bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of agricultural intervention on nutrient stoichiometry from root to leaf in the helophyte species Glyceria spiculosa
Authors: Wei Tian , Dongjie Zhang , Guanglan Cao , Wanling Xu , Weihong Zhu , Lei Qin
Published: August 2022

Plant nutrient stoichiometry indicates the balance of plant internal nutrients and its nutrient-use strategies in response to environmental changes. However, the responses of nutrient stoichiometry in different wetland plant organs under agricultural intervention are poorly understood. Here, we compared the nitrogen (N), phosphorus (P), and the ratio of N:P in the plant organs (leaves, stems, roots, and root hair) of a typical helophyte plant (Glyceria spiculosa) in reference, drained, nutrient-rich, and cultivated wetlands (CW) located downstream of the Tumen River in Northeast China. Compared with that in reference wetlands (RW), the results indicate that the average N content in plant leaves, stems, roots, and root hair in nutrient-rich wetlands (NW) was significantly higher by 76, 61, 56, and 39%, respectively (p < 0.05), whereas the N content of roots and root hair in drained wetlands (DW) was significantly higher by 17 and 32%, respectively (p < 0.05). It was found that plant root P increased only in nutrient-rich and DW (p < 0.05). Interestingly, the agricultural interventions significantly affected soil N and P availability, resulting in positive effects on plant leaves, stems, roots, and root hair. Nutrient stoichiometry analysis showed the highest increase in plant leaf N:P ratio in NW, followed by that in drained and CW, but its ratio in root and root hair showed no significant changes under different agricultural interventions, which suggests that G. spiculosa allocates nutrients differently in different organs under agricultural interventions. These results imply that plant nutrient stoichiometry should incorporate various plant organs for an in-depth understanding of plant strategies against environmental changes.
Homologous recombination repair gene mutations as a predictive biomarker for immunotherapy in patients with advanced melanoma
Authors: You Zhixuan , Lv Meng , He Xuanyu , Pan Yingqin , Ge Junfeng , Hu Xue , Zheng Yating , Huang Mengli , Zhou Chengzhi , You Changxuan
Published: August 2022

Background

Nowadays, immunotherapy targeting immune checkpoint receptors is one of the cornerstones of systemic treatment in melanoma. Homologous recombination repair (HRR) is one of the DNA damage response (DDR) pathways, which has been proved to correlate with the efficacy of platinum-based chemotherapy, PARP inhibitor therapy, and immunotherapy in a variety of cancers. However, their predictive value of HRR remained unknown in patients with advanced melanoma.

Methods

Data of advanced melanoma patients from an independent cohort (Samstein2018) were used to analyze the correlation with immunogenic markers and the prognostic effect of HRR on immunotherapy, and another four cohorts (pooled cohort: Miao2018, Allen 2015, Hugo2016, and Synder2014) were used for validation. Immune infiltration cell scores analyzed by TCGA-SKCM cohort were used to explore potential mechanisms related to the immune microenvironment.

Results

Compared to patients with an HRR wild type (HRRwt), those with HRR mutations (HRRmut) in anti-CTLA-4-treated patients of the Samstein2018 cohort had higher tumor mutation burden (TMB; P = 0.0041) and longer median overall survival (mOS; P = 0.0094). In terms of results validation, it was also confirmed that the mOS (P = 0.0014) of HRRmut patients receiving anti-CTLA-4 therapy was significantly better than that of HRRwt patients in the pooled cohort, and objective response rates (ORR; P = 0.0053) were also found to be significant. However, there was no significant difference in mOS between HRRmut patients who received anti-PD-1/L1 therapy and HRRwt patients in either the discovery (Samstein2018 cohort, P = 0.94) or validation (pooled cohort, P = 0.96) set. Exploratory analysis found that although HRRmut patients showed no significant difference in mOS between anti-CTLA-4 and anti-PD-1/L1 therapy (P = 0.79), the mOS value of the anti-CTLA-4 therapy group (31.7 months) in HRRmut patients was numerically superior to the anti-PD-1/L1 therapy group (27.5 months). In contrast, the mOS of the anti-CTLA-4 therapy group was significantly lower than that of the anti-PD-1/L1 therapy group (12.4 vs. 32.0 months) in HRRwt patients. In addition, transcriptome profiling analysis revealed that the 29 (65.9%)-gene mutation of the HRR pathway associated with reshaping of the immunological microenvironment in melanoma.

Conclusions

HRR mutations were associated with a higher TMB level, and better anti-CTLA-4 therapy outcomes. HRR may serve as an independent predictor of anti-CTLA-4 therapy efficacy in patients with advanced melanoma and their clinical value warrants further investigation.
From rough to precise: PD-L1 evaluation for predicting the efficacy of PD-1/PD-L1 blockades
Authors: Zhao Xuan , Bao Yulin , Meng Bi , Xu Zijian , Li Sijin , Wang Xu , Hou Rui , Ma Wen , Liu Dan , Zheng Junnian , Shi Ming
Published: August 2022

Developing biomarkers for accurately predicting the efficacy of immune checkpoint inhibitor (ICI) therapies is conducive to avoiding unwanted side effects and economic burden. At the moment, the quantification of programmed cell death ligand 1 (PD-L1) in tumor tissues is clinically used as one of the combined diagnostic assays of response to anti-PD-1/PD-L1 therapy. However, the current assays for evaluating PD-L1 remain imperfect. Recent studies are promoting the methodologies of PD-L1 evaluation from rough to precise. Standardization of PD-L1 immunohistochemistry tests is being promoted by using optimized reagents, platforms, and cutoff values. Combining novel in vivo probes with PET or SPECT will probably be of benefit to map the spatio-temporal heterogeneity of PD-L1 expression. The dynamic change of PD-L1 in the circulatory system can also be realized by liquid biopsy. Consider PD-L1 expressed on non-tumor (immune and non-immune) cells, and optimized combination detection indexes are further improving the accuracy of PD-L1 in predicting the efficacy of ICIs. The combinations of artificial intelligence with novel technologies are conducive to the intelligence of PD-L1 as a predictive biomarker. In this review, we will provide an overview of the recent progress in this rapidly growing area and discuss the clinical and technical challenges.
Single-cell RNA sequencing reveals distinct immunology profiles in human keloid
Authors: Feng Cheng , Shan Mengjie , Xia Yijun , Zheng Zhi , He Kai , Wei Yingxin , Song Kexin , Meng Tian , Liu Hao , Hao Yan , Liang Zhengyun , Wang Youbin , Huang Yongsheng
Published: August 2022

Keloids, characterized by skin fibrosis and excessive accumulation of extracellular matrix, remain a therapeutic challenge. In this study, we systematically capture the cellular composition of keloids by the single-cell RNA sequencing technique. Our results indicated that there are significant differences in most cell types present between 12 pairs of keloid and adjacent normal tissue. We found that fibroblasts, endothelial cells, mast cells, mural cells, and Schwann cells increased significantly in keloid. The proportion of mesenchymal fibroblast subpopulations in keloids was markedly higher than those in the surrounding normal skin tissue. Furthermore, we found that the immune profiles between two groups varied significantly. The proportion of macrophages in the keloid was significantly elevated compared to the surrounding normal tissue, while cDC2 cells significantly decreased. Hotspot and pseudotime trajectory analysis indicated two modules of macrophage cells (Module2: highly expresses RNASE1, C1QA, CD163, CD14, C1QC, FCGRT, MS4A7; Module10: highly expresses APOC1, CTSB, CTSL, TYROBP), which exhibited the characteristics of tumor-associated macrophages, were upregulated in more-advanced keloid cells. Subsequently, the analysis of cellular communication networks suggested that a macrophage-centered communication regulatory network may exist in keloids and that fibroblasts in keloids may facilitate the transition and proliferation of M2 macrophages, which contributes to further comprehension of the immunological features of keloids. Overall, we delineate the immunology landscape of keloids and present new insights into the mechanisms involved in its formation in this study.
Optimization of cancer immunotherapy through pyroptosis: A pyroptosis-related signature predicts survival benefit and potential synergy for immunotherapy in glioma
Authors: Zeng Yu , Cai Yonghua , Chai Peng , Mao Yangqi , Chen Yanwen , Wang Li , Zeng Kunlin , Zhan Ziling , Xie Yuxin , Li Cuiying , Zhan Hongchao , Zhao Liqian , Chen Xiaoxia , Zhu Xiaoxia , Liu Yu , Chen Ming , Song Ye , Zhou Aidong
Published: August 2022

Background

Pyroptosis is a critical type of programmed cell death that is strongly associated with the regulation of tumor and immune cell functions. However, the role of pyroptosis in tumor progression and remodeling of the tumor microenvironment in gliomas has not been extensively studied. Thus, in this study, we aimed to establish a comprehensive pyroptosis-related signature and uncover its potential clinical application in gliomas.

Methods

The TCGA glioma cohort was obtained and divided into training and internal validation cohorts, while the CGGA glioma cohort was used as an external validation cohort. Unsupervised consensus clustering was performed to identify pyroptosis-related expression patterns. A Cox regression analysis was performed to establish a pyroptosis-related risk signature. Real-time quantitative PCR was performed to analyze the expression of signature genes in glioma tissues. Immune infiltration was analyzed and validated by immunohistochemical staining. The expression patterns of signature genes in different cell types were analyzed using single-cell RNA sequencing data. Finally, therapeutic responses to chemotherapy, immunotherapy, and potential small-molecule inhibitors were investigated.

Results

Patients with glioma were stratified into clusters 1 and 2 based on the expression patterns of pyroptosis-related genes. Cluster 2 showed a longer overall (P<0.001) and progression-free survival time (P<0.001) than Cluster 1. CD8+ T cell enrichment was observed in Cluster 1. A pyroptosis-related risk signature (PRRS) was then established. The high PRRS group showed a significantly poorer prognosis than the low PRRS group in the training cohort (P<0.001), with validation in the internal and external validation cohorts. Immunohistochemical staining demonstrated that CD8+ T cells were enriched in high PRRS glioma tissues. PRRS genes also showed cell-specific expression in tumor and immune cells. Moreover, the high PRRS risk group showed higher temozolomide sensitivity and increased response to anti-PD1 treatment in a glioblastoma immunotherapy cohort. Finally, Bcl-2 inhibitors were screened as candidates for adjunct immunotherapy of gliomas.

Conclusion

The pyroptosis-related signature established in this study can be used to reliably predict clinical outcomes and immunotherapy responses in glioma patients. The correlation between the pyroptosis signature and the tumor immune microenvironment may be used to further guide the sensitization of glioma patients to immunotherapy.
Application of a new protocol for providing obstetric care in an outpatient service during the COVID-19 pandemic in a public hospital in Madrid, Spain
Authors: Rayo Maria N. , Fernández-Buhigas Irene , Ferrer Emilia , Arrébola María , Gil María M. , Santacruz Belén
Published: August 2022

Objective

To evaluate the clinical implementation of a preventive COVID-19 protocol regarding re-organization of appointments and documented infections among health workers in an obstetric outpatient service.

Methods

Descriptive analysis of the antenatal care at our obstetric outpatient service and infection rates among health care providers from March 19th to May 22nd, 2020. Appointments were divided into telephone calls or face-to-face examinations. A pre-consultation triage was implemented to identify suspected SARS-CoV2 infected women to reschedule them 14 days later or, if the consultation was non-delayable, to use complete Personal Protective Equipment (PPE). Firstly, the number of face-to-face appointments, telephone appointments, and COVID-19 diagnoses in pregnant women were analyzed. Secondly, the number of obstetricians and nurses diagnosed with SARS-CoV2 infection and their serologic status during universal screening in May 2020 were recorded.

Results

One thousand eight hundred forty-two obstetric appointments were scheduled during this period, including 432 (23.5%) telephone appointments (96.53% according to clinical protocol, 1.62% symptomatic patients advised to stay at home, and 1.85% COVID-19 confirmed cases), and 1,410 (76.5%) face-to-face appointments (9.7% did not attend due to fear of getting the infection, 3.1% were lost-to-follow-up, 0.5% were rescheduled due to COVID-19 symptoms and 86.7% who did attend). Of the 1,223 women attending their hospital appointment, 3.6% screened positive at the triage (72.7% rescheduled and 27.3% seen with PPE). 43 rRT-PCR-SARS-CoV2 tests were performed, and two tested positive. No COVID-19 symptoms were reported among health workers at the outpatient obstetric service, and only one nurse presented immunoglobulin (Ig)G anti-SARS-CoV2.

Conclusion

A prompt implementation of a preventive protocol in a hospital obstetric outpatient service, including triage, hygienic and preventive measurements, and rescheduling pregnancy appointments, reduces the percentage of health workers affected by SARS-CoV2.
The microbiota diversity of Festuca sinensis seeds in Qinghai-Tibet Plateau and their relationship with environments
Authors: Gao Yue , Chen Youjun , Luo Yang , Liu Junying , Tian Pei , Nan Zhibiao , Zhou Qingping
Published: August 2022

A total of 14 Festuca sinensis seed lots were collected from different geographical locations on the Qinghai-Tibet Plateau to study the seed microbiota and determine the abiotic (temperature, precipitation, and elevation) and biotic (Epichloë sinensis infection rate) factors likely to shape the seed microbiome. The 14 seed lots had different bacterial and fungal structures and significantly different diversities (p < 0.05). The α-diversity indices of the bacteria were significantly correlated with precipitation (p < 0.05), whereas those of the fungi were significantly correlated with temperature (p < 0.05). Microbiota analysis showed that Proteobacteria, Cyanobacteria, and Bacteroidetes were the most abundant bacteria at the phylum level in the seeds, and Ascomycota and Basidiomycota were the most abundant fungi. β-diversity analysis suggested large differences in the microbial communities of each sample. Redundancy analysis showed that temperature and precipitation were the main environmental factors that drive variations in the microbial community, at the medium-high elevation (3,000–4,500 m), the impact of temperature and precipitation on microbial community is different, and the other elevations that effect on microbial community were basically identical. Spearman's correlation analysis showed that the relative abundances of the most abundant bacterial phyla were significantly correlated with temperature (p < 0.05), whereas those of the most abundant fungal phyla were significantly correlated with precipitation (p < 0.05). E. sinensis infection rates were significantly correlated with elevation and temperature (p < 0.05). These results suggest that temperature and precipitation are the key factors driving the microbial community, that temperature and elevation also had a great influence on the E. sinensis infection rate, and that environmental factors (temperature and elevation) may further affect the microbial community by regulating the E. sinensis infection rate.
Efficacy of a gB + gD-based subunit vaccine and the adjuvant granulocyte-macrophage colony stimulating factor for pseudorabies virus in rabbits
Authors: Cao Zhi , Zhang Ke , Zhang Heng , Zhang Hongliang , Yu Ying , Yin Dehua , Shan Hu , Qin Zhihua
Published: August 2022

Pseudorabies (PR), which is caused by the pseudorabies virus (PRV), is a severe infectious disease that causes abortions in adult sows and fatal encephalitis in piglets; the disease can occur in pigs of all ages and other mammals, which can lead to significant economic loss around the worldwide. The new PRV variant invalidated the available commercial attenuated and inactivated vaccines. Consequently, subunit vaccines have been suggested as novel strategies for PR control, while they are usually formulated with adjuvants due to their lower immunogenicity. We aimed to select a safe and efficient adjuvant for subunit vaccines for PR. In our study, glycoprotein B (gB) and glycoprotein D (gD) were expressed based on a baculovirus expression system, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was expressed using an Escherichia coli (E. coli) expression system; subsequently, a gB + gD subunit vaccine adjuvanted by GM-CSF was constructed. A rabbit model infected with a PRV SD-2017 strain was established, the TCID50 and LD50 were measured, and the typical clinical symptoms were observed. After a lethal challenge of 5 LD50 with a PRV SD-2017 strain, the rabbits exhibited typical clinical symptoms, including itching and high temperature, and histopathology revealed severe inflammation in the brain, which is the dominant target organ of PRV. Rabbits immunized with the gB + gD + GM-CSF subunit vaccines produced higher levels of antibodies than those immunized with gB + gD + ISA 201, which was adjuvanted with a frequently used oil adjuvant. The survival rate of rabbits vaccinated with gB + gD + GM-CSF was 100%, which was superior to that of rabbits vaccinated with gB + gD + ISA 201 (80%), inactivated PRV + GM-CSF (60%) and commercial inactivated vaccine (60%) after challenge with PRV SD-2017. These data suggested that the gB + gD + GM-CSF-based subunit vaccine had good protective efficacy against the PRV SD-2017 strain in rabbits and that GM-CSF could be developed as a candidate adjuvant for use in a vaccine regimen to prevent and even eradicate PR.
Quartz crystal microbalance and atomic force microscopy to characterize mimetic systems based on supported lipids bilayer
Authors: Bonet Noel F. , Cava Daniel G. , Vélez Marisela
Published: August 2022

Quartz Crystal Microbalance (QCM) with dissipation and Atomic Force Microscopy (AFM) are two characterization techniques that allow describing processes taking place at solid-liquid interfaces. Both are label-free and, when used in combination, provide kinetic, thermodynamic and structural information at the nanometer scale of events taking place at surfaces. Here we describe the basic operation principles of both techniques, addressing a non-specialized audience, and provide some examples of their use for describing biological events taking place at supported lipid bilayers (SLBs). The aim is to illustrate current strengths and limitations of the techniques and to show their potential as biophysical characterization techniques.
Neuromodulating roles of estrogen and phytoestrogens in cognitive therapeutics through epigenetic modifications during aging
Authors: Singh Padmanabh , Paramanik Vijay
Published: August 2022

Estrogen (E2) plays important role in regulating hippocampal learning and memory. The decline of E2 after menopause affects learning and memory and increases the risk of neurodegenerative diseases like Alzheimer's disease (AD). Additionally, from the estrogen receptor (ER) mediated gene regulation; E2 also regulates gene expression at the transcriptional and posttranscriptional levels through epigenetic modifications. E2 recruits a number of proteins called co-regulators at the promoter region of genes. These co-regulators act as chromatin modifiers, alter DNA and histone modifications and regulate gene expression. Several studies show that E2 regulates learning and memory by altering chromatin at the promoters of memory-linked genes. Due to structural similarities with E2 and low side effects, phytoestrogens are now used as neuroprotective agents to recover learning and memory in animal models as well as human subjects during aging and different neurological disorders. Growing evidence suggests that apart from anti-oxidative and anti-inflammatory properties, phytoestrogens also act as epigenetic modifiers and regulate gene expression through epigenetic modifications. The epigenetic modifying properties of phytoestrogens are mostly studied in cancer cells but very little is known regarding the regulation of synaptic plasticity genes, learning and memory, and neurological disorders. In this article, we discuss the epigenetic modifying properties of E2 and the roles of phytoestrogens as epigenetic modifiers in the brain to recover and maintain cognitive functions.
Gut microbiota may be involved in Alzheimer’s disease pathology by dysregulating pyrimidine metabolism in APP/PS1 mice
Authors: Feng Min , Hou Tianshu , Zhou Mingze , Cen Qiuyu , Yi Ting , Bai Jinfeng , Zeng Yun , Liu Qi , Zhang Chengshun , Zhang Yingjun
Published: August 2022

Introduction

Alzheimer’s disease (AD) is the most common form of dementia worldwide. The biological mechanisms underlying the pathogenesis of AD aren’t completely clear. Studies have shown that the gut microbiota could be associated with AD pathogenesis; however, the pathways involved still need to be investigated.

Aims

To explore the possible pathways of the involvement of gut microbiota in AD pathogenesis through metabolites and to identify new AD biomarkers.

Methods

Seven-month-old APP/PS1 mice were used as AD models. The Morris water maze test was used to examine learning and memory ability. 16S rRNA gene sequencing and widely targeted metabolomics were used to identify the gut microbiota composition and fecal metabolic profile, respectively, followed by a combined analysis of microbiomics and metabolomics.

Results

Impaired learning abilities were observed in APP/PS1 mice. Statistically significant changes in the gut microbiota were detected, including a reduction in β-diversity, a higher ratio of Firmicutes/Bacteroidota, and multiple differential bacteria. Statistically significant changes in fecal metabolism were also detected, with 40 differential fecal metabolites and perturbations in the pyrimidine metabolism. Approximately 40% of the differential fecal metabolites were markedly associated with the gut microbiota, and the top two bacteria associated with the most differential metabolites were Bacillus firmus and Rikenella. Deoxycytidine, which causes changes in the pyrimidine metabolic pathway, was significantly correlated with Clostridium sp. Culture-27.

Conclusions

Gut microbiota may be involved in the pathological processes associated with cognitive impairment in AD by dysregulating pyrimidine metabolism. B. firmus, Rikenella, Clostridium sp. Culture-27, and deoxyuridine may be important biological markers for AD. Our findings provide new insights into the host-microbe crosstalk in AD pathology and contribute to the discovery of diagnostic markers and therapeutic targets for AD.
Temporal alteration of microglia to microinfarcts in rat brain induced by the vascular occlusion with fluorescent microspheres
Authors: Shen Yi , Cui Jingjing , Zhang Shuang , Wang Yuqing , Wang Jia , Su Yuxin , Xu Dongsheng , Liu Yihan , Guo Yating , Bai Wanzhu
Published: August 2022

Microglia, the resident immune cells in the central nervous system, can monitor the microenvironment and actively respond to ischemic stroke and other brain injuries. In this procedure, microglia and neurons can cross-talk via transmembrane chemokine, Fractalkine (CX3CL1), to impact one another. We used a rat model of multifocal microinfarcts induced by the injection of fluorescent microspheres into the right common carotid artery and examined the morphological alteration of blood vessels, microglia, astrocytes, and neurons at 6 h, 1, 7, and 14 days after modeling, along with neurobehavioral tests and the staining of CX3CL1 in this study. Our results demonstrated that in the infarcted regions, astrocytes and microglia activated in response to neuronal degeneration and upregulation of cleaved caspase-3, which occurred concurrently with vascular alteration and higher expression of CX3CL1. We provided sequential histological data to shed light on the morphological changes after modeling, which would help in the identification of new targets and the choice of the ideal time window for therapeutic intervention in ischemic stroke.
Ultrasound stimulation for non-invasive visual prostheses
Authors: Badadhe Jaya Dilip , Roh Hyeonhee , Lee Byung Chul , Kim Jae Hun , Im Maesoon
Published: August 2022

Globally, it is estimated there are more than 2.2 billion visually impaired people. Visual diseases such as retinitis pigmentosa, age-related macular degeneration, glaucoma, and optic neuritis can cause irreversible profound vision loss. Many groups have investigated different approaches such as microelectronic prostheses, optogenetics, stem cell therapy, and gene therapy to restore vision. However, these methods have some limitations such as invasive implantation surgery and unknown long-term risk of genetic manipulation. In addition to the safety of ultrasound as a medical imaging modality, ultrasound stimulation can be a viable non-invasive alternative approach for the sight restoration because of its ability to non-invasively control neuronal activities. Indeed, recent studies have demonstrated ultrasound stimulation can successfully modulate retinal/brain neuronal activities without causing any damage to the nerve cells. Superior penetration depth and high spatial resolution of focused ultrasound can open a new avenue in neuromodulation researches. This review summarizes the latest research results about neural responses to ultrasound stimulation. Also, this work provides an overview of technical viewpoints in the future design of a miniaturized ultrasound transducer for a non-invasive acoustic visual prosthesis for non-surgical and painless restoration of vision.
Moderate and severe TBI in children and adolescents: The effects of age, sex, and injury severity on patient outcome 6 months after injury
Authors: Kennedy Lori , Nuno Miriam , Gurkoff Gene G. , Nosova Kristin , Zwienenberg Marike
Published: August 2022

The interaction of age, sex, and outcomes of children with head injury remains incompletely understood and these factors need rigorous evaluation in prognostic models for pediatric head injury. We leveraged our large institutional pediatric TBI population to evaluate age and sex along with a series of predictive factors used in the acute care of injury to describe the response and outcome of children and adolescents with moderate to severe injury. We hypothesized that younger age at injury and male sex would be associated with adverse outcomes and that a novel GCS-based scale incorporating pupillary response (GCS-P) would have superior performance in predicting 6-month outcome. GCS and GCS-P along with established CT scan variables associated with neurologic outcomes were retrospectively reviewed in children (age birth to 18 years) with moderate or severe head injury. GOS-E was prospectively collected 6 months after injury; 570 patients were enrolled in the study, 520 with TBI and 50 with abusive head trauma, each analyzed separately. In the TBI cohort, the median age of patients was 8 years and 42.7% had a severe head injury. Multiple predictors of outcome were identified in univariate analysis; however, based on a multivariate analysis, the GCS was identified as most reliable, outperforming GCS-P, pupil score, and other clinical and CT scan predictors. After stratifying patients for severity of injury by GCS, no age- or sex-related effects were observed in our patient population, except for a trend toward worse outcomes in the neonatal group. Patients with abusive head trauma were more likely to have severe injury on presentation, increased mortality rate, and unfavorable outcome. Additionally, there was clear evidence that secondary injuries, including hypoxia, hypotension, and hypothermia were significantly associated with lower GCS and higher mortality in both AHT and TBI populations. Our findings support the use of GCS to guide clinical decision-making and prognostication in addition to emphasizing the need to stratify head injuries for severity when undertaking outcome studies. Finally, secondary injuries are a clear predictor of poor outcome and how we record and manage these events need to be considered moving forward.
Balance impairment in patients with moderate-to-severe traumatic brain injury: Which measures are appropriate for assessment?
Authors: Joyce Julie M. , Debert Chantel T. , Chevignard Mathilde , Sorek Gilad , Katz-Leurer Michal , Gagnon Isabelle , Schneider Kathryn J.
Published: August 2022

Left untreated, balance impairment following moderate-to-severe traumatic brain injury (TBI) can be highly debilitating and hinder activities of daily life. To detect impairments, clinicians need appropriate assessment tools. The objective of this study was to evaluate the feasibility and utility of a battery of clinical balance assessments in adults with moderate-to-severe TBI within 6-months of injury. Thirty-seven adults with TBI [Glasgow Coma Scale score ≤ 12 (33 M/4 F) age 18–50 years] participated in balance testing. Assessments included the Balance Error Scoring System (BESS), National Institutes of Health Standing Balance Test (NIH-SBT), Functional Gait Assessment (FGA), Advanced Functional Gait Assessment (FGA-A), Tandem Gait Test (TGT), Berg Balance Scale (BBS), and Walking While Talking Test (WWTT). We identified pronounced ceiling effects on the BBS and FGA, two widely used clinical balance assessments. The NIH-SBT, WWTT, and FGA used in conjunction with the FGA-A, offered versatility in their capacity to assess patients across the balance severity spectrum. This study provides evidence to support a stepwise approach to balance assessment that can be adapted to the broad range of balance ability found in moderate-to-severe TBI.
Potential modifiable factors associated with late-life cognitive trajectories
Authors: Wu Zimu , Woods Robyn L. , Chong Trevor T. -J. , Orchard Suzanne G. , McNeil John J. , Shah Raj C. , Wolfe Rory , Murray Anne M. , Storey Elsdon , Ryan Joanne
Published: August 2022

Objective

There is variability across individuals in cognitive aging. To investigate the associations of several modifiable factors with high and low cognitive performance.

Methods

Data came from 17,724 community-dwelling individuals aged 65–98 years. Global cognition, verbal fluency, episodic memory, and psychomotor speed were assessed over up to seven years. Group-based multi-trajectory modeling identified distinct cognitive trajectories. Structural equation modeling examined the direct/indirect associations of social/behavioral factors and several chronic conditions with cognitive trajectories.

Results

Seven trajectory subgroups were identified. In the structural equation modeling we compared two subgroups-participants with the highest (14.2%) and lowest (4.1%) cognitive performance with the average subgroup. Lower education, never alcohol intake, and frailty directly predicted increased risk of low performance, and decreased likelihood of high performance. Hypertension (RR: 0.69, 95%CI: 0.60–0.80), obesity (RR: 0.84, 95%CI: 0.73–0.97), diabetes (RR: 0.69, 95%CI: 0.56–0.86) and depression (RR: 0.68, 95%CI: 0.54–0.85) only predicted lower likelihood of high cognitive performance, while dyslipidemia was only associated with low performance (RR: 1.30, 95%CI: 1.07–1.57). Living alone predicted increased risk of low cognitive performance and several comorbidities. Smoking did not predict cognitive trajectories but was associated with increased risk of diabetes, obesity and frailty. Findings were similar when examining the direct associations between modifiable risk factors and all seven cognitive subgroups.

Conclusions

Although several modifiable factors were associated with high performance, and reversely with low performance, this was not observed for obesity, hypertension and dyslipidemia. Further, health behaviors may affect cognitive function indirectly, via geriatric conditions. This indicates that strategies to promote healthy cognitive aging, may be distinct from those targeting dementia prevention.
Neurofilament light chain and S100B serum levels are associated with disease severity and outcome in patients with aneurysmal subarachnoid hemorrhage
Authors: Zhou Zhangming , Zeng Junyi , Yu Shui , Zhao Ying , Yang Xiaoyi , Zhou Yiren , Liang Qingle
Published: August 2022

Objectives

Serum neurofilament light chain (NfL) is a biomarker for neuroaxonal damage, and S100B is a blood marker for cerebral damage. In the present study, we investigated the relationship between serum NfL and S100B levels, severity, and outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Methods

We prospectively recruited aSAH patients and healthy controls between January 2016 and January 2021. Clinical results included mortality and poor outcomes (modified Rankin scale score of 3-6) after 6 months. The ultrasensitive Simoa technique was used to evaluate NfL levels in the blood, and ELISA was used to detect S100B.

Results

A total of 91 patients and 25 healthy controls were included in the study, with a death rate of 15.4%. The group of aSAH patients had significantly higher serum levels of NfL and S100B (P < 0.01). Furthermore, the levels of NfL and S100B increased when the Hunt-Hess, World Federation of Neurological Surgeons (WFNS), and Fisher grades increased (P < 0.01). Serum NfL and S100B levels were linked to poor prognoses and low survival rates. The blood levels of NfL and S100B were found to be an independent predictor related to 6-month mortality in multivariable analysis. Additionally, the areas under the curves for NfL and S100B levels in serum were 0.959 and 0.912, respectively; the clinical diagnostic critical thresholds were 14.275 and 26.54 pg/ml, respectively; sensitivities were 0.947 and 0.921, and specificities were 0.849 and 0.811.

Conclusions

The NfL and S100B values for aSAH patients within 12 days of admission were considerably associated with Hunt-Hess grade, WFNS, and Fisher grade. The higher the grade, the higher the NfL and S100B value, and the poorer the prognosis. Serum NfL and S100B values could be feasible biomarkers to predict the clinical prognosis of patients with aSAH.
Opening a window into the riddle of misophonia, sensory over-responsiveness, and pain
Authors: Efraim Kaufman Adi , Weissman-Fogel Irit , Rosenthal M. Zachary , Kaplan Neeman Ricky , Bar-Shalita Tami
Published: August 2022

Introduction

Misophonia and sensory over-responsiveness (SOR) share physiological and psychological symptoms. While individuals with SOR demonstrate pain perception alterations, these were not explored in misophonia.

Methods

This exploratory study comprised thirty healthy adults with (n = 15; based on the Misophonia Questionnaire) and without misophonia. The Sensory Responsiveness Questionnaire (SRQ) was used for evaluating sensory responsiveness. In addition, psychophysical tests were applied for quantification of: (i) stimulus-response function of painful stimuli, (ii) the individual perceived pain intensity, (iii) pain modulation efficiency, (iv) auditory intensity discrimination capability, and (v) painful and unpleasantness responses to six ecological daily sounds using the Battery of Aversiveness to Sounds (BAS).

Results

Individuals with misophonia reported higher scores in the SRQ-Aversive (p = 0.022) and SRQ-Hedonic (p = 0.029) scales as well as in auditory (p = 0.042) and smell (p = 0.006) sub-scales, indicating higher sensory responsiveness. Yet they were not identified with the SOR type of sensory modulation dysfunction. Groups did not differ in the pain psychophysical tests, and in auditory discrimination test scores (p > 0.05). However, in the misophonia group the BAS evoked higher pain intensity (p = 0.046) and unpleasantness (p <0.001) ratings in the apple biting sound, and higher unpleasantness rating in the scraping a dish sound (p = 0.007), compared to the comparison group.

Conclusion

Findings indicate increased sensory responsiveness in individuals with misophonia, yet not defined as SOR. Thus, this suggests that misophonia and SOR are two distinct conditions, differing in their behavioral responses to painful and non-painful stimuli.
Brain-machine interface-based training for improving upper extremity function after stroke: A meta-analysis of randomized controlled trials
Authors: Xie Yu-lei , Yang Yu-xuan , Jiang Hong , Duan Xing-Yu , Gu Li-jing , Qing Wu , Zhang Bo , Wang Yin-xu
Published: August 2022

Background

Upper extremity dysfunction after stroke is an urgent clinical problem that greatly affects patients' daily life and reduces their quality of life. As an emerging rehabilitation method, brain-machine interface (BMI)-based training can extract brain signals and provide feedback to form a closed-loop rehabilitation, which is currently being studied for functional restoration after stroke. However, there is no reliable medical evidence to support the effect of BMI-based training on upper extremity function after stroke. This review aimed to evaluate the efficacy and safety of BMI-based training for improving upper extremity function after stroke, as well as potential differences in efficacy of different external devices.

Methods

English-language literature published before April 1, 2022, was searched in five electronic databases using search terms including “brain-computer/machine interface”, “stroke” and “upper extremity.” The identified articles were screened, data were extracted, and the methodological quality of the included trials was assessed. Meta-analysis was performed using RevMan 5.4.1 software. The GRADE method was used to assess the quality of the evidence.

Results

A total of 17 studies with 410 post-stroke patients were included. Meta-analysis showed that BMI-based training significantly improved upper extremity motor function [standardized mean difference (SMD) = 0.62; 95% confidence interval (CI) (0.34, 0.90); I2 = 38%; p < 0.0001; n = 385; random-effects model; moderate-quality evidence]. Subgroup meta-analysis indicated that BMI-based training significantly improves upper extremity motor function in both chronic [SMD = 0.68; 95% CI (0.32, 1.03), I2 = 46%; p = 0.0002, random-effects model] and subacute [SMD = 1.11; 95%CI (0.22, 1.99); I2 = 76%; p = 0.01; random-effects model] stroke patients compared with control interventions, and using functional electrical stimulation (FES) [SMD = 1.11; 95% CI (0.67, 1.54); I2 = 11%; p < 0.00001; random-effects model]or visual feedback [SMD = 0.66; 95% CI (0.2, 1.12); I2 = 4%; p = 0.005; random-effects model;] as the feedback devices in BMI training was more effective than using robot. In addition, BMI-based training was more effective in improving patients' activities of daily living (ADL) than control interventions [SMD = 1.12; 95% CI (0.65, 1.60); I2 = 0%; p < 0.00001; n = 80; random-effects model]. There was no statistical difference in the dropout rate and adverse effects between the BMI-based training group and the control group.

Conclusion

BMI-based training improved upper limb motor function and ADL in post-stroke patients. BMI combined with FES or visual feedback may be a better combination for functional recovery than robot. BMI-based trainings are well-tolerated and associated with mild adverse effects.
Two novel heterozygous truncating variants in NR4A2 identified in patients with neurodevelopmental disorder and brief literature review
Authors: Song Xiaozhen , Xu Wuhen , Xiao Man , Lu Yanfen , Lan Xiaoping , Tang Xiaojun , Xu Nanjie , Yu Guangjun , Zhang Hong , Wu Shengnan
Published: August 2022

Pathogenic variants in the nuclear receptor superfamily 4 group A member 2 (NR4A2) cause an autosomal dominant neurodevelopmental disorder with or without seizures. Here, we described two patients presenting with developmental delay, language impairment, and attention-deficit hyperactivity disorder. Trio-based whole exome sequencing revealed two novel heterozygous variants, c.1541-2A > C and c.915C > A, in NR4A2. Both variants were identified as de novo and confirmed by Sanger sequencing. In vitro functional analyses were performed to assess their effects on expression of mRNA or protein. The canonical splicing variant c.1541-2A > C caused aberrant splicing, leading to the retention of intron 7 and a truncated protein due to an early termination codon within intron 7 with decreased protein expression, while the variant c.915C > A was shown to result in a shorter protein with increased expression level unexpectedly. The clinical and genetic characteristics of the previously published patients were briefly reviewed for highlighting the potential link between mutations and phenotypes. Our research further confirms that NR4A2 is a disease-causing gene of neurodevelopmental disorders and suggests alterations in different domains of NR4A2 cause various severity of symptoms.
Fluorine impairs carboxylesterase 1-mediated hydrolysis of T-2 toxin and increases its chondrocyte toxicity
Authors: Jia Yumeng , Shi Sirong , Cheng Bolun , Cheng Shiqiang , Liu Li , Meng Peilin , Yang Xuena , Chu Xiaoge , Wen Yan , Zhang Feng , Guo Xiong
Published: August 2022

Background

T-2 toxin is recognized as one of the high-risk environmental factors for etiology and pathogenesis of Kashin-Beck disease (KBD). Previous evidence indicates decreased serum fluorine level in KBD patients. However, whether fluoride could regulate carboxylesterase 1 (CES1)-mediated T-2 toxin hydrolysis and alter its chondrocyte toxicity remains largely unknown.

Methods

In this study, in vitro hydrolytic kinetics were explored using recombinant human CES1. HPLC-MS/MS was used to quantitative determination of hydrolytic metabolites of T-2 toxin. HepG2 cells were treated with different concentration of sodium fluoride (NaF). qRT-PCR and western blot analysis were used to compare the mRNA and protein expression levels of CES1. C28/I2 cells were treated with T-2 toxin, HT-2 toxin, and neosolaniol (NEO), and then cell viability was determined by MTT assay, cell apoptosis was determined by Annexin V-FITC/PI, Hoechst 33258 staining, and cleaved caspase-3, and cell cycle was monitored by flow cytometry assay, CKD4 and CDK6.

Results

We identified that recombinant human CES1 was involved in T-2 toxin hydrolysis to generate HT-2 toxin, but not NEO, and NaF repressed the formation of HT-2 toxin. Both mRNA and protein expression of CES1 were significantly down-regulated in a dose-dependent manner after NaF treatment in HepG2 cells. Moreover, we evaluated the chondrocyte toxicity of T-2 toxin and its hydrolytic metabolites. Results showed that T-2 toxin induced strongest cell apoptosis, followed by HT-2 toxin and NEO. The decreased the proportion of cells in G0/G1 phase was observed with the descending order of T-2 toxin, HT-2 toxin, and NEO.

Conclusions

This study reveals that CES1 is responsible for the hydrolysis of T-2 toxin, and that fluoride impairs CES1-mediated T-2 toxin detoxification to increase its chondrocyte toxicity. This study provides novel insight into understanding the relationship between fluoride and T-2 toxin in the etiology of KBD.
Hawthorn fruit acid consumption attenuates hyperlipidemia-associated oxidative damage in rats
Authors: Feng Yicheng , Gao Shan , Zhu Ting , Sun Guibo , Zhang Peisen , Huang Yichun , Qu Shuang , Du Xiaomeng , Mou Dehua
Published: August 2022

Context

Hyperlipidemia is a highly prevalent risk factor for atherosclerosis and stroke. The currently available medications used to treat Hyperlipidemia cannot improve its oxidative stress damage. Consumption of hawthorn can regulate blood sugar and blood lipids, and its rich fruit acid is a natural antioxidant that can improve oxidative stress damage.

Objective

The present research aimed to investigate the protective effect of hawthorn fruit acid (HFA) on hyperlipidemia and to determine its potential molecular mechanism.

Materials and methods

Sprague-Dawley rats were fed a high-fat diet (HFD) to induce hyperlipidemia and treated orally with hawthorn fruit acids (HFA). Serum and liver levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD), hydrogen peroxide (CAT), and malondialdehyde (MDA) were measured. Human hepatocellular carcinoma cell lines (HepG2) cells were treated with 0.1 mM oleic acid and HFA (0.125, 0.25 mg/mL), and intracellular TC, TG, HDL-C, SOD, CAT and MDA were measured. Changes in LDLR, HMGCR, Nrf2, HO-1, NQO1 protein and gene expression were analyzed by Western blot and qPCR.

Results

This study found that HFA treatment effectively reduced the level of triglyceride, cholesterol, and glucose, and attenuated hepatic steatosis in rats. Additionally, oxidative stress damage of rats was effectively reduced by treatment with HFA. Western blot and qPCR analysis indicated that HFA treatment inhibited fat accumulation in HepG2 cells by upregulating LDLR and downregulating HMGCR gene expression. HFA inhibits oleic acid (OA)-induced oxidative damage to HepG2 by activating the Nrf2/HO-1 signaling pathway.

Conclusion

HFA administration can provide health benefits by counteracting the effects of hyperlipidemia caused by an HFD in the body, and the underlying mechanism of this event is closely related to the activation of the Nrf2/HO-1 signaling pathway.
Determination of factors associated with serum cholesterol response to dairy fat consumption in overweight adults: Secondary analysis from an RCT
Authors: O'Connor Aileen , Feeney Emma L. , Bhargava Nupur , Noronha Nessa , Gibney Eileen R.
Published: August 2022

Elevated intakes of saturated fatty acids (SFA) can adversely affect serum cholesterol levels. Dairy fat contains ~60% SFA, prompting healthy eating guidelines to recommend low-fat dairy. Physiological, and environmental factors influence inter-individual variance in response to food consumption. Evidence exploring the dairy matrix has differing effects of dairy fat consumption on serum cholesterol levels when consumed in the form of cheese. The extent of this variability and determinants of response to dairy fat are currently unknown. The objective of this study was to determine factors associated with lipid metabolism response to a dairy fat intervention, with a focus on serum cholesterol. A 6-week randomized parallel intervention trial was carried out in healthy volunteers (≥50 years, BMI ≥25 kg/m2). Participants (n = 104) consumed ~40 g dairy fat daily in addition to their usual diet, in 1 of 3 forms: butter, cheese, or reduced-fat cheese and butter. For this analysis, “response” was based on the percentage (%) change in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) from pre- to post-intervention. Participants were divided into tertiles for each lipid response. The upper and lower tertiles were used to categorize participants as “responders” and “non-responders.” For TC and LDL-c, response was classified as a decrease, whereas “response” was defined as an increase for HDL-c. Clinical response was also considered, by calculating pre- and post-intervention prevalence of those meeting target levels of cholesterol recommendations. Participants demonstrating the largest % decrease (Tertile 1; “responders”) in TC had significantly higher levels of TC and HDL-c, at baseline, and lower levels of triglycerides (TAGs) compared to those in tertile 3 (i.e., TC non-responders). Those with the largest % decrease in LDL-c (Tertile 1: LDL-c responders) had higher baseline levels of LDL-c and lower levels of TAGs. Multiple regression analysis revealed that the % change in TC and LDL-c was associated with baseline TC, TAG, body weight and high-sensitivity C-reactive protein (hsCRP; P < 0.05). Previous work has demonstrated the dairy food matrix affects lipid response to dairy consumption. This study suggests that phenotypic differences may also influence response to dairy fat in overweight individuals.