bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular RNA in melanoma: Advances, challenges, and opportunities
Authors: Li Zhouxiao , Gao Yiyang , Cao Yang , He Feifan , Jiang Runyi , Liu Hanyuan , Cai Hongzhou , Zan Tao
Published: May 2023

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%–3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According to previous studies, extracellular RNAs (exRNAs) have been implicated in tumorigenesis and spread of melanoma. They can influence the proliferation, invasion and metastasis of melanoma by controlling the expression of target genes and can also influence tumor progression by participating in signal transduction mechanisms. Therefore, understanding the relationship between exRNA and malignant melanoma and targeting therapy is of positive significance for its prevention and treatment. In this review, we did an analysis of extracellular vesicles of melanoma which focused on the role of exRNAs (lncRNAs, miRNAs, and mRNAs) and identifies several potential therapeutic targets. In addition, we discuss the typical signaling pathways involved in exRNAs, advances in exRNA detection and how they affect the tumor immune microenvironment in melanoma.
Birth weight and large for gestational age trends in offspring of pregnant women with gestational diabetes mellitus in southern China, 2012-2021
Authors: He Li-Rong , Yu Li , Guo Yong
Published: May 2023

Background

With increasing prevalence of gestational diabetes mellitus (GDM) and changing management of GDM in pregnancy, it is imperative to understand the evolution of its current outcomes. The present study aimed to explore whether birth weight and large for gestational age (LGA) trends in women with GDM have changed over time in southern China.

Methods

In this hospital-based retrospective study, all singleton live births for the period 2012 to 2021 were collected from the Guangdong Women and Children Hospital, China. GDM was diagnosed following the criteria of the International Association of Diabetes and Pregnancy Study Group. The cutoff points for defining LGA (>90th centile) at birth based on INTERGROWTH-21st gender-specific standards. Linear regression was used to evaluate trends for birth weight over the years. Logistic regression analysis was used to determine the odds ratios (ORs) of LGA between women with GDM and those without GDM.

Results

Data from 115097 women with singleton live births were included. The total prevalence of GDM was 16.8%. GDM prevalence varied across different years, with the lowest prevalence in 2014 (15.0%) and the highest prevalence in 2021 (19.2%). The mean birth weight displayed decrease in women with GDM from 3.224kg in 2012 to 3.134kg in 2021, and the z score for mean birth weight decreased from 0.230 to -0.037 (P for trend < 0.001). Among women with GDM, the prevalence of macrosomia and LGA reduced significantly during the study period (from 5.1% to 3.0% in macrosomia and from 11.8% to 7.7% in LGA, respectively). Compared to women without GDM, women with GDM had 1.30 (95% CI: 1.23 - 1.38) times odds for LGA, and the ORs remained stable over the study period.

Conclusions

Among offspring of women with GDM, there are decreased trends of birth weight in parallel with reductions in LGA prevalence between 2012 and 2021. However, the risk of LGA in women with GDM remains stable at relatively high level over the 10-year period, and efforts are still needed to address regarding causes and effective intervention strategies.
Approximation method for the sewer drainage effect for urban flood modeling in areas without drainage-pipe data
Authors: Li Donglai , Hou Jingming , Shen Ruozhu , Li Bingyao , Tong Yu , Wang Tian
Published: May 2023

Introduction: The underground drainage-pipe network is one of the vital components of a modern city, and it plays an important role in preventing or mitigating urban flooding. Thus, pipe network data are necessary for simulation of the entire urban rainfall–runoff process. However, pipe network data are sparse or unavailable in most urban areas.

Methods: To solve this problem, we developed a novel approximation method that can be used calculate the drainage capacity of the pipe system. This method is named the road-drainage method, and it works under the assumption that the pipe network functions by subtracting the corresponding mass from the water conservation equation only from areas of road. The mass is determined from weir flow formulas together with the road properties and correction for this mass is applied to the rainfall source term.

Results: Two test cases were used to compare the performance of the new method with an existing method, under which mass is subtracted from the entire area during the rainfall–runoff process. The results showed that the new method considerably improves the accuracy of simulated peak volume, with an improvement of 2.62%–58.75% compared with the existing method across various scenarios. Moreover, the proposed new method reduces the time shift of the rise and peak of surface inundation by 10–45 min in various scenarios, which reflects a more realistic model of the rainfall–runoff process.

Discussion: These results demonstrate that the proposed new method can represent the drainage capability more accurately and is more consistent with reality. The road-drainage method has promising potential for application in urban flood simulation in areas without drainage system data and for the support of large-scale urban hydrologic modeling.
Spectrum of genetic disorders and gene variants in the United Arab Emirates national population: insights from the CTGA database
Authors: Bizzari Sami , Nair Pratibha , Hana Sayeeda , Deepthi Asha , Al-Ali Mahmoud Taleb , Al-Gazali Lihadh , El-Hayek Stephany
Published: May 2023

Like many other Arab countries, the United Arab Emirates (UAE) has a relatively high prevalence of genetic disorders. Here we present the first review and analysis of all genetic disorders and gene variants reported in Emirati nationals and hosted on the Catalogue for Transmission Genetics in Arabs (CTGA), an open-access database hosting bibliographic data on human gene variants associated with inherited or heritable phenotypes in Arabs. To date, CTGA hosts 665 distinct genetic conditions that have been described in Emiratis, 621 of which follow a clear Mendelian inheritance. Strikingly, over half of these are extremely rare according to global prevalence rates, predominantly with an autosomal recessive mode of inheritance. This is likely due to the relatively high consanguinity rates within the Emirati population. The 665 conditions include disorders that are unique to the Emirati population, as well as clearly monogenic disorders that have not yet been mapped to a causal genetic locus. We also describe 1,365 gene variants reported in Emiratis, most of which are substitutions and over half are classified as likely pathogenic or pathogenic. Of these, 235 had not been reported on the international databases dbSNP and Clinvar, as of December 2022. Further analysis of this Emirati variant dataset allows a comparison of clinical significance as reported by Clinvar and CTGA, where the latter is derived from the study cited. A total of 307 pathogenic/likely pathogenic variants from CTGA’s Emirati dataset, were classified as benign, variants of uncertain significance, or were missing a clinical significance or had not been reported by Clinvar. In conclusion, we present here the spectrum of genetic disorders and gene variants reported in Emiratis. This review emphasizes the importance of ethnic databases such as CTGA in addressing the underrepresentation of Arab variant data in international databases and documenting population-specific discrepancies in variant interpretation, reiterating the value of such repositories for clinicians and researchers, especially when dealing with rare disorders.
TCR T cells overexpressing c-Jun have better functionality with improved tumor infiltration and persistence in hepatocellular carcinoma
Authors: Hussein Mohamed S. , Li Qi , Mao Rui , Peng Yibing , He Yukai
Published: May 2023

Background

The overall 5-year survival rate of hepatocellular carcinoma (HCC), a major form of liver cancer, is merely 20%, underscoring the need for more effective therapies. We recently identified T cell receptors (TCR) specific for the HLA-A2/alpha fetoprotein amino acids 158-166 (AFP158) and showed that these TCR engineered T cells could control HCC xenografts in NSG mice. However, their efficacy was limited by poor expansion, loss of function, and short persistence of the TCR T cells. Here, we studied whether overexpression of c-Jun, a transcription factor required for T cell activation, in the TCR T cells could enhance their expansion, function, and persistence in HCC tumor models.

Methods

Recombinant lentiviral vectors (lv), expressing either the HLA-A2/AFP158-specific TCR or both the TCR and c-Jun (TCR-JUN), were constructed and used to transduce primary human T cells to generate the TCR or TCR-JUN T cells, respectively. We compared the expansion, effector function, and exhaustion status of the TCR and TCR-JUN T cells in vitro after HCC tumor stimulation. Additionally, we studied the persistence and antitumor effects of the TCR and TCR-JUN T cells using the HCC xenografts in NSG mice.

Results

We could effectively transduce primary human T cells to express both TCR and c-Jun. Compared to the HLA-A2/AFP158 TCR T cells, the TCR-JUN T cells have better expansion potential in culture, with enhanced functional capacity against HCC tumor cells. In addition, the TCR-JUN T cells were less apoptotic and more resistant to exhaustion after HepG2 tumor stimulation. In the HCC xenograft tumor model, c-Jun overexpression enhanced the TCR T cell expansion and increased the overall survival rate of the treated mice. Importantly, the TCR-JUN T cells were less exhausted in the tumor lesions and demonstrated enhanced tumor infiltration, functionality, and persistence.

Conclusion

c-Jun overexpression can enhance the expansion, function, and persistence of the A2/AFP158 TCR engineered T cells. The c-Jun gene co-delivery has the potential to enhance the antitumor efficacy of AFP specific TCR T cells when treating patients with HCC.
Single-cell detection of primary transcripts, their genomic loci and nuclear factors by 3D immuno-RNA/DNA FISH in T cells
Authors: Salataj Eralda , Spilianakis Charalampos G. , Chaumeil Julie
Published: May 2023

Over the past decades, it has become increasingly clear that higher order chromatin folding and organization within the nucleus is involved in the regulation of genome activity and serves as an additional epigenetic mechanism that modulates cellular functions and gene expression programs in diverse biological processes. In particular, dynamic allelic interactions and nuclear locations can be of functional importance during the process of lymphoid differentiation and the regulation of immune responses. Analyses of the proximity between chromatin and/or nuclear regions can be performed on populations of cells with high-throughput sequencing approaches such as chromatin conformation capture (“3C”-based) or DNA adenine methyltransferase identification (DamID) methods, or, in individual cells, by the simultaneous visualization of genomic loci, their primary transcripts and nuclear compartments within the 3-dimensional nuclear space using Fluorescence In Situ Hybridization (FISH) and immunostaining. Here, we present a detailed protocol to simultaneously detect nascent RNA transcripts (3D RNA FISH), their genomic loci (3D DNA FISH) and/or their chromosome territories (CT paint DNA FISH) combined with the antibody-based detection of various nuclear factors (immunofluorescence). We delineate the application and effectiveness of this robust and reproducible protocol in several murine T lymphocyte subtypes (from differentiating thymic T cells, to activated splenic and peripheral T cells) as well as other murine cells, including embryonic stem cells, B cells, megakaryocytes and macrophages.
The transcriptional control of the VEGFA-VEGFR1 (FLT1) axis in alternatively polarized murine and human macrophages
Authors: Domokos Apolka , Varga Zsofia , Jambrovics Karoly , Caballero-Sánchez Noemí , Szabo Eniko , Nagy Gergely , Scholtz Beata , Halasz Laszlo , Varadi Eszter , Bene Krisztian P. , Mazlo Anett , Bacsi Attila , Jeney Viktoria , Szebeni Gabor J. , Nagy Laszlo , Czimmerer Zsolt
Published: May 2023

Introduction

Macrophages significantly contribute to the regulation of vessel formation under physiological and pathological conditions. Although the angiogenesis-regulating role of alternatively polarized macrophages is quite controversial, a growing number of evidence shows that they can participate in the later phases of angiogenesis, including vessel sprouting and remodeling or regression. However, the epigenetic and transcriptional regulatory mechanisms controlling this angiogenesis-modulating program are not fully understood.

Results

Here we show that IL-4 can coordinately regulate the VEGFA-VEGFR1 (FLT1) axis via simultaneously inhibiting the proangiogenic Vegfa and inducing the antiangiogenic Flt1 expression in murine bone marrow-derived macrophages, which leads to the attenuated proangiogenic activity of alternatively polarized macrophages. The IL-4-activated STAT6 and IL-4-STAT6 signaling pathway-induced EGR2 transcription factors play a direct role in the transcriptional regulation of the Vegfa-Flt1 axis. We demonstrated that this phenomenon is not restricted to the murine bone marrow-derived macrophages, but can also be observed in different murine tissue-resident macrophages ex vivo and parasites-elicited macrophages in vivo with minor cell type-specific differences. Furthermore, IL-4 exposure can modulate the hypoxic response of genes in both murine and human macrophages leading to a blunted Vegfa/VEGFA and synergistically induced Flt1/FLT1 expression.

Discussion

Our findings establish that the IL-4-activated epigenetic and transcriptional program can determine angiogenesis-regulating properties in alternatively polarized macrophages under normoxic and hypoxic conditions.
Gut microbiota in perioperative neurocognitive disorders: current evidence and future directions
Authors: Sun Yan , Wang Kexin , Zhao Weiliang
Published: May 2023

Perioperative neurocognitive disorders (PND) is a common surgical anesthesia complication characterized by impairment of memory, attention, language understanding and social ability, which can lead to a decline in the quality of life of patients, prolong the hospitalization period and increase the mortality rate. PND has a high incidence rate, which has a great impact on postoperative recovery and quality of life of patients, and has caused a heavy economic burden to society and families. In recent years, PND has become an important public health problem. The high risk population of PND is more prone to gut microbiota imbalance, and gut microbiota may also affect the inflammatory response of the central nervous system through the microbiota-gut-brain axis. Meanwhile, Neuroinflammation and immune activation are important mechanisms of PND. Regulating gut microbiota through probiotics or fecal bacteria transplantation can significantly reduce neuroinflammation, reduce the abnormal activation of immune system and prevent the occurrence of PND. This review summarizes the research progress of gut microbiota and PND, providing basis for the prevention and treatment of PND.
Morphological characterization of nevi on the caruncle conjunctiva under in vivo confocal microscopy
Authors: Cai Jianhao , Xu Cangeng , Ng Tsz Kin , Li Zeyi
Published: May 2023

Objective

This study aimed to investigate the microscopic structure and characteristics of nevi on the conjunctiva of the lacrimal caruncle by in vivo confocal microscopy.

Methods

In total, four patients with nevi growing on the lacrimal caruncle conjunctiva were recruited. The morphological characteristics of the nevi were evaluated by in vivo confocal microscopy before excision surgery; the results were compared with histopathological analyses of the surgical specimens.

Results

The nevi of the four patients were all located at the conjunctiva of the lacrimal caruncle, with a slightly nodular surface, mixed black and brown color, and clear boundary. The nevi were round and highly protruded on the surface of the lacrimal caruncle, with an average diameter of 4.5 ± 1.29 mm. Under in vivo confocal microscopy, the pigmented nevus cells on the conjunctiva of the lacrimal caruncle were observed to be clustered in nests with irregular boundaries. The cells were round or irregular, with clear cell boundaries, hyper-reflective at the periphery, with low reflectivity in the center. Vascular crawling was observed in some regions. Histopathological analysis showed that nevus cells were roughly equal in size and distributed in a nodular pattern. Melanin granules were observed in the cytoplasm. No atypia or mitotic figures of the cells were found.

Conclusion

This study revealed that the microstructure of nevi growing on the conjunctiva of the lacrimal caruncle can be identified by in vivo confocal microscopy.
Assessing the impact of neurosurgery and neuroanatomy simulation using 3D non-cadaveric models amongst selected African medical students
Authors: Takoutsing Berjo Dongmo , Wunde Ubraine Njineck , Zolo Yvan , Endalle Geneviève , Djaowé Dieunedort Arnold Menga , Tatsadjieu Léopoldine Sybile Ngoune , Zourmba Ines Miste , Dadda Aminatou , Nchufor Roland Ndouh , Nkouonlack Cyrille Duquesne , Bikono Ernestine Renée Atangana , Magadji Jean Paul Oumarou , Fankem Casimir , Jibia Alain Bertrand Tchoupo , Esene Ignatius
Published: May 2023

Background

Laboratory dissections are essential to acquire practical skills to perform neurosurgical procedures. Despite being traditionally done on cadavers, they are often unavailable and suffer from cultural barriers in the African context. Non-cadaveric UpSurgeOn neurosurgery models have been developed to bridge this barrier, providing an almost similar experience with the human body. This study aimed to assess the impact of the UpSurgeOn hands-on-touch non-cadaver model training amongst selected Cameroon medical students.

Methods

An anonymous 35-item questionnaire was distributed online using Google drive systems to medical students who attended UpSurgeOn's hands-on-touch non-cadaver model training course. These questions aimed to capture data on previous experience with neuroanatomy and neurosurgery practicals and the perception, attitudes, and impact of the UpSurgeOn neurosurgery tool.

Results

Eighty-six students completed the survey. The mean age was 21.2 ± 1.868 years, 61.6% were males with 62.8% of respondents being medical students in preclinical years. Before the training, 29.4% had a fair knowledge of neuroanatomy. Textbooks and Youtube videos were the main sources of neuroanatomy and neurosurgery knowledge for more than half of the respondents. Up to 91.5% had no prior exposure to a neuroanatomy/neurosurgery cadaver laboratory dissection, and 22.6% and 17.6% had witnessed and performed at least one craniotomy before, respectively. There were 11.1%, 15.5%, and 31.3% of our respondents who had used a surgical microscope, a neurosurgical instrument, and the UpSurgeOn Neurosurgery tool before, respectively. The majority perceived the UpSurgeOn tool easy to use and felt they needed to learn just a few things before getting going with the box. Most thought of increasing the use of the UpSurgeOn Box and saw the need to be part of the training curriculum. Finally, the majority felt this tool helped to increase familiarity and acquire neurosurgical skills, and to develop the orientation skills needed during neurosurgical approaches.

Conclusion

Undergraduate exposure to traditional neurosurgery/neuroanatomy labs is limited in Cameroon. Neurosurgery/neuroanatomy practical skills are gained essentially using non-practical means. Most students found the UpSurgeOn tool user-friendly, saw the need to incorporate it as part of their training, and perceived it to be essential in getting acquainted with neurosurgical skills.
Co-infection of the respiratory epithelium, scene of complex functional interactions between viral, bacterial, and human neuraminidases
Authors: Escuret Vanessa , Terrier Olivier
Published: May 2023

The activity of sialic acids, known to play critical roles in biology and many pathological processes, is finely regulated by a class of enzymes called sialidases, also known as neuraminidases. These are present in mammals and many other biological systems, such as viruses and bacteria. This review focuses on the very particular situation of co-infections of the respiratory epithelium, the scene of complex functional interactions between viral, bacterial, and human neuraminidases. This intrinsically multidisciplinary topic combining structural biology, biochemistry, physiology, and the study of host-pathogen interactions, opens up exciting research perspectives that could lead to a better understanding of the mechanisms underlying virus-bacteria co-infections and their contribution to the aggravation of respiratory pathology, notably in the context of pre-existing pathological contexts. Strategies that mimic or inhibit the activity of the neuraminidases could constitute interesting treatment options for viral and bacterial infections.
Detecting anomalies from liquid transfer videos in automated laboratory setting
Authors: Sarker Najibul Haque , Hakim Zaber Abdul , Dabouei Ali , Uddin Mostofa Rafid , Freyberg Zachary , MacWilliams Andy , Kangas Joshua , Xu Min
Published: May 2023

In this work, we address the problem of detecting anomalies in a certain laboratory automation setting. At first, we collect video images of liquid transfer in automated laboratory experiments. We mimic the real-world challenges of developing an anomaly detection model by considering two points. First, the size of the collected dataset is set to be relatively small compared to large-scale video datasets. Second, the dataset has a class imbalance problem where the majority of the collected videos are from abnormal events. Consequently, the existing learning-based video anomaly detection methods do not perform well. To this end, we develop a practical human-engineered feature extraction method to detect anomalies from the liquid transfer video images. Our simple yet effective method outperforms state-of-the-art anomaly detection methods with a notable margin. In particular, the proposed method provides 19% and 76% average improvement in AUC and Equal Error Rate, respectively. Our method also quantifies the anomalies and provides significant benefits for deployment in the real-world experimental setting.
Electrically stimulated gene expression under exogenously applied electric fields
Authors: Abasi Sara , Jain Abhishek , Cooke John P. , Guiseppi-Elie Anthony
Published: May 2023

Introduction: Electrical stimulation, the application of an electric field to cells and tissues grown in culture to accelerate growth and tight junction formation among endothelial cells, could be impactful in cardiovascular tissue engineering, allotransplantation, and wound healing.

Methods: Using Electrical Cell Stimulation And Recording Apparatus (ECSARA), the exploration of the stimulatory influences of electric fields of different magnitude and frequencies on growth and proliferation, trans endothelial electrical resistance (TEER) and gene expression of human endothelia cells (HUVECs) were explored.

Results: Within the range of endogenous electrical pulses studied, frequency was found to be more significant (p = 0.05) than voltage in influencing HUVEC gene expression. Localization of Yes Associated Protein (YAP) and expression of CD-144 are shown to be consistent with temporal manifestations of TEER.

Discussion: This work introduces the field of electromics, the study of cellular gene expression profiles and their implications under the influence of exogenously applied electric fields. Homology of electrobiology and mechanobiology suggests use of such exogenous cues in tissue and regenerative engineering.
Correlation analysis of monocyte chemoattractant protein-1 and clinical characteristics and cognitive impairment in type 2 diabetes mellitus comorbid major depressive disorder
Authors: Cao Fang , Yang Mei , Cheng Yuqi , Zhang Xiuyue , Shi Li , Li Na
Published: May 2023

Introduction

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are both chronic diseases, and they are often co-morbid. Usually, T2DM and MDD are associated with cognitive impairment, and the comorbidity status of both may increase the risk of cognitive impairment, but the underlying pathogenesis is not clear. Studies have shown that inflammation, especially monocyte chemoattractant protein-1 (MCP-1), could be associated with the pathogenesis of type 2 diabetes mellitus comorbid major depressive disorder.

Aims

To investigate the correlations of MCP-1 with clinical characteristics and cognitive impairment in type 2 diabetes mellitus patients combined with major depressive disorder.

Methods

A total of 84 participants were recruited in this study, including 24 healthy controls (HC), 21 T2DM patients, 23 MDD patients, and 16 T2DM combined with MDD (TD) patients, to measure the serum MCP-1 levels using Enzyme-linked Immunosorbent Assay (ELISA). And the cognitive function, depression, and anxiety degree were assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA), respectively.

Results

(1) Serum MCP-1 expression levels in the TD group were higher than HC, T2DM, and MDD groups, respectively (p < 0.05). And compared with HC and MDD groups, serum MCP-1 levels in the T2DM group were higher (p < 0.05) statistically. Receiver Operating Characteristic (ROC) curve showed that MCP-1 could diagnose T2DM at cut-off values of 503.8 pg./mL (sensitivity 80.95%, specificity 79.17%, AUC = 0.7956) and of 718.1 pg./mL for TD (sensitivity 81.25%, specificity 91.67%, AUC = 0.9271). (2) Group differences in cognitive function were significant. Compared with the HC group, total RBANS scores, attention scores, and language scores in the TD group were lower, respectively (p < 0.05), and total RBANS scores, attention scores, and visuospatial/constructional scores in the MDD group were lower, respectively (p < 0.05). Compared with the T2DM group, immediate memory scores in HC, MDD, and TD groups were lower, respectively, and total RBANS scores in TD were lower (p < 0.05). (3) Correlation analysis showed that hip circumference was negatively correlated with MCP-1 levels in the T2DM group (R = −0.483, p = 0.027), but the correlation disappeared after adjusting age and gender (r = −0.372; p = 0.117), and there were no significant correlations between MCP-1 and other variables.

Conclusion

MCP-1 may be involved in the pathophysiology of type 2 diabetes mellitus patients combined with major depressive disorder. And MCP-1 may be significant for the early evaluation and diagnosis of TD in the future.
Loud noise-exposure changes the firing frequency of subtypes of layer 5 pyramidal neurons and Martinotti cells in the mouse auditory cortex
Authors: Nogueira Ingrid , Lima Thiago Z. , Malfatti Thawann , Leao Katarina E.
Published: May 2023

Introduction

Loud noise-exposure can generate noise-induced tinnitus in both humans and animals. Imaging and in vivo studies show that noise exposure affects the auditory cortex; however, cellular mechanisms of tinnitus generation are unclear.

Methods

Here we compare membrane properties of layer 5 (L5) pyramidal cells (PCs) and Martinotti cells expressing the cholinergic receptor nicotinic alpha 2 subunit gene (Chrna2) of the primary auditory cortex (A1) from control and noise-exposed (4–18 kHz, 90 dB, 1.5 h, followed by 1.5 h silence) 5–8 week old mice. PCs were furthermore classified in type A or type B based on electrophysiological membrane properties, and a logistic regression model predicting that afterhyperpolarization (AHP) and afterdepolarization (ADP) are sufficient to predict cell type, and these features are preserved after noise trauma.

Results

One week after a loud noise-exposure no passive membrane properties of type A or B PCs were altered but principal component analysis showed greater separation between type A PCs from control and noise-exposed mice. When comparing individual firing properties, noise exposure differentially affected type A and B PC firing frequency in response to depolarizing current steps. Specifically, type A PCs decreased initial firing frequency in response to +200 pA steps (p = 0.020) as well as decreased steady state firing frequency (p = 0.050) while type B PCs, on the contrary, significantly increased steady state firing frequency (p = 0.048) in response to a + 150 pA step 1 week after noise exposure. In addition, L5 Martinotti cells showed a more hyperpolarized resting membrane potential (p = 0.04), higher rheobase (p = 0.008) and an increased initial (p = 8.5 × 10–5) and steady state firing frequency (p = 6.3 × 10–5) in slices from noise-exposed mice compared to control.

Discussion

These results show that loud noise can cause distinct effects on type A and B L5 PCs and inhibitory Martinotti cells of the primary auditory cortex 1 week following noise exposure. As the L5 comprises PCs that send feedback to other areas, loud noise exposure appears to alter levels of activity of the descending and contralateral auditory system.
Beyond passive observation: feedback anticipation and observation activate the mirror system in virtual finger movement control via P300-BCI
Authors: Syrov Nikolay , Yakovlev Lev , Miroshnikov Andrei , Kaplan Alexander
Published: May 2023

Action observation (AO) is widely used as a post-stroke therapy to activate sensorimotor circuits through the mirror neuron system. However, passive observation is often considered to be less effective and less interactive than goal-directed movement observation, leading to the suggestion that observation of goal-directed actions may have stronger therapeutic potential, as goal-directed AO has been shown to activate mechanisms for monitoring action errors. Some studies have also suggested the use of AO as a form of Brain–computer interface (BCI) feedback. In this study, we investigated the potential for observation of virtual hand movements within a P300-based BCI as a feedback system to activate the mirror neuron system. We also explored the role of feedback anticipation and estimation mechanisms during movement observation. Twenty healthy subjects participated in the study. We analyzed event-related desynchronization and synchronization (ERD/S) of sensorimotor EEG rhythms and Error-related potentials (ErrPs) during observation of virtual hand finger flexion presented as feedback in the P300-BCI loop and compared the dynamics of ERD/S and ErrPs during observation of correct feedback and errors. We also analyzed these EEG markers during passive AO under two conditions: when subjects anticipated the action demonstration and when the action was unexpected. A pre-action mu-ERD was found both before passive AO and during action anticipation within the BCI loop. Furthermore, a significant increase in beta-ERS was found during AO within incorrect BCI feedback trials. We suggest that the BCI feedback may exaggerate the passive-AO effect, as it engages feedback anticipation and estimation mechanisms as well as movement error monitoring simultaneously. The results of this study provide insights into the potential of P300-BCI with AO-feedback as a tool for neurorehabilitation.
Network pharmacology reveals that Berberine may function against Alzheimer’s disease via the AKT signaling pathway
Authors: Wei Wei , Yao Jiu-xiu , Zhang Ting-ting , Wen Jia-yu , Zhang Zhen , Luo Yi-miao , Cao Yu , Li Hao
Published: May 2023

Objective

To investigate the mechanism underlying the effects of berberine (BBR) in the treatment of Alzheimer’s disease (AD).

Methods

3 × Tg AD mice were treated with BBR for 3 months, then the open field test (OFT), the novel object recognition test (NOR) and the Morris water maze (MWM) test were performed to assess behavioral performance. Hematoxylin–eosin (HE) staining, Nissl staining were used to examine histopathological changes. The pharmacological and molecular properties of BBR were obtained from the TCMSP database. BBR-associated AD targets were identified using the PharmMapper (PM), the comparative toxicogenomics database (CTD), DisGeNet and the human gene database (GeneCards). Core networks and BBR targets for the treatment of AD were identified using PPI network and functional enrichment analyses. AutoDock software was used to model the interaction between BBR and potential targets. Finally, RT-qPCR, western blotting were used to validate the expression of core targets.

Results

Behavioral experiments, HE staining and Nissl staining have shown that BBR can improve memory task performance and neuronal damage in the hippocampus of AD mice. 117 BBR-associated targets for the treatment of AD were identified, and 43 genes were used for downstream functional enrichment analysis in combination with the results of protein–protein interaction (PPI) network analysis. 2,230 biological processes (BP) terms, 67 cell components (CC) terms, 243 molecular function (MF) terms and 118 KEGG terms were identified. ALB, EGFR, CASP3 and five targets in the PI3K-AKT signaling pathway including AKT1, HSP90AA1, SRC, HRAS, IGF1 were selected by PPI network analysis, validated by molecular docking analysis and RT-q PCR as core targets for further analysis. Akt1 mRNA expression levels were significantly decreased in AD mice and significantly increased after BBR treatment (p < 0.05). Besides, AKT and ERK phosphorylation decreased in the model group, and BBR significantly increased their phosphorylation levels.

Conclusion

AKT1, HSP90AA1, SRC, HRAS, IGF1 and ALB, EGFR, CASP3 were core targets of BBR in the treatment of AD. BBR may exert a neuroprotective effect by modulating the ERK and AKT signaling pathways.
Quality control in resting-state fMRI: the benefits of visual inspection
Authors: Lepping Rebecca J. , Yeh Hung-Wen , McPherson Brent C. , Brucks Morgan G. , Sabati Mohammad , Karcher Rainer T. , Brooks William M. , Habiger Joshua D. , Papa Vlad B. , Martin Laura E.
Published: May 2023

Background

A variety of quality control (QC) approaches are employed in resting-state functional magnetic resonance imaging (rs-fMRI) to determine data quality and ultimately inclusion or exclusion of a fMRI data set in group analysis. Reliability of rs-fMRI data can be improved by censoring or “scrubbing” volumes affected by motion. While censoring preserves the integrity of participant-level data, including excessively censored data sets in group analyses may add noise. Quantitative motion-related metrics are frequently reported in the literature; however, qualitative visual inspection can sometimes catch errors or other issues that may be missed by quantitative metrics alone. In this paper, we describe our methods for performing QC of rs-fMRI data using software-generated quantitative and qualitative output and trained visual inspection.

Results

The data provided for this QC paper had relatively low motion-censoring, thus quantitative QC resulted in no exclusions. Qualitative checks of the data resulted in limited exclusions due to potential incidental findings and failed pre-processing scripts.

Conclusion

Visual inspection in addition to the review of quantitative QC metrics is an important component to ensure high quality and accuracy in rs-fMRI data analysis.
Child health screening program in French nursery schools: Results and related socioeconomic factors
Authors: Milcent Karen , Gassama Malamine , Dufourg Marie-Noëlle , Thierry Xavier , Charles Marie-Aline , Bois Corinne
Published: May 2023

Objectives

The study aims to describe the output of routine health screening performed in French nursery schools by the maternal and child health services among children aged 3–4 years and to quantify the level of early socioeconomic health disparities.

Methods

In 30 participating départements, data on screening for vision and hearing impairments, overweight and thinness, dental health, language, psychomotor development, and immunizations were collected for children born on specific dates in 2011 and enrolled in nursery school in 2014–2016. Information was collected on the children, their socioeconomic characteristics and on the school attended. Odds of abnormal screening results were compared for each socioeconomic factor by logistic regressions adjusted for age, sex, prematurity and bilingualism.

Results

Among the 9,939 children screened, prevalence of disorders was 12.3% for vision, 10.9% for hearing, 10.4% for overweight, 7.3% for untreated caries, 14.2% for language and 6.6% for psychomotricity. Newly detected visual disorders were more frequent in disadvantaged areas. Children with unemployed parents were three time more likely to have untreated caries and twice as likely to present language or psychomotor impairments; 52% were referred to a health professional following screening compared to 39% of children with employed parents. Except for children in disadvantaged areas, vaccine coverage was lower among disadvantaged groups.

Conclusion

The prevalences of impairments, which are higher among disadvantaged children, highlight the potential preventive impact of systematic screening under the comprehensive maternal and child healthcare program. These results are important to quantify early socioeconomic inequalities in a Western country known for its generous social welfare system. A more holistic approach to child health is needed with a coherent system involving families and aligning primary care, local child health professionals, general practitioners, and specialists. Further results are needed to evaluate its impact on later child development and health.
A novel method to estimate the absorption rate constant for two-compartment model fitted drugs without intravenous pharmacokinetic data
Authors: Liu Fan , Yi Hanxi , Wang Lei , Cheng Zeneng , Zhang Guoqing
Published: May 2023

The in vivo performances of most drugs after extravascular administration are fitted well with the two-compartment pharmacokinetic (PK) model, but the estimation of absorption rate constant (ka) for these drugs becomes difficult during unavailability of intravenous PK data. Herein, we developed a novel method, called the direct method, for estimating the ka values of drugs without using intravenous PK data, by proposing a new PK parameter, namely, maximum apparent rate constant of disposition (kmax). The accuracy of the direct method in ka estimation was determined using the setting parameters (k12, k21, and k10 values at high, medium, and low levels, respectively) and clinical data. The results showed that the absolute relative error of ka estimated using the direct method was significantly lower than that obtained using both the Loo-Riegelman method and the statistical moment method for the setting parameters. Human PK studies of telmisartan, candesartan cilexetil, and tenofovir disoproxil fumarate indicated that the ka values of these drugs were accurately estimated using the direct method based on good correlations between the ka values and other PK parameters that reflected the absorption properties of drugs in vivo (Tmax, Cmax, and Cmax/AUC0-t). This novel method can be applied in situations where intravenous PK data cannot be obtained and is expected to provide valuable support for PK evaluation and in vitro-in vivo correlation establishment.
Efficacy and safety of abrocitinib for moderate-to-severe atopic dermatitis in adolescents and adults: Meta-analysis
Authors: Li Ling , Yu Jiajun , Chen Baoqing , Guo Ying , Yang Yufeng
Published: May 2023

Objective: This study aims to investigate the safety and efficacy of abrocitinib in treating moderate-to-severe AD in adolescents and adults.

Methods: Pubmed, Cochrane, Embase, and Web of science data base were searched from inception to 9 August 2022. All randomized controlled trials (RCTs) evaluating the efficacy and safety of abrocitinib in moderate to severe AD were included in the meta-analysis.

Results: This meta-analysis comprised 7 studies and found that 100 mg or 200 mg of abrocitinib significantly improved IGA {[RR = 2.44, 95% CI (1.93–3.08)] [RR = 3.16, 95% CI (2.52–3.96)]} and EASI-75{[RR = 2.18, 95%CI (1.78–2.67)] [RR = 3.04, 95%CI (2.22–4.16)]} responses compared to placebo. Following that, the population was divided into adolescent and adult groups. The abrocitinib improved IGA, EASI-75 responses, and it was still superior to placebo in both the adolescent and the adult groups. PP-NRS4 response index demonstrated that abrocitinib had a greater effect than placebo at 100 mg [RR = 2.22, 95% CI 1.80–2.72] and 200 mg [RR = 3.28, 95% CI 2.59–4.17]. Abrocitinib improved PSAAD, POEM, DLQI, CDLQI, and HADS more than a placebo.

Conclusion: In conclusion, this meta-analysis preliminarily demonstrated that abrocitinib had higher efficacy and safety in the treatment of moderate-to-severe AD in adolescents and adults. In addition, abrocitinib could rapidly relieve itching, and effectively improve symptoms and signs, with a greater effect at the dosage of 200 mg than 100 mg.
Effectiveness and safety of vedolizumab for ulcerative colitis: a single-center retrospective real-world study in China
Authors: Huang Kaituo , Liu Jing , Xia Wenhao , Tian Chuwen , Yao Lingya , Cao Qian , Chen Haotian
Published: May 2023

Introduction: The effectiveness and safety of vedolizumab (VDZ) against ulcerative colitis (UC) have been validated in several randomized controlled trials and real-world studies in Western countries. However, there are few studies on VDZ in Asia, and the follow-up period for these studies is generally short. Therefore, this study evaluates the long-term effectiveness and safety of VDZ in Chinese patients with UC.

Methods: This retrospective study included patients with moderate to severe UC treated with VDZ between September 2019 and April 2022 at Sir Run Run Shaw Hospital, College of Medicine Zhejiang University. Clinical response and remission were assessed using the patient reported outcomes and the partial Mayo Score, and mucosal remission and healing were assessed using the Mayo Endoscopy Score. The primary endpoint was defined as clinical remission at week 14, and secondary endpoints included clinical response and steroid-free clinical remission at week 14, clinical response, clinical remission, and steroid-free clinical remission at week 52, and mucosal remission and healing at weeks 14 ± 8 and 52 ± 8.

Results: Overall, 64 patients with moderate to severe UC were enrolled. The clinical response, clinical remission, and steroid-free clinical remission rates at week 14 were 73.4% (47/64), 65.6% (42/64), and 54.7% (35/64), respectively. Mucosal remission and healing rates at week 14 ± 8 were 64.7% (22/34) and 38.2% (13/34), respectively. A total of 48 patients were treated with VDZ for 52 weeks. Based on intention-to-treat analysis, the clinical response, clinical remission, and steroid-free clinical remission rates at week 52 were 68.8% (44/64), 64.1% (41/64), and 64.1% (41/64), respectively. Mucosal remission and healing rates at week 52 ± 8 were 70.6% (12/17) and 35.3% (6/17), respectively. During the follow-up period, the most common adverse event was skin rash (6/64). No cases of acute infusion reactions, delayed allergic reactions, new hepatitis B infections, active tuberculosis, or malignant tumors were reported.

Conclusion: In this single-center retrospective real-world study, the effectiveness of long-term use of VDZ for Chinese patients with UC was similar to the outcomes previously reported in other geographical regions and populations; no new safety signals were found compared with other registered studies.
Exploring the different cognitive, emotional and imaginative experiences of autistic and non-autistic adult readers when contemplating serious literature as compared to non-fiction
Authors: Chapple Melissa , Davis Philip , Billington Josie , Corcoran Rhiannon
Published: May 2023

Introduction

Recent research has demonstrated how reflections on serious literature can challenge dominant social-deficit views of autism. This method enables autistic readers to explore social realities more slowly and carefully, encouraging detail-focused considerations. Previous research has also shown that autistic and non-autistic readers reflecting on serious literature together are able to achieve mutuality in a way that enables them to overcome the double empathy problem. However, the advantages of reading aloud designs have yet to be explored with autistic and non-autistic readers due to previous concerns amongst autistic people on the issue of being read aloud to. The present study aimed to explore how an adapted shared reading design that compared serious literature and non-fiction would enable autistic and non-autistic readers to imaginatively engage in the reading experience.

Methods

Seven autistic and six non-autistic participants read 8 short text extracts alone while listening to pre-recorded audio of an experienced reader reading each text aloud. Participants completed a reflective questionnaire for each text and a follow-up interview where moving parts of the text were then re-read aloud before discussion. Half of these texts were serious literature, while the other half were non-fiction. Similarly, half of the texts explored fictional social realities that depicted a lack of mutuality, or non-fiction accounts of autism; while the other half explored broader emotional experiences.

Results

Thematic and literary analysis of participant reflections and follow-up interviews revealed three main themes: (1) From Surface Reading to Intuitive Engagement, (2) Imaginative Feeling and (3) Going Forward from the Reading Experience.

Discussion

The findings showed that autistic readers were better able to hold onto the detailed complexity of serious literature, while non-autistic readers tended to reduce information down to key ideas and understandings for later generalization. Findings are discussed in relation to future shared reading designs.