bluuebunny/crossref_metadata_2025 huggingface dataset:
The Protein Losses of Three Major Cereal Crops by Natural Disasters in China From 1988 to 2020
Authors: Huang Dongmei , Chen Yifei , Chen Pinghua , Zheng Qingchang
Published: April 2022

Natural disasters have a major detrimental impact on agricultural production. In recent decades, China has experienced more frequent natural disasters as a result of climate change. Although the spatial and temporal changes in natural disasters for individual catastrophic activities are well understood, the impact of several disasters on cereal crop productivity and subsequent quality loss remains unknown. Furthermore, due to the key significance of cereal in China’s daily diet, a decrease in cereal quality, namely protein, will have a detrimental effect on nutrient supply. To better understand the relationship between natural disasters and cereal crop food quality in China, we used province-level data from 1988 to 2020 to construct a dataset of natural disasters, crop production, and protein contents of cereal crops (rice, wheat, and maize). Our findings suggest that activities in areas affected by natural disasters have decreased dramatically since the 21st century, with changes in areas affected by such disasters varying by province. Between 1988 and 2020, the total protein losses from grain and straw harvests due to natural disasters were 11.93 and 391.27 million tons. Overall, the annual mean total protein loss in maize, rice, and wheat was 4,982.26, 5,055.4, and 4,200.34 thousand tons, respectively. Although was responsible for half of the protein losses in more than half of the provinces. Drought and floods accounted for 80% of the total area affected by all natural disasters.
Pathway-Based Analysis Revealed the Role of Keap1-Nrf2 Pathway and PI3K-Akt Pathway in Chinese Esophageal Squamous Cell Carcinoma Patients With Definitive Chemoradiotherapy
Authors: Dai Honghai , Wei Yanjun , Liu Yunxia , Liu Jingwen , Yu Ruoying , Zhang Junli , Pang Jiaohui , Shao Yang , Li Qiang , Yang Zhe
Published: April 2022

Esophageal squamous cell carcinoma (ESCC) is the major type of EC in China. Chemoradiotherapy is a standard definitive treatment for early-stage EC and significantly improves local control and overall survival for late-stage patients. However, chemoradiotherapy resistance, which limits therapeutic efficacy and treatment-induced toxicity, is still a leading problem for treatment break. To optimize the selection of ESCC patients for chemoradiotherapy, we retrospectively analyzed the clinical features and genome landscape of a Chinese ESCC cohort of 58 patients. TP53 was the most frequent mutation gene, followed by NOTCH1. Frequently, copy number variants were found in MCL1 (24/58, 41.4%), FGF19 (23/58, 39.7%), CCND1 (22/58, 37.9%), and MYC (20/58, 34.5%). YAP1 and SOX2 amplifications were mutually exclusive in this cohort. Using univariate and multivariate analyses, the YAP1 variant and BRIP1 mutant were identified as adverse factors for OS. Patients with PI3K-Akt pathway alterations displayed longer PFS and OS than patients with an intact PI3K-Akt pathway. On the contrary, two patients with Keap1-Nrf2 pathway alterations displayed significantly shortened PFS and OS, which may be associated with dCRT resistance. Our data highlighted the prognostic value of aberrant cancer pathways in ESCC patients, which may provide guidance for better chemoradiotherapy management.
Integrated Analysis of Angiogenesis Related lncRNA-miRNA-mRNA in Patients With Coronary Chronic Total Occlusion Disease
Authors: Gao Wei , Zhang Jianhui , Wu Runda , Yuan Jie , Ge Junbo
Published: April 2022

Background: Coronary chronic total occlusion (CTO) disease is common and its specific characteristic is collateral formation. The Integrated analysis of angiogenesis related lncRNA-miRNA-mRNA network remains unclear and might provide target for future studies.

Methods: A total of five coronary artery disease (control group) and five CTO (CTO group) patients were selected for deep RNA and miRNA sequencing. The expression profiles of lncRNAs, mRNAs circRNA and miRNAs were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were then performed. The expression of a 14q32 miRNA gene cluster, including miRNA-494, miRNA-495 and miRNA-329, were selected to be determined in another larger patient cohort. Analysis of the lncRNA-miRNA495-mRNA network was constructed to find potential targets for future studies.

Results: A total of 871 lncRNAs, 1,080 mRNAs, 138 circRNAs and 56 miRNAs were determined as differentially expressed (DE) in CTO patients compared with control patients. GO and KEGG analyses revealed that the top terms included MAPK signaling pathway, HIF-1 signaling pathway, EGFR tyrosine kinase inhibitor resistance, embryonic organ development, wound healing, MAPK signaling pathway and JAK-STAT signaling pathway, which are related to angiogenesis. The expression of miRNA-494, miRNA-495 and miRNA-329 were all significantly down-regulated in CTO patients and they were confirmed to be down-regulated in another cohort of 68 patients. Then we divided the CTO patients into two groups according to CC grade (poor CC group, CC = 0 or one; good CC group, CC = 2). MiRNA-494, miRNA-495 and miRNA-329 were found to be down-regulated in good CC group compared with poor CC group. Analysis of the lncRNA-miRNA495-mRNA network showed 3 DE lncRNA sponges (NONHSAG008675, NONHSAG020957 and NONHSAG010989), 4 DE lncRNA targets (NONHSAT079547.2, NONHSAT081776.2, NONHSAT148555.1 and NONHSAT150928.1) and 2 DE mRNA targets (RAD54L2 and ZC3H4) of miRNA495.

Conclusion: This study revealed that the lncRNA-miRNA-mRNA network might play a critical role in angiogenesis in CTO patients.
Molecular Portrait of GISTs Associated With Clinicopathological Features: A Retrospective Study With Molecular Analysis by a Custom 9-Gene Targeted Next-Generation Sequencing Panel
Authors: Qian Haoran , Yan Na , Hu Xiaotong , Jiang Junchang , Cao Zhengzheng , Shen Dan
Published: April 2022

Objectives: The study aims to investigate genetic characterization of molecular targets and clinicopathological features with gastrointestinal stromal tumors based on targeted next-generation sequencing.

Materials and Methods: We selected 106 patients with GISTs from Sir Run Run Shaw Hospital between July 2019 and March 2021. FFPE samples and paired blood samples were obtained from these patients who underwent excision of the tumor. A customized targeted-NGS panel of nine GIST-associated genes was designed to detect variants in the coding regions and the splicing sites of these genes.

Results: In total, 106 patients with a GIST were included in the study which presented with various molecular driver alterations in this study. KIT mutations occurred most often in GISTs (94/106, 95.92%), followed by point mutations in PDGFRA. KIT or PDGFRA mutations were detected to be mutually exclusive in the GIST. A total of eight patients with wide-type KIT/PDGFRA were characterized as WT-GISTs, according to clinical diagnosis which included six quadruple-WT GISTs, 1 BRAF-mutant, and 1 NF1-mutant GIST. In KIT exon 11, the most common mutation type was the codon Mutation (in-frame deletion or indels), whereas the missense mutation was the dominant type in KIT exon 13 and KIT exon 17. All variations in KIT exon 11 observed in this study were concentrated at a certain position of codon 550 to codon 576. Mutation in KIT exon 9 was mostly located at codon 502–503. Two germline pathogenic mutations were detected: NF1-R681* and KRAS-T58I. NF1-L591P was a germline mutation to be identified for the first time and is not recorded in the database. The frequency of driving mutations differed between the primary anatomical site in the GIST (p = 0.0206). KIT exon 11 mutants had a lower proliferation index of Ki67 (68.66%,≤5%), while 50.00% of KIT exon 9 mutants had the Ki67 status greater than 10%.

Conclusion: The occurrence and development of a GIST is driven by different molecular variations. Resistance to TKIs arises mainly with resistance mutations in KIT or PDGFRA when they are the primary drivers. Targeted NGS can simultaneously and efficiently detect nine GIST-related gene mutations and provide reference for clinicians’ individualized diagnosis and treatment. Our results have important implications for clinical management.
Case Report: Rabies Vaccine-Induced Thrombotic Thrombocytopenic Purpura in a Patient With Systemic Lupus Erythematosus
Authors: Cui Yanming , Wei Jianbo , Peng Xiang
Published: April 2022

For patients with autoimmune diseases, vaccination is controversial. The use of vaccination in patients with autoimmune diseases is controversial. There are many reports of secondary thrombotic thrombocytopenic purpura cases after various vaccinations. Thrombotic thrombocytopenic purpura is a rare thrombotic microangiopathy characterized by microvascular pathological hemolytic anemia, severe thrombocytopenia, and ischemic organ damage with a very high fatality rate. We report a case of thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus after rabies vaccination. She developed gastrointestinal bleeding nearly a month after the vaccination. Laboratory tests confirmed a severe deficiency of ADAMTS13 and the presence of ADAMTS13 autoantibodies. Through early identification of thrombotic thrombocytopenic purpura, immunosuppressive therapy, and plasma exchange treatment, the patient was saved from danger. This case suggests that attenuated vaccines may also have unexpected adverse effects in patients with long-term use of immunosuppressive drugs and autoimmune diseases. To our knowledge, this is the first case report of thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus secondary to rabies vaccination.
Efficacy of Bioenergetic Health Index to Predict Delirium After Major Abdominal Surgery in Elderly Patients: A Protocol for a Prospective Observational Cohort Study
Authors: Zhao Yi , Liu Juan , Ou Mengchan , Hao Xuechao
Published: April 2022

Introduction

Postoperative delirium (POD) is a common disorder following surgery, which seriously threatens the quality of patients’ life, especially the older people. The multifactorial manner of this syndrome has made it hard to define an ideal method to predict individual risk. Mitochondria play a key role in the process of POD, which include inflammatory on the brain caused by surgeries and aging related neurodegeneration. As BHI (Bioenergetic Health Index) could be calculated in cells isolated from an individual’s blood to represent the patient’s composite mitochondrial statue, we hypotheses that HBI of monocytes isolated from individual’s peripheral blood can predict POD after major non-cardiac surgery in elderly patients.

Methods and Analysis

This is a prospective, observational single-blinded study in a single center. 124 patients aged ≥ 65 years and scheduled for major abdominal surgery (>3 h) under general anesthesia will be enrolled. Preoperative and postoperative delirium will be assessed by trained members using Confusion Assessment Method (CAM). For patients unable to speak in the ICU after the surgery, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) will be used. All patients will undergo venous blood sampling twice to measure BHI (1–2 tubes, 5 ml/tube): before the surgery and 1 day after surgery in wards. After discharge, patients will be contacted by telephone 30 days after surgery to confirm the incidence of post-discharge complications. The severity of complications will be categorized as mild, moderate, severe or fatal using a modified Clavien-Dindo Classification (CDC) scheme.

Ethics and Dissemination

The study has been approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University, Sichuan, China (Chairperson Prof Shaolin Deng, No. 2021-502). Study data will be disseminated in manuscripts submitted to peer-reviewed medical journals as well as in abstracts submitted to congresses.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [ChiCTR2100047554].
Cabotegravir, the Long-Acting Integrase Strand Transfer Inhibitor, Potently Inhibits Human T-Cell Lymphotropic Virus Type 1 Transmission in vitro
Authors: Schneiderman Bethany S. , Barski Michal S. , Maertens Goedele N.
Published: April 2022

Human T-cell lymphotropic virus type 1 (HTLV-1) is a deltaretrovirus most prevalent in southwestern Japan, sub-Saharan Africa, Australia, South America, and the Caribbean. Latest figures approximate 10 million people worldwide to be infected with HTLV-1. This is likely a significant underestimation due to lack of screening in endemic areas and absence of seroconversion symptoms. The two primary diseases associated with HTLV-1 infection are adult T cell leukaemia-lymphoma, a malignant and, sometimes, aggressive cancer; and HTLV-1 associated myelopathy/tropical spastic paraparesis, a debilitating neurological degenerative disease. Unfortunately, despite the poor prognosis, there is currently no effective treatment for HTLV-1 infection. We previously showed that integrase strand transfer inhibitors (INSTIs) clinically used for human immunodeficiency virus type 1 (HIV-1) prophylaxis and treatment are also effective against HTLV-1 transmission in vitro. In 2021 a new INSTI, cabotegravir, was approved by the FDA for HIV-1 treatment. We thus set out to evaluate its efficacy against HTLV-1 infection in vitro. Strand transfer assays performed using recombinant HTLV-1 integrase treated with increasing concentrations of cabotegravir, effectively inhibited strand transfer activity, displaying an IC50 of 77.8 ± 22.4 nM. Furthermore, cabotegravir blocked HTLV-1 transmission in tissue culture; we determined an EC50 of 0.56 ± 0.26 nM, similar to bictegravir. Alu-PCR confirmed the block in integration. Thus, there are four INSTIs and one reverse transcriptase inhibitor approved by the FDA for HIV-1 treatment, that potently block HTLV-1 infection in vitro. This should strongly encourage the establishment of a new standard of HTLV-1 treatment – particularly for pre-exposure prophylaxis and prevention of mother-to-child transmission.
Regulatory Authority Evaluation of the Effectiveness and Efficiency of the ZaZiBoNa Collaborative Medicines Registration Initiative: The Way Forward
Authors: Sithole Tariro , Mahlangu Gugu , Walker Stuart , Salek Sam
Published: April 2022

Introduction

ZaZiBoNa, the work-sharing initiative in the Southern African Development Community (SADC) that has been in operation for 8 years has successfully assessed over 300 dossiers/applications, with an overall median time to recommendation of 12 months. All 16 SADC countries participate in the initiative as either active or non-active members. While the successes of ZaZiBoNa are evident, some challenges still exist. The aim of this study was to solicit the views of the participating authorities on the effectiveness and efficiency of the current operating model of the ZaZiBoNa initiative.

Methods

Data were collected in 2021 using the Process, Effectiveness and Efficiency Rating (PEER) questionnaire developed by the authors. The questionnaire was completed by the focal person in each country and approved by the head of the authority.

Results

ZaZiBoNa serves as a platform for work sharing, information exchange, capacity building and harmonisation of registration requirements. One of the benefits to regulators has been the improvement in the capacity to conduct assessments. Manufacturers have benefited from compiling one package (modules 2–5) for the initial submission as well as a single response package to the consolidated list of questions, which saves time and resources. Respondents were of the view that patients have benefited as the ZaZiBoNa has contributed to an improved availability and accessibility to quality-assured medicines. Some of the challenges identified were the inadequacy of resources and differences in time to the implementation of ZaZiBoNa recommendations by the individual countries. The establishment of a regional unit hosted in one of the member countries to enable centralised submission and coordination was identified as the best strategy to improve the effectiveness and efficiency of the initiative in the interim, with the long-term goal being the establishment of a regional medicines authority.

Conclusion

The study identified the strengths of the ZaZiBoNa initiative as well as the opportunities for improvement. The recommendations made would further strengthen this initiative.
Evaluation of Virucidal Efficacy of Human Norovirus Using Combined Sprayed Slightly Acidic Electrolyzed Water and Ultraviolet C-Light-Emitting Diode Irradiation Treatment Based on Optimized Capture Assay for Quantitative RT-qPCR
Authors: Song Hyeyeon , Dang Yun-Mi , Ha Sanghyun , Ha Ji-Hyoung
Published: April 2022

Slightly acidic electrolyzed water (SAEW), an effective non-thermal virucidal treatment, is used widely to prevent infectious viral cross-contamination. Surface disinfection technologies using ultraviolet C-light-emitting diode (UVC-LED) irradiation have recently attracted considerable attention. The SAEW sprayer technique is an efficient approach to preventing the spread of infectious viral pathogens in the public healthcare sector. Therefore, we investigated a small-scale system comprising sprayed SAEW disinfection combined with UVC-LED irradiation to inactivate the human norovirus (HuNoV) in the environment. A stainless-steel surface was inoculated with a HuNoV genogroup II genotype 4 (GII.4) to achieve maximum reduction values of 3.21 log10 genomic copies. For optimal disinfection conditions, the response surface methodology based on the Box–Behnken design revealed that the specific treatment conditions for inactivation of HuNoV GII.4 were an SAEW droplet volume of 180 μL, 30 ppm available chlorine concentration of SAEW, and a UVC-LED exposure dose of 2 mJ/cm2. The results indicate that the combined disinfection treatment could efficiently prevent the spread of HuNoVs in environment. Furthermore, the quadratic polynomial equations of the 3-D response surface can be employed to predict the effects of combined disinfection treatment on HuNoV contamination on environmental surfaces. Therefore, sprayed SAEW disinfection combined with UVC-LED irradiation proposed in this study may offer insights for designing optimal control strategies and techniques to prevent the transmission of infectious diseases, particularly HuNoV.
Enhanced Biosynthesis of Fatty Acids Contributes to Ciprofloxacin Resistance in Pseudomonas aeruginosa
Authors: Su Yu-bin , Tang Xi-kang , Zhu Ling-ping , Yang Ke-xin , Pan Li , Li Hui , Chen Zhuang-gui
Published: April 2022

Antibiotic-resistant Pseudomonas aeruginosa is insensitive to antibiotics and difficult to deal with. An understanding of the resistance mechanisms is required for the control of the pathogen. In this study, gas chromatography–mass spectrometer (GC-MS)-based metabolomics was performed to identify differential metabolomes in ciprofloxacin (CIP)-resistant P. aeruginosa strains that originated from P. aeruginosa ATCC 27853 and had minimum inhibitory concentrations (MICs) that were 16-, 64-, and 128-fold (PA-R16CIP, PA-R64CIP, and PA-R128CIP, respectively) higher than the original value, compared to CIP-sensitive P. aeruginosa (PA-S). Upregulation of fatty acid biosynthesis forms a characteristic feature of the CIP-resistant metabolomes and fatty acid metabolome, which was supported by elevated gene expression and enzymatic activity in the metabolic pathway. The fatty acid synthase inhibitor triclosan potentiates CIP to kill PA-R128CIP and clinically multidrug-resistant P. aeruginosa strains. The potentiated killing was companied with reduced gene expression and enzymatic activity and the returned abundance of fatty acids in the metabolic pathway. Consistently, membrane permeability was reduced in the PA-R and clinically multidrug-resistant P. aeruginosa strains, which were reverted by triclosan. Triclosan also stimulated the uptake of CIP. These findings highlight the importance of the elevated biosynthesis of fatty acids in the CIP resistance of P. aeruginosa and provide a target pathway for combating CIP-resistant P. aeruginosa.
Exploring the Extent of Phosphorus and Heavy Metal Uptake by Single Cells of Saccharomyces cerevisiae and Their Effects on Intrinsic Elements by SC-ICP-TOF-MS
Authors: Qin Wen , Stärk Hans-Joachim , Müller Susann , Reemtsma Thorsten
Published: April 2022

The effect of six heavy metals, namely, silver (Ag), lead (Pb), palladium (Pd), copper (Cu), nickel (Ni), and chromium (Cr), on phosphorus (P) uptake by yeast was investigated by single-cell analysis using inductively coupled plasma time-of-flight mass spectrometry (SC-ICP-TOF-MS). It was found that the P content in cells with 1.55 g L–1 P feeding after P starvation was increased by ∼70% compared to control cells. Heavy metals at 10 ppm, except Cu, had a negative impact on P accumulation by cells. Pd reduced the P content by 26% in single cells compared to control cells. Metal uptake was strongest for Ag and Pd (0.7 × 10–12 L cell–1) and weakest for Cr (0.05 × 10–12 L cell–1). Exposure to Cr markedly reduced (−50%) Mg in cells and had the greatest impact on the intrinsic element composition. The SC-ICP-TOF-MS shows the diversity of elemental content in single cells: for example, the P content under standard conditions varied between 12.4 and 890 fg cell–1. This technique allows studying both the uptake of elements and sublethal effects on physiology at a single-cell level.
Triazoles and Their Derivatives: Chemistry, Synthesis, and Therapeutic Applications
Authors: Matin Mohammed M. , Matin Priyanka , Rahman Md. Rezaur , Ben Hadda Taibi , Almalki Faisal A. , Mahmud Shafi , Ghoneim Mohammed M. , Alruwaily Maha , Alshehri Sultan
Published: April 2022

Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications. Structurally, there are two types of five-membered triazoles: 1,2,3-triazole and 1,2,4-triazole. Due to the structural characteristics, both 1,2,3- and 1,2,4-triazoles are able to accommodate a broad range of substituents (electrophiles and nucleophiles) around the core structures and pave the way for the construction of diverse novel bioactive molecules. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities. These are also important in organocatalysis, agrochemicals, and materials science. Thus, they have a broad range of therapeutic applications with ever-widening future scope across scientific disciplines. However, adverse events such as hepatotoxicity and hormonal problems lead to a careful revision of the azole family to obtain higher efficacy with minimum side effects. This review focuses on the structural features, synthesis, and notable therapeutic applications of triazoles and related compounds.
Structural Basis for Allostery in PLP-dependent Enzymes
Authors: Tran Jenny U. , Brown Breann L.
Published: April 2022

Pyridoxal 5′-phosphate (PLP)-dependent enzymes are found ubiquitously in nature and are involved in a variety of biological pathways, from natural product synthesis to amino acid and glucose metabolism. The first structure of a PLP-dependent enzyme was reported over 40 years ago, and since that time, there is a steady wealth of structural and functional information revealed for a wide array of these enzymes. A functional mechanism that is gaining more appreciation due to its relevance in drug design is that of protein allostery, where binding of a protein or ligand at a distal site influences the structure, organization, and function at the active site. Here, we present a review of current structure-based mechanisms of allostery for select members of each PLP-dependent enzyme family. Knowledge of these mechanisms may have a larger potential for identifying key similarities and differences among enzyme families that can eventually be exploited for therapeutic development.
Effects of Repetitive Transcranial Magnetic Stimulation on Cerebellar Metabolism in Patients With Spinocerebellar Ataxia Type 3
Authors: Chen Xin-Yuan , Lian Yan-Hua , Liu Xia-Hua , Sikandar Arif , Li Meng-Cheng , Xu Hao-Ling , Hu Jian-Ping , Chen Qun-Lin , Gan Shi-Rui
Published: April 2022

Background

Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant hereditary ataxia, and, thus far, effective treatment remains low. Repetitive transcranial magnetic stimulation (rTMS) can improve the symptoms of spinal cerebellar ataxia, but the mechanism is unclear; in addition, whether any improvement in the symptoms is related to cerebellar metabolism has not yet been investigated. Therefore, the purpose of this study was to investigate the effects of low-frequency rTMS on local cerebellar metabolism in patients with SCA3 and the relationship between the improvement in the symptoms and cerebellar metabolism.

Methods

A double-blind, prospective, randomized, sham-controlled trial was carried out among 18 SCA3 patients. The participants were randomly assigned to the real stimulation group (n = 9) or sham stimulation group (n = 9). Each participant in both the groups underwent 30 min of 1 Hz rTMS stimulation (a total of 900 pulses), differing only in terms of stimulator placement, for 15 consecutive days. To separately compare pre- and post-stimulation data (magnetic resonance spectroscopy (MRS) data and the International Cooperative Ataxia Rating Scale (ICARS) score) in the real and sham groups, paired-sample t-tests and Wilcoxon’s signed-rank tests were used in the analyses. The differences in the ICARS and MRS data between the two groups were analyzed with independent t-tests and covariance. To explore the association between the changes in the concentration of cerebellar metabolism and ICARS, we applied Pearson’s correlation analysis.

Results

After 15 days of treatment, the ICARS scores significantly decreased in both the groups, while the decrease was more significant in the real stimulation group compared to the sham stimulation group (p < 0.001). The analysis of covariance further confirmed that the total ICARS scores decreased more dramatically in the real stimulation group after treatment compared to the sham stimulation group (F = 31.239, p < 0.001). The values of NAA/Cr and Cho/Cr in the cerebellar vermis, bilateral dentate nucleus, and bilateral cerebellar hemisphere increased significantly in the real stimulation group (p < 0.05), but no significant differences were found in the sham stimulation group (p > 0.05). The analysis of covariance also confirmed the greater change in the real stimulation group. This study also demonstrated that there was a negative correlation between NAA/Cr in the right cerebellar hemisphere and ICARS in the real stimulation group (r = − 0.831, p = 0.02).

Conclusion

The treatment with rTMS over the cerebellum was found to induce changes in the cerebellar local metabolism and microenvironment in the SCA3 patients. The alterations may contribute to the improvement of the symptoms of ataxia in SCA3 patients.
The Value of Patient Registries to Advance Basic and Translational Research in the Area of Traumatic Brain Injury
Authors: Duff Melissa C. , Morrow Emily L. , Edwards Malcolm , McCurdy Ryan , Clough Sharice , Patel Nirav , Walsh Kimberly , Covington Natalie V.
Published: April 2022

The number of individuals affected by traumatic brain injury (TBI) is growing globally. TBIs may cause a range of physical, cognitive, and psychiatric deficits that can negatively impact employment, academic attainment, community independence, and interpersonal relationships. Although there has been a significant decrease in the number of injury related deaths over the past several decades, there has been no corresponding reduction in injury related disability over the same time period. We propose that patient registries with large, representative samples and rich multidimensional and longitudinal data have tremendous value in advancing basic and translational research and in capturing, characterizing, and predicting individual differences in deficit profile and outcomes. Patient registries, together with recent theoretical and methodological advances in analytic approaches and neuroscience, provide powerful tools for brain injury research and for leveraging the heterogeneity that has traditionally been cited as a barrier inhibiting progress in treatment research and clinical practice. We report on our experiences, and challenges, in developing and maintaining our own patient registry. We conclude by pointing to some future opportunities for discovery that are afforded by a registry model.
Self-Concern Across Scales: A Biologically Inspired Direction for Embodied Artificial Intelligence
Authors: Sims Matthew
Published: April 2022

Intelligence in current AI research is measured according to designer-assigned tasks that lack any relevance for an agent itself. As such, tasks and their evaluation reveal a lot more about our intelligence than the possible intelligence of agents that we design and evaluate. As a possible first step in remedying this, this article introduces the notion of “self-concern,” a property of a complex system that describes its tendency to bring about states that are compatible with its continued self-maintenance. Self-concern, as argued, is the foundation of the kind of basic intelligence found across all biological systems, because it reflects any such system's existential task of continued viability. This article aims to cautiously progress a few steps closer to a better understanding of some necessary organisational conditions that are central to self-concern in biological systems. By emulating these conditions in embodied AI, perhaps something like genuine self-concern can be implemented in machines, bringing AI one step closer to its original goal of emulating human-like intelligence.
Assessment of Anxiety in Patients With Epilepsy: A Literature Review
Authors: Rauh Raphael , Schulze-Bonhage Andreas , Metternich Birgitta
Published: April 2022

Objective

Approximately 20% of people with epilepsy (PWE) suffer from anxiety. These fears are quite diverse and may manifest periictally or interictally, be part of the seizure's semiology, or an expression of reactive psychological distress from seizures themselves. Our review addresses the question of what screening tools are used in clinical care and epileptological research to capture the complexity of epilepsy-specific anxieties.

Method

On 2021/11/11, we entered a search string in PubMed that covered our research interest as completely as possible. We also screened the bibliographies of our findings and followed PubMed's recommendations. From the assessments we found in the included studies, we extracted domains that represent the range of manifestations of anxiety, in order to compare the tools and to discuss to what extent they are suitable for assessing epilepsy-specific anxieties.

Results

We screened 1,621 abstracts. In total, we identified 24 different anxiety assessments. In addition to the psychiatric assessments in use, we found 7 tools that were designed to assess epilepsy-specific anxieties. The latter focus on different aspects of epilepsy-specific anxieties. In some cases, the conceptual frameworks are not sufficiently transparent or divergent.

Conclusion

Because a diagnosis of epilepsy can result in, or seizures may appear as, anxiety, it is important to better understand this psychological burden and address it therapeutically, if necessary. There is a need for screening tools that integrate specific points of a variety of assessments, so as to cover the broad range of epilepsy-specific fears. None of the assessments we found meets this integrative perspective. At the same time, the appropriate design of such a required tool presupposes a conceptual framework of what should be considered as epilepsy-specific anxiety.
Fundus Changes Evaluated by OCTA in Patients With Cerebral Small Vessel Disease and Their Correlations: A Cross-Sectional Study
Authors: Fu Wang , Zhou Xiaoyu , Wang Minli , Li Ping , Hou Jingjing , Gao Peng , Wang Jue
Published: April 2022

Objective

To detect fundus changes in patients with cerebral small vessel disease (CSVD) using optical coherence tomography angiography (OCTA) and to investigate the correlations between CSVD and fundus changes.

Methods

From January 2019 to January 2020, patients diagnosed with CSVD by magnetic resonance imaging (MRI) were enrolled in our study and received fundus examinations using OCTA. CSVD was defined as white matter hyperintensities, enlarged perivascular spaces, lacunes, or microbleeds on MRI. OCTA parameters included foveal avascular zone areas, retinal nerve fiber layer thickness, and capillary densities of the superficial retinal capillary plexuses, deep retinal capillary plexuses, and the radial peripapillary capillary network of the disc. Univariate and multivariate logistic regression analyses were performed to explore the correlation between CSVD and fundus changes.

Results

A total of 115 patients (40% male) were enrolled and analyzed, and the mean age was 65.11 ± 11.23 years. After multivariate logistic regression analysis, the radial peripapillary capillary network density was negatively correlated with severity of deep white matter lesions (OR: 0.909; 95% CI: 0.828–0.998; p = 0.046) and perivascular spaces (OR: 0.881; 95% CI: 0.779–0.995; p = 0.041). Parafoveal vessel densities of the superficial retinal capillary plexuses were independently correlated with lacunes (OR: 0.889; 95% CI: 0.817–0.967; p = 0.006).

Conclusion

OCTA parameters were correlated with CSVD, indicating that OCTA is a potential method for CSVD screening.
An Optimal Animal Model of Ischemic Stroke Established by Digital Subtraction Angiography-Guided Autologous Thrombi in Cynomolgus Monkeys
Authors: Ye Juan , Shang Hailong , Du Hongdi , Cao Ying , Hua Lei , Zhu Feng , Liu Wei , Wang Ying , Chen Siyu , Qiu Zhifu , Shen Hailin
Published: April 2022

Objective

Ischemic stroke seriously threatens human health, characterized by the high rates of incidence, disability, and death. Developing a reliable animal model that mimics most of the features of stroke is critical for pathological studies and clinical research. In this study, we aimed to establish and examine a model of middle cerebral artery occlusion (MCAO) guided by digital subtraction angiography (DSA) in cynomolgus monkeys.

Materials and Methods

In this study, 15 adult male cynomolgus monkeys were enrolled. Under the guidance of DSA, a MCAO model was established by injecting an autologous venous clot into the middle cerebral artery (MCA) via femoral artery catheter. Thrombolytic therapy with alteplase (rt-PA) was given to eight of these monkeys at 3 h after the occlusion. Blood test and imaging examination, such as computed tomography angiography (CTA), CT perfusion (CTP), brain magnetic resonance imaging (MRI), and brain magnetic resonance angiography (MRA), were performed after the operation to identify the post-infarction changes. The behavioral performance of cynomolgus monkeys was continuously observed for 7 days after operation. The animals were eunthanized on the 8th day after operation, and then the brain tissues of monkeys were taken for triphenyltetrazolium chloride (TTC) staining.

Results

Among the 15 cynomolgus monkeys, 12 of them were successfully modeled, as confirmed by the imaging findings and staining assessment. One monkey died of brain hernia resulted from intracranial hemorrhage confirmed by necropsy. DSA, CTA, and MRA indicated the presence of an arterial occlusion. CTP and MRI showed acute focal cerebral ischemia. TTC staining revealed infarct lesions formed in the brain tissues.

Conclusion

Our study may provide an optimal non-human primate model for an in-depth study of the pathogenesis and treatment of focal cerebral ischemia.
Influenza A H3N2-Associated Meningoencephalitis in an Older Adult With Viral RNA in Cerebrospinal Fluid: Case Report
Authors: Dou Yu-chao , Li Yu-qing
Published: April 2022

Influenza-associated encephalopathy (IAE) is most frequently observed in young children, but less reported in adults. Diagnosis of IAE is difficult, as clinical presentations vary significantly and the influenza virus is rarely detected in cerebrospinal fluid (CSF). Herein, we described the case of an older adult presenting with acute meningoencephalitis due to an influenza A (H3N2) infection and the influenza A (H3N2) RNA is detected in cerebrospinal fluid. To the best of our knowledge, this is infrequently reported in the literature. We emphasize that, in adults presenting with acute viral encephalitis, clinicians should consider an influenza infection as part of the differential diagnosis and that metagenomic next-generation sequencing of CSF for IAE may help establish an accurate diagnosis. It must be emphasized that the administration of steroids in a timely manner following the onset of symptoms may yield a better outcome in patients.
The Complex Relationship Between Cooling Parameters and Neuroprotection in a Model of Selective Hypothermia
Authors: Mattingly Thomas K. , McDavid Andrew , Wolf Amparo , Lieber Glen , Solar Ronald , Lee Donald , Lownie Stephen P.
Published: April 2022

Background

Hypothermia remains the best studied neuroprotectant. Despite extensive positive large and small animal data, side effects continue to limit human applications. Selective hypothermia is an efficient way of applying neuroprotection to the brain without the systemic complications of global hypothermia. However, optimal depth and duration of therapeutic hypothermia are still unknown. We analyzed a large animal cohort study of selective hypothermia for statistical relationships between depth or duration of hypothermia and the final stroke volume.

Methods

A cohort of 30 swine stroke subjects provided the dataset for normothermic and selective hypothermic animals. Hypothermic parameters including duration, temperature nadir, and an Area Under the Curve measurement for 34 and 30°C were correlated with the final infarct volumes measured by MRI and histology.

Results

Between group comparisons continue to demonstrate a reduction in infarct volume with selective hypothermia. Histologically-derived infarct volumes were 1.2 mm3 smaller in hypothermia-treated pigs (P = 0.04) and showed a similar, but non-significant reduction in MRI (P = 0.15). However, within the selective hypothermia group, more intense cooling, as measured through increased AUC 34 and decreased temperature nadir was associated with larger infarct proportions by MRI [Pearson's r = 0.48 (p = 0.05) and r = −0.59 (p = 0.01), respectively]. Reevaluation of the entire cohort with quadratic regression demonstrated a U-shaped pattern, wherein the average infarct proportion was minimized at 515 degree-minutes (AUC34) of cooling, and increased thereafter. In a single case of direct brain tissue oxygen monitoring during selective hypothermia, brain tissue oxygen strongly correlated with brain temperature reduction over the course of selective hypothermia to 23°C.

Conclusions

In a large animal model of selective hypothermia applied to focal ischemia, there is a non-monotone relationship between duration and depth of hypothermia and stroke volume reduction. This suggests a limit to depth or duration of selective hypothermia for optimal neuroprotection. Further research is required to delineate more precise depth and duration limits for selective hypothermia.
Impulsivity Moderates the Effect of Neurofeedback Training on the Contingent Negative Variation in Autism Spectrum Disorder
Authors: Prillinger Karin , Radev Stefan T. , Doganay Kamer , Poustka Luise , Konicar Lilian
Published: April 2022

Background

The contingent negative variation (CNV) is a well-studied indicator of attention- and expectancy-related processes in the human brain. An abnormal CNV amplitude has been found in diverse neurodevelopmental psychiatric disorders. However, its role as a potential biomarker of successful clinical interventions in autism spectrum disorder (ASD) remains unclear.

Methods

In this randomized controlled trial, we investigated how the CNV changes following an intensive neurofeedback training. Therefore, twenty-one adolescents with ASD underwent 24 sessions of slow cortical potential (SCP) neurofeedback training. Twenty additional adolescents with ASD formed a control group and received treatment as usual. CNV waveforms were obtained from a continuous performance test (CPT), which all adolescents performed before and after the corresponding 3-month long training period. In order to utilize all available neural time series, trial-based area under the curve values for all four electroencephalogram (EEG) channels were analyzed with a hierarchical Bayesian model. In addition, the model included impulsivity, inattention, and hyperactivity as potential moderators of change in CNV.

Results

Our model implies that impulsivity moderates the effects of neurofeedback training on CNV depending on group. In the control group, the average CNV amplitude decreased or did not change after treatment as usual. In the experimental group, the CNV changed depending on the severity of comorbid impulsivity symptoms. The average CNV amplitude of participants with low impulsivity scores decreased markedly, whereas the average CNV amplitude of participants with high impulsivity increased.

Conclusion

The degree of impulsivity seems to play a crucial role in the changeability of the CNV following an intensive neurofeedback training. Therefore, comorbid symptomatology should be recorded and analyzed in future EEG-based brain training interventions.

Clinical Trial Registration

https://www.drks.de, identifier DRKS00012339.
Weakly Supervised Skull Stripping of Magnetic Resonance Imaging of Brain Tumor Patients
Authors: Ranjbar Sara , Singleton Kyle W. , Curtin Lee , Rickertsen Cassandra R. , Paulson Lisa E. , Hu Leland S. , Mitchell Joseph Ross , Swanson Kristin R.
Published: April 2022

Automatic brain tumor segmentation is particularly challenging on magnetic resonance imaging (MRI) with marked pathologies, such as brain tumors, which usually cause large displacement, abnormal appearance, and deformation of brain tissue. Despite an abundance of previous literature on learning-based methodologies for MRI segmentation, few works have focused on tackling MRI skull stripping of brain tumor patient data. This gap in literature can be associated with the lack of publicly available data (due to concerns about patient identification) and the labor-intensive nature of generating ground truth labels for model training. In this retrospective study, we assessed the performance of Dense-Vnet in skull stripping brain tumor patient MRI trained on our large multi-institutional brain tumor patient dataset. Our data included pretreatment MRI of 668 patients from our in-house institutional review board–approved multi-institutional brain tumor repository. Because of the absence of ground truth, we used imperfect automatically generated training labels using SPM12 software. We trained the network using common MRI sequences in oncology: T1-weighted with gadolinium contrast, T2-weighted fluid-attenuated inversion recovery, or both. We measured model performance against 30 independent brain tumor test cases with available manual brain masks. All images were harmonized for voxel spacing and volumetric dimensions before model training. Model training was performed using the modularly structured deep learning platform NiftyNet that is tailored toward simplifying medical image analysis. Our proposed approach showed the success of a weakly supervised deep learning approach in MRI brain extraction even in the presence of pathology. Our best model achieved an average Dice score, sensitivity, and specificity of, respectively, 94.5, 96.4, and 98.5% on the multi-institutional independent brain tumor test set. To further contextualize our results within existing literature on healthy brain segmentation, we tested the model against healthy subjects from the benchmark LBPA40 dataset. For this dataset, the model achieved an average Dice score, sensitivity, and specificity of 96.2, 96.6, and 99.2%, which are, although comparable to other publications, slightly lower than the performance of models trained on healthy patients. We associate this drop in performance with the use of brain tumor data for model training and its influence on brain appearance.
Nonconvex Nonlocal Tucker Decomposition for 3D Medical Image Super-Resolution
Authors: Jia Huidi , Chen Xi'ai , Han Zhi , Liu Baichen , Wen Tianhui , Tang Yandong
Published: April 2022

Limited by hardware conditions, imaging devices, transmission efficiency, and other factors, high-resolution (HR) images cannot be obtained directly in clinical settings. It is expected to obtain HR images from low-resolution (LR) images for more detailed information. In this article, we propose a novel super-resolution model for single 3D medical images. In our model, nonlocal low-rank tensor Tucker decomposition is applied to exploit the nonlocal self-similarity prior knowledge of data. Different from the existing methods that use a convex optimization for tensor Tucker decomposition, we use a tensor folded-concave penalty to approximate a nonlocal low-rank tensor. Weighted 3D total variation (TV) is used to maintain the local smoothness across different dimensions. Extensive experiments show that our method outperforms some state-of-the-art (SOTA) methods on different kinds of medical images, including MRI data of the brain and prostate and CT data of the abdominal and dental.