bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical, Biochemical, Molecular, and Outcome Features of Mitochondrial 3-Hydroxy-3-Methylglutaryl-CoA Synthase Deficiency in 10 Chinese Patients
Authors: Wu Shengnan , Shen Linghua , Chen Qiong , Gong Chunxiu , Yang Yanling , Wei Haiyan , Cao Bingyan , Chen Yongxing
Published: March 2022

Background: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMGCS2D) is a rare autosomal recessive metabolic disorder caused by mutations of the HMGCS2 gene. To date, no more than 60 patients have been reported throughout the world.

Purpose: To analyze the clinical, biochemical, molecular, and outcome features of HMGCS2D in a case series of 10 new Chinese patients.

Methods: This retrospective study includes 10 Chinese patients diagnosed with HMGCS2D. We collected and analyzed clinical data for all patients. We also reviewed clinical data for 39 cases that had been reported previously.

Results: All of our patients had experienced their first metabolic crisis before 12 months old. The most common clinical manifestations were anorexia, dyspnea, and disturbance of consciousness (10/10), followed by vomiting (8/10), fever (7/10), cough (4/10), diarrhea, and seizures (3/10). Each patient (10/10) had a different degree of hepatomegaly and increased aminotransferase, severe metabolic acidosis, and hypofibrinogenemia. 9 patients presented with severe hypoglycemia and weak positives on qualitative tests of urinary ketone body. Patient 3 was the only one without hypoglycemia. Five patients had hypocalcemia, five patients had hyperammonemia, four patients had hyperuricemia, and three had hypertriglyceridemia. During the metabolic acidosis episode, we observed high dicarboxylic acid values in urine, and the elevated ratio of blood acetylcarnitine to free carnitine may have been an additional biochemical signature. However, all returned to normal during the interictal interval. Molecular analysis identified 15 variants in the HMGCS2 gene, of which 10 were novel (c.220G>A/p.E74K, c.407A>G/p.D136G, c.422T>A/p.V141D, c.719A>C/p.D240A, c.821G>A/p.R274H, c.39dupA/p.L14Tfs*59, c.1394delA/p.N465Tfs*10, c.788delT/p.L263Cfs*36, c.717T>G/p.Y239*, and c.1017-2A>G). Combining these with previous cases, the known mutation c.1201G>T/p.E401* has been found in 6/40 (15.0%) of mutated alleles in 21 Chinese patients from 20 families, while none have been found in other populations. We found that patients with biallelic truncation mutation appeared to show a more severe clinical condition through a literature review.

Conclusion: This study analyzed the phenotypic and genetic features of HMGCS2D in a Chinese case series. We also expanded the HMGCS2 mutational spectrum with 10 novel variants. The c.1201G>T/p.E401* mutation was the most frequent, representing 15.0% of the mutated alleles in reported unrelated Chinese patients, and thus, it may be a hot spot mutation.
High Resolution HLA ∼A, ∼B, ∼C, ∼DRB1, ∼DQA1, and ∼DQB1 Diversity in South African Populations
Authors: Tshabalala Mqondisi , Mellet Juanita , Vather Kuben , Nelson Derrick , Mohamed Fathima , Christoffels Alan , Pepper Michael S.
Published: March 2022

Background: Lack of HLA data in southern African populations hampers disease association studies and our understanding of genetic diversity in these populations. We aimed to determine HLA diversity in South African populations using high resolution HLA ∼A, ∼B, ∼C, ∼DRB1, ∼DQA1 and ∼DQB1 data, from 3005 previously typed individuals.

Methods: We determined allele and haplotype frequencies, deviations from Hardy-Weinberg equilibrium (HWE), linkage disequilibrium (LD) and neutrality test. South African HLA class I data was additionally compared to other global populations using non-metrical multidimensional scaling (NMDS), genetic distances and principal component analysis (PCA).

Results: All loci strongly (p < 0.0001) deviated from HWE, coupled with excessive heterozygosity in most loci. Two of the three most frequent alleles, HLA ∼DQA1*05:02 (0.2584) and HLA ∼C*17:01 (0.1488) were previously reported in South African populations at lower frequencies. NMDS showed genetic distinctness of South African populations. Phylogenetic analysis and PCA clustered our current dataset with previous South African studies. Additionally, South Africans seem to be related to other sub-Saharan populations using HLA class I allele frequencies.

Discussion and Conclusion: Despite the retrospective nature of the study, data missingness, the imbalance of sample sizes for each locus and haplotype pairs, and induced methodological difficulties, this study provides a unique and large HLA dataset of South Africans, which might be a useful resource to support anthropological studies, disease association studies, population based vaccine development and donor recruitment programs. We additionally provide simulated high resolution HLA class I data to augment the mixed resolution typing results generated from this study.
DNA Methylation: An Important Biomarker and Therapeutic Target for Gastric Cancer
Authors: Zeng Yunqing , Rong Huimin , Xu Jianwei , Cao Ruyue , Li Shuhua , Gao Yanjing , Cheng Baoquan , Zhou Tao
Published: March 2022

Gastric cancer (GC) is a very common malignancy with a poor prognosis, and its occurrence and development are closely related to epigenetic modifications. Methylation of DNA before or during gastric cancer is an interesting research topic. This article reviews the studies on DNA methylation related to the cause, diagnosis, treatment, and prognosis of gastric cancer and aims to find cancer biomarkers to solve major human health problems.
Tear miRNAs Identified in a Murine Model of Sjögren’s Syndrome as Potential Diagnostic Biomarkers and Indicators of Disease Mechanism
Authors: Kakan Shruti Singh , Edman Maria C. , Yao Alexander , Okamoto Curtis T. , Nguyen Annie , Hjelm Brooke E. , Hamm-Alvarez Sarah F.
Published: March 2022

Objective

The tear miRNAome of the male NOD mouse, a model of ocular symptoms of Sjögren’s syndrome (SS), was analyzed to identify unique miRNAs.

Methods

Male NOD mice, aged 12-14 weeks, were used to identify tear miRNAs associated with development of autoimmune dacryoadenitis. Age- and sex-matched male BALB/c mice served as healthy controls while age-matched female NOD mice that do not develop the autoimmune dacryoadenitis characteristic of SS were used as additional controls. Total RNA was isolated from stimulated tears pooled from 5 mice per sample and tear miRNAs were sequenced and analyzed. Putative miRNA hits were validated in additional mouse cohorts as well as in tears of SS patients versus patients with another form of dry eye disease, meibomian gland disease (MGD) using qRT-PCR. The pathways influenced by the validated hits were identified using Ingenuity Pathway Analysis.

Results

In comparison to tears from both healthy (male BALB/c) and additional control (female NOD) mice, initial analy1sis identified 7 upregulated and 7 downregulated miRNAs in male NOD mouse tears. Of these, 8 were validated by RT-qPCR in tears from additional mouse cohorts. miRNAs previously implicated in SS pathology included mmu-miR-146a/b-5p, which were significantly downregulated, as well as mmu-miR-150-5p and mmu-miR-181a-5p, which were upregulated in male NOD mouse tears. All other validated hits including the upregulated miR-181b-5p and mmu-miR-203-3p, as well as the downregulated mmu-miR-322-5p and mmu-miR-503-5p, represent novel putative indicators of autoimmune dacryoadenitis in SS. When compared to tears from patients with MGD, miRNAs hsa-miR-203a-3p, hsa-miR-181a-5p and hsa-miR-181b-5p were also significantly increased in tears of SS patients.

Conclusions

A panel of differentially expressed miRNAs were identified in tears of male NOD mice, with some preliminary validation in SS patients, including some never previously linked to SS. These may have potential utility as indicators of ocular symptoms of SS; evaluation of the pathways influenced by these dysregulated miRNAs may also provide further insights into SS pathogenesis.
Coexistence of Anti-p200 Pemphigoid and Psoriasis: A Systematic Review
Authors: Xie Ying-Han , Wang Si-Hang , Li Si-Zhe , Zuo Ya-Gang
Published: March 2022

Background

A close association between psoriasis and anti-p200 pemphigoid has been demonstrated by numerous studies. However, the clinical characteristics of patients suffering from these two entities have not yet been well-elucidated.

Objective

This study aimed to review the case reports and case series, summarizing clinical features and therapeutic strategies in patients suffering from anti-p200 pemphigoid and psoriasis.

Methods

A systematic review was conducted by searching PubMed, EMBASE, and Web of Science databases for studies published in English involving patients with psoriasis and anti-p200 pemphigoid on 6 September 2021. All case reports and case series reporting patients diagnosed with anti-p200 pemphigoid and psoriasis were included in this systematic review.

Results

A total of 21 eligible studies comprising 26 anti-p200 pemphigoid patients with preceding psoriasis were included in the qualitative synthesis. The average age at blisters eruption was 62.5 years, and the mean duration between the two entities was 15.6 years. Twenty-four percent of patients developed bullous lesions during UV therapy. Clinical manifestation of bullae and/or vesicles was recorded in all patients, and the trunk (94.7%) was most frequently involved, with only 15.8% reporting mucosal involvement. Epitope spreading was detected by immunoblotting in 33.3% of patients. All the patients reached completed remission during the course of disease, with 36.8% experiencing at least one relapse. Monotherapy of prednisolone was the leading therapeutic approach (n=6, 31.6%) required for disease control, but 5 (83.3%) of them suffered from blister recurrence after tapering or ceasing corticosteroid.

Conclusion

Most of the clinical aspects of patients with anti-p200 pemphigoid and psoriasis were similar to what was demonstrated in previous articles on anti-p200 pemphigoid. Nevertheless, compared with other anti-p200 pemphigoid cases without psoriasis, a clinical manifestation pattern with more frequent involvement of the trunk and less mucosal involvement was illustrated in those with psoriasis. Generally, monotherapy is sufficient for a complete remission for such patients. However, one or more relapses have been recorded in a considerable portion of patients, especially those prescribed with prednisolone. It reminded us to be more cautious during a tapering of medication.
Class I/Class II HLA Evolutionary Divergence Ratio Is an Independent Marker Associated With Disease-Free and Overall Survival After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia
Authors: Daull Anne-Marie , Dubois Valérie , Labussière-Wallet Hélène , Venet Fabienne , Barraco Fiorenza , Ducastelle-Lepretre Sophie , Larcher Marie-Virginie , Balsat Marie , Gilis Lila , Fossard Gaëlle , Ghesquières Hervé , Heiblig Maël , Ader Florence , Alcazer Vincent
Published: March 2022

Class I Human Leukocyte Antigen (HLA) evolutionary divergence (HED) is a metric which reflects immunopeptidome diversity and has been associated with immune checkpoint inhibitor responses in solid tumors. Its impact and interest in allogeneic hematopoietic stem cell transplantation (HCT) have not yet been thoroughly studied. This study analyzed the clinical and immune impact of class I and II HED in 492 acute myeloid leukemia (AML) recipients undergoing HCT. The overall cohort was divided into a training (n=338) and a testing (n=132) set. Univariate cox screening found a positive impact of a high class I HED and a negative impact of a high class II HED on both disease-free (DFS) and overall survival (OS). These results were combined in a unique marker, class I/class II HED ratio, and assessed in the testing cohort. The final multivariate cox model confirmed the positive impact of a high versus low class I/class II HED ratio on both DFS (Hazard Ratio (HR) 0.41 [95% CI 0.2-0.83]; p=0.01) and OS (HR 0.34 [0.19-0.59]; p<0.001), independently of HLA matching and other HCT parameters. No significant association was found between the ratio and graft-versus-host disease (GvHD) nor with neutrophil and platelet recovery. A high class I HED was associated with a tendency for an increase in NK, CD8 T-cell, and B cell recovery at 12 months. These results introduce HED as an original and independent prognosis marker reflecting immunopeptidome diversity and alloreactivity after HCT.
Platelets, Thromboinflammation and Neurovascular Disease
Authors: Sun Ying , Langer Harald F.
Published: March 2022

The brain and spinal cord are immune-privileged organs, but in the disease state protection mechanisms such as the blood brain barrier (BBB) are ineffective or overcome by pathological processes. In neuroinflammatory diseases, microglia cells and other resident immune cells contribute to local vascular inflammation and potentially a systemic inflammatory response taking place in parallel. Microglia cells interact with other cells impacting on the integrity of the BBB and propagate the inflammatory response through the release of inflammatory signals. Here, we discuss the activation and response mechanisms of innate and adaptive immune processes in response to neuroinflammation. Furthermore, the clinical importance of neuroinflammatory mediators and a potential translational relevance of involved mechanisms are addressed also with focus on non-classical immune cells including microglia cells or platelets. As illustrative examples, novel agents such as Anfibatide or Revacept, which result in reduced recruitment and activation of platelets, a subsequently blunted activation of the coagulation cascade and further inflammatory process, demonstrating that mechanisms of neuroinflammation and thrombosis are interconnected and should be further subject to in depth clinical and basic research.
Clinical Significance of Novel Neutrophil-Based Biomarkers in the Diagnosis and Prediction of Response to Infliximab Therapy in Crohn’s Disease
Authors: Zhou Zhou , Zhang Yinghui , Yang Xue , Pan Yan , Li Liangping , Gao Caiping , He Chong
Published: March 2022

With the increasing incidence and prevalence, Crohn’s disease (CD) has become one of the most challenging diseases in both diagnosis and treatment of gastroenterology. Evaluation of the disease activity and mucosal healing guides clinical decisions regarding subsequent therapy for CD. In this study, we enrolled a total of 144 patients with CD and 239 healthy controls were enrolled. Clinical characteristics and laboratory parameters of enrolled subjects were retrieved from the electronic medical record database of our hospital. Serum cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). Mucosa expression levels of inflammatory agents were measured by quantitative RT-PCR (qRT-PCR). We identified two neutrophil-based indexes, the neutrophil-to-albumin ratio (NAR) and neutrophil-to-bilirubin ratio (NBR), both of which had not yet been explored in CD or UC. NAR and NBR were significantly increased in patients with CD compared to those in healthy controls, and both indexes showed significantly positive correlations with CD activity and inflammatory load. In note, NAR and NBR showed better performance than blood neutrophil percentage, serum albumin, or bilirubin alone in these scenarios. More importantly, both NAR and NBR discriminated CD patients who completely or partially responded to infliximab (IFX) induction therapy from those with primary non-response. Our observations suggest that NAR and NBR may serve as promising biomarkers in the diagnosis and prediction of response to IFX therapy in CD.
Canonical and Non-Canonical Functions of the Autophagy Machinery in MHC Restricted Antigen Presentation
Authors: Münz Christian
Published: March 2022

Macroautophagy delivers cytoplasmic constituents for lysosomal degradation. Since major histocompatibility complex (MHC) class II molecules sample peptides after lysosomal degradation for presentation to CD4+ T cells, it was originally described that these peptides can also originate from macroautophagy substrates. In recent years it has become clear that in addition to this canonical function of the macroautophagy machinery during MHC class II restricted antigen presentation at least parts of this machinery are also used to regulate phagocytosis of antigens, degradation of MHC class I molecules, and unconventional secretion of antigens in extracellular vesicles, including virus particles. This review discusses how both canonical and non-canonical functions of the macroautophagy machinery influence antigen presentation on MHC class I and II molecules to CD8+ and CD4+ T cells. A better understanding of the molecular mechanisms by which the macroautophagy machinery is distributed between its canonical and non-canonical functions should allow targeting of antigens to these different pathways to influence MHC restricted presentation during vaccination against infectious diseases and tumors.
Temperature Effect on Mohr–Coulomb’s Effective Strength Parameters of Paste Backfill
Authors: Hasan Alsidqi , Ting Wee Kiet
Published: March 2022

In-stope paste backfill monitoring at different mine sites showed anomalous increase in total stress during rest periods. One of the explanations according to a recent laboratory- model experiment was attributed to volumetric expansion caused by temperature increase within the backfill. This paper extends the understanding whether the Mohr–Coulomb’s effective strength parameters are affected by such temperature increase. The effects are explained through evaluating the apparent cohesion and the effective internal and interfacial friction angles under different temperature conditions. A series of modified direct shear tests were performed on saturated specimens under three controlled temperature levels: 25°C, 50°C, and 70°C. The specimens consist of cemented paste backfill and uncemented paste backfill. The results show that the effective internal and the interfacial friction angles increase as the temperature increases, depending on the type of material and the shearing condition, whereas the temperature increase does not significantly affect the apparent cohesion. The findings serve as a reference for engineers and academics in explaining the stress anomaly and to better understand the shear behavior of paste backfill under different temperature conditions for mine stope backfill design.
Effect of Levosimendan on Acute Decompensated Right Heart Failure in Patients With Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
Authors: Qu Chao , Feng Wei , Zhao Qi , Liu Qi , Luo Xing , Wang Gang , Sun Meng , Yao Zhibo , Sun Yufei , Hou Shenglong , Zhao Chunyang , Zhang Ruoxi , Qu Xiufen
Published: March 2022

Aims

Acute decompensated right heart failure (RHF) in chronic precapillary pulmonary hypertension is often typified by a swiftly progressive syndrome involving systemic congestion. This results from the impairment of the right ventricular filling and/or a reduction in the flow output of the right ventricle, which has been linked to a dismal prognosis of short duration. Despite this, there are limited therapeutic data regarding these acute incidents. This study examined the effect of levosimendan on acute decompensated RHF in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH).

Methods

This retrospective study included 87 patients with confirmed CTD-PAH complicated acute decompensated RHF between November 2015 and April 2021. We collected biological, clinical, and demographic data, as well as therapy data, from patients with acute decompensated RHF who required levosimendan treatment in the cardiac care unit (CCU) for CTD-PAH. The patients were divided into two groups according to the levosimendan treatment. Patient information between the two groups was systematically compared in hospital and at follow-up.

Results

Oxygen saturation of mixed venose blood (SvO2), estimated glomerular filtration rate (eGFR), 24-h urine output, and tricuspid annular plane systolic excursion (TAPSE) were found to be considerably elevated in the levosimendan cohort compared with the control cohort. Patients in the levosimendan cohort exhibited considerably reduced levels of C-reactive protein (CRP), white blood cell (WBC), troponin I, creatinine, NT-proBNP, and RV diameter compared with those in the control cohort. A higher survival rate was observed in the levosimendan cohort.

Conclusions

Levosimendan treatment could effectively improve acute decompensated RHF and systemic hemodynamics in CTD-PAH patients, with positive effects on survival in hospital and can, therefore, be considered as an alternative treatment option for improving clinical short-term outcomes.
Global Research Status of Multiple Organ Dysfunction Syndrome During 2001–2021: A 20-Year Bibliometric Analysis
Authors: Zhao Peng-yue , Xia Yun , Tao Zheng-bo , Li Song-yan , Mao Zhi , Yang Xing-peng , Yao Ren-qi , Du Xiao-hui
Published: March 2022

Background

Multiple Organ Dysfunction Syndrome (MODS) is a major cause of high morbidity and mortality among patients in intensive care units (ICU). Although numerous basic and clinical researches on MODS have been conducted, there is still a long way to go to prevent patients from entering this stage. To our knowledge, no bibliometric analyses of MODS have been reported, this study, therefore, was conducted to reveal MODS research status and trends during 2001–2021.

Methods

All relevant literature covering MODS during 2001–2021 were extracted from Web of Science. An online analysis platform of literature metrology was used to analyze the publication trends. VOSviewer software was used to collect and analyze the keywords and research hotspots related to MODS.

Results

As of July 31, 2021, a total of 994 MODS-related articles from 2001 to 2021 were identified. The United States accounted for the largest number of publications (31.1%), followed by China and Germany, with 186 and 75 publications, respectively. Among all the institutions, the University of Pittsburgh published the most papers related to MODS (21). Critical Care Medicine published the most papers in this field (106). Professor Moore EE, who had the most citation frequency (1847), made great achievements in MODS research. Moreover, analysis of the keywords identified three MODS research hotspot clusters: “mechanism-related research,” “clinical research,” and “diagnostic research.”

Conclusions

The United States maintained a top position worldwide and made the most outstanding contribution in the MODS field. In terms of publication, China was next only to the United States, but there was a disproportion between the quantity of publications and citation frequency. The institution University of Pittsburgh and journal Critical Care Medicine represent the highest level of research in this field. During the 20 years from 2001 to 2021, basic MODS research has been in-depth yet progressed relatively slowly recently, but the outbreak of COVID-19 has to some extent set off an upsurge of clinical research in MODS field.
Case Report: SARS-CoV-2 Gamma Isolation From Placenta of a Miscarriage in Midwest, Brazil
Authors: Fernandez Zoraida , Lichs Gislene G. C. , Zubieta Claudia S. , Machado Ana B. , Ferreira Mia A. , Valente Natalia , Keren Thayssa , Arantes Ighor , Nacife Valeria , Pereira Elisa Cavalcante , Appolinario Luciana , Lacerda Thays E. J. , Siqueira Marilda M. , Esposito Ana O. P. , Demarchi Luiz H. F. , Zardin Marina C. S. U. , Goncalves Crhistinne C. M. , Maziero Livia M. A. , Miziara Luciana A. F. , Naveca Felipe G. , Pauvolid-Corrêa Alex , Resende Paola C. , Favacho Alexsandra R. M.
Published: March 2022

The present study investigated a SARS-CoV-2 infection in placenta and fetal samples from an early pregnancy miscarriage in Midwest Brazil. The Gamma variant was isolated and fully sequenced from the placenta sample, but not from fetal samples. Our findings highlight potential adverse perinatal outcomes caused by SARS-CoV-2 Gamma infection during pregnancy.
Acetate Degradation at Low pH by the Moderately Acidophilic Sulfate Reducer Acididesulfobacillus acetoxydans gen. nov. sp. nov.
Authors: Sánchez-Andrea Irene , van der Graaf Charlotte M. , Hornung Bastian , Bale Nicole J. , Jarzembowska Monika , Sousa Diana Z. , Rijpstra W. Irene C. , Sinninghe Damsté Jaap S. , Stams Alfons J. M.
Published: March 2022

In acid drainage environments, biosulfidogenesis by sulfate-reducing bacteria (SRB) attenuates the extreme conditions by enabling the precipitation of metals as their sulfides, and the neutralization of acidity through proton consumption. So far, only a handful of moderately acidophilic SRB species have been described, most of which are merely acidotolerant. Here, a novel species within a novel genus of moderately acidophilic SRB is described, Acididesulfobacillus acetoxydans gen. nov. sp. nov. strain INE, able to grow at pH 3.8. Bioreactor studies with strain INE at optimum (5.0) and low (3.9) pH for growth showed that strain INE alkalinized its environment, and that this was more pronounced at lower pH. These studies also showed the capacity of strain INE to completely oxidize organic acids to CO2, which is uncommon among acidophilic SRB. Since organic acids are mainly in their protonated form at low pH, which increases their toxicity, their complete oxidation may be an acid stress resistance mechanism. Comparative proteogenomic and membrane lipid analysis further indicated that the presence of saturated ether-bound lipids in the membrane, and their relative increase at lower pH, was a protection mechanism against acid stress. Interestingly, other canonical acid stress resistance mechanisms, such as a Donnan potential and increased active charge transport, did not appear to be active.
Identification of a Pyroptosis-Related Prognostic Signature Combined With Experiments in Hepatocellular Carcinoma
Authors: Li Huihui , Li Tang , Zhang Xiaohua
Published: March 2022

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis. There is a necessary search for improvement in diagnosis and treatment methods to improve the prognosis. Some useful prognostic markers of HCC are still lacking. Pyroptosis is a type of programmed cell death caused by the inflammasome. It is still unknown whether pyroptosis-related genes (PRGs) are involved in the prognosis in HCC. The gene expression and clinical data of LIHC (liver hepatocellular carcinoma) patients were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium database (ICGC). In this study, we identified 40 PRGs that were differentially expressed between LIHC and normal liver tissues. Based on the TCGA-LIHC cohort, a 9-gene prediction model was established with the Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression. The risk score was calculated according to the model in the TCGA-LIHC cohort and the ICGC-LIHC cohort. Utilizing the median risk score from the TCGA cohort, LIHC patients from the ICGC-LIHC cohort were divided into two risk subgroups. The Kaplan–Meier (KM) survival curves demonstrated that patients with lower risk scores had significantly favorable overall survival (OS). Combined with the clinical characteristics, the risk score was an independent factor for predicting the OS of LIHC patients in both the TCGA-LIHC cohort and the ICGC-LIHC cohort. Functional enrichment and immune function analysis were carried out. Furthermore, a nomogram based on risk score, age, gender, and tumor stage was used to predict mortality of patients with LIHC. Moreover, KM survival analysis was performed for 9 genes in the risk model, among which CHMP4A, SCAF11, and GSDMC had significantly different results and the ceRNA network was constructed. Based on the core role of SCAF11, we performed loss-of-function experiments to explore the function of SCAF11 in vitro. Suppression of SCAF11 expression inhibited the proliferation, attenuated the migration and invasion, and induced apoptosis of liver cancer cell lines. In conclusion, the pyroptosis-related model and nomogram can be utilized for the clinical prognostic prediction in LIHC. This study has demonstrated for the first time that SCAF11 promotes the progression of liver cancer.
Selective Targeting of Cancer Cells by Copper Ionophores: An Overview
Authors: Oliveri Valentina
Published: March 2022

Conventional cancer therapies suffer from severe off-target effects because most of them target critical facets of cells that are generally shared by all rapidly proliferating cells. The development of new therapeutic agents should aim to increase selectivity and therefore reduce side effects. In addition, these agents should overcome cancer cell resistance and target cancer stem cells. Some copper ionophores have shown promise in this direction thanks to an intrinsic selectivity in preferentially inducing cuproptosis of cancer cells compared to normal cells. Here, Cu ionophores are discussed with a focus on selectivity towards cancer cells and on the mechanisms responsible for this selectivity. The proposed strategies, to further improve the targeting of cancer cells by copper ionophores, are also reported.
Inhibition of Adult Hippocampal Neurogenesis Plays a Role in Sevoflurane-Induced Cognitive Impairment in Aged Mice Through Brain-Derived Neurotrophic Factor/Tyrosine Receptor Kinase B and Neurotrophin-3/Tropomyosin Receptor Kinase C Pathways
Authors: Xu Lichi , Guo Yanjing , Wang Gongming , Sun Guoqing , Sun Wei , Li Jingjing , Li Xinlei , Wu Jiangnan , Zhang Mengyuan
Published: March 2022

Sevoflurane anesthesia induces cognitive impairment, which may lead to perioperative neurocognitive disorders (PND). However, the factors and molecular mechanism underlying this impairment remains unclear. Adult hippocampal neurogenesis (AHN) in the subgranular zone of the hippocampus has been implicated in cognitive processes. Nonetheless, the direct role of AHN in sevoflurane-induced cognitive impairment has never been demonstrated. In this study, we explored the age and the concentration factors and the role of AHN inhibition in sevoflurane-induced cognitive impairment in sevoflurane inhalation model mice. We found that 3% sevoflurane exposure induced significant cognitive impairment and inhibition of AHN in aged mice but not adult mice. Expression of BDNF/TrkB and NT-3/TrkC was also decreased by 3% sevoflurane exposure in aged mice. Hippocampal brain-derived neurotrophic factor (BDNF) or Neurotrophin-3 (NT-3) microinjection could partially improve the sevoflurane-induced cognitive impairment and AHN inhibition, respectively. These results demonstrate that the cognitive impairment caused by sevoflurane inhalation is related to patient age and sevoflurane concentration. In conclusion, the molecular mechanism of cognitive impairment in the elderly is related to the inhibition of AHN through the BDNF/TrkB and NT-3/TrkC pathways. Thus, sevoflurane inhalation anesthesia may be safe for adult patients, but caution should be exercised when administering it to the elderly.
Bubble Test and Carotid Ultrasound to Guide Indication of Transesophageal Echocardiography in Young Patients With Stroke
Authors: Mayerhofer Ernst , Kanz Dirk , Guschlbauer Brigitte , Anderson Christopher D. , Asmussen Alexander , Grundmann Sebastian , Strecker Christoph , Harloff Andreas
Published: March 2022

Background and Purpose

Indication of transesophageal echocardiography (TEE) in patients ≤60 years with brain ischemia is uncertain.

Methods

This prospective double-blinded study included patients with cryptogenic acute ischemic stroke or transient ischemic attack (TIA) ≥18 and ≤60 years. After routine diagnostics, all patients underwent patent foramen ovale (PFO) screening by transcranial Doppler (TCD) bubble test, carotid ultrasound for atherosclerosis screening (intima-media-thickness >0.90 mm or plaques), and TEE. We calculated sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of the combined non-invasive ultrasound to predict therapy-relevant TEE findings.

Results

We included 240 consecutive patients (median 51 years, 39% women) of which 68 (28.3%) had both a negative bubble test and no carotid atherosclerosis. Of these, 66 (97.1%) had unremarkable TEE findings; in one patient a small PFO was found and closed subsequently, in another patient a 4.9 mm thick aortic atheroma was found, and double platelet inhibition initiated. Of the other 172 (71.7%) patients, 93 (54%) had PFO and 9 (5.2%) complex aortic plaques. No other therapy-relevant findings were present in both groups. Non-invasive ultrasound had a sensitivity of 98.0%, specificity of 47.8%, NPV of 97.1%, and PPV of 58.1% for therapy-relevant TEE findings.

Conclusions

Bubble test and carotid ultrasound could be used for the individual decision for/against TEE in patients with cryptogenic stroke ≤60 years. If they are unremarkable, TEE can be omitted with high safety regarding secondary prevention. If bubble test is positive and/or carotid ultrasound shows atherosclerosis, TEE should be carried out if PFO or aortic atheroma are potentially relevant for further patient management.
What Does the General Public Know (or Not) About Neuroscience? Effects of Age, Region and Profession in Brazil
Authors: Arévalo Analía , Simoes Estefania , Petinati Fernanda , Lepski Guilherme
Published: March 2022

The field of Neuroscience has experienced a growing interest in recent decades, which has led to an exponential growth in the amount of related information made available online as well as the market for Neuroscience-related courses. While this type of knowledge can be greatly beneficial to people working in science, health and education, it can also benefit individuals in other areas. For example, neuroscience knowledge can help people from all fields better understand and critique information about new discoveries or products, and even make better education- and health-related decisions. Online platforms are fertile ground for the creation and spread of fake information, including misrepresentations of scientific knowledge or new discoveries (e.g., neuromyths). These types of false information, once spread, can be difficult to tear down and may have widespread negative effects. For example, even scientists are less likely to access retractions of peer-reviewed articles than the original discredited articles. In this study we surveyed general knowledge about neuroscience and the brain among volunteers in Brazil, Latin America’s largest country. We were interested in evaluating the prevalence of neuromyths in this region, and test whether knowledge/neuromyth endorsement differs by age, region, and/or profession. To that end, we created a 30-item survey that was anonymously answered online by 1128 individuals. While younger people (20–29-year-olds) generally responded more accurately than people 60 and older, people in the North responded significantly worse than those in the South and Southeast. Most interestingly, people in the biological sciences consistently responded best, but people in the health sciences responded no better than people in the exact sciences or humanities. Furthermore, years of schooling did not correlate with performance, suggesting that quantity may surpass quality when it comes to extension or graduate-level course offerings. We discuss how our findings can help guide efforts toward improving access to quality information and training in the region.
Titles and Semantic Violations Affect Eye Movements When Viewing Contemporary Paintings
Authors: Ganczarek Joanna , Pietras Karolina , Stolińska Anna , Szubielska Magdalena
Published: March 2022

The role of titles in perception of visual art is a topic of interesting discussions that brings together artists, curators, and researchers. Titles provide contextual cues and guide perception. They can be particularly useful when paintings include semantic violations that make them challenging for viewers, especially viewers lacking expert knowledge. The aim of this study is to investigate the effects of titles and semantic violations on eye movements. A total of 127 participants without expertise in visual art viewed 40 paintings with and without semantic violations (20 each) in one of three conditions: untitled, consistent titles and inconsistent titles. After each painting was viewed participants also rated liking and understanding. Our results suggest that titles affect the way paintings are viewed: both titled conditions were associated with shorter first fixation duration, longer saccade durations, and amplitudes and higher dynamic entropy than the untitled conditions. Titles were fixated on more frequently (but only in the time window between 1,200 and 2,800 ms) when presented alongside paintings with semantic violations than paintings without violations, and the percentage of fixations to titles was particularly high in the case of paintings with double inconsistencies (inconsistent titles and semantic violations). Also, we found that semantic violations attracted attention early on (300–900 ms), whereas titles received attention later (average first fixation on title was at 936.28 ms) and inconsistencies in titles were processed even later (after 4,000 ms). Finally, semantic violations were associated with higher dynamic entropy than paintings without violations. Our results demonstrate the importance of titles for processing of artworks, especially artworks that present a challenge for the viewers.
Memory Modulation Via Non-invasive Brain Stimulation: Status, Perspectives, and Ethical Issues
Authors: Farina Mirko , Lavazza Andrea
Published: March 2022

While research to improve memory or counter decay caused by neurodegenerative diseases has a fairly long history, scientific attempts to erase memories are very recent. The use of non-invasive brain stimulation for memory modulation represents a new and promising application for the treatment of certain disorders [such as Post-Traumatic Stress Disorder (PTSD)]. However, numerous ethical issues are related to memory intervention. In particular, the possibility of using forms of non-invasive brain stimulation requires to distinguish treatment interventions from the enhancement of the healthy. Furthermore, a range of important societal and legal concerns arise when manipulating memories. In this short contribution, we address some of the most significant ethical, social, and legal implications surrounding the application of memory-modulation techniques and offer a series of reflections and considerations, which we hope can be of use to guide -and perhaps regulate- their potential, future implementation in society.
The Influence of a Competitive Field Hockey Match on Cognitive Function
Authors: Malcolm Rachel , Cooper Simon , Folland Jonathan P. , Tyler Christopher J. , Sunderland Caroline
Published: March 2022

Despite the known positive effects of acute exercise on cognition, the effects of a competitive team sport match are unknown. In a randomized crossover design, 20 female and 17 male field hockey players (19.7 ± 1.2 years) completed a battery of cognitive tests (Visual Search, Stroop, Corsi Blocks, and Rapid Visual Information Processing) prior to, at half-time, and immediately following a competitive match (or control trial of seated rest); with effect sizes (ES) presented as raw ES from mixed effect models. Blood samples were collected prior to and following the match and control trial, and analyzed for adrenaline, noradrenaline, brain derived neurotrophic factor (BDNF), cathepsin B, and cortisol. The match improved response times for a simple perception task at full-time (ES = –14 ms; P < 0.01) and response times on the complex executive function task improved at half-time (ES = –44 ms; P < 0.01). Working memory declined at full-time on the match (ES = –0.6 blocks; P < 0.01). The change in working memory was negatively correlated with increases in cortisol (r = –0.314, P = 0.01; medium), as was the change in simple perception response time and the change in noradrenaline concentration (r = –0.284, P = 0.01; small to medium). This study is the first to highlight the effects a competitive hockey match can have on cognition. These findings have implications for performance optimization, as understanding the influence on specific cognitive domains across a match allows for the investigation into strategies to improve these aspects.
Design and Evaluation of a Custom-Made Electromyographic Biofeedback System for Facial Rehabilitation
Authors: Machetanz Kathrin , Grimm Florian , Schäfer Ruth , Trakolis Leonidas , Hurth Helene , Haas Patrick , Gharabaghi Alireza , Tatagiba Marcos , Naros Georgios
Published: March 2022

Background

In the rehabilitation of postoperative facial palsy, physical therapy is of paramount importance. However, in the early rehabilitation phase, voluntary movements are often limited, and thus, the motivation of patients is impacted. In these situations, biofeedback of facial electromyographic (EMG) signals enables the visual representation of the rehabilitation progress, even without apparent facial movements. In the present study, we designed and evaluated a custom-made EMG biofeedback system enabling cost-effective facial rehabilitation.

Methods

This prospective study describes a custom-made EMG system, consisting of a microcontroller board and muscle sensors, which was used to record the EMG of frontal and zygomatic facial muscles during frowning and smiling. First, the mean EMG amplitudes and movement onset detection rates (ACC) achieved with the custom-made EMG system were compared with a commercial EMG device in 12 healthy subjects. Subsequently, the custom-made device was applied to 12 patients with and without postoperative facial paresis after neurosurgical intervention. Here, the ratio [laterality index (LI)] between the mean EMG amplitude of the healthy and affected side was calculated and related to the facial function as measured by the House and Brackmann scale (H&B) ranging from 1 (normal) to 6 (total paralysis).

Results

In healthy subjects, a good correlation was measured between the mean EMG amplitudes of the custom-made and commercial EMG device for both frontal (r = 0.84, p = 0.001) and zygomatic muscles (r = 0.8, p = 0.002). In patients, the LI of the frontal and zygomatic muscles correlated significantly with the H&B (r = −0.83, p = 0.001 and r = −0.65, p = 0.023). The ACC of the custom-made EMG system varied between 65 and 79% depending on the recorded muscle and cohort.

Conclusion

The present study demonstrates a good application potential of our custom-made EMG biofeedback device to detect facial EMG activity in healthy subjects as well as patients with facial palsies. There is a correlation between the electrophysiological measurements and the clinical outcome. Such a device might enable cost-efficient home-based facial EMG biofeedback. However, movement detection accuracy should be improved in future studies to reach ranges of commercial devices.
Evaluation of the Glymphatic System With Diffusion Tensor Imaging-Along the Perivascular Space in Cancer Pain
Authors: Wang Aibo , Chen Lei , Tian Can , Yin Xiaoyu , Wang Xinyue , Zhao Yize , Zhang Miao , Yang Lili , Ye Zhaoxiang
Published: March 2022

Cancer pain (CP) is one of the most common symptoms affecting life quality, and there is considerable variation in pain experience among patients with malignant tumors. Previously, it has been found that the fluid drainage function in the brain can be regulated by peripheral pain stimulation. However, the relationship between cancer pain and functional changes of the glymphatic system (an important pathway for fluid drainage in the brain) remains unclear. In this study, 97 participants were enrolled, which included 40 participants in the cancer pain (CP) group, 27 participants in the painless cancer (PLC) group and 30 participants in the control (NC) group. Differences in glymphatic system function among the three groups and between before and after pain pharmacological intervention were analyzed by measuring diffusivity and the index along the perivascular space (ALPS index) using diffusion tensor imaging. We found that diffusivity and the ALPS index were significantly lower in the CP group than in the PLC and NC group and increased following intervention with pain relief. Moreover, the ALPS index was negatively correlated with the degree of pain in the CP group. The present study verified that alterations in glymphatic function are closely related to cancer pain, and the quantification of functional changes reflects pain severity. Our findings support the use of neuroimaging biomarkers for cancer pain assessment and indicate that pain can be alleviated by regulating brain function status.
Consistent Changes in Cortico-Subthalamic Directed Connectivity Are Associated With the Induction of Parkinsonism in a Chronically Recorded Non-human Primate Model
Authors: Bore Joyce Chelangat , Toth Carmen , Campbell Brett A. , Cho Hanbin , Pucci Francesco , Hogue Olivia , Machado Andre G. , Baker Kenneth B.
Published: March 2022

Parkinson’s disease is a neurological disease with cardinal motor signs including bradykinesia and tremor. Although beta-band hypersynchrony in the cortico-basal ganglia network is thought to contribute to disease manifestation, the resulting effects on network connectivity are unclear. We examined local field potentials from a non-human primate across the naïve, mild, and moderate disease states (model was asymmetric, left-hemispheric dominant) and probed power spectral density as well as cortico-cortical and cortico-subthalamic connectivity using both coherence and Granger causality, which measure undirected and directed effective connectivity, respectively. Our network included the left subthalamic nucleus (L-STN), bilateral primary motor cortices (L-M1, R-M1), and bilateral premotor cortices (L-PMC, R-PMC). Results showed two distinct peaks (Peak A at 5–20 Hz, Peak B at 25–45 Hz) across all analyses. Power and coherence analyses showed widespread increases in power and connectivity in both the Peak A and Peak B bands with disease progression. For Granger causality, increases in Peak B connectivity and decreases in Peak A connectivity were associated with the disease. Induction of mild disease was associated with several changes in connectivity: (1) the cortico-subthalamic connectivity in the descending direction (L-PMC to L-STN) decreased in the Peak A range while the reciprocal, ascending connectivity (L-STN to L-PMC) increased in the Peak B range; this may play a role in generating beta-band hypersynchrony in the cortex, (2) both L-M1 to L-PMC and R-M1 to R-PMC causalities increased, which may either be compensatory or a pathologic effect of disease, and (3) a decrease in connectivity occurred from the R-PMC to R-M1. The only significant change seen between mild and moderate disease was increased right cortical connectivity, which may reflect compensation for the left-hemispheric dominant moderate disease state.