bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction and comprehensive analysis of a novel prognostic signature associated with pyroptosis molecular subtypes in patients with pancreatic adenocarcinoma
Authors: Huang Qian , Peng Xingyu , Li Qingqing , Zhu Jinfeng , Xue Ju , Jiang Hua
Published: February 2023

Background

Treatment of cancer with pyroptosis is an emerging strategy. Molecular subtypes based on pyroptosis-related genes(PRGs) seem to be considered more conducive to individualized therapy. It is meaningful to construct a pyroptosis molecular subtypes-related prognostic signature (PMSRPS) to predict the overall survival (OS) of patients with pancreatic adenocarcinoma(PAAD) and guide treatment.

Methods

Based on the transcriptome data of 23 PRGs, consensus clustering was applied to divide the TCGA and GSE102238 combined cohort into three PRGclusters. Prognosis-related differentially expressed genes(DEGs) among PRGclusters were subjected to LASSO Cox regression analysis to determine a PMSRPS. External cohort and in vitro experiments were conducted to verify this PMSRPS. The CIBERSORT algorithm, the ESTIMATE algorithm and the Immunophenoscore (IPS) were used to analyze the infiltrating abundance of immune cells, the tumor microenvironment (TME), and the response to immunotherapy, respectively. Wilcoxon analysis was used to compare tumor mutational burden (TMB) and RNA stemness scores (RNAss) between groups. RT-qPCR and in vitro functional experiments were used for evaluating the expression and function of SFTA2.

Results

Based on three PRGclusters, 828 DEGs were obtained and a PMSRPS was subsequently constructed. In internal and external validation, patients in the high-risk group had significantly lower OS than those in the low-risk group and PMSRPS was confirmed to be an independent prognostic risk factor for patients with PAAD with good predictive performance. Immune cell infiltration abundance and TME scores indicate patients in the high-risk group have typical immunosuppressive microenvironment characteristics. Analysis of IPS suggests patients in the high-risk group responded better to novel immune checkpoint inhibitors (ICIs) than PD1/CTLA4. The high-risk group had higher TMB and RNAss. In addition, 10 potential small-molecule compounds were screened out. Finally, we found that the mRNA expression of SFTA2 gene with the highest risk coefficient in PMSRPS was significantly higher in PAAD than in paracancerous tissues, and knockdown of it significantly delayed the progression of PAAD.

Conclusions

PMSRPS can well predict the prognosis, TME and immunotherapy response of patients with PAAD, identify potential drugs, and provide treatment guidance based on individual needs.
Galectins as pivotal components in oncogenesis and immune exclusion in human malignancies
Authors: Kapetanakis Nikiforos-Ioannis , Busson Pierre
Published: February 2023

Galectins are galactoside-binding proteins, exerting numerous functions inside and outside the cell, particularly conferring adaptation to stress factors. For most of them, aberrant expression profiles have been reported in the context of cancer. Albeit not being oncogenic drivers, galectins can be harnessed to exacerbate the malignant phenotype. Their impact on disease establishment and progression is not limited to making cancer cells resistant to apoptosis, but is prominent in the context of the tumor microenvironment, where it fosters angiogenesis, immune escape and exclusion. This review focuses mainly on Gal-1, Gal-3 and Gal-9 for which the involvement in cancer biology is best known. It presents the types of galectin dysregulations, attempts to explain the mechanisms behind them and analyzes the different ways in which they favor tumour growth. In an era where tumour resistance to immunotherapy appears as a major challenge, we highlight the crucial immunosuppressive roles of galectins and the potential therapeutic benefits of combinatorial approaches including galectin inhibition.
Desalination effects on macroalgae (part A): Laboratory-controlled experiments with Dictyota spp. from the Pacific Ocean and Mediterranean Sea
Authors: Muñoz Pamela T. , Rodríguez-Rojas Fernanda , Celis-Plá Paula S. M. , López-Marras Américo , Blanco-Murillo Fabio , Sola Iván , Lavergne Céline , Valenzuela Fernando , Orrego Rodrigo , Sánchez-Lizaso José Luis , Sáez Claudio A.
Published: February 2023

Desalination brines from direct seawater intake that get discharged to coastal areas may produce stress responses on benthic marine communities, mostly due to its excess salinity, and especially on sessile organisms; in this context, macroalgae have been understudied in desalination ecotoxicological investigations. In this study, we assessed the short- and long-term cellular tolerance responses in two brown species of the macroalgae genus Dictyota through controlled laboratory conditions. Dictyota kunthii was collected from the eastern Pacific Ocean (average salinity, ~34 psu), whereas Dictyota dichotoma was from the Mediterranean Sea (average salinity, ~37 psu). Each macroalgae species was exposed for up to 7 days to two conditions with increased salinity values: +2 and +7 psu above their natural average salinity. Photosynthetic parameters and oxidative stress measurements were determined. The results showed that, in both Dictyota species, high salinity values induced reduced photoinhibition (Fv/Fm) but increased the primary productivity (ETRmax) and light requirement (EkETR) especially after 7 days. Conversely, the photosynthetic efficiency (αETR) decreased in hypersalinity treatments in D. dichotoma, while there were no changes in D. kunthii. The reactive oxygen species hydrogen peroxide (H2O2) was greater at high salinity values at 3 days for D. dichotoma and after 7 days in D. kunthii, while lipid peroxidation decreases under hypersalinity with time in both species. Despite the evident H2O2 accumulation in both species against hypersalinity, it did not produce oxidative damage and important impairment in the photosynthetic apparatus. These results contribute to understanding the tolerance strategies at the cellular level of Dictyota spp., which may be considered as potential candidates for biomonitoring of desalination impacts in the field.
Distinct responses of abundant and rare foraminifera to environmental variables in the Antarctic region revealed by DNA metabarcoding
Authors: Li Qingxia , Lei Yanli , Li Haotian , Li Tiegang
Published: February 2023

The Antarctic region plays a key role in regulating the Earth’s climate and contains a unique record of environmental change. Foraminifera, a group of shell-bearing protists, are widely used as paleoenvironmental proxies. However, core-based reconstructions of Antarctic paleoenvironments are often hindered by the lack of foraminiferal fossil record. Foraminiferal ancient DNA provides new avenues for understanding environmental change, but the correlation between molecular ecological features of foraminifera and environmental conditions remains poorly understood. Here, we obtained surface sediment samples from the Southern Ocean at water depths ranging from 50 to 4399 m and measured eight environmental variables. We generated a DNA metabarcoding dataset of foraminifera and presented the first assessment of relationships between foraminiferal molecular diversity and environmental variables in the Antarctic region. The results showed that the alpha diversity of whole community and abundant subcommunity was positively correlated with water depth and negatively correlated with temperature, chlorophyll a and pheophytin a, while the alpha diversity of rare subcommunity had no linear correlation with the above environmental variables. Both rare and abundant foraminiferal subcommunities exhibited distance-decay relationships, but only the beta diversity of rare subcommunity showed a significant positive correlation with water depth. This study reveals contrasting biogeographical patterns of abundant and rare foraminifera and their different correlations with Antarctic environmental variables, holding promise to provide more proxies for reconstructing past environments using foraminiferal ancient DNA and more information for predicting the impact of future environmental changes on polar biodiversity.
Machine learning approach for automated beach waste prediction and management system: A case study of Mumbai
Authors: Apte Sayali Deepak , Sandbhor Sayali , Kulkarni Rushikesh , Khanum Humera
Published: February 2023

Asia’s coastlines are choking in waste. The region is now home to many of the world’s most polluted beaches. The populous Indian Cities are growing economically but in an unsustainable manner. With Mumbai counted among topmost polluted beaches in the world, it is the need of the hour to take necessary steps for effective waste management by systematic data analysis for deriving useful information from waste generation patterns. The major objective of the study is pattern recognition and beach waste quantum prediction based on 5 years data, with a frequency of daily waste collection. The size of the training data set is 1,661 days and the validation data set is 335 days. The influence of population trend, waste generation during festivals, special days, weekends, and seasonal variations form the basis for the analysis. Using machine learning algorithms, the study identifies and investigates data patterns for the case study of Dadar-Mahim beach. Data frequency and weights are correlated with occurrence of events, festivals, weekends, and seasons. Exploratory Data Analysis (EDA) is employed for data preprocessing and wrangling, followed by a Random Forest algorithm-based model for the prediction of waste generated at Dadar-Mahim beach. The major challenges in data prediction are limited data availability and variation in the dates of festivals and holidays as well as lack of waste segregation information. Despite the above-mentioned challenges, the observations indicate the model’s average accuracy for making predictions of around 60%. The Graphic User Interface (GUI) developed based on the model provides a user-friendly application for predicting the total daily generation of beach waste with reasonable precision. On the basis of the model’s outcome and applicability, a schematic approach for efficient beach waste management is proposed. The recommendations would serve as guidelines for Urban Local Bodies (ULBs) to automate the collection, transport, and disposal of beach waste.
Adverse perinatal outcomes associated with antiretroviral therapy in women living with HIV: A systematic review and meta-analysis
Authors: Portwood Clara , Sexton Harriet , Kumarendran Mary , Brandon Zoe , Kirtley Shona , Hemelaar Joris
Published: February 2023

Background

Maternal HIV infection is associated with an increased risk of adverse perinatal outcomes. The World Health Organization (WHO) recommends immediate initiation of lifelong antiretroviral therapy (ART) for all people living with HIV, including pregnant women living with HIV (WLHIV). We aimed to assess the risk of adverse perinatal outcomes in WLHIV receiving ART compared to ART-naïve WLHIV and HIV-negative women.

Materials and methods

We conducted a systematic literature review by searching PubMed, CINAHL, Global Health, and EMBASE for studies published between Jan 1, 1980, and April 20, 2020. Two investigators independently selected relevant studies and extracted data from studies reporting on the association of pregnant WLHIV receiving ART with adverse perinatal outcomes. Perinatal outcomes examined were preterm birth (PTB), very PTB, spontaneous PTB (sPTB), low birth weight (LBW), very LBW (VLBW), term LBW, preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, and neonatal death. Random-effects meta-analyses examined the risk of adverse perinatal outcomes in WLHIV receiving ART compared to ART-naïve WLHIV and HIV-negative women. Subgroup and sensitivity analyses were performed based on country income status and study quality, and adjustment for confounding factors assessed.

Results

Of 94,594 studies identified, 73 cohort studies, including 424,277 pregnant women, met the inclusion criteria. We found that WLHIV receiving ART are associated with a significantly decreased risk of PTB (relative risk 0.79, 95% CI 0.67–0.93), sPTB (0.46, 0.32–0.66), LBW (0.86, 0.79–0.93), and VLBW (0.62, 0.39–0.97) compared to ART-naïve WLHIV. However, WLHIV receiving ART are associated with a significantly increased risk of PTB (1.42, 1.28–1.57), sPTB (2.20, 1.32–3.67), LBW (1.58, 1.36–1.84), term LBW (1.88, 1.23–2.85), SGA (1.69, 1.32–2.17), and VSGA (1.22, 1.10–1.34) compared to HIV-negative women.

Conclusion

ART reduces the risk of adverse perinatal outcomes in pregnant WLHIV, but the risk remains higher than in HIV-negative women. Our findings support the WHO recommendation of immediate initiation of lifelong ART for all people living with HIV, including pregnant WLHIV.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42021248987.
The mammalian target of rapamycin contributes to synovial fibroblast pathogenicity in rheumatoid arthritis
Authors: Barker Brianne E. , Hanlon Megan M. , Marzaioli Viviana , Smith Conor M. , Cunningham Clare C. , Fletcher Jean M. , Veale Douglas J. , Fearon Ursula , Canavan Mary
Published: February 2023

Objectives

The mammalian target of Rapamycin (mTOR) is a metabolic master regulator of both innate and adaptive immunity; however, its exact role in stromal cell biology is unknown. In this study we explored the role of the mTOR pathway on Rheumatoid Arthritis synovial fibroblast (RASF) metabolism and activation and determined if crosstalk with the Hippo-YAP pathway mediates their effects.

Methods

Primary RA synovial fibroblasts (RASF) were cultured with TNFα alone or in combination with the mTOR inhibitor Rapamycin or YAP inhibitor Verteporfin. Chemokine production, matrix metalloproteinase (MMP) production, and adhesion marker expression were quantified by real-time PCR, ELISA, and/or Flow Cytometry. Invasion assays were performed using Transwell invasion chambers, while wound repair assays were used to assess RASF migration. Cellular bioenergetics was assessed using the Seahorse XFe96 Analyzer. Key metabolic genes (GLUT-1, HK2, G6PD) were measured using real-time PCR. Reanalysis of RNA-Seq analysis was performed on RA (n = 151) and healthy control (HC) (n = 28) synovial tissue biopsies to detect differential gene and pathway expression. The expression of YAP was measured by Western Blot.

Results

Transcriptomic analysis of healthy donor and RA synovial tissue revealed dysregulated expression of several key components of the mTOR pathway in RA. Moreover, the expression of phospho-ribosomal protein S6 (pS6), the major downstream target of mTOR is specifically increased in RA synovial fibroblasts compared to healthy tissue. In the presence of TNFα, RASF display heightened phosphorylation of S6 and are responsive to mTOR inhibition via Rapamycin. Rapamycin effectively alters RASF cellular bioenergetics by inhibiting glycolysis and the expression of rate limiting glycolytic enzymes. Furthermore, we demonstrate a key role for mTOR signaling in uniquely mediating RASF migratory and invasive mechanisms, which are significantly abrogated in the presence of Rapamycin. Finally, we report a significant upregulation in several genes involved in the Hippo-YAP pathway in RA synovial tissue, which are predicted to converge with the mTOR pathway. We demonstrate crosstalk between the mTOR and YAP pathways in mediating RASF invasive mechanism whereby Rapamycin significantly abrogates YAP expression and YAP inhibition significantly inhibits RASF invasiveness.

Conclusion

mTOR drives pathogenic mechanisms in RASF an effect which is in part mediated via crosstalk with the Hippo-YAP pathway.
Fast myocardial perfusion SPECT denoising using an attention-guided generative adversarial network
Authors: Sun Jingzhang , Yang Bang-Hung , Li Chien-Ying , Du Yu , Liu Yi-Hwa , Wu Tung-Hsin , Mok Greta S. P.
Published: February 2023

Purpose

Deep learning-based denoising is promising for myocardial perfusion (MP) SPECT. However, conventional convolutional neural network (CNN)-based methods use fixed-sized convolutional kernels to convolute one region within the receptive field at a time, which would be ineffective for learning the feature dependencies across large regions. The attention mechanism (Att) is able to learn the relationships between the local receptive field and other voxels in the image. In this study, we propose a 3D attention-guided generative adversarial network (AttGAN) for denoising fast MP-SPECT images.

Methods

Fifty patients who underwent 1184 MBq 99mTc-sestamibi stress SPECT/CT scan were retrospectively recruited. Sixty projections were acquired over 180° and the acquisition time was 10 s/view for the full time (FT) mode. Fast MP-SPECT projection images (1 s to 7 s) were generated from the FT list mode data. We further incorporated binary patient defect information (0 = without defect, 1 = with defect) into AttGAN (AttGAN-def). AttGAN, AttGAN-def, cGAN, and Unet were implemented using Tensorflow with the Adam optimizer running up to 400 epochs. FT and fast MP-SPECT projection pairs of 35 patients were used for training the networks for each acquisition time, while 5 and 10 patients were applied for validation and testing. Five-fold cross-validation was performed and data for all 50 patients were tested. Voxel-based error indices, joint histogram, linear regression, and perfusion defect size (PDS) were analyzed.

Results

All quantitative indices of AttGAN-based networks are superior to cGAN and Unet on all acquisition time images. AttGAN-def further improves AttGAN performance. The mean absolute error of PDS by AttcGAN-def was 1.60 on acquisition time of 1 s/prj, as compared to 2.36, 2.76, and 3.02 by AttGAN, cGAN, and Unet.

Conclusion

Denoising based on AttGAN is superior to conventional CNN-based networks for MP-SPECT.
AAV- based vector improvements unrelated to capsid protein modification
Authors: Shitik Ekaterina M. , Shalik Igor K. , Yudkin Dmitry V.
Published: February 2023

Recombinant adeno-associated virus (rAAV) is the leading platform for delivering genetic constructs in vivo. To date, three AAV-based gene therapeutic agents have been approved by the FDA and are used in clinical practice. Despite the distinct advantages of gene therapy development, it is clear that AAV vectors need to be improved. Enhancements in viral vectors are mainly associated with capsid protein modifications. However, there are other structures that significantly affect the AAV life cycle and transduction. The Rep proteins, in combination with inverted terminal repeats (ITRs), determine viral genome replication, encapsidation, etc. Moreover, transgene cassette expression in recombinant variants is directly related to AAV production and transduction efficiency. This review discusses the ways to improve AAV vectors by modifying ITRs, a transgene cassette, and the Rep proteins.
Seasonal variation in the Canastra cheese mycobiota
Authors: Martin José Guilherme Prado , Silva João Marcos Maia , César Isabel Cristina da Rocha , da Silva Meiriele , Santana Samara Aparecida , Veloso Tomás Gomes Reis , Silva Jonas Guimarães e , Ferreira Celia Lucia de Luces Fortes , Leech John , Cotter Paul D.
Published: February 2023

Canastra cheese is the most well-known artisanal cheese produced in Brazil. Although its production includes a step to remove fungi from the cheese surface, in recent years some cheesemakers have preserved the autochthonous fungi grown during ripening due to an interest in the sensory characteristics attributed to these microorganisms. In this work, the mycobiota of artisanal cheeses produced in the Canastra region was characterized based on ITS marker gene analysis. A total of 96 artisanal cheeses from 16 different farms across 9 cities were collected during two different periods (dry and wet seasons). The Canastra cheese mycobiota was significantly impacted by the season, the city of production and the farm but altitude did not affect the fungal community of the cheeses analyzed. Debaryomyces prosopidis was most abundant in the majority of samples across both seasons. During the wet season, Trichosporon asahii, Kluyveromyces lactis and Fusarium solani were the next most abundant species, followed by Torulaspora delbrueckii and Acremonium citrinum. These results highlight the importance of manufacturing practices and seasonality on the fungal composition of Canastra cheeses. These insights are particularly important in light of recent new regulation in Brazil, removing previous obstacles for surface fungi to persist on cheese. These new regulations will allow new approaches to cheese production, and ultimately, novel products.
Recent advances in constructed wetlands methane reduction: Mechanisms and methods
Authors: Yu Guanlong , Chen Jundan , Wang Guoliang , Chen Huifang , Huang Jiajun , Li Yifu , Wang Wenming , Song Fengming , Ma Yuanjun , Wang Qi , Wang Miaomiao , Ling Tao , Shu Zhilai , Sun Julong , Yu Zhi
Published: February 2023

Constructed wetlands (CWs) are artificial systems that use natural processes to treat wastewater containing organic pollutants. This approach has been widely applied in both developing and developed countries worldwide, providing a cost-effective method for industrial wastewater treatment and the improvement of environmental water quality. However, due to the large organic carbon inputs, CWs is produced in varying amounts of CH4 and have the potential to become an important contributor to global climate change. Subsequently, research on the mitigation of CH4 emissions by CWs is key to achieving sustainable, low-carbon dependency wastewater treatment systems. This review evaluates the current research on CH4 emissions from CWs through bibliometric analysis, summarizing the reported mechanisms of CH4 generation, transfer and oxidation in CWs. Furthermore, the important environmental factors driving CH4 generation in CW systems are summarized, including: temperature, water table position, oxidation reduction potential, and the effects of CW characteristics such as wetland type, plant species composition, substrate type, CW-coupled microbial fuel cell, oxygen supply, available carbon source, and salinity. This review provides guidance and novel perspectives for sustainable and effective CW management, as well as for future studies on CH4 reduction in CWs.
Mechanisms of host manipulation by Neisseria gonorrhoeae
Authors: Walker Emma , van Niekerk Stacy , Hanning Kyrin , Kelton William , Hicks Joanna
Published: February 2023

Neisseria gonorrhoeae (also known as gonococcus) has been causing gonorrhoea in humans since ancient Egyptian times. Today, global gonorrhoea infections are rising at an alarming rate, in concert with an increasing number of antimicrobial-resistant strains. The gonococcus has concurrently evolved several intricate mechanisms that promote pathogenesis by evading both host immunity and defeating common therapeutic interventions. Central to these adaptations is the ability of the gonococcus to manipulate various host microenvironments upon infection. For example, the gonococcus can survive within neutrophils through direct regulation of both the oxidative burst response and maturation of the phagosome; a concerning trait given the important role neutrophils have in defending against invading pathogens. Hence, a detailed understanding of how N. gonorrhoeae exploits the human host to establish and maintain infection is crucial for combating this pathogen. This review summarizes the mechanisms behind host manipulation, with a central focus on the exploitation of host epithelial cell signaling to promote colonization and invasion of the epithelial lining, the modulation of the host immune response to evade both innate and adaptive defenses, and the manipulation of host cell death pathways to both assist colonization and combat antimicrobial activities of innate immune cells. Collectively, these pathways act in concert to enable N. gonorrhoeae to colonize and invade a wide array of host tissues, both establishing and disseminating gonococcal infection.
Longitudinal real world correlation study of blood pressure and novel features of cerebral magnetic resonance angiography by artificial intelligence analysis on elderly cognitive impairment
Authors: Sun Shasha , Liu Dongyue , Zhou Yanfeng , Yang Ge , Cui Long-Biao , Xu Xian , Guo Yuanhao , Sun Ting , Jiang Jiacheng , Li Na , Wang Yabin , Li Sulei , Wang Xinjiang , Fan Li , Cao Feng
Published: February 2023

Objective

This study aims to investigate novel clinical risk factors for cognitive impairment (CI) in elderly.

Methods

A total of 3221 patients (259 patients with CI and 2,962 subjects without CI) were recruited into this nested case-control study who underwent cerebral magnetic resonance angiography (MRA) from 2007 to 2021. All of the clinical data with MRA imaging were recorded followed by standardization processing blindly. The maximum stenosis score of the posterior circulatory artery, including the basilar artery, and bilateral posterior cerebral artery (PCA), was calculated by the cerebral MRA automatic quantitative analysis method. Logistic regression (LR) analysis was used to evaluate the relationship between risk factors and CI. Four machine learning approaches, including LR, decision tree (DT), random forest (RF), and support vector machine (SVM), employing 5-fold cross-validation were used to establish CI predictive models.

Results

After matching with age and gender, 208 CI patients and 208 control subjects were finalized the follow-up (3.46 ± 3.19 years) with mean age at 84.47 ± 6.50 years old. Pulse pressure (PP) in first tertile (<58 mmHg) (OR 0.588, 95% confidence interval (CI): 0.362–0.955) was associated with a decreased risk for CI, and ≥50% stenosis of the left PCA (OR 2.854, 95% CI: 1.387–5.872) was associated with an increased risk for CI after adjusting for body mass index, myocardial infarction, and stroke history. Based on the means of various blood pressure (BP) parameters, the performance of the LR, DT, RF and SVM models accurately predicted CI (AUC 0.740, 0.786, 0.762, and 0.753, respectively) after adding the stenosis score of posterior circulatory artery.

Conclusion

Elderly with low pulse differential pressure may have lower risk for cognitive impairment. The hybrid model combined with the stenosis score of posterior circulatory artery, clinical indicators, and the means of various BP parameters can effectively predict the risk of CI in elderly individuals.
When neuro-robots go wrong: A review
Authors: Khan Muhammad Salar , Olds James L.
Published: February 2023

Neuro-robots are a class of autonomous machines that, in their architecture, mimic aspects of the human brain and cognition. As such, they represent unique artifacts created by humans based on human understanding of healthy human brains. European Union’s Convention on Roboethics 2025 states that the design of all robots (including neuro-robots) must include provisions for the complete traceability of the robots’ actions, analogous to an aircraft’s flight data recorder. At the same time, one can anticipate rising instances of neuro-robotic failure, as they operate on imperfect data in real environments, and the underlying AI behind such neuro-robots has yet to achieve explainability. This paper reviews the trajectory of the technology used in neuro-robots and accompanying failures. The failures demand an explanation. While drawing on existing explainable AI research, we argue explainability in AI limits the same in neuro-robots. In order to make robots more explainable, we suggest potential pathways for future research.
Electrical stimulation for the treatment of spinal cord injuries: A review of the cellular and molecular mechanisms that drive functional improvements
Authors: Dorrian Ryan M. , Berryman Carolyn F. , Lauto Antonio , Leonard Anna V.
Published: February 2023

Spinal cord injury (SCI) is a devastating condition that causes severe loss of motor, sensory and autonomic functions. Additionally, many individuals experience chronic neuropathic pain that is often refractory to interventions. While treatment options to improve outcomes for individuals with SCI remain limited, significant research efforts in the field of electrical stimulation have made promising advancements. Epidural electrical stimulation, peripheral nerve stimulation, and functional electrical stimulation have shown promising improvements for individuals with SCI, ranging from complete weight-bearing locomotion to the recovery of sexual function. Despite this, there is a paucity of mechanistic understanding, limiting our ability to optimize stimulation devices and parameters, or utilize combinatorial treatments to maximize efficacy. This review provides a background into SCI pathophysiology and electrical stimulation methods, before exploring cellular and molecular mechanisms suggested in the literature. We highlight several key mechanisms that contribute to functional improvements from electrical stimulation, identify gaps in current knowledge and highlight potential research avenues for future studies.
Building thalamic neuronal networks during mouse development
Authors: Huerga-Gómez Irene , Martini Francisco J. , López-Bendito Guillermina
Published: February 2023

The thalamic nuclear complex contains excitatory projection neurons and inhibitory local neurons, the two cell types driving the main circuits in sensory nuclei. While excitatory neurons are born from progenitors that reside in the proliferative zone of the developing thalamus, inhibitory local neurons are born outside the thalamus and they migrate there during development. In addition to these cell types, which occupy most of the thalamus, there are two small thalamic regions where inhibitory neurons target extra-thalamic regions rather than neighboring neurons, the intergeniculate leaflet and the parahabenular nucleus. Like excitatory thalamic neurons, these inhibitory neurons are derived from progenitors residing in the developing thalamus. The assembly of these circuits follows fine-tuned genetic programs and it is coordinated by extrinsic factors that help the cells find their location, associate with thalamic partners, and establish connections with their corresponding extra-thalamic inputs and outputs. In this review, we bring together what is currently known about the development of the excitatory and inhibitory components of the thalamocortical sensory system, in particular focusing on the visual pathway and thalamic interneurons in mice.
Integration of structural MRI and epigenetic analyses hint at linked cellular defects of the subventricular zone and insular cortex in autism: Findings from a case study
Authors: Takahashi Emi , Allan Nina , Peres Rafael , Ortug Alpen , van der Kouwe Andre J. W. , Valli Briana , Ethier Elizabeth , Levman Jacob , Baumer Nicole , Tsujimura Keita , Vargas-Maya Nauru Idalia , McCracken Trevor A. , Lee Rosa , Maunakea Alika K.
Published: February 2023

Introduction

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, communication and repetitive, restrictive behaviors, features supported by cortical activity. Given the importance of the subventricular zone (SVZ) of the lateral ventrical to cortical development, we compared molecular, cellular, and structural differences in the SVZ and linked cortical regions in specimens of ASD cases and sex and age-matched unaffected brain.

Methods

We used magnetic resonance imaging (MRI) and diffusion tractography on ex vivo postmortem brain samples, which we further analyzed by Whole Genome Bisulfite Sequencing (WGBS), Flow Cytometry, and RT qPCR.

Results

Through MRI, we observed decreased tractography pathways from the dorsal SVZ, increased pathways from the posterior ventral SVZ to the insular cortex, and variable cortical thickness within the insular cortex in ASD diagnosed case relative to unaffected controls. Long-range tractography pathways from and to the insula were also reduced in the ASD case. FACS-based cell sorting revealed an increased population of proliferating cells in the SVZ of ASD case relative to the unaffected control. Targeted qPCR assays of SVZ tissue demonstrated significantly reduced expression levels of genes involved in differentiation and migration of neurons in ASD relative to the control counterpart. Finally, using genome-wide DNA methylation analyses, we identified 19 genes relevant to neurological development, function, and disease, 7 of which have not previously been described in ASD, that were significantly differentially methylated in autistic SVZ and insula specimens.

Conclusion

These findings suggest a hypothesis that epigenetic changes during neurodevelopment alter the trajectory of proliferation, migration, and differentiation in the SVZ, impacting cortical structure and function and resulting in ASD phenotypes.
A prediction model of clinical outcomes in prolonged disorders of consciousness: A prospective cohort study
Authors: Xiong Qi , Le Kai , Wang Yong , Tang Yunliang , Dong Xiaoyang , Zhong Yuan , Zhou Yao , Feng Zhen
Published: February 2023

Objective

This study aimed to establish and validate a prediction model for clinical outcomes in patients with prolonged disorders of consciousness (pDOC).

Methods

A total of 170 patients with pDOC enrolled in our rehabilitation unit were included and divided into training (n = 119) and validation sets (n = 51). Independent predictors for improved clinical outcomes were identified by univariate and multivariate logistic regression analyses, and a nomogram model was established. The nomogram performance was quantified using receiver operating curve (ROC) and calibration curves in the training and validated sets. A decision curve analysis (DCA) was performed to evaluate the clinical usefulness of this nomogram model.

Results

Univariate and multivariate logistic regression analyses indicated that age, diagnosis at entry, serum albumin (g/L), and pupillary reflex were the independent prognostic factors that were used to construct the nomogram. The area under the curve in the training and validation sets was 0.845 and 0.801, respectively. This nomogram model showed good calibration with good consistency between the actual and predicted probabilities of improved outcomes. The DCA demonstrated a higher net benefit in clinical decision-making compared to treating all or none.

Conclusion

Several feasible, cost-effective prognostic variables that are widely available in hospitals can provide an efficient and accurate prediction model for improved clinical outcomes and support clinicians to offer suitable clinical care and decision-making to patients with pDOC and their family members.
The effect of prestimulus low-frequency neural oscillations on the temporal perception of audiovisual speech
Authors: Jiang Zeliang , An Xingwei , Liu Shuang , Wang Lu , Yin Erwei , Yan Ye , Ming Dong
Published: February 2023

Objective

Perceptual integration and segregation are modulated by the phase of ongoing neural oscillation whose frequency period is broader than the size of the temporal binding window (TBW). Studies have shown that the abstract beep-flash stimuli with about 100 ms TBW were modulated by the alpha band phase. Therefore, we hypothesize that the temporal perception of speech with about hundreds of milliseconds of TBW might be affected by the delta-theta phase.

Methods

Thus, we conducted a speech-stimuli-based audiovisual simultaneity judgment (SJ) experiment. Twenty human participants (12 females) attended this study, recording 62 channels of EEG.

Results

Behavioral results showed that the visual leading TBWs are broader than the auditory leading ones [273.37 ± 24.24 ms vs. 198.05 ± 19.28 ms, (mean ± sem)]. We used Phase Opposition Sum (POS) to quantify the differences in mean phase angles and phase concentrations between synchronous and asynchronous responses. The POS results indicated that the delta-theta phase was significantly different between synchronous and asynchronous responses in the A50V condition (50% synchronous responses in auditory leading SOA). However, in the V50A condition (50% synchronous responses in visual leading SOA), we only found the delta band effect. In the two conditions, we did not find a consistency of phases over subjects for both perceptual responses by the post hoc Rayleigh test (all ps > 0.05). The Rayleigh test results suggested that the phase might not reflect the neuronal excitability which assumed that the phases within a perceptual response across subjects concentrated on the same angle but were not uniformly distributed. But V-test showed the phase difference between synchronous and asynchronous responses across subjects had a significant phase opposition (all ps < 0.05) which is compatible with the POS result.

Conclusion

These results indicate that the speech temporal perception depends on the alignment of stimulus onset with an optimal phase of the neural oscillation whose frequency period might be broader than the size of TBW. The role of the oscillatory phase might be encoding the temporal information which varies across subjects rather than neuronal excitability. Given the enriched temporal structures of spoken language stimuli, the conclusion that phase encodes temporal information is plausible and valuable for future research.
Women in the field of multiple sclerosis: How they contributed to paradigm shifts
Authors: Barateiro Andreia , Barros Catarina , Pinto Maria V. , Ribeiro Ana Rita , Alberro Ainhoa , Fernandes Adelaide
Published: February 2023

History is full of women who made enormous contributions to science. While there is little to no imbalance at the early career stage, a decreasing proportion of women is found as seniority increases. In the multiple sclerosis (MS) field, 44% of first authors and only 35% of senior authors were female. So, in this review, we highlight ground-breaking research done by women in the field of MS, focusing mostly on their work as principal investigators. MS is an autoimmune disorder of the central nervous system (CNS), with evident paradigm shifts in the understating of its pathophysiology. It is known that the immune system becomes overactivated and attacks myelin sheath surrounding axons. The resulting demyelination disrupts the communication signals to and from the CNS, which causes unpredictable symptoms, depending on the neurons that are affected. Classically, MS was reported to cause mostly physical and motor disabilities. However, it is now recognized that cognitive impairment affects more than 50% of the MS patients. Another shifting paradigm was the involvement of gray matter in MS pathology, formerly considered to be a white matter disease. Additionally, the identification of different T cell immune subsets and the mechanisms underlying the involvement of B cells and peripheral macrophages provided a better understanding of the immunopathophysiological processes present in MS. Relevantly, the gut-brain axis, recognized as a bi-directional communication system between the CNS and the gut, was found to be crucial in MS. Indeed, gut microbiota influences not only different susceptibilities to MS pathology, but it can also be modulated in order to positively act in MS course. Also, after the identification of the first microRNA in 1993, the role of microRNAs has been investigated in MS, either as potential biomarkers or therapeutic agents. Finally, concerning MS therapeutical approaches, remyelination-based studies have arisen on the spotlight aiming to repair myelin loss/neuronal connectivity. Altogether, here we emphasize the new insights of remarkable women that have voiced the impact of cognitive impairment, white and gray matter pathology, immune response, and that of the CNS-peripheral interplay on MS diagnosis, progression, and/or therapy efficacy, leading to huge breakthroughs in the MS field.
Purine signaling pathway dysfunction in autism spectrum disorders: Evidence from multiple omics data
Authors: Dai Si , Lin Jingjing , Hou Yanting , Luo Xuerong , Shen Yidong , Ou Jianjun
Published: February 2023

Introduction

Previous studies have suggested that the dysregulation of purine metabolism may be associated with autism spectrum disorder (ASD). Here, we adopted metabolomics and transcriptomics to verify and explore the underlying molecular mechanism of purine metabolism dysfunction in ASD and identify potential biomarkers within the purine metabolism pathway.

Methods

Ultra-high-performance liquid chromatography-mass spectrometry was used to obtain the plasma metabolic profiles of 12 patients with ASD and 12 typically developing (TD) children. RNA sequencing was used to screen differentially expressed genes related to the purine metabolic pathway and purine receptor-coding genes in 24 children with ASD and 21 healthy controls. Finally, serum uric acid levels were compared in 80 patients with ASD and 174 TD children to validate the omics results.

Results

A total of 66 identified metabolites showed significant between-group differences. Network analysis showed that purine metabolism was the most strongly enriched. Uric acid was one of the most highlighted nodes within the network. The transcriptomic study revealed significant differential expression of three purine metabolism-related genes (adenosine deaminase, adenylosuccinate lyase, and bifunctional enzyme neoformans 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase) (p < 0.01) and five purinergic receptor genes (P2X7, P2Y2, P2Y6, P2Y8, and P2Y10) (p < 0.05). In the validation sample, there was a significant difference in serum uric acid levels between the two groups (p < 0.001), and the area under the curve for uric acid was 0.812 (sensitivity, 82.5%; specificity, 63.8%).

Discussion

Patients with ASD had dysfunctional purine metabolic pathways, and blood uric acid may be a potential biomarker for ASD.
Frequency matters: how changes in hippocampal theta frequency can influence temporal coding, anxiety-reduction, and memory
Authors: Hines Miranda , Poulter Steven , Douchamps Vincent , Pibiri Francesca , McGregor Anthony , Lever Colin
Published: February 2023

Hippocampal theta frequency is a somewhat neglected topic relative to theta power, phase, coherence, and cross-frequency coupling. Accordingly, here we review and present new data on variation in hippocampal theta frequency, focusing on functional associations (temporal coding, anxiety reduction, learning, and memory). Taking the rodent hippocampal theta frequency to running-speed relationship as a model, we identify two doubly-dissociable frequency components: (a) the slope component of the theta frequency-to-stimulus-rate relationship (“theta slope”); and (b) its y-intercept frequency (“theta intercept”). We identify three tonic determinants of hippocampal theta frequency. (1) Hotter temperatures increase theta frequency, potentially consistent with time intervals being judged as shorter when hot. Initial evidence suggests this occurs via the “theta slope” component. (2) Anxiolytic drugs with widely-different post-synaptic and pre-synaptic primary targets share the effect of reducing the “theta intercept” component, supporting notions of a final common pathway in anxiety reduction involving the hippocampus. (3) Novelty reliably decreases, and familiarity increases, theta frequency, acting upon the “theta slope” component. The reliability of this latter finding, and the special status of novelty for learning, prompts us to propose a Novelty Elicits Slowing of Theta frequency (NEST) hypothesis, involving the following elements: (1) Theta frequency slowing in the hippocampal formation is a generalised response to novelty of different types and modalities; (2) Novelty-elicited theta slowing is a hippocampal-formation-wide adaptive response functioning to accommodate the additional need for learning entailed by novelty; (3) Lengthening the theta cycle enhances associativity; (4) Even part-cycle lengthening may boost associativity; and (5) Artificial theta stimulation aimed at enhancing learning should employ low-end theta frequencies.
Development and validation of an inflammatory bowel disease nutrition self-screening tool (IBD-NST) for digital use
Authors: Wall Catherine L. , Wilson Bridgette , Lomer Miranda C. E.
Published: February 2023

Background and aim

The identification of, and timely intervention for, patients with impaired nutritional status may reduce inflammatory bowel disease (IBD) complications. This study aimed to develop and validate an IBD-specific nutrition self-screening tool (IBD-NST) that identifies patients at nutrition risk.

Methods

An expert IBD panel was consulted to support development of an IBD-NST. The tool was assessed in different cohorts of patients attending IBD outpatient clinics for face, content and convergent validity and repeat reliability. The tool was compared with (i) the malnutrition universal screening tool to assess face validity and (ii) subjective global assessment (SGA), hand-grip strength (HGS) and mid-arm muscle circumference to assess convergent validity. Tool content was informed by agreement between assessment tools, sensitivity analysis and chi-squared tests. The IBD-NST was completed electronically twice, 1 week apart to assess repeat reliability using observed agreement and kappa statistic. Statistical significance assumed at p < 0.05.

Results

In total, 282 IBD patients (175 with Crohn’s disease) were recruited to validate the IBD-NST. The final validated IBD-NST includes body mass index (BMI), weight loss and IBD-specific nutrition-focussed questions which were acceptable to patients. It identified patients at risk of malnutrition, moderately or severely malnourished patients and patients at nutritional risk. The IBD-NST identified 54/179 (30%) patients at moderate or high nutrition risk and had excellent repeat reliability in 85 patients [r = 0.77 (95% CI 0.669 to 0.746)].

Conclusion

The IBD-NST is a self-screening tool, validated for use as either a paper or e-health version, that identifies patients at nutrition risk who are likely to benefit from dietetic assessment and intervention. Furthermore, patients with IBD symptoms who are concerned about their dietary intake can potentially access dietetic care more easily therefore encouraging greater self-management of IBD-related symptoms. The routine use of the IBD-NST as a self-screening tool would enable patient-led care in the outpatient setting and may facilitate timely access to dietetic care.
High gelatinous salted duck egg white protein powder gel: Physicochemical, microstructure and techno-functional properties
Authors: Yao Xinjun , Xu Jicheng , Xun Yu , Du Tianyin , Huang Mengqi , Guo Jun
Published: February 2023

Salted duck egg is one of the most popular products, and China is one of the major countries consuming salted duck egg products. However, due to the high salt content of salted egg white and low physical and chemical properties such as gel, many factories generally only use salted egg yolk and discard salted duck egg white (SDEW) as a waste liquid when processing. This is not only a waste of resources, but also a pollution to the environment. In this paper, protein powder was prepared from salted egg white. Then xanthan gum (XG) was added to make it co-gel with ovalbumin to achieve the purpose of preparing high gelatinous salted egg white protein powder. The results showed that the optimum conditions of SDEW-XG composite gel were as follows: the xanthan gum content was 0.08% (w/w), the reaction pH was 6.5, and the heating temperature was 100°C. Under these conditions, the gel strength reaches the maximum value. Meanwhile, compared with the protein powder without xanthan gum, the addition of xanthan gum significantly affected the secondary structure of the protein powder of SDEW and improved the water holding capacity of the gel. In conclusion, the addition of xanthan gum can significantly improve the gel quality of SDEW protein powder, which provides a theoretical basis for the quality improvement of salted egg white.