bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Xpert in tuberculosis diagnosis based on various specimens: a systematic review and meta-analysis
Authors: Gong Xue , He Yunru , Zhou Kaiyu , Hua Yimin , Li Yifei
Published: May 2023

Objective

The GeneXpert MTB/RIF assay (Xpert) is a diagnostic tool that has been shown to significantly improve the accuracy of tuberculosis (TB) detection in clinical settings, with advanced sensitivity and specificity. Early detection of TB can be challenging, but Xpert has improved the efficacy of the diagnostic process. Nevertheless, the accuracy of Xpert varies according to different diagnostic specimens and TB infection sites. Therefore, the selection of adequate specimens is critical when using Xpert to identify suspected TB. As such, we have conducted a meta-analysis to evaluate the effectiveness of Xpert for diagnosis of different TB types using several specimens.

Methods

We conducted a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the World Health Organization clinical trials registry center, covering studies published from Jan 2008 to July 2022. Data were extracted using an adapted version of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies. Where appropriate, meta-analysis was performed using random-effects models. The risk of bias and level of evidence was assessed using the Quality in Prognosis Studies tool and a modified version of the Grading of Recommendations Assessment, Development, and Evaluation. RStudio was utilized to analyze the results, employing the meta4diag, robvis, and metafor packages.

Results

After excluding duplicates, a total of 2163 studies were identified, and ultimately, 144 studies from 107 articles were included in the meta-analysis based on predetermined inclusion and exclusion criteria. Sensitivity, specificity and diagnostic accuracy were estimated for various specimens and TB types. In the case of pulmonary TB, Xpert using sputum (0.95 95%CI 0.91–0.98) and gastric juice (0.94 95%CI 0.84–0.99) demonstrated similarly high sensitivity, surpassing other specimen types. Additionally, Xpert exhibited high specificity for detecting TB across all specimen types. For bone and joint TB, Xpert, based on both biopsy and joint fluid specimens, demonstrated high accuracy in TB detection. Furthermore, Xpert effectively detected unclassified extrapulmonary TB and tuberculosis lymphadenitis. However, the Xpert accuracy was not satisfactory to distinguish TB meningitis, tuberculous pleuritis and unclassified TB.

Conclusions

Xpert has exhibited satisfactory diagnostic accuracy for most TB infections, but the efficacy of detection may vary depending on the specimens analyzed. Therefore, selecting appropriate specimens for Xpert analysis is essential, as using inadequate specimens can reduce the ability to distinguish TB.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=370111, identifier CRD42022370111.
PCSK9 inhibitors for acute coronary syndrome: the era of early implementation
Authors: Chen Hongzhen , Chen Xiaomin
Published: May 2023

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a new cholesterol-lowering strategy, can decrease low-density lipoprotein cholesterol (LDL-C) levels by inhibiting PCSK9 and reducing the degradation of LDL receptors; thus, they are impacting the management of dyslipidemia to the prevention of cardiovascular events. Recent guidelines recommend PCSK9 inhibitors for patients who fail to achieve target lipids after ezetimibe/statin therapy. As PCSK9 inhibitors have been demonstrated to significantly and safely reduce LDL-C, discussions have begun to explore its optimal timing in coronary artery disease, especially in subjects with acute coronary syndrome (ACS). Also, their additional benefits, such as anti-inflammatory effects, plaque regression effects, and cardiovascular event prevention, have become the focus of recent research. Several studies, including EPIC-STEMI, suggest the lipid-lowering effects of early PCSK9 inhibitors in ACS patients, while some studies such as PACMAN-AMI suggest that early PCSK9 inhibitors can decelerate plaque progression and reduce short-term risks of cardiovascular events. Thus, PCSK9 inhibitors are entering the era of early implementation. In this review, we are committed to summarizing the multidimensional benefits of early implementation of PCSK9 inhibitors in ACS.
Global burden of myocarditis and cardiomyopathy in children and prediction for 2035 based on the global burden of disease study 2019
Authors: Ba Hongjun , Zhang Daoqi , Guan Shiyang , Zheng Jinxin
Published: May 2023

Background

Myocarditis and cardiomyopathy are commonly occurring cardiovascular diseases that seriously threaten children's health. It was urgent to update the global incidence and mortality of childhood myocarditis and cardiomyopathy, and to predict the incidence rate of 2035 by the Global Burden of Disease database.

Methods

The Global Burden of Disease study data from 1990 to 2019 in 204 countries and territories were used to determine: global incidence and mortality rates of childhood myocarditis and cardiomyopathy from 0 to 19 by five age groups; relationship between sociodemographic index (SDI) and incidence and mortality rates by age group; and, based on an age-period-cohort model, the projected incidence of childhood myocarditis and cardiomyopathy for 2035.

Results

From 1990 to 2019, global age-standardized incidence rate decreased by 0.1% (95% UI 0.0–0.1) to 7.7% (95% UI 5.1–11.1). Boys had higher age-standardized incidence of childhood myocarditis and cardiomyopathy than girls [9.12, (95% UI 6.05–13.07) vs. 6.18, (95% UI 4.06–8.92)]. Childhood myocarditis and cardiomyopathy affected 121,259 (95% UI 80,467–173,790) boys and 77,216 (95% UI 50,684–111,535) girls in 2019. At the regional level, SDI changes in most areas showed no meaningful difference. In East Asia and high-income Asia Pacific, increased SDI was associated with decreased and increased incidence rate, respectively. In 2019, 11,755 (95% UI 9,611–14,509) children died from myocarditis and cardiomyopathy worldwide. Age-standardized mortality rate decreased significantly by 0.4% (95% UI 0.2–0.6)–0.5% (95% UI 0.4–0.6). Number of deaths from childhood myocarditis and cardiomyopathy in 2019 was highest in the <5-year-old group [7,442 (95% UI 5,834–9,699)]. Myocarditis and cardiomyopathy incidence in 10–14- and 15–19-year-olds is projected to increase by 2035.

Conclusion

Global data on childhood myocarditis and cardiomyopathy from 1990 to 2019 showed a decreasing trend in incidence and mortality, and an increasing trend in older children, especially in high SDI regions.
Emerging trends in DNA and RNA methylation modifications in type 2 diabetes mellitus: a bibliometric and visual analysis from 1992 to 2022
Authors: Jiang Cai , Hu Yue , Wang Sinuo , Chen Cong
Published: May 2023

Background

Type 2 diabetes mellitus (T2DM) is a pathological metabolic disorder induced by the interaction of genetic and environmental factors. Epigenetic modifications, especially DNA and RNA methylation, might be the bridge between hereditary and environmental factors. This study aimed to comprehensively analyze the status and prospective trends of the association between T2DM and DNA/RNA methylation modifications by using bibliometric software.

Methods

All the publications in the Web of Science database for the research of T2DM with DNA and RNA methylation modifications were obtained from the earliest mention to December 2022. CiteSpace software was used to analyze countries, institutions, journals/cited-references, authors/cited-authors, and keywords. Results of the comprehensive visualization and bibliometric analysis were displayed relative to the research hotspots and knowledge structure.

Results

A total of 1,233 publications related to DNA and RNA methylation modifications and T2DM were collected. The number of publications per year and the overall trend consistently and significantly increased during the investigation period. Based on the highest publication counts, the most influential country was the USA, while Lund University was the most productive institution. DIABETES was considered the most popular journal. The most frequent keywords identified in the field of methylation and T2DM were mainly involved in developmental origin, insulin resistance, and metabolism. The study suggested that the study of methylation modifications had an increasingly significant role in understanding the progression of T2DM.

Conclusion

CiteSpace visualization software was utilized to investigate the status and trends of DNA and RNA methylation modifications in the pathology of T2DM over the past 30 years. Findings from the study provide a guiding perspective for researchers regarding future research directions in this field.
Island and Rensch’s rules do not apply to cave vs. surface populations of Asellus aquaticus
Authors: Herczeg Gábor , Balázs Gergely , Biró Anna , Fišer Žiga , Kralj-Fišer Simona , Fišer Cene
Published: May 2023

Body size is a trait of fundamental ecological and evolutionary importance that is often different between males and females (sexual size dimorphism; SSD). The island rule predicts that small-bodied species tend to evolve larger following a release from interspecific competition and predation in insular environments. According to Rensch’s rule, male body size relative to female body size increases with increasing mean body size. This allometric body size – SSD scaling is explained by male-driven body size evolution. These ecogeographical rules are rarely tested within species, and has not been addressed in a cave–surface context, even though caves represent insular environments (small and isolated with simple communities). By analyzing six cave and nine surface populations of the widespread, primarily surface-dwelling freshwater isopod Asellus aquaticus with male-biased SSD, we tested whether cave populations evolved larger and showed higher SSD than the surface populations. We found extensive between-population variation in body size (maximum divergence being 74%) and SSD (males being 15%–50% larger than females). However, habitat type did not explain the body size and SSD variation and we could not reject isometry in the male–female body size relationship. Hence, we found no support for the island or Rensch’s rules. We conclude that local selective forces stemming from environmental factors other than island vs. mainland or the general surface vs. cave characteristics are responsible for the reported population variation.
Validation of phylogenetic informative Y-InDels in Y-chromosomal haplogroup O-M175
Authors: Zhou Zhihan , Li Zhimin , Yao Yining , Qian Jinglei , Ji Qiqi , Shao Chengchen , Xie Jianhui
Published: May 2023

The Y-chromosomal haplogroup tree, which consists of a group of Y-chromosomal loci with phylogenetic information, has been widely applied in anthropology, archaeology and population genetics. With the continuous updating of the phylogenetic structure, Y-chromosomal haplogroup tree provides more information for recalling the biogeographical origin of Y chromosomes. Generally, Y-chromosomal insertion-deletion polymorphisms (Y-InDels) are genetically stable as Y-chromosomal single nucleotide polymorphisms (Y-SNPs), and therefore carry mutations that can accumulate over generations. In this study, potential phylogenetic informative Y-InDels were filtered out in haplogroup O-M175, which is dominant in East Asia, based on population data retrieved from the 1000 Genomes Project. A group of 22 phylogenetic informative Y-InDels were identified and then assigned to their corresponding subclades of haplogroup O-M175, which provided a supplement for the update and application of Y-chromosomal markers. Especially, four Y-InDels were introduced to define subclades determined using a single Y-SNP.
Clinical, imaging features and outcomes of patients with anti-GFAP antibodies: a retrospective study
Authors: Zhu Bingqing , Sun Mengyang , Yang Ting , Yu Haizhen , Wang Limei
Published: May 2023

Objective

To evaluate and compare the clinical features, imaging, overlapping antibodies, and prognosis of pediatric and adult patients with anti-GFAP antibodies.

Methods

This study included 59 patients with anti-GFAP antibodies (28 females and 31 males) who were admitted between December 2019 and September 2022.

Results

Out of 59 patients, 18 were children (under 18 years old), and 31 were adults. The overall cohort’s median age at onset was 32 years old, 7 for children, and 42 for adults. There were 23 (41.1%) patients with prodromic infection, 1 (1.7%) patient with a tumor, 29 (53.7%) patients with other non-neurological autoimmune diseases, and 17 (22.8%) patients with hyponatremia. Fourteen (23.7%) patients had multiple neural autoantibodies, with the AQP4 antibody being the most common. Encephalitis (30.5%) was the most common phenotypic syndrome. Common clinical symptoms included fever (59.3%), headache (47.5%), nausea and vomiting (35.6%), limb weakness (35.6%), and disturbance of consciousness (33.9%). Brain MRI lesions were primarily located in the cortex/subcortex (37.3%), brainstem (27.1%), thalamus (23.7%), and basal ganglia (22.0%). Spinal cord MRI lesions often involved the cervical and thoracic spinal cord. There was no statistically significant difference in the MRI lesion site between children and adults. Out of 58 patients, 47 (81.0%) had a monophasic course, and 4 died. The last follow-up showed that 41/58 (80.7%) patients had an improved functional outcome (mRS <3), and children were more likely than adults to have no residual disability symptoms (p = 0.001).

Conclusion

There was no statistically significant difference in clinical symptoms and imaging findings between children and adult patients with anti-GFAP antibodies; Patients with anti-GFAP antibodies may present with normal MRI findings or delayed MRI abnormalities, and patients with overlapping antibodies were common. Most patients had monophasic courses, and those with overlapping antibodies were more likely to relapse. Children were more likely than adults to have no disability. Finally, we hypothesize that the presence of anti-GFAP antibodies is a non-specific witness of inflammation.
Type I and III interferons shape the retinal cytokine network and barrier function in an in vitro model of ocular toxoplasmosis
Authors: Geiller Benjamin , Greigert Valentin , Hillenbrand Caroline A. , Gommenginger Chloé , Beal Laetitia , Brunet Julie , Filisetti Denis , Villard Odile , Denis Julie , Pfaff Alexander W.
Published: May 2023

Introduction

The particularities of the ocular immune environment and its barrier protection in the context of infection are not well elucidated. The apicomplexan parasite Toxoplasma gondii is one of the pathogens successfully crossing this barrier and establishing chronic infection in retinal cells.

Methods

As a first approach, we studied the initial cytokine network in vitro in four human cell lines: Retinal pigmented epithelial (RPE), microglial, astrocytic and Müller cells. Furthermore, we looked at the consequences of retinal infection on the integrity of the outer blood-retina barrier (oBRB). We particularly focused on the roles of type I and type III interferons, (IFN-β and IFN-λ). Especially IFN-λ is known for its significant role in barrier defense. However, its effect on the retinal barrier or T. gondii infection remains unexplored, unlike IFN-γ, which has been extensively studied in this context.

Results and Discussion

Here, we show that stimulation with type I and III interferons did not limit parasite proliferation in retinal cells we tested. However, IFN-β and IFN-γ strongly induced inflammatory or cell-attracting cytokine production, whereas IFN-λ1 showed less inflammatory activity. Concomitant T. gondii infection influenced these cytokine patterns, distinctly depending on the parasite strain. Interestingly, all these cells could be stimulated to produce IFN-λ1. Using an in vitro oBRB model based on RPE cells, we observed that interferon stimulation strengthened membrane localization of the tight junction protein ZO-1 and enhanced their barrier function, in a STAT1-independent manner.

Conclusion

Together, our model shows how T. gondii infection shapes the retinal cytokine network and barrier function, and demonstrates the role of type I and type III interferons in these processes.
Classification of tuberculosis-related programmed cell death-related patient subgroups and associated immune cell profiling
Authors: Shen Jie , Zhao Chao , Zhang Hong , Zhou Peipei , Li Zhenpeng
Published: May 2023

Background

Tuberculosis (TB) is the deadliest communicable disease in the world with the exception of the ongoing COVID-19 pandemic. Programmed cell death (PCD) patterns play key roles in the development and progression of many disease states such that they may offer value as effective biomarkers or therapeutic targets that can aid in identifying and treating TB patients.

Materials and methods

The Gene Expression Omnibus (GEO) was used to gather TB-related datasets after which immune cell profiles in these data were analyzed to examine the potential TB-related loss of immune homeostasis. Profiling of differentially expressed PCD-related genes was performed, after which candidate hub PCD-associated genes were selected via a machine learning approach. TB patients were then stratified into two subsets based on the expression of PCD-related genes via consensus clustering. The potential roles of these PCD-associated genes in other TB-related diseases were further examined.

Results

In total, 14 PCD-related differentially expressed genes (DEGs) were identified and highly expressed in TB patient samples and significantly correlated with the abundance of many immune cell types. Machine learning algorithms enabled the selection of seven hub PCD-related genes that were used to establish PCD-associated patient subgroups, followed by the validation of these subgroups in independent datasets. These findings, together with GSVA results, indicated that immune-related pathways were significantly enriched in TB patients exhibiting high levels of PCD-related gene expression, whereas metabolic pathways were significantly enriched in the other patient group. Single cell RNA-seq (scRNA-seq) further highlighted significant differences in the immune status of these different TB patient samples. Furthermore, we used CMap to predict five potential drugs for TB-related diseases.

Conclusion

These results highlight clear enrichment of PCD-related gene expression in TB patients and suggest that this PCD activity is closely associated with immune cell abundance. This thus indicates that PCD may play a role in TB progression through the induction or dysregulation of an immune response. These findings provide a foundation for further research aimed at clarifying the molecular drivers of TB, the selection of appropriate diagnostic biomarkers, and the design of novel therapeutic interventions aimed at treating this deadly infectious disease.
Clinical benefits of PD-1 inhibitors in specific subgroups of patients with advanced esophageal squamous cell carcinoma: a systematic review and meta-analysis of phase 3 randomized clinical trials
Authors: Lu Yao , Wang Wenkang , Wang Feng
Published: May 2023

Purpose

In recent years, a number of clinical trials have shown that programmed death 1 (PD-1) inhibitors offer significant survival benefits in patients with esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis to explore the antitumour efficacy of PD-1 inhibitor-based therapy in specific subgroups of patient with advanced ESCC.

Methods

We searched for eligible studies from the PubMed, Embase, Web of Science, Cochrane Library databases and conference abstracts. The indicators related to survival outcomes were extracted. The pooled hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS) and duration of response (DOR) and the pooled odds ratio (OR) for objective response rate (ORR) were calculated to evaluate the efficacy of PD-1 inhibitor-based therapy in ESCC. Data regarding treatment lines, treatment regimens, programmed death ligand 1 (PD-L1) status, baseline demographic and disease characteristics were extracted. Subgroup analyses were conducted in specific populations of ESCC patients. The Cochrane risk of bias tool and sensitivity analysis were used to assess the quality of the meta-analysis.

Results

Eleven phase 3 randomized controlled trials (RCTs) involving 6267 patients with ESCC were included in this meta-analysis. Compared with standard chemotherapy, PD-1 inhibitor-based therapy provided benefits in terms of OS, PFS, ORR, and DOR in all populations, the first-line treatment group, the second-line treatment group, the immunotherapy group, and the immunochemotherapy group. Although a limited PFS benefit was observed in second-line treatments and immunotherapy alone, PD-1 inhibitor-based therapy still reduced the risk of disease progression or death. Patients with high PD-L1 expression had a better OS benefit than those with low PD-L1 expression. The HR for OS favoured PD-1 inhibitor-based therapy over standard chemotherapy for all prespecified clinical subgroups.

Conclusions

Compared with standard chemotherapy, PD-1 inhibitor-based therapy exhibited clinically meaningful benefits in patients with ESCC. Survival benefits were better in patients with high PD-L1 expression than in those with low PD-L1 expression, suggesting that the PD-L1 expression level can be used as a predictor of survival benefit from PD-1 inhibitor therapy. PD-1 inhibitor-based therapy provided a consistent benefit in reducing the risk of death according to prespecified subgroup analyses of clinical characteristics.
Whale falls as chemosynthetic refugia: a perspective from free-living deep-sea nematodes
Authors: Avila Ana K. F. , Shimabukuro Maurício , Couto Daniel M. , Alfaro-Lucas Joan M. , Sumida Paulo Y. G. , Gallucci Fabiane
Published: May 2023

Whale carcasses create habitats in the deep sea which are colonized by organisms related to other chemosynthetic environments suggesting that whale falls may act as intermediate refugia for the dispersal and evolution of deep-sea organisms. Such evidence comes mainly from macrofaunal organisms whereas for the smaller meiofauna, data on whalebone assemblages is lacking. In this study, we investigated nematode colonization of whalebones experimentally deployed at 1500 and 3300 m depth and bones from a natural whale carcass found at 4204 m, in the Southwest Atlantic Ocean, off Brazil. By comparing whalebone assemblages to other deep-sea environments, we tested the hypothesis that whale fall nematode assemblages are more similar to those from other cognate chemosynthetic-based habitats, rather than those from sediments surrounding the carcass or other deep-sea habitats. Our results showed that whalebone nematode assemblages resemble those of hydrothermal vents and cold seeps and suggest that organic falls may act as intermediate refugia for meiofauna from chemosynthetic environments. It also showed that oceanographic conditions and the age of the carcasses on the ocean floor could influence nematode assemblage composition and richness. Such findings highlight the importance of organic falls for understanding the connectivity and phylogeny of benthic organisms, including representatives of the meiofauna.
Person-attuned musical interactions (PAMI) in dementia care. Complex intervention research for constructing a training manual
Authors: Ridder Hanne Mette , Krøier Julie Kolbe , Anderson-Ingstrup Jens , McDermott Orii
Published: May 2023

Introduction

Music is of vital importance for cognition, human care, and the formation of social communities throughout life. Dementia is a neurocognitive disorder that affects cognitive domains, and in late-stage dementia, care is needed in all aspects of daily living. Within residential care home contexts, carers play a significant role for the “caring culture” but often lack professional training in verbal and non-verbal communication skills. Thus, there is a need for training carers to respond to the multidimensional needs of persons with dementia. Music therapists use musical interactions but are not trained to train carers. Therefore, our aim was to explore person-attuned musical interactions (PAMI), and additionally, to develop and evaluate a training manual to be used by music therapists when supporting and training carers in non-verbal communication with persons with late-stage dementia in residential care home contexts.

Research process

With a realist perspective and systems thinking and within the framework for complex intervention research, the research group integrated several overlapping subprojects by applying a non-linear and iterative research process. Core elements related to person-centered dementia care as well as learning objectives were considered through the following four phases; Developing, Feasibility, Evaluation, and Implementation.

Results

The result was a training manual for qualified music therapists to use when teaching and collaborating with carers about how to implement PAMI in dementia care. The manual included comprehensive resources, a clear structure for training, defined learning objectives, and integration of theory.

Discussion

With increased knowledge about caring values and non-verbal communication, residential care home cultures may develop carer competencies and provide professional attuned care for persons with dementia. Further piloting and testing to examine the general effect on caring cultures is needed.
The identification of the new species Nitratireductor thuwali sp. nov. reveals the untapped diversity of hydrocarbon-degrading culturable bacteria from the arid mangrove sediments of the Red Sea
Authors: Marasco Ramona , Michoud Grégoire , Sefrji Fatmah O. , Fusi Marco , Antony Chakkiath P. , Seferji Kholoud A. , Barozzi Alan , Merlino Giuseppe , Daffonchio Daniele
Published: May 2023

Introduction

The geological isolation, lack of freshwater inputs and specific internal water circulations make the Red Sea one of the most extreme—and unique—oceans on the planet. Its high temperature, salinity and oligotrophy, along with the consistent input of hydrocarbons due to its geology (e.g., deep-sea vents) and high oil tankers traffic, create the conditions that can drive and influence the assembly of unique marine (micro)biomes that evolved to cope with these multiple stressors. We hypothesize that mangrove sediments, as a model-specific marine environment of the Red Sea, act as microbial hotspots/reservoirs of such diversity not yet explored and described.

Methods

To test our hypothesis, we combined oligotrophic media to mimic the Red Sea conditions and hydrocarbons as C-source (i.e., crude oil) with long incubation time to allow the cultivation of slow-growing environmentally (rare or uncommon) relevant bacteria.

Results and discussion

This approach reveals the vast diversity of taxonomically novel microbial hydrocarbon degraders within a collection of a few hundred isolates. Among these isolates, we characterized a novel species, Nitratireductor thuwali sp. nov., namely, Nit1536T. It is an aerobic, heterotrophic, Gram-stain-negative bacterium with optimum growth at 37°C, 8 pH and 4% NaCl, whose genome and physiological analysis confirmed the adaptation to extreme and oligotrophic conditions of the Red Sea mangrove sediments. For instance, Nit1536T metabolizes different carbon substrates, including straight-chain alkanes and organic acids, and synthesizes compatible solutes to survive in salty mangrove sediments. Our results showed that the Red Sea represent a source of yet unknown novel hydrocarbon degraders adapted to extreme marine conditions, and their discovery and characterization deserve further effort to unlock their biotechnological potential.
Arginine anchor points govern H3 tail dynamics
Authors: Jennings Christine E. , Zoss Casey J. , Morrison Emma A.
Published: May 2023

Chromatin is dynamically reorganized spatially and temporally, and the post-translational modification of histones is a key component of this regulation. The basic subunit of chromatin is the nucleosome core particle, consisting of two copies each of the histones H2A, H2B, H3, and H4 around which ∼147 base pairs of DNA wrap. The intrinsically disordered histone termini, or tails, protrude from the core and are heavily post-translationally modified. Previous studies have shown that the histone tails exist in dynamic ensembles of DNA-bound states within the nucleosome. Histone tail interactions with DNA are involved in nucleosome conformation and chromatin organization. Charge-modulating histone post-translational modifications (PTMs) are poised to perturb the dynamic interactions between histone tails and DNA. Arginine side chains form favorable interactions with DNA and are sites of charge-modulating PTMs such as citrullination. Our current focus is on the H3 tail, the longest histone tail. Four arginine residues are relatively evenly spaced along the H3 tail sequence, suggesting multivalent interactions with DNA poised for regulation by PTMs. In this study, we use NMR nuclear spin relaxation experiments to investigate the contribution of arginine residues to H3 tail dynamics within the nucleosome core particle. By neutralizing arginine via mutation to glutamine, we begin to work towards a comprehensive understanding of the contribution of individual residues to H3 tail dynamics. We find that neutralization of arginine residues results in increased regional mobility of the H3 tails, with implications for understanding the direct effects of arginine citrullination. Altogether, these studies support a role for dynamics within the histone language and emphasize the importance of charge-modulating histone PTMs in regulating chromatin dynamics, starting at the level of the basic subunit of chromatin.
Assistance level quantification-based human-robot interaction space reshaping for rehabilitation training
Authors: Li Xiangyun , Lu Qi , Chen Peng , Gong Shan , Yu Xi , He Hongchen , Li Kang
Published: May 2023

Stroke has become a major disease that seriously threatens human health due to its high incidence and disability rates. Most patients undergo upper limb motor dysfunction after stroke, which significantly impairs the ability of stroke survivors in their activities of daily living (ADL). Robots provide an optional solution for stroke rehabilitation by attending therapy in the hospital and the community, however, the rehabilitation robot still has difficulty in providing needed assistance interactively like human clinicians in conventional therapy. For safe and rehabilitation training, a human-robot interaction space reshaping method was proposed based on the recovery states of patients. According to different recovery states, we designed seven experimental protocols suitable for distinguishing rehabilitation training sessions. To achieve assist-as-needed (AAN) control, a PSO-SVM classification model and an LSTM-KF regression model were introduced to recognize the motor ability of patients with electromyography (EMG) and kinematic data, and a region controller for interaction space shaping was studied. Ten groups of offline and online experiments and corresponding data processing were conducted, and the machine learning and AAN control results were presented, which ensured the effective and the safe upper limb rehabilitation training. To discuss the human-robot interaction in different training stages and sessions, we defined a quantified assistance level index that characterizes the rehabilitation needs by considering the engagement of the patients and had the potential to apply in clinical upper limb rehabilitation training.
SNAP25 differentially contributes to Gi/o-coupled receptor function at glutamatergic synapses in the nucleus accumbens
Authors: Manz Kevin M. , Zepeda José C. , Zurawski Zack , Hamm Heidi E. , Grueter Brad A.
Published: May 2023

The nucleus accumbens (NAc) guides reward-related motivated behavior implicated in pathological behavioral states, including addiction and depression. These behaviors depend on the precise neuromodulatory actions of Gi/o-coupled G-protein-coupled receptors (GPCRs) at glutamatergic synapses onto medium spiny projection neurons (MSNs). Previous work has shown that discrete classes of Gi/o-coupled GPCR mobilize Gβγ to inhibit vesicular neurotransmitter release via t-SNARE protein, SNAP25. However, it remains unknown which Gαi/o systems in the NAc utilize Gβγ-SNARE signaling to dampen glutamatergic transmission. Utilizing patch-clamp electrophysiology and pharmacology in a transgenic mouse line with a C-terminal three-residue deletion of SNAP25 (SNAP25Δ3) weaking the Gβγ-SNARE interaction, we surveyed a broad cohort of Gi/o-coupled GPCRs with robust inhibitory actions at glutamatergic synapses in the NAc. We find that basal presynaptic glutamate release probability is reduced in SNAP25Δ3 mice. While κ opioid, CB1, adenosine A1, group II metabotropic glutamate receptors, and histamine H3 receptors inhibit glutamatergic transmission onto MSNs independent of SNAP25, we report that SNAP25 contributes significantly to the actions of GABAB, 5-HT1B/D, and μ opioid receptors. These findings demonstrate that presynaptic Gi/o-coupled GPCRs recruit heterogenous effector mechanisms at glutamatergic synapses in the NAc, with a subset requiring SNA25-dependent Gβγ signaling.
Cultured brain pericytes adopt an immature phenotype and require endothelial cells for expression of canonical markers and ECM genes
Authors: Oliveira Fabiana , Bondareva Olga , Rodríguez-Aguilera Jesús Rafael , Sheikh Bilal N.
Published: May 2023

Pericytes (PCs) are essential components of the blood brain barrier. Brain PCs are critical for dynamically regulating blood flow, for maintaining vascular integrity and their dysregulation is associated with a myriad of disorders such as Alzheimer’s disease. To understand their physiological and molecular functions, studies have increasingly focused on primary brain PC isolation and culture. Multiple methods for PC culture have been developed over the years, however, it is still unclear how primary PCs compare to their in vivo counterparts. To address this question, we compared cultured brain PCs at passage 5 and 20 to adult and embryonic brain PCs directly isolated from mouse brains via single cell RNA-seq. Cultured PCs were highly homogeneous, and were most similar to embryonic PCs, while displaying a significantly different transcriptional profile to adult brain PCs. Cultured PCs downregulated canonical PC markers and extracellular matrix (ECM) genes. Importantly, expression of PC markers and ECM genes could be improved by co-culture with brain endothelial cells, showing the importance of the endothelium in maintaining PC identity and function. Taken together, these results highlight key transcriptional differences between cultured and in vivo PCs which should be considered when performing in vitro experiments with brain PCs.
Feasibility, acceptability, and preliminary efficacy of yoga to improve maternal mental health and immune function during the COVID-19 crisis (Yoga-M2 trial): a pilot randomized controlled trial
Authors: Shidhaye Rahul , Bangal Vidyadhar , Bhargav Hemant , Tilekar Swanand , Thanage Chitra , Gore Suryabhan , Doifode Akshada , Thete Unnati , Game Kalpesh , Hake Vaishali , Kunkulol Rahul
Published: May 2023

Introduction

Women are vulnerable during pregnancy as they experience multiple physical and psychological problems which can lead to stress and poor quality of life ultimately affecting the development of the fetus and their health during and after pregnancy. Prior evidence suggests that prenatal yoga can improve maternal health and well-being and can have a beneficial effect on immune system functioning. To date, no study has been conducted in a rural, low-resource setting in India to assess the feasibility, acceptability, and preliminary efficacy of a yoga-based intervention on perceived stress, quality of life, pro-inflammatory biomarkers, and symptoms of upper respiratory tract infections.

Methods

To address this gap and assess whether a yoga-based intervention could improve maternal mental health and immunity during the COVID-19 crisis (Yoga-M2 trial), a single-blind individual randomized parallel group-controlled pilot trial with a 1:1 allocation ratio was implemented. We randomly allocated 51 adult pregnant women, with gestational age between 12-24 weeks in the Yoga-M2 arm (n = 25) or the enhanced usual care arm (EUC) (n = 26). Feasibility and acceptability were assessed using the process data and In-Depth Interviews (IDIs) with the trial participants and yoga instructors. Multiple linear regression was used to compare follow-up scores for quantitative outcomes.

Results

A three-month follow-up assessment was completed for 48 out of 51 participants (94.12%). We did not find any statistically significant difference between both arms in total Perceived Stress Scale scores, quality of life (Eq-5D-5L index), and serum C Reactive Protein levels at the three-month follow-up assessment. The critical barriers to practicing yoga were lack of knowledge about the benefits of yoga, lack of ‘felt need' to practice yoga, lack of time to practice, lack of space, lack of transport, and lack of peer group to practice yoga. Despite this, women who regularly practiced yoga described the benefits and factors which motivated them to practice regularly.

Discussion

The learnings from this trial will help design the explanatory trial in the future and the study findings can also be used by the primary health care system to deliver yoga-based interventions in the newly created health and wellness centers.

Trial registration

This trial was prospectively registered with the Clinical Trials Registry of India on 25 January 2022. https://www.ctri.nic.in/Clinicaltrials/showallp.php?mid1=65173&EncHid=&userName=CTRI/2022/01/039701. Trial registration number: CTRI/2022/01/039701.
Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis
Authors: Conroy Andrea L. , Datta Dibyadyuti , Opoka Robert O. , Batte Anthony , Bangirana Paul , Gopinadhan Adnan , Mellencamp Kagan A. , Akcan-Arikan Ayse , Idro Richard , John Chandy C.
Published: May 2023

Introduction

Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria.

Methods

We evaluated 30 cerebrospinal fluid (CSF) markers of inflammation, oxidative stress, and brain injury in 168 Ugandan children aged 18 months to 12 years hospitalized with cerebral malaria. Eligible children were infected with Plasmodium falciparum and had unexplained coma. Acute kidney injury (AKI) on admission was defined using the Kidney Disease: Improving Global Outcomes criteria. We further evaluated blood-brain-barrier integrity and malaria retinopathy, and electrolyte and metabolic complications in serum.

Results

The mean age of children was 3.8 years (SD, 1.9) and 40.5% were female. The prevalence of AKI was 46.3% and multi-organ dysfunction was common with 76.2% of children having at least one organ system affected in addition to coma. AKI and elevated blood urea nitrogen, but not other measures of disease severity (severe coma, seizures, jaundice, acidosis), were associated with increases in CSF markers of impaired blood-brain-barrier function, neuronal injury (neuron-specific enolase, tau), excitatory neurotransmission (kynurenine), as well as altered nitric oxide bioavailability and oxidative stress (p < 0.05 after adjustment for multiple testing). Further evaluation of potential mechanisms suggested that AKI may mediate or be associated with CSF changes through blood-brain-barrier disruption (p = 0.0014), ischemic injury seen by indirect ophthalmoscopy (p < 0.05), altered osmolality (p = 0.0006) and through alterations in the amino acids transported into the brain.

Conclusion

In children with cerebral malaria, there is evidence of kidney-brain injury with multiple potential pathways identified. These changes were specific to the kidney and not observed in the context of other clinical complications.
The brain-inspired decoder for natural visual image reconstruction
Authors: Li Wenyi , Zheng Shengjie , Liao Yufan , Hong Rongqi , He Chenggang , Chen Weiliang , Deng Chunshan , Li Xiaojian
Published: May 2023

The visual system provides a valuable model for studying the working mechanisms of sensory processing and high-level consciousness. A significant challenge in this field is the reconstruction of images from decoded neural activity, which could not only test the accuracy of our understanding of the visual system but also provide a practical tool for solving real-world problems. Although recent advances in deep learning have improved the decoding of neural spike trains, little attention has been paid to the underlying mechanisms of the visual system. To address this issue, we propose a deep learning neural network architecture that incorporates the biological properties of the visual system, such as receptive fields, to reconstruct visual images from spike trains. Our model outperforms current models and has been evaluated on different datasets from both retinal ganglion cells (RGCs) and the primary visual cortex (V1) neural spikes. Our model demonstrated the great potential of brain-inspired algorithms to solve a challenge that our brain solves.
Scoping out noisy galvanic vestibular stimulation: a review of the parameters used to improve postural control
Authors: McLaren Ruth , Smith Paul F. , Taylor Rachael L. , Niazi Imran Khan , Taylor Denise
Published: May 2023

Objective

Noisy galvanic vestibular stimulation (nGVS) has been used to facilitate vestibular function and improve gait and balance in people with poor postural control. The aim of this scoping review is to collate, summarize and report on the nGVS parameters that have been used to augment postural control.

Method

A systematic scoping review was conducted up to December 2022. Data were extracted and synthesized from 31 eligible studies. Key nGVS parameters were identified, and the importance of these parameters and their influence on postural control evaluated.

Results

A range of nGVS parameters have been used to augment postural control, including; noise waveform, amplitude, frequency band, duration of stimulation, method of amplitude optimization, size and composition of electrodes and the electrode skin interface.

Conclusion

Systematic evaluation of the individual parameters that can be manipulated in the nGVS waveform identified that a broad array of settings have been utilized in each parameter across the studies. Choices made around the electrode and electrode-skin interface, as well as the amplitude, frequency band, duration and timing of the waveform are likely to influence the efficacy of nGVS. The ability to draw robust conclusions about the selection of optimal nGVS parameters to improve postural control, is hindered by a lack of studies that directly compare parameter settings or consider the variability in individuals’ response to nGVS. We propose a guideline for the accurate reporting of nGVS parameters, as a first step toward establishing standardized stimulation protocols.
The influence of action on perception spans different effectors
Authors: Bosco Annalisa , Sanz Diez Pablo , Filippini Matteo , Fattori Patrizia
Published: May 2023

Perception and action are fundamental processes that characterize our life and our possibility to modify the world around us. Several pieces of evidence have shown an intimate and reciprocal interaction between perception and action, leading us to believe that these processes rely on a common set of representations. The present review focuses on one particular aspect of this interaction: the influence of action on perception from a motor effector perspective during two phases, action planning and the phase following execution of the action. The movements performed by eyes, hands, and legs have a different impact on object and space perception; studies that use different approaches and paradigms have formed an interesting general picture that demonstrates the existence of an action effect on perception, before as well as after its execution. Although the mechanisms of this effect are still being debated, different studies have demonstrated that most of the time this effect pragmatically shapes and primes perception of relevant features of the object or environment which calls for action; at other times it improves our perception through motor experience and learning. Finally, a future perspective is provided, in which we suggest that these mechanisms can be exploited to increase trust in artificial intelligence systems that are able to interact with humans.
Dynamic brain states in spatial neglect after stroke
Authors: Spadone Sara , de Pasquale Francesco , Digiovanni Anna , Grande Eleonora , Pavone Luigi , Sensi Stefano L. , Committeri Giorgia , Baldassarre Antonello
Published: May 2023

Previous studies indicated that spatial neglect is characterized by widespread alteration of resting-state functional connectivity and changes in the functional topology of large-scale brain systems. However, whether such network modulations exhibit temporal fluctuations related to spatial neglect is still largely unknown. This study investigated the association between brain states and spatial neglect after the onset of focal brain lesions. A cohort of right-hemisphere stroke patients (n = 20) underwent neuropsychological assessment of neglect as well as structural and resting-state functional MRI sessions within 2 weeks from stroke onset. Brain states were identified using dynamic functional connectivity as estimated by the sliding window approach followed by clustering of seven resting state networks. The networks included visual, dorsal attention, sensorimotor, cingulo-opercular, language, fronto-parietal, and default mode networks. The analyses on the whole cohort of patients, i.e., with and without neglect, identified two distinct brain states characterized by different degrees of brain modularity and system segregation. Compared to non-neglect patients, neglect subjects spent more time in less modular and segregated state characterized by weak intra-network coupling and sparse inter-network interactions. By contrast, patients without neglect dwelt mainly in more modular and segregated states, which displayed robust intra-network connectivity and anti-correlations among task-positive and task-negative systems. Notably, correlational analyses indicated that patients exhibiting more severe neglect spent more time and dwelt more often in the state featuring low brain modularity and system segregation and vice versa. Furthermore, separate analyses on neglect vs. non-neglect patients yielded two distinct brain states for each sub-cohort. A state featuring widespread strong connections within and between networks and low modularity and system segregation was detected only in the neglect group. Such a connectivity profile blurred the distinction among functional systems. Finally, a state exhibiting a clear separation among modules with strong positive intra-network and negative inter-network connectivity was found only in the non-neglect group. Overall, our results indicate that stroke yielding spatial attention deficits affects the time-varying properties of functional interactions among large-scale networks. These findings provide further insights into the pathophysiology of spatial neglect and its treatment.