICU-admission, birth trauma, and LBW both groups.

Conclusions

It is found that treating women with first-trimester FPG values of 5.1-5.6 mmol/l could not improve adverse pregnancy outcomes including macrosomia, Primary C-S, Preterm birth, hypoglycemia, hypocalcemia, preeclampsia, NICU admission, Birth trauma and LBW. Therefore, extrapolating the FPG cut-off point of the second trimester to the first –which has been proposed by the IADPSG, might therefore not be appropriate.

Clinical Trial Registration

https://www.irct.ir/trial/518, identifier IRCT138707081281N1.
Transoral endoscopic thyroidectomy vestibular approach as a novel technique for pediatric populations: Results from a single surgeon
Authors: Ngo Duy Quoc , Le Duong The , Ngo Quy Xuan , Van Le Quang
Published: June 2023

Background

The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is increasingly being adopted worldwide because of its many advantages. However, there are few reports on the effectiveness and safety of TOETVA in children. In this study, we report the results of the application of TOETVA on 27 pediatric patients in Vietnam. To the best of our knowledge, this is also the largest sample size of the TOETVA technique performed by a single surgeon on pediatric patients worldwide. Patients and methods: From June 2020 to February 2022, we performed TOETVA on 27 pediatric patients (≤ 18 years old). The outcomes of the procedure were retrospectively reviewed.

Results

Our study was conducted on 27 pediatric patients, of whom 24 were female (88.9%). The mean age was 16.3 ± 2 (range 10-18). Fifteen patients had benign thyroid nodules with a mean nodule size of 31.6 ± 7.1 (range 20-50mm), and 12 patients had papillary thyroid carcinoma with a mean nodule size of 10.2 ± 5.6 (range 4-19mm). All 27 patients underwent successful TOETVA without any conversion to open surgery. The 15 patients with benign thyroid nodules had lobectomies with a mean operative time of 83.3 ± 10.5 (range 60-105 minutes). Among the 12 patients diagnosed with thyroid cancer, ten had a lobectomy, isthmusectomy, and central neck dissection, with a mean operative time of 89.8 ± 5.7 (range 80-100 minutes). The other two underwent total thyroidectomy with central lymph node dissection with a mean operative time of 132.5 minutes. The mean hospital stay was 4.7 ± 0.9 (range 3-7 days). No patient had permanent complications, such as hypocalcemia, recurrent laryngeal nerve injury, or mental nerve injury. The rates of temporary recurrent laryngeal nerve injury and mental nerve injury were 3.7% and 11.1% respectively.

Conclusions

TOETVA may be a feasible and safe surgical method for children with thyroid disease. However, we recommend that only high-volume thyroid surgeons with experience in TOETVA should perform TOETVA on the pediatric population.
Optimized hydrophobic magnetic nanoparticles stabilized pickering emulsion for enhanced oil recovery in complex porous media of reservoir
Authors: Hu Xiaojuan , Long Yunqian , Xuan Gong , Wang Yuyi , Huang Xiaohe , Xu Yupeng , Liu Jing , Wang Bohong , Song Fuquan
Published: June 2023

With an extensive application of flooding technologies in oil recovery, traditional emulsion flooding has seen many limits due to its poor stability and easy demulsification. Pursuing a new robust emulsion plays a fundamental role in developing highly effective emulsion flooding technology. In this work, a novel Pickering emulsion with special magnetic nanoparticles Fe3O4@PDA@Si was designed and prepared. To disclose the flooding mechanism from magnetic nanoparticles, the physico-chemical characterization of Fe3O4@PDA@Si was systematically examined. Meanwhile, the flooding property of the constructed Pickering emulsion was evaluated on the basis of certain downhole conditions. The results showed that the synthesis of Fe3O4@PDA@Si nanoparticles was found to have a hydrophobic core-shell structure with a diameter of 30 nm. Pickering emulsions based on Fe3O4@PDA@Si nanoparticles at an oil-to-water ratio of 5:5, 50°C, the water separation rate was only 6% and the droplet diameter of the emulsion was approximately 15 μm in the ultra-depth-of-field microscope image. This demonstrates the excellent stability of Pickering emulsions and improves the problem of easy demulsification. We further discussed the oil displacement mechanism and enhanced oil recovery effect of this type of emulsion. The microscopic flooding experiment demonstrated that profile control of the Pickering emulsion played a more important role in enhanced recovery than emulsification denudation, with the emulsion system increasing oil recovery by 10.18% in the micro model. Core flooding experiments have established that the incremental oil recovery of the Pickering emulsion increases with decreasing core permeability, from 12.36% to 17.39% as permeability drops from 834.86 to 219.34 × 10−3 μm2. This new Pickering emulsion flooding system stabilized by Fe3O4@PDA@Si nanoparticles offers an option for enhanced oil recovery (EOR).
Oral small-molecule tyrosine kinase 2 and phosphodiesterase 4 inhibitors in plaque psoriasis: a network meta-analysis
Authors: Xu Yuanyuan , Li Zhixuan , Wu Shuwei , Guo Linghong , Jiang Xian
Published: June 2023

Background

Orally administered small-molecule drugs including tyrosine kinase 2 (TYK2) inhibitors and phosphodiesterase 4 (PDE4) inhibitors are new candidates for systemic therapy in plaque psoriasis. However, no previous articles evaluated the benefit and risk profile of TYK2 and PDE4 inhibitors in psoriasis.

Objectives

The objective of this study was to compare the efficacy and safety of oral small-molecule drugs, including TYK2 and PDE4 inhibitors, in treating moderate-to-severe plaque psoriasis.

Methods

PubMed, Embase, and Cochrane library were searched for eligible randomized clinical trials (RCTs). Response rates for a 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75) and Physician’s Global Assessment score of 0 or 1 (PGA 0/1) were used for efficacy assessment. Safety was evaluated with the incidence of adverse events (AEs). A Bayesian multiple treatment network meta-analysis (NMA) was performed.

Results

In total, 13 RCTs (five for TYK2 inhibitors and eight for PDE4 inhibitors) involving 5274 patients were included. The study found that deucravacitinib at any dose (except for 3 mg QOD), ropsacitinib (200 and 400 mg QD), and apremilast (20 and 30 mg BID) had higher PASI and PGA response rates than placebo. In addition, deucravacitinib (3 mg BID, 6 mg QD, 6 mg BID, and 12 mg QD), and ropsacitinib (400 mg QD) showed superior efficacy than apremilast (30 mg BID). In terms of safety, deucravacitinib or ropsacitinib at any dose did not lead to a higher incidence of AEs than apremilast (30 mg BID). The ranking analysis of efficacy revealed that deucravacitinib 12 mg QD and deucravacitinib 3 mg BID had the highest chance of being the most effective oral treatment, followed by deucravacitinib 6 mg BID and ropsacitinib 400 mg QD.

Conclusions

Oral TYK2 inhibitors demonstrated satisfactory performance in treating psoriasis, surpassing apremilast at certain doses. More large-scale, long-term studies focusing on novel TYK2 inhibitors are needed.

Systematic review registration

PROSPERO (ID: CRD42022384859), available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022384859, identifier CRD42022384859.
Cathepsins in oral diseases: mechanisms and therapeutic implications
Authors: Jiang Hao , Dong Zuoxiang , Xia Xiaomin , Li Xue
Published: June 2023

Cathepsins are a type of lysosomal globulin hydrolase and are crucial for many physiological processes, including the resorption of bone matrix, innate immunity, apoptosis, proliferation, metastasis, autophagy, and angiogenesis. Findings regarding their functions in human physiological processes and disorders have drawn extensive attention. In this review, we will focus on the relationship between cathepsins and oral diseases. We highlight the structural and functional properties of cathepsins related to oral diseases, as well as the regulatory mechanisms in tissue and cells and their therapeutic uses. Elucidating the associated mechanism between cathepsins and oral diseases is thought to be a promising strategy for the treatment of oral diseases and may be a starting point for further studies at the molecular level.
Targeting CD137 (4-1BB) towards improved safety and efficacy for cancer immunotherapy
Authors: Liu Guizhong , Luo Peter
Published: June 2023

T cells play a critical role in antitumor immunity, where T cell activation is regulated by both inhibitory and costimulatory receptor signaling that fine-tune T cell activity during different stages of T cell immune responses. Currently, cancer immunotherapy by targeting inhibitory receptors such as CTLA-4 and PD-1/L1, and their combination by antagonist antibodies, has been well established. However, developing agonist antibodies that target costimulatory receptors such as CD28 and CD137/4-1BB has faced considerable challenges, including highly publicized adverse events. Intracellular costimulatory domains of CD28 and/or CD137/4-1BB are essential for the clinical benefits of FDA-approved chimeric antigen receptor T cell (CAR-T) therapies. The major challenge is how to decouple efficacy from toxicity by systemic immune activation. This review focuses on anti-CD137 agonist monoclonal antibodies with different IgG isotypes in clinical development. It discusses CD137 biology in the context of anti-CD137 agonist drug discovery, including the binding epitope selected for anti-CD137 agonist antibody in competition or not with CD137 ligand (CD137L), the IgG isotype of antibodies selected with an impact on crosslinking by Fc gamma receptors, and the conditional activation of anti-CD137 antibodies for safe and potent engagement with CD137 in the tumor microenvironment (TME). We discuss and compare the potential mechanisms/effects of different CD137 targeting strategies and agents under development and how rational combinations could enhance antitumor activities without amplifying the toxicity of these agonist antibodies.
Genome-wide identification of the GT7 and GH16 genes and their correlations with agar metabolism in the agarophyte Gracilariopsis lemaneiformis
Authors: Chen Qionglin , Ying Xiao , Hu Chaoyang , Liu Shixia , Xu Nianjun , Sun Xue
Published: June 2023

The economically important seaweed Gracilariopsis lemaneiformis (Gp. lemaneiformis) is the main resource for agar production and abalone bait. Few studies have focused on the functions of glycosyltransferases (GTs) and glycoside hydrolases (GHs) involved in saccharometabolism, including that of agar. To investigate the possible functions of glycosyltransferase family 7 (GT7) and glycoside hydrolase family 16 (GH16) members in agar metabolism, analyses of these gene families were conducted using bioinformatics-based and physiological methods. In total, five GlGT7 genes and four GlGH16 genes from the Gp. lemaneiformis genome were identified and analyzed. These GT7 and GH16 members are absent in higher plants, and the majority of GlGT7s and GlGH16s have no introns. Catalytic pocket residue analysis revealed that GlGT7s may function as β-1,4-galactosyltransferases and that GlGH16s play roles as agarases. Promoter prediction and qRT-PCR experiments verified that these genes can be regulated by light and phytohormones. GlGT7s were predicted to interact with carbohydrate sulfotransferases (STs), whereas yeast two-hybrid (Y2H) assays revealed no interactions between these proteins. Under heat stress, no significant difference was found in agar content; however, the expression of GlGT7s fluctuated and that of GlGH16 increased. Low nitrogen stress significantly increased the agar content, and the expression of GlGT7s increased, whereas that of GlGH16s decreased. In three cultivars of Gp. lemaneiformis, the expression of GlGT7 genes in cultivars 981 and Lulong No. 1 was upregulated relative to that in the wild type, whereas GlGH16 expression levels were significantly decreased. Fluorescence microscopy further showed that β-1,4-galactose accumulation was consistent with increases in agar content and GlGT7 expression. Pearson correlation analysis confirmed that the expression levels of GlGT7s and GlGH16s were positively and negatively correlated with agar accumulation, respectively. Taken together, these results demonstrated that GlGT7 and GlGH16 are intimately correlated with agar metabolism; in particular, GlGT7-2, GlGT7-5, and GlGH16-4 could act as molecular markers to indicate agar yield. This study will provide a valuable basis for breeding new cultivars with high agar content.
Generalised deep learning model for semi-automated length measurement of fish in stereo-BRUVS
Authors: Marrable Daniel , Tippaya Sawitchaya , Barker Kathryn , Harvey Euan , Bierwagen Stacy L. , Wyatt Mathew , Bainbridge Scott , Stowar Marcus
Published: June 2023

Assessing the health of fish populations relies on determining the length of fish in sample species subsets, in conjunction with other key ecosystem markers; thereby, inferring overall health of communities. Despite attempts to use artificial intelligence (AI) to measure fish, most measurement remains a manual process, often necessitating fish being removed from the water. Overcoming this limitation and potentially harmful intervention by measuring fish without disturbance in their natural habitat would greatly enhance and expedite the process. Stereo baited remote underwater video systems (stereo-BRUVS) are widely used as a non-invasive, stressless method for manually counting and measuring fish in aquaculture, fisheries and conservation management. However, the application of deep learning (DL) to stereo-BRUVS image processing is showing encouraging progress towards replacing the manual and labour-intensive task of precisely locating the heads and tails of fish with computer-vision-based algorithms. Here, we present a generalised, semi-automated method for measuring the length of fish using DL with near-human accuracy for numerous species of fish. Additionally, we combine the DL method with a highly precise stereo-BRUVS calibration method, which uses calibration cubes to ensure precision within a few millimetres in calculated lengths. In a human versus DL comparison of accuracy, we show that, although DL commonly slightly over-estimates or under-estimates length, with enough repeated measurements, the two values average and converge to the same length, demonstrated by a Pearson correlation coefficient (r) of 0.99 for n=3954 measurement in ‘out-of-sample’ test data. We demonstrate, through the inclusion of visual examples of stereo-BRUVS scenes, the accuracy of this approach. The head-to-tail measurement method presented here builds on, and advances, previously published object detection for stereo-BRUVS. Furthermore, by replacing the manual process of four careful mouse clicks on the screen to precisely locate the head and tail of a fish in two images, with two fast clicks anywhere on that fish in those two images, a significant reduction in image processing and analysis time is expected. By reducing analysis times, more images can be processed; thereby, increasing the amount of data available for environmental reporting and decision making.
Mycobacterium gordonae infection in a free-ranging green turtle (Chelonia mydas), Brazil
Authors: Goldberg Daphne Wrobel , Alcala Marina Molinas , Nóbrega Daniela Farias da , Sellera Fábio Parra , Fonseca Solange , Neto José Soares Ferreira , Nogueira Denise Batista , Heinemann Marcos Bryan
Published: June 2023

Mycobacteriosis is a well-known disease that has been reported in a variety of reptiles species. However, the occurrence of mycobacteriosis in sea turtles has been rarely documented, and most reports are from captive-reared animals. A juvenile green turtle (Chelonia mydas) was found stranded in March 2020, in Guanabara Bay, one of the most urbanized and polluted coastal areas in Rio de Janeiro, Southeastern Brazil. The turtle was in fair body condition and exhibited multiple cutaneous fibropapillomas, covering almost 60% of its body. Despite continued medical therapy, the animal died 60 days after initial supportive care. Necropsy revealed granulomatous pneumonia, hydropericardium, small granulomas in the myocardium, liver, spleen, thyroid and brain and caseous exudate in the meninges of the brain. The histopathological analysis showed disseminated granulomatous inflammation in various organs examined during necropsy. Intrahistiocytic acid-fast bacteria were observed in the liver, heart, lungs, kidneys, spleen, brain and adrenals. The blood culture collected shortly after the animal was admitted tested positive for Mycobacterium gordonae, after an 8-week incubation period; however, the animal had already died by the time the results were obtained. Postmortem examination confirmed systemic mycobacteriosis, identified as M. gordonae in blood, liver and lung cultures and by PCR amplification of DNA extracts from frozen tissue samples. This is the first report of a disseminated infection caused by M. gordonae in a free-ranging sea turtle. Although the source of this Mycobacterium remains unknown, it could potentially be related to anthropogenic activities (e.g., waste dumping or leakage from landfill sites). Increasing surveillance of Mycobacterium in wild sea turtles is of paramount importance to better understand the role of mycobacterial species as causative agents of infections in marine species.
The fundamental need for unifying phenotypes in sudden unexpected pediatric deaths
Authors: Wojcik Monica H. , Poduri Annapurna H. , Holm Ingrid A. , MacRae Calum A. , Goldstein Richard D.
Published: June 2023

A definitive, authoritative approach to evaluate the causes of unexpected, and ultimately unexplained, pediatric deaths remains elusive, relegating final conclusions to diagnoses of exclusion in the vast majority of cases. Research into unexplained pediatric deaths has focused primarily on sudden infant deaths (under 1 year of age) and led to the identification of several potential, albeit incompletely understood, contributory factors: nonspecific pathology findings, associations with sleep position and environment that may not be uniformly relevant, and the elucidation of a role for serotonin that is practically difficult to estimate in any individual case. Any assessment of progress in this field must also acknowledge the failure of current approaches to substantially decrease mortality rates in decades. Furthermore, potential commonalities with pediatric deaths across a broader age spectrum have not been widely considered. Recent epilepsy-related observations and genetic findings, identified post-mortem in both infants and children who died suddenly and unexpectedly, suggest a role for more intense and specific phenotyping efforts as well as an expanded role for genetic and genomic evaluation. We therefore present a new approach to reframe the phenotype in sudden unexplained deaths in the pediatric age range, collapsing many distinctions based on arbitrary factors (such as age) that have previously guided research in this area, and discuss its implications for the future of postmortem investigation.
Correlating nanoscale motion and ATP production in healthy and favism erythrocytes: a real-time nanomotion sensor study
Authors: Girasole Marco , Dinarelli Simone , Longo Giovanni
Published: June 2023

Introduction

Red blood cells (RBCs) are among the simplest, yet physiologically relevant biological specimens, due to their peculiarities, such as their lack of nucleus and simplified metabolism. Indeed, erythrocytes can be seen as biochemical machines, capable of performing a limited number of metabolic pathways. Along the aging path, the cells’ characteristics change as they accumulate oxidative and non-oxidative damages, and their structural and functional properties degrade.

Methods

In this work, we have studied RBCs and the activation of their ATP-producing metabolism using a real-time nanomotion sensor. This device allowed time-resolved analyses of the activation of this biochemical pathway, measuring the characteristics and the timing of the response at different points of their aging and the differences observed in favism erythrocytes in terms of the cellular reactivity and resilience to aging. Favism is a genetic defect of erythrocytes, which affects their ability to respond to oxidative stresses but that also determines differences in the metabolic and structural characteristic of the cells.

Results

Our work shows that RBCs from favism patients exhibit a different response to the forced activation of the ATP synthesis compared to healthy cells. In particular, the favism cells, compared to healthy erythrocytes, show a greater resilience to the aging-related insults which was in good accord with the collected biochemical data on ATP consumption and reload.

Conclusion

This surprisingly higher endurance against cell aging can be addressed to a special mechanism of metabolic regulation that permits lower energy consumption in environmental stress conditions.
Novel gold(III)-dithiocarbamate complex targeting bacterial thioredoxin reductase: antimicrobial activity, synergy, toxicity, and mechanistic insights
Authors: Ratia Carlos , Ballén Victoria , Gabasa Yaiza , Soengas Raquel G. , Velasco-de Andrés María , Iglesias María José , Cheng Qing , Lozano Francisco , Arnér Elias S. J. , López-Ortiz Fernando , Soto Sara M.
Published: June 2023

Introduction

Antimicrobial resistance is a pressing global concern that has led to the search for new antibacterial agents with novel targets or non-traditional approaches. Recently, organogold compounds have emerged as a promising class of antibacterial agents. In this study, we present and characterize a (C^S)-cyclometallated Au(III) dithiocarbamate complex as a potential drug candidate.

Methods and results

The Au(III) complex was found to be stable in the presence of effective biological reductants, and showed potent antibacterial and antibiofilm activity against a wide range of multidrug-resistant strains, particularly gram-positive strains, and gram-negative strains when used in combination with a permeabilizing antibiotic. No resistant mutants were detected after exposing bacterial cultures to strong selective pressure, indicating that the complex may have a low propensity for resistance development. Mechanistic studies indicate that the Au(III) complex exerts its antibacterial activity through a multimodal mechanism of action. Ultrastructural membrane damage and rapid bacterial uptake suggest direct interactions with the bacterial membrane, while transcriptomic analysis identified altered pathways related to energy metabolism and membrane stability including enzymes of the TCA cycle and fatty acid biosynthesis. Enzymatic studies further revealed a strong reversible inhibition of the bacterial thioredoxin reductase. Importantly, the Au(III) complex demonstrated low cytotoxicity at therapeutic concentrations in mammalian cell lines, and showed no acute in vivo toxicity in mice at the doses tested, with no signs of organ toxicity.

Discussion

Overall, these findings highlight the potential of the Au(III)-dithiocarbamate scaffold as a basis for developing novel antimicrobial agents, given its potent antibacterial activity, synergy, redox stability, inability to produce resistant mutants, low toxicity to mammalian cells both in vitro and in vivo, and non-conventional mechanism of action.
Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach
Authors: Reivan Ortiz Geovanny Genaro , Ciongradi Carmen Iulia , Chaitanya M. V. N. L. , Narayanan Jayasankar , Mohany Mohamed , Al-Rejaie Salim S. , Arias-Gonzáles José Luis , Sârbu Ioan , Assefi Marjan , Akram Shaik Vaseem , Döğüş Yusuf , Bahrami Abolfazl , Akhavan-Sigari Reza
Published: June 2023

Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix’s structure and composition and/or initiating the epithelial cells (EPT). IL-33/ST2 signaling has drawn a lot of attention since it acts as a pro-tumor alarmin and encourages spread by altering TM.

Methods: Differentially expressed genes (DEGs) of the OvC tumor microenvironment were found in the GEO database, qRT-PCR, western blotting, and immunohistochemistry, and their presence and changes in healthy and tumor tissue content were examined. Primary cultures of healthy fibroblasts and CAFs obtained from healthy and tumor tissues retrieved from OvC samples were used for in vitro and in vivo investigations. Cultured primary human CAFs were utilized to investigate the regulation and the IL-33/ST2 axis role in the inflammation reactions.

Results: Although ST2 and IL-33 expression was detected in both epithelial (EPT) and fibroblast cells of ovarian cancer, they are more abundant in CAFs. Lipopolysaccharides, serum amyloid A1, and IL-1β, the inflammatory mediators, could all induce IL-33 expression through NF-κB activation in human CAFs. In turn, via the ST2 receptor, IL-33 affected the production of IL-6, IL-1β, and PTGS2 in human CAFs via the MAPKs-NF-κB pathway.

Conclusion: Our findings suggest that IL-33/ST2 is affected by the interaction of CAFs and epithelial cells inside the tumor microenvironment. Activation of this axis leads to increased expression of inflammatory factors in tumor CAFs and EPT cells. Therefore, targeting the IL-33/ST2 axis could have potential value in the prevention of OvC progression.
Research progress in delineating the pathological mechanisms of GJB2-related hearing loss
Authors: Wang Yujun , Jin Yuan , Zhang Qiong , Xiong Ying , Gu Xiang , Zeng Shan , Chen Wei
Published: June 2023

Hearing loss is the most common congenital sensory impairment. Mutations or deficiencies of the GJB2 gene are the most common genetic cause of congenital non-syndromic deafness. Pathological changes such as decreased potential in the cochlea, active cochlear amplification disorders, cochlear developmental disorders and macrophage activation have been observed in various GJB2 transgenic mouse models. In the past, researchers generally believed that the pathological mechanisms underlying GJB2-related hearing loss comprised a K+ circulation defect and abnormal ATP-Ca2+ signals. However, recent studies have shown that K+ circulation is rarely associated with the pathological process of GJB2-related hearing loss, while cochlear developmental disorders and oxidative stress play an important, even critical, role in the occurrence of GJB2-related hearing loss. Nevertheless, these research has not been systematically summarized. In this review, we summarize the pathological mechanisms of GJB2-related hearing loss, including aspects of K+ circulation, developmental disorders of the organ of Corti, nutrition delivery, oxidative stress and ATP-Ca2+ signals. Clarifying the pathological mechanism of GJB2-related hearing loss can help develop new prevention and treatment strategies.
Neural bases of freedom and responsibility
Authors: Gruart Agnès , Delgado-García José M.
Published: June 2023

This review presents a broad perspective of the Neuroscience of our days with special attention to how the brain generates our behaviors, emotions, and mental states. It describes in detail how unconscious and conscious processing of sensorimotor and mental information takes place in our brains. Likewise, classic and recent experiments illustrating the neuroscientific foundations regarding the behavioral and cognitive abilities of animals and, in particular, of human beings are described. Special attention is applied to the description of the different neural regulatory systems dealing with behavioral, cognitive, and emotional functions. Finally, the brain process for decision-making, and its relationship with individual free will and responsibility, are also described.
Wall enhancement predictive of abnormal hemodynamics and ischemia in vertebrobasilar non-saccular aneurysms: a pilot study
Authors: Jiang Yeqing , Ge Liang , Lu Gang , Wan Hailin , Chen Qi , Zou Rong , Leng Xiaochang , Xiang Jianping , Zhang Xiaolong
Published: June 2023

Objective

To analyze how wall enhancement affects hemodynamics and cerebral ischemic risk factors in vertebrobasilar non-saccular intracranial aneurysms (VBNIAs).

Materials and methods

Ten consecutive non-saccular aneurysms were collected, including three transitional vertebrobasilar dolichoectasia (TVBD). A wall enhancement model was quantitatively constructed to analyze how wall enhancement interacts with hemodynamics and cerebral ischemic factors.

Results

Enhanced area revealed low wall shear stress (WSS) and wall shear stress gradient (WSSG), with high oscillatory shear index (OSI), relative residence time (RRT), and gradient oscillatory number (GON) while the vortex and slow flow region in fusiform aneurysms are similar to TVBD fusiform aneurysms. With low OSI, high RRT and similar GON in the dilated segment, the enhanced area still manifests low WSS and WSSG in the slow flow area with no vortex. In fusiform aneurysms, wall enhancement was negatively correlated with WSS (except for case 71, all p values  < 0.05, r = −0.52 ~ −0.95), while wall enhancement was positively correlated with OSI (except for case 5, all p values < 0.05, r = 0.50 ~ 0.83). For the 10 fusiform aneurysms, wall enhancement is significantly positively correlated with OSI (p = 0.0002, r = 0.75) and slightly negatively correlated with WSS (p = 0.196, r = −0.30) throughout the dataset. Aneurysm length, width, low wall shear stress area (LSA), high OSI, low flow volume (LFV), RRT, and high aneurysm-to-pituitary stalk contrast ratio (CRstalk) area plus proportion may be predictive of cerebral ischemia.

Conclusion

A wall enhancement quantitative model was established for vertebrobasilar non-saccular aneurysms. Low WSS was negatively correlated with wall enhancement, while high OSI was positively correlated with wall enhancement. Fusiform aneurysm hemodynamics in TVBD are similar to simple fusiform aneurysms. Cerebral ischemia risk appears to be correlated with large size, high OSI, LSA, and RRT, LFV, and wall enhancement.
Neuroprotection after cardiac arrest with 2-iminobiotin: a single center phase IIa study on safety, tolerability, and pharmacokinetics
Authors: Admiraal M. M. , Velseboer D. C. , Tjabbes H. , Vis P. , Peeters-Scholte C. , Horn J.
Published: June 2023

Background

Brain injury is a serious problem in patients who survive out-of-hospital cardiac arrest (OHCA). Neuroprotective drugs could reduce hypoxic–ischemic reperfusion injury. The aim of this study was to investigate the safety, tolerability, and pharmacokinetics (PK) of 2-iminobiotin (2-IB), a selective inhibitor of neuronal nitric oxide synthase.

Methods

Single-center, open-label dose-escalation study in adult OHCA patients, investigating three 2-IB dosing schedules (targeting an AUC0-24h of 600–1,200 ng*h/m in cohort A, of 2,100–3,300 ng*h/mL in cohort B, and 7,200–8,400 of ng*h/mL in cohort C). Safety was investigated by monitoring vital signs until 15 min after study drug administration and adverse events up to 30 days after admission. Blood sampling for PK analysis was performed. Brain biomarkers and patient outcomes were collected 30 days after OHCA.

Results

A total of 21 patients was included, eight in cohort A and B and five in cohort C. No changes in vital signs were observed, and no adverse events related to 2-IB were reported. A two-compartment PK model described data the best. Exposure in group A (dosed on bodyweight) was three times higher than targeted (median AUC0-24h 2,398 ng*h/mL). Renal function was an important covariate; therefore, in cohort B, dosing was performed on eGFR on admission. In cohort B and C, the targeted exposure was met (median AUC0-24h 2,917 and 7,323 ng*h/mL, respectively).

Conclusion

The administration of 2-IB to adults after OHCA is feasible and safe. PK can be well predicted with correction for renal function on admission. Efficacy studies with 2-IB after OHCA are needed.
Prognostic changes after sudden deafness in patients with inner ear malformations characterized by LSCC: a retrospective study
Authors: Chen Lei , Dai Qinglei , Gao Xin , Hu Na , Sun Xiao , Wang Haibo , Wang Mingming
Published: June 2023

Introduction

This study aimed to investigate the clinical features and prognosis of sudden sensorineural hearing loss in patients with lateral semicircular canal (LSCC) malformation.

Methods

This study enrolled patients with LSCC malformation and sudden sensorineural hearing loss (SSNHL) who were admitted to Shandong ENT Hospital between 2020 and 2022. We collected and analyzed data on examinations of audiology, vestibular function, and imaging records of patients and summarized the clinical characteristics and prognosis of these patients.

Results

Fourteen patients were enrolled. Patients with LSCC malformation was noted in 0.42% of all SSNHL cases during the same period. One patients had bilateral SSNHL and the rest had unilateral SSNHL. Of them, eight and six patients had unilateral and bilateral LSCC malformations, respectively. Flat hearing loss was noted in 12 ears (80.0%) and severe or profound hearing loss was noted in 10 ears (66.7%). After treatment, the total efficacy rate of SSNHL with LSCC malformation was 40.0%. Vestibular function was abnormal in all patients, but only five patients (35.7%) had dizziness. There were statistically significant differences in the vestibular functions between patients with LSCC malformation and matched patients without the malformation hospitalized during the same period (p < 0.05).

Conclusion

Patients with SSNHL and LSCC malformation had flat-type and severe hearing loss and worse disease prognosis compared to those with SSNHL without LSCC malformation. Vestibular function is more likely to be abnormal; however, there was no significant difference in vestibular symptoms between patients with and without LSCC malformation. LSCC is a risk factor for the prognosis of SSNHL.
A comprehensive review on motion trajectory reconstruction for EEG-based brain-computer interface
Authors: Wang Pengpai , Cao Xuhao , Zhou Yueying , Gong Peiliang , Yousefnezhad Muhammad , Shao Wei , Zhang Daoqiang
Published: June 2023

The advance in neuroscience and computer technology over the past decades have made brain-computer interface (BCI) a most promising area of neurorehabilitation and neurophysiology research. Limb motion decoding has gradually become a hot topic in the field of BCI. Decoding neural activity related to limb movement trajectory is considered to be of great help to the development of assistive and rehabilitation strategies for motor-impaired users. Although a variety of decoding methods have been proposed for limb trajectory reconstruction, there does not yet exist a review that covers the performance evaluation of these decoding methods. To alleviate this vacancy, in this paper, we evaluate EEG-based limb trajectory decoding methods regarding their advantages and disadvantages from a variety of perspectives. Specifically, we first introduce the differences in motor execution and motor imagery in limb trajectory reconstruction with different spaces (2D and 3D). Then, we discuss the limb motion trajectory reconstruction methods including experiment paradigm, EEG pre-processing, feature extraction and selection, decoding methods, and result evaluation. Finally, we expound on the open problem and future outlooks.
Deregulation of mTORC1-TFEB axis in human iPSC model of GBA1-associated Parkinson’s disease
Authors: Mubariz Fahad , Saadin Afsoon , Lingenfelter Nicholas , Sarkar Chinmoy , Banerjee Aditi , Lipinski Marta M. , Awad Ola
Published: June 2023

Mutations in the GBA1 gene are the single most frequent genetic risk factor for Parkinson’s disease (PD). Neurodegenerative changes in GBA1-associated PD have been linked to the defective lysosomal clearance of autophagic substrates and aggregate-prone proteins. To elucidate novel mechanisms contributing to proteinopathy in PD, we investigated the effect of GBA1 mutations on the transcription factor EB (TFEB), the master regulator of the autophagy-lysosomal pathway (ALP). Using PD patients’ induced-pluripotent stem cells (iPSCs), we examined TFEB activity and regulation of the ALP in dopaminergic neuronal cultures generated from iPSC lines harboring heterozygous GBA1 mutations and the CRISPR/Cas9-corrected isogenic controls. Our data showed a significant decrease in TFEB transcriptional activity and attenuated expression of many genes in the CLEAR network in GBA1 mutant neurons, but not in the isogenic gene-corrected cells. In PD neurons, we also detected increased activity of the mammalian target of rapamycin complex1 (mTORC1), the main upstream negative regulator of TFEB. Increased mTORC1 activity resulted in excess TFEB phosphorylation and decreased nuclear translocation. Pharmacological mTOR inhibition restored TFEB activity, decreased ER stress and reduced α-synuclein accumulation, indicating improvement of neuronal protiostasis. Moreover, treatment with the lipid substrate reducing compound Genz-123346, decreased mTORC1 activity and increased TFEB expression in the mutant neurons, suggesting that mTORC1-TFEB alterations are linked to the lipid substrate accumulation. Our study unveils a new mechanism contributing to PD susceptibility by GBA1 mutations in which deregulation of the mTORC1-TFEB axis mediates ALP dysfunction and subsequent proteinopathy. It also indicates that pharmacological restoration of TFEB activity could be a promising therapeutic approach in GBA1-associated neurodegeneration.
Clinical assessment of the TechArm system on visually impaired and blind children during uni- and multi-sensory perception tasks
Authors: Morelli Federica , Schiatti Lucia , Cappagli Giulia , Martolini Chiara , Gori Monica , Signorini Sabrina
Published: June 2023

We developed the TechArm system as a novel technological tool intended for visual rehabilitation settings. The system is designed to provide a quantitative assessment of the stage of development of perceptual and functional skills that are normally vision-dependent, and to be integrated in customized training protocols. Indeed, the system can provide uni- and multisensory stimulation, allowing visually impaired people to train their capability of correctly interpreting non-visual cues from the environment. Importantly, the TechArm is suitable to be used by very young children, when the rehabilitative potential is maximal. In the present work, we validated the TechArm system on a pediatric population of low-vision, blind, and sighted children. In particular, four TechArm units were used to deliver uni- (audio or tactile) or multi-sensory stimulation (audio-tactile) on the participant's arm, and subject was asked to evaluate the number of active units. Results showed no significant difference among groups (normal or impaired vision). Overall, we observed the best performance in tactile condition, while auditory accuracy was around chance level. Also, we found that the audio-tactile condition is better than the audio condition alone, suggesting that multisensory stimulation is beneficial when perceptual accuracy and precision are low. Interestingly, we observed that for low-vision children the accuracy in audio condition improved proportionally to the severity of the visual impairment. Our findings confirmed the TechArm system's effectiveness in assessing perceptual competencies in sighted and visually impaired children, and its potential to be used to develop personalized rehabilitation programs for people with visual and sensory impairments.
Tau expression and phosphorylation in enteroendocrine cells
Authors: Chapelet Guillaume , Béguin Nora , Castellano Blandine , Grit Isabelle , de Coppet Pierre , Oullier Thibauld , Neunlist Michel , Blottière Hervé , Rolli-Derkinderen Malvyne , Le Dréan Gwenola , Derkinderen Pascal
Published: June 2023

Background and objective

There is mounting evidence to suggest that the gut-brain axis is involved in the development of Parkinson’s disease (PD). In this regard, the enteroendocrine cells (EEC), which faces the gut lumen and are connected with both enteric neurons and glial cells have received growing attention. The recent observation showing that these cells express alpha-synuclein, a presynaptic neuronal protein genetically and neuropathologically linked to PD came to reinforce the assumption that EEC might be a key component of the neural circuit between the gut lumen and the brain for the bottom-up propagation of PD pathology. Besides alpha-synuclein, tau is another key protein involved in neurodegeneration and converging evidences indicate that there is an interplay between these two proteins at both molecular and pathological levels. There are no existing studies on tau in EEC and therefore we set out to examine the isoform profile and phosphorylation state of tau in these cells.

Methods

Surgical specimens of human colon from control subjects were analyzed by immunohistochemistry using a panel of anti-tau antibodies together with chromogranin A and Glucagon-like peptide-1 (two EEC markers) antibodies. To investigate tau expression further, two EEC lines, namely GLUTag and NCI-H716 were analyzed by Western blot with pan-tau and tau isoform specific antibodies and by RT-PCR. Lambda phosphatase treatment was used to study tau phosphorylation in both cell lines. Eventually, GLUTag were treated with propionate and butyrate, two short chain fatty acids known to sense EEC, and analyzed at different time points by Western blot with an antibody specific for tau phosphorylated at Thr205.

Results

We found that tau is expressed and phosphorylated in EEC in adult human colon and that both EEC lines mainly express two tau isoforms that are phosphorylated under basal condition. Both propionate and butyrate regulated tau phosphorylation state by decreasing its phosphorylation at Thr205.

Conclusion and inference

Our study is the first to characterize tau in human EEC and in EEC lines. As a whole, our findings provide a basis to unravel the functions of tau in EEC and to further investigate the possibility of pathological changes in tauopathies and synucleinopathies.
Neural correlates of perceptual texture change during active touch
Authors: Henderson Jessica , Mari Tyler , Hopkinson Andrew , Hewitt Danielle , Newton-Fenner Alice , Giesbrecht Timo , Marshall Alan , Stancak Andrej , Fallon Nicholas
Published: June 2023

Introduction

Texture changes occur frequently during real-world haptic explorations, but the neural processes that encode perceptual texture change remain relatively unknown. The present study examines cortical oscillatory changes during transitions between different surface textures during active touch.

Methods

Participants explored two differing textures whilst oscillatory brain activity and finger position data were recorded using 129-channel electroencephalography and a purpose-built touch sensor. These data streams were fused to calculate epochs relative to the time when the moving finger crossed the textural boundary on a 3D-printed sample. Changes in oscillatory band power in alpha (8–12 Hz), beta (16–24 Hz) and theta (4–7 Hz) frequency bands were investigated.

Results

Alpha-band power reduced over bilateral sensorimotor areas during the transition period relative to ongoing texture processing, indicating that alpha-band activity is modulated by perceptual texture change during complex ongoing tactile exploration. Further, reduced beta-band power was observed in central sensorimotor areas when participants transitioned from rough to smooth relative to transitioning from smooth to rough textures, supporting previous research that beta-band activity is mediated by high-frequency vibrotactile cues.

Discussion

The present findings suggest that perceptual texture change is encoded in the brain in alpha-band oscillatory activity whilst completing continuous naturalistic movements across textures.
Gut microbiota-derived metabolite trimethylamine-N-oxide and stroke outcome: a systematic review
Authors: Zhang Peng , Wang Rui , Qu Yang , Guo Zhen-Ni , Yang Yi
Published: June 2023

Introduction

The relationship between baseline trimethylamine N-oxide (TMAO) levels and stroke outcomes remains unclear. Therefore, this systematic review aimed to summarize the existing relevant research.

Methods

We searched for studies on the association between baseline plasma levels of TMAO and stroke outcomes in the PubMed, EMBASE, Web of Science, and Scopus databases from their inception to 12 October 2022. Two researchers independently reviewed the studies for inclusion and extracted the relevant data.

Results

Seven studies were included in the qualitative analysis. Among them, six studies reported the outcome of acute ischemic stroke (AIS) and one study of intracerebral hemorrhage (ICH), respectively. Furthermore, no study reported the outcome of subarachnoid hemorrhage. Among patients with AIS, high baseline TMAO levels were associated with unfavorable functional outcomes or mortality at 3 months, as well as a high hazard ratio of mortality, recurrence, or major adverse cardiac event. Moreover, TMAO levels showed predictive utility for unfavorable functional outcomes or mortality at 3 months. Among patients with ICH, high TMAO levels were associated with unfavorable functional outcomes at 3 months, regardless of whether the TMAO value was considered a continuous or a categorical variable.

Conclusion

Limited evidence indicates that high baseline plasma levels of TMAO may be associated with poor stroke outcomes. Further studies are warranted to confirm the relationship between TMAO and stroke outcomes.