bluuebunny/crossref_metadata_2025 huggingface dataset:
Granulomatous Sarcoidosis Mimics
Authors: Judson Marc A.
Published: July 2021

Many granulomatous diseases can mimic sarcoidosis histologically and in terms of their clinical features. These mimics include infectious granulomatous diseases, granulomatous reactions to occupational and environmental exposures, granulomatous drug reactions, vasculitides and idiopathic granulomatous conditions. It is important to distinguish sarcoidosis from these mimics, as a misdiagnosis of these diseases may have serious consequences. This manuscript reviews numerous sarcoidosis mimics and describes features of these diseases that may allow them to be differentiated from sarcoidosis. Distinguishing features between sarcoidosis and its mimics requires a careful review of the medical history, symptoms, demographics, radiographic findings, histologic features, and additional laboratory data. Understanding the clinical characteristics of sarcoidosis and its mimics should lead to more accurate diagnoses and treatment of granulomatous disorders that should improve the care of these patients. As the diagnostic criteria of sarcoidosis are not standardized, it is possible that some of these sarcoidosis mimics may represent varied clinical presentations of sarcoidosis itself.
Higher Prevalence of Non-thyroidal-Illness Syndrome in Elderly Male Patients With Active Helicobacter pylori Infection
Authors: Sun Banruo , Wang Xuanping , McLarnon Michael Edmund David , Ding Yu , Liu Miao , Dai Wei , Wang Gangshi
Published: July 2021

Objective: It is currently unclear whether the Helicobacter pylori (H. pylori) infection leads to associated alterations in thyroid functions and thyroidal illnesses. This study aims to analyse this relationship in an elderly male cohort over a five-year period.

Design: A case retrospective study.

Methods: A longitudinal study was designed to collect subjects (≥65 years old) receiving both a thyroid examination and H. pylori infection status determined by 13C-urea breath test in 2013 at our unit. Subjects were followed every 1 to 2 years until December 2017 for laboratory results, visits to outpatient clinics/emergency departments etc. Blood tests and thyroid ultrasonography were performed to determine thyroid function and morphology.

Results: 356 male subjects with mean age 78.5 ± 9.8 years were included. Active H. pylori infection was positive in 88 subjects (24.7%). Thyroid function tests and ultrasonography showed similar patterns between H. pylori positive and negative groups. Non-thyroidal-illness syndrome (NTIS) was diagnosed in 30/210 (14%) patients who experienced acute illnesses and hospitalization over five-year follow-up. Notably, NTIS demonstrated significantly higher prevalence in the H. pylori positive group compared to the negative group (17.1 vs. 5.6%, P = 0.001). Multivariate analysis showed that when age, APACHE II score and hemoglobin levels were adjusted, H. pylori status still has significant interrelationship with NTIS (OR = 3.497, P = 0.003).

Conclusions: There is a positive association between chronic active H. pylori infection and NTIS prevalence in this elderly male cohort. Further studies are needed to elucidate the role of H. pylori infection on NTIS in elderly male patients.
Deletion of Viral microRNAs in the Oncogenesis of Epstein–Barr Virus-Associated Lymphoma
Authors: Kimura Hiroshi , Okuno Yusuke , Sato Yoshitaka , Watanabe Takahiro , Murata Takayuki
Published: July 2021

Epstein–Barr virus (EBV), which encodes >80 genes and nearly 50 non-coding RNAs, is a double-stranded DNA virus. EBV is associated with various types of lymphomas and lymphoproliferative disorders not only of B-cell but also T/NK-cell origin. However, the oncogenic mechanism remains poorly understood, including the EBV receptors expressed on T/NK cells, relationship of EBV with host genes, and epigenetic regulation of EBV and host genes. The roles of host and viral non-coding RNAs during tumorigenesis have been elucidated. EBV encodes at least 49 mature microRNAs (miRNAs), of which 44 are located in BamHI-A rightward transcripts (BARTs) region, and the remaining five are located in BamHI-H rightward fragment 1. BART miRNAs modulate cell differentiation, proliferation, apoptosis, and the cell cycle, and they are considered positive regulators of oncogenesis. We and others have recently reported that EBV-positive lymphomas frequently possess large deletions in BART miRNA clusters, suggesting that some viral miRNAs have suppressive effects on oncogenesis, and that deletion of these miRNAs may aid lymphoma formation.
Strong Replication Interference Between Hepatitis Delta Viruses in Human Liver Chimeric Mice
Authors: Giersch Katja , Hermanussen Lennart , Volz Tassilo , Volmari Annika , Allweiss Lena , Sureau Camille , Casey John , Huang Jiabin , Fischer Nicole , Lütgehetmann Marc , Dandri Maura
Published: July 2021

Background

Hepatitis D Virus (HDV) is classified into eight genotypes with distinct clinical outcomes. Despite the maintenance of highly conserved functional motifs, it is unknown whether sequence divergence between genotypes, such as HDV-1 and HDV-3, or viral interference mechanisms may affect co-infection in the same host and cell, thus hindering the development of HDV inter-genotypic recombinants. We aimed to investigate virological differences of HDV-1 and HDV-3 and assessed their capacity to infect and replicate within the same liver and human hepatocyte in vivo.

Methods

Human liver chimeric mice were infected with hepatitis B virus (HBV) and with one of the two HDV genotypes or with HDV-1 and HDV-3 simultaneously. In a second set of experiments, HBV-infected mice were first infected with HDV-1 and after 9 weeks with HDV-3, or vice versa. Also two distinct HDV-1 strains were used to infect mice simultaneously and sequentially. Virological parameters were determined by strain-specific qRT-PCR, RNA in situ hybridization and immunofluorescence staining.

Results

HBV/HDV co-infection studies indicated faster spreading kinetics and higher intrahepatic levels of HDV-3 compared to HDV-1. In mice that simultaneously received both HDV strains, HDV-3 became the dominant genotype. Interestingly, antigenomic HDV-1 and HDV-3 RNA were detected within the same liver but hardly within the same cell. Surprisingly, sequential super-infection experiments revealed a clear dominance of the HDV strain that was inoculated first, indicating that HDV-infected cells may acquire resistance to super-infection.

Conclusion

Infection with two largely divergent HDV genotypes could be established in the same liver, but rarely within the same hepatocyte. Sequential super-infection with distinct HDV genotypes and even with two HDV-1 isolates was strongly impaired, suggesting that virus interference mechanisms hamper productive replication in the same cell and hence recombination events even in a system lacking adaptive immune responses.
Emendation of the Coccoid Cyanobacterial Genus Gloeocapsopsis and Description of the New Species Gloeocapsopsis diffluens sp. nov. and Gloeocapsopsis dulcis sp. nov. Isolated From the Coastal Range of the Atacama Desert (Chile)
Authors: Jung Patrick , Azua-Bustos Armando , Gonzalez-Silva Carlos , Mikhailyuk Tatiana , Zabicki Daniel , Holzinger Andreas , Lakatos Michael , Büdel Burkhard
Published: July 2021

The taxonomy of coccoid cyanobacteria, such as Chroococcidiopsis, Pleurocapsa, Chroococcus, Gloeothece, Gloeocapsa, Gloeocapsopsis, and the related recent genera Sinocapsa and Aliterella, can easily be intermixed when solely compared on a morphological basis. There is still little support on the taxonomic position of some of the addressed genera, as genetic information is available only for a fraction of species that have been described solely on morphology. Modern polyphasic approaches that combine classic morphological investigations with DNA-based molecular analyses and the evaluation of ecological properties can disentangle these easily confusable unicellular genera. By using such an approach, we present here the formal description of two novel unicellular cyanobacterial species that inhabit the Coastal Range of the Atacama Desert, Gloeocapsopsis dulcis (first reported as Gloeocapsopsis AAB1) and Gloeocapsopsis diffluens. Both species could be clearly separated from previously reported species by 16S rRNA and 16S–23S ITS gene sequencing, the resulting secondary structures, p-distance analyses of the 16S–23S ITS, and morphology. For avoiding further confusions emendation of the genus Gloeocapsopsis as well as epitypification of the type species Gloeocapsopsis crepidinum based on the strain LEGE06123 were conducted.
Inhibitory Role of an Aeromonas hydrophila TIR Domain Effector in Antibacterial Immunity by Targeting TLR Signaling Complexes in Zebrafish
Authors: Tang Huai-ping , Huang Chen , Hu Chong-bin , Li Hao , Shao Tong , Ji Jian-fei , Bai Jun , Fan Dong-dong , Lin Ai-fu , Xiang Li-xin , Shao Jian-zhong
Published: July 2021

The Toll/interleukin-1 receptor (TIR) domain is a structural unit responsible for the assembly of signal protein complexes in Toll-like receptor (TLR) and interleukin-1 receptor signaling pathways. TIR domain homologs are found in a considerable number of bacteria and enhance bacterial infection and survival in host organisms. However, whether TIR domain homologs exist in Aeromonas hydrophila, a ubiquitous waterborne bacterium in aquatic environments, remains poorly understood. In this study, a TIR domain protein (TcpAh) was identified from A. hydrophila JBN2301. TIR domain of TcpAh is highly homologous to the counterpart domains in TLRs and myeloid differentiation factor 88 (MyD88). The zebrafish infected with mutant A. hydrophila with tcpAh deletion had a remarkably lower mortality than those infected with the wild-type strain. This result suggests that TcpAh is a crucial virulence factor for A. hydrophila infection. TcpAh exhibited a strong ability to associate with MyD88, tumor necrosis factor receptor-associated factor 3 (TRAF3) and TRAF-associated NF-κB activator-binding kinase 1 (TBK1) in TIR–TIR, TIR–Death domain (DD), and other alternative interactions. This finding suggests that TcpAh extensively interferes with MyD88 and TIR domain-containing adapter inducing interferon (IFN)-β (TRIF) signaling pathways downstream of TLRs. Consequently, CD80/86 expression was suppressed by TcpAh via attenuating TLR-stimulated NF-κB activation, which ultimately led to the impairment of the major costimulatory signal essential for the initiation of adaptive humoral immunity against A. hydrophila infection. We believe that this study is the first to show a previously unrecognized mechanism underlying A. hydrophila evades from host antibacterial defense by intervening CD80/86 signal, which bridges innate and adaptive immunity. The mechanism will benefit the development of therapeutic interventions for A. hydrophila infection and septicemia by targeting TcpAh homologs.
Influence of Pyroligneous Acid on Fermentation Parameters, CO2 Production and Bacterial Communities of Rice Straw and Stylo Silage
Authors: Guo Xiang , Zheng Peng , Zou Xuan , Chen Xiaoyang , Zhang Qing
Published: July 2021

Carbon dioxide (CO2) is a primary greenhouse gas and the main cause of global warming. Respiration from plant cells and microorganisms enables CO2 to be produced during ensiling, a method of moist forage preservation applied worldwide. However, limited information is available regarding CO2 emissions and mitigation during ensiling. Pyroligneous acid, a by-product of plant biomass pyrolysis, has a strong antibacterial capacity. To investigate CO2 production and the influence of pyroligneous acid, fresh stylo, and rice straw were ensiled with or without 1% or 2% pyroligneous acid. Dynamics of the fermentation characteristics, CO2 production, and bacterial communities during ensiling were analyzed. Pyroligneous acid increased the lactic acid content and decreased the weight losses, pH, ammonia-N content, butyric acid content, and coliform bacterial numbers (all P < 0.05). It also increased the relative abundance of Lactobacillus and decreased the relative abundances of harmful bacteria such as Enterobacter and Lachnoclostridium. Adding pyrolytic acids reduced the gas production, especially of CO2. It also increased the relative abundances of CO2-producing bacterial genera and of genera with the potential for CO2 fixation. In conclusion, adding pyroligneous acid improved the fermentation quality of the two silages. During ensiling, CO2 production was correlated with bacterial community alterations. Using pyroligneous acid altered the bacterial community to reduce CO2 production during ensiling. Given the large production and demand for silage worldwide, application of pyroligneous acid may be an effective method of mitigating global warming via CO2 emissions.
Structural Basis of Glycan Recognition of Rotavirus
Authors: Sun Xiaoman , Li Dandi , Duan Zhaojun
Published: July 2021

Rotavirus (RV) is an important pathogen causing acute gastroenteritis in young humans and animals. Attachment to the host receptor is a crucial step for the virus infection. The recent advances in illustrating the interactions between RV and glycans promoted our understanding of the host range and epidemiology of RVs. VP8*, the distal region of the RV outer capsid spike protein VP4, played a critical role in the glycan recognition. Group A RVs were classified into different P genotypes based on the VP4 sequences and recognized glycans in a P genotype-dependent manner. Glycans including sialic acid, gangliosides, histo-blood group antigens (HBGAs), and mucin cores have been reported to interact with RV VP8*s. The glycan binding specificities of VP8*s of different RV genotypes have been studied. Here, we mainly discussed the structural basis for the interactions between RV VP8*s and glycans, which provided molecular insights into the receptor recognition and host tropism, offering new clues to the design of RV vaccine and anti-viral agents.
Plasma Levels of Heat Shock Protein 90 Alpha Associated With Colorectal Cancer Development
Authors: Wei Wene , Zhou Jiahui , Chen Lipeng , Liu Haizhou , Zhang Fuyong , Li Jilin , Ning Shufang , Li Shirong , Wang Chen , Huang Yi , Zou Chang , Zhang Litu
Published: July 2021

Aim: The role of plasma heat shock protein 90 alpha (HSP90α) in colorectal cancer patients remains unclear. This study aimed to evaluate the relationship between HSP90α and the occurrence and development of colorectal cancer through diagnosis and prognosis value.

Methods: 635 colorectal cancer patients and 295 healthy controls were recruited. The HSP90α was measured by using the ELISA kit in all objects and the immune cells and common biomarkers as CEA, AFP, CA125, CA153 and CA199 were measured in all colorectal cancer patients. The relationship between plasma HSP90α with clinical features, common tumor markers and immune cells were also conducted. The survival analysis endpoint was progression-free survival (PFS).

Results: The levels of plasma HSP90α were significantly higher in colorectal cancer patients compared to healthy controls [51.4 (ng/ml) vs. 43.7 (ng/ml), p < 0.001]. In additional, the levels of plasma HSP90α were associated with gender and disease progress as stage, lymphatic and distant metastasis. Furthermore, plasma HSP90α was closed correlation with CEA, CA125, CA199 and percentage of B cells. However, the initial expression level of plasma HSP90α failed to show a prognostic value for progression-free survival in colorectal cancer.

Conclusion: The plasma Hsp90α was remarkable higher in colorectal cancer and correlated with common tumor biomarkers and immune cells. Plasma Hsp90α levels were associated with disease progress but a poor diagnosis performance and also failed to show a prognostic value in colorectal cancer.
Cholesterol Hydroxylating Cytochrome P450 46A1: From Mechanisms of Action to Clinical Applications
Authors: Pikuleva Irina A. , Cartier Nathalie
Published: July 2021

Cholesterol, an essential component of the brain, and its local metabolism are involved in many neurodegenerative diseases. The blood-brain barrier is impermeable to cholesterol; hence, cholesterol homeostasis in the central nervous system represents a balance betweenin situbiosynthesis and elimination. Cytochrome P450 46A1 (CYP46A1), a central nervous system-specific enzyme, converts cholesterol to 24-hydroxycholesterol, which can freely cross the blood-brain barrier and be degraded in the liver. By the dual action of initiating cholesterol efflux and activating the cholesterol synthesis pathway, CYP46A1 is the key enzyme that ensures brain cholesterol turnover. In humans and mouse models, CYP46A1 activity is altered in Alzheimer’s and Huntington’s diseases, spinocerebellar ataxias, glioblastoma, and autism spectrum disorders. In mouse models, modulations of CYP46A1 activity mitigate the manifestations of Alzheimer’s, Huntington’s, Nieman-Pick type C, and Machao-Joseph (spinocerebellar ataxia type 3) diseases as well as amyotrophic lateral sclerosis, epilepsy, glioblastoma, and prion infection. Animal studies revealed that the CYP46A1 activity effects are not limited to cholesterol maintenance but also involve critical cellular pathways, like gene transcription, endocytosis, misfolded protein clearance, vesicular transport, and synaptic transmission. How CYP46A1 can exert central control of such essential brain functions is a pressing question under investigation. The potential therapeutic role of CYP46A1, demonstrated in numerous models of brain disorders, is currently being evaluated in early clinical trials. This review summarizes the past 70 years of research that has led to the identification of CYP46A1 and brain cholesterol homeostasis as powerful therapeutic targets for severe pathologies of the CNS.
The Frequency of Genetic Mutations Associated With Behavioral Variant Frontotemporal Dementia in Chinese Han Patients
Authors: Liu Li , Cui Bo , Chu Min , Cui Yue , Jing Donglai , Li Dan , Xie Kexin , Kong Yu , Xia Tianxinyu , Wang Chaodong , Wu Liyong
Published: July 2021

Background

Behavioral variant frontotemporal dementia (bvFTD) is a clinically heterogeneous syndrome with high heredity. However, the frequencies of mutations associated with bvFTD have yet to be determined. The aim of the current study was to investigate the frequency of Chinese Han patients harboring genetic bvFTD variants.

Methods

A total of 49 bvFTD patients selected from our frontotemporal lobar degeneration database, including 14 familial cases belonging to eight families and 35 sporadic cases were consecutively recruited from July 2014 to December 2019 at Xuanwu Hospital (Beijing, China). Whole-exome sequencing (WES) was performed and repeat-primed PCR was used to test samples for the C9orf72 hexanucleotide repeat expansion mutation. The frequency of genetic variants and the pathogenicity of the novel variants were analyzed.

Results

Ten pathogenic or likely pathogenic variants were identified in 17 bvFTD patients, including C9orf72 repeat expansions, six previously reported mutations and three novel mutations (MAPT p. R5C, p. D54N, GRN p. P451L). Genetic mutations accounted for 27.9% (12/43) of total cases, 87.5% (7/8) of patients with familial bvFTD, and 14.3% (5/35) with sporadic bvFTD. Pathogenic variants mostly occurred in MAPT gene (20.9%, 9/43), followed by C9orf72 repeat expansions (2.3%, 1/43), GRN gene (2.3%, 1/43) and FUS gene (2.3%, 1/43).

Conclusion

There was a high prevalence of genetic variants in Chinese bvFTD patients, highlighting the necessity of genetic testing for bvFTD.
Update on the Mechanism and Treatment of Sevoflurane-Induced Postoperative Cognitive Dysfunction
Authors: Wang Cong-mei , Chen Wei-can , Zhang Yan , Lin Shu , He He-fan
Published: July 2021

Sevoflurane is one of the most widely used anesthetics for the induction and maintenance of general anesthesia in surgical patients. Sevoflurane treatment may increase the incidence of postoperative cognitive dysfunction (POCD), and patients with POCD exhibit lower cognitive abilities than before the operation. POCD affects the lives of patients and places an additional burden on patients and their families. Understanding the mechanism of sevoflurane-induced POCD may improve prevention and treatment of POCD. In this paper, we review the diagnosis of POCD, introduce animal models of POCD in clinical research, analyze the possible mechanisms of sevoflurane-induced POCD, and summarize advances in treatment for this condition.
Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough
Authors: Ganguly Upasana , Singh Sukhpal , Pal Soumya , Prasad Suvarna , Agrawal Bimal K. , Saini Reena V. , Chakrabarti Sasanka
Published: July 2021

Parkinson’s disease (PD) is the second most common neurodegenerative disorder of the elderly, presenting primarily with symptoms of motor impairment. The disease is diagnosed most commonly by clinical examination with a great degree of accuracy in specialized centers. However, in some cases, non-classical presentations occur when it may be difficult to distinguish the disease from other types of degenerative or non-degenerative movement disorders with overlapping symptoms. The diagnostic difficulty may also arise in patients at the early stage of PD. Thus, a biomarker could help clinicians circumvent such problems and help them monitor the improvement in disease pathology during anti-parkinsonian drug trials. This review first provides a brief overview of PD, emphasizing, in the process, the important role of α-synuclein in the pathogenesis of the disease. Various attempts made by the researchers to develop imaging, genetic, and various biochemical biomarkers for PD are then briefly reviewed to point out the absence of a definitive biomarker for this disorder. In view of the overwhelming importance of α-synuclein in the pathogenesis, a detailed analysis is then made of various studies to establish the biomarker potential of this protein in PD; these studies measured total α-synuclein, oligomeric, and post-translationally modified forms of α-synuclein in cerebrospinal fluid, blood (plasma, serum, erythrocytes, and circulating neuron-specific extracellular vesicles) and saliva in combination with certain other proteins. Multiple studies also examined the accumulation of α-synuclein in various forms in PD in the neural elements in the gut, submandibular glands, skin, and the retina. The measurements of the levels of certain forms of α-synuclein in some of these body fluids or their components or peripheral tissues hold a significant promise in establishing α-synuclein as a definitive biomarker for PD. However, many methodological issues related to detection and quantification of α-synuclein have to be resolved, and larger cross-sectional and follow-up studies with controls and patients of PD, parkinsonian disorders, and non-parkinsonian movement disorders are to be undertaken.
The Straw That Broke the Camel’s Back: Natural Variations in 17β-Estradiol and COMT-Val158Met Genotype Interact in the Modulation of Model-Free and Model-Based Control
Authors: Diekhof Esther K. , Geana Andra , Ohm Frederike , Doll Bradley B. , Frank Michael J.
Published: July 2021

The sex hormone estradiol has recently gained attention in human decision-making research. Animal studies have already shown that estradiol promotes dopaminergic transmission and thus supports reward-seeking behavior and aspects of addiction. In humans, natural variations of estradiol across the menstrual cycle modulate the ability to learn from direct performance feedback (“model-free” learning). However, it remains unclear whether estradiol also influences more complex “model-based” contributions to reinforcement learning. Here, 41 women were tested twice – in the low and high estradiol state of the follicular phase of their menstrual cycle – with a Two-Step decision task designed to separate model-free from model-based learning. The results showed that in the high estradiol state women relied more heavily on model-free learning, and accomplished reduced performance gains, particularly during the more volatile periods of the task that demanded increased learning effort. In contrast, model-based control remained unaltered by the influence of hormonal state across the group. Yet, when accounting for individual differences in the genetic proxy of the COMT-Val158Met polymorphism (rs4680), we observed that only the participants homozygote for the methionine allele (n = 12; with putatively higher prefrontal dopamine) experienced a decline in model-based control when facing volatile reward probabilities. This group also showed the increase in suboptimal model-free control, while the carriers of the valine allele remained unaffected by the rise in endogenous estradiol. Taken together, these preliminary findings suggest that endogenous estradiol may affect the balance between model-based and model-free control, and particularly so in women with a high prefrontal baseline dopamine capacity and in situations of increased environmental volatility.
NLRP3 Inflammasome: A Potential Target in Isoflurane Pretreatment Alleviates Stroke-Induced Retinal Injury in Diabetes
Authors: Lin Hong-Bin , Lin Ying-Hui , Zhang Jin-Yu , Guo Wen-Jing , Ovcjak Andrea , You Zhi-Jian , Feng Zhong-Ping , Sun Hong-Shuo , Li Feng-Xian , Zhang Hong-Fei
Published: July 2021

Ischemic stroke remains a devastating disease which is the leading cause of death worldwide. Visual impairment after stroke is a common complication which may lead to vision loss, greatly impacting life quality of patients. While ischemic stroke is traditionally characterized by a blockage of blood flow to the brain, this may coincide with reduced blood flow to the eye, resulting in retinal ischemia and leading to visual impairment. Diabetes increases the risk of ischemic stroke and induces diabetic retinopathy; the latter may be more sensitive to the ischemic retinal injury. In diabetic status, the underlying mechanism in stroke-induced retinal injury has not been fully clarified. The NLR pyrin domain containing 3 (NLRP3) inflammasome is an important activator of inflammation, which may play a critical role in catalyzing and forming certain pro-inflammatory cytokines in both cerebral and retinal ischemia. Isoflurane has been demonstrated to inhibit the activation of the NLRP3 inflammasome and show neuroprotective effects. In this study, we established a diabetic mouse model and performed the middle cerebral artery occlusion procedure to induce ischemic stroke. Our results revealed that cerebral ischemia-induced retinal injury in the diabetic model. Isoflurane pretreatment alleviated the cerebral and retinal injury after ischemic stroke. Of note, isoflurane pretreatment inhibited the NLRP3 inflammasome activation in the retina, indicating that isoflurane pretreatment may provide substantial retinal protection in stroke-induced retinal injury in diabetes.
Quantitative Evaluation of Gait Changes Using APDM Inertial Sensors After the External Lumbar Drain in Patients With Idiopathic Normal Pressure Hydrocephalus
Authors: He Mengmeng , Qi Zhenyu , Shao Yunxiang , Yao Hui , Zhang Xuewen , Zhang Yang , Shi Yu , E Qinzhi , Liu Chengming , Hu Hongwei , Liu Jiangang , Sun Xiaoou , Wang Zhong , Huang Yulun
Published: July 2021

Objectives: Gait and balance disturbances are common symptoms of idiopathic normal pressure hydrocephalus (iNPH). This study aimed to quantitatively evaluate gait and balance parameters after external lumbar drainage (ELD) using APDM inertial sensors.

Methods: Two-minute walkway tests were performed in 36 patients with suspected iNPH and 20 healthy controls. A total of 36 patients underwent ELD. According to clinical outcomes, 20 patients were defined as responders, and the other 16 as non-responders. The gait parameters were documented, and the corresponding differences between responders and non-responders were calculated.

Results: When compared with healthy controls, patients with suspected iNPH exhibited decreased cadence, reduced gait speed, a higher percentage of double support, decreased elevation at mid-swing, reduced foot strike angle, shorter stride length, difficulty in turning, and impaired balance functions. After the ELD, all these manifestations, except elevation at mid-swing and balance functions, were significantly improved in responders. The change of Z-score absolute value in the six parameters, except for foot strike angle, was >1. No significant improvement was observed in non-responders.

Conclusion: APDM inertial sensors are useful for the quantitative assessment of gait impairment in patients with iNPH, which may be a valuable tool for identifying candidates that are suitable for shunting operations.
Case Report: Cognitive Conversion in a Non-brazilian VAPB Mutation Carrier (ALS8)
Authors: Temp Anna G. M. , Dyrba Martin , Kasper Elisabeth , Teipel Stefan , Prudlo Johannes
Published: July 2021

Amyotrophic lateral sclerosis 8 (ALS8) is a predominantly lower motor neuron syndrome originally described in a Portuguese–Brazilian family, which originated from a common founder. ALS8 is caused by a VAPB mutation and extremely rare in Central Europe. We present a 51-year-old German man with ALS8 who had the P56S VAPB mutation independently of the founder effect. In the final 4 years of his life (disease duration 10 years), the patient had five MRI scans and four in-depth neuropsychological assessments. This paper addresses the course of the patient's cognitive status and relates cognitive performance to structural brain changes in order to determine whether this ALS8 case showed a different pattern of cognitive decline compared with sporadic ALS. The executive functions, verbal fluency, and memory of the patient and 17 age-, sex-, and education-matched controls were assessed on four different occasions. His cognitive performance and decline were investigated for abnormality using cross-sectional and longitudinal matched case–control analysis. We obtained five T1-weighted MRI, which we analyzed using voxel-wise non-parametric analysis with statistical non-parametric mapping in Matlab. Moreover, we conducted a single-subject correlation between cognitive performance and brain atrophy. The cognitive profile of the index patient featured executive dysfunction. Notably, his working memory and shifting ability declined from a healthy baseline to an impaired performance, leading to a transition from cognitively non-impaired (ALSni) to cognitively impaired (ALSci). The correlations we observed between cerebellar atrophy and verbal fluency in addition to fusiform gyrus atrophy and shifting are novel findings. We found that the conversion from ALSni to ALSci was associated with widespread cerebral atrophy, which extended beyond the primary motor and premotor cortex and affected, among others, the cerebellum and left fusiform gyrus. The index patients' cognitive profile resembles that of other ALS phenotypes, but the extensive atrophy beyond extra-motor areas has not yet been described.
Interaction Effect of Baseline Serum Glucose and Early Ischemic Water Uptake on the Risk of Secondary Hemorrhage After Ischemic Stroke
Authors: Nawabi Jawed , Elsayed Sarah , Scholz Henriette , Kemmling André , Meyer Lukas , Kniep Helge , Bechstein Matthias , Flottmann Fabian , Faizy Tobias D. , Schön Gerhard , Fiehler Jens , Hanning Uta , Broocks Gabriel
Published: July 2021

Background and Purpose: Intracerebral hemorrhage (ICH) after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) remains a major complication and its early prediction is of high relevance. Baseline serum glucose (BGL) is a known predictor of ICH, but its interaction with early ischemic changes remains uncertain. We hypothesized that BGL interacts with the effect of tissue water uptake on the occurrence of ICH.

Methods: Three hundred and thirty-six patients with acute ischemic stroke treated with MT were retrospectively analyzed. ICH was diagnosed within 24 h on non-enhanced CT (NECT) and classified according to the Heidelberg Bleeding Classification. Early tissue water homeostasis has been assessed using quantitative lesion net water uptake (NWU) on admission CT. Multivariate logistic regression was used to identify predictors of ICH.

Results: One hundred and seven patients fulfilled the inclusion criteria of which 37 (34.6%) were diagnosed with ICH. Patients with ICH had a significant higher BGL on admission (median 177 mg/dl, IQR: 127–221.75, P < 0.001). In patients with low BGL (<120 mg/dl), higher NWU was associated with 1.34-fold increased likelihood of ICH, while higher NWU was associated with a 2.08-fold increased likelihood of ICH in patients with a high BGL (>200 mg/dl). In multivariable logistic regression analysis, BGL (OR: 1.02, 95% CI: 1.00–1.04, P = 0.01) and NWU (OR: 2.32, 95% CI: 1.44–3.73, P < 0.001) were significantly and independently associated with ICH, showing a significant interaction (P = 0.04).

Conclusion: A higher degree of early tissue water uptake and high admission BGL were both independent predictors of ICH. Higher BGL was significantly associated with accelerated effects of NWU on the likelihood of ICH. Although a clear causal relationship remains speculative, stricter BGL control and monitoring may be tested to reduce the risk of ICH in patients undergoing thrombectomy.
Robot-Assisted Arm Training in Stroke Individuals With Unilateral Spatial Neglect: A Pilot Study
Authors: Chen Ze-Jian , Gu Ming-Hui , He Chang , Xiong Cai-Hua , Xu Jiang , Huang Xiao-Lin
Published: July 2021

Background: Robot-assisted arm training (RAT) is an innovative exercise-based therapy that provides highly intensive, adaptive, and task-specific training, yet its effects for stroke individuals with unilateral spatial neglect remain to be explored. The study was aimed to investigate the effects of RAT on unilateral spatial neglect, arm motor function, activities of daily living, and social participation after stroke.

Methods: In a pilot randomized controlled trial, individuals with unilateral spatial neglect after right hemisphere stroke were equally allocated to intervention group and control group, 45-min training daily, 5 days/week, for 4 weeks. Outcome measures included the Behavioral Inattention Test-conventional section (BIT-C), Catherine Bergego Scale (CBS), Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Modified Barthel Index (MBI), and World Health Organization Disability Assessment Schedule Version 2.0 (WHODAS 2.0).

Results: From November 2018 to February 2021, 20 stroke patients (mean age 47.40 ± 8.47) were enrolled in the study. Robot-assisted arm training was feasible and safe for individuals with unilateral spatial neglect. Both groups had significant improvements in all outcome measures. Participants assigned to RAT therapy had significantly greater improvements in BIT-C (difference, 7.70; 95% CI, 0.55–14.85, P = 0.04), FMA-UE (difference, 5.10; 95% CI, 1.52–8.68, P = 0.01), and WHODAS 2.0 (difference, −7.30; 95% CI, −12.50 to −2.10, P = 0.01). However, the change scores on CBS and MBI demonstrated no significance between the groups.

Conclusion: Our findings provide preliminary support for introducing robot-assisted arm training to remediate unilateral spatial neglect after stroke. The training program focusing on neglect of contralateral space and affected upper extremity may be effective in neglect symptoms, motor function recovery, and social participation, while not generalizing into improvements in activities of daily living.

Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/) on 17 October 2019, identifier: ChiCTR1900026656.
Methods for the Development of Healthcare Practice Recommendations Using Systematic Reviews and Meta-Analyses
Authors: Platz Thomas
Published: July 2021

Quality of healthcare can be improved when the best external evidence available is integrated in clinical decision-making in a systematic explicit manner. With the rapid expansion of clinical evidence, the opportunities for evidence-based high-quality healthcare increase. Paradoxically, the likelihood of any one person to get a complete and balanced picture of the evidence available decreases. This is especially true for rehabilitation interventions that are complex in nature and where clinical research is rather diverse. Given the complex nature of the evidence, there is a substantial risk of misinterpreting the complex information both at the level of individual sources (e.g., reports of clinical trials) and for aggregated data syntheses (e.g., systematic reviews and meta-analyses). These risks are inherent in these sources themselves and are in addition related to the methodological expertise necessary to make valid use of the evidence for clinical decision-making. Taken together, there is a great demand for systematic structured guidance from evidence to clinical decision. This methodology paper describes a structured process for the development and report of evidence-based clinical practice recommendations that uses systematic reviews and meta-analyses as evidence source. It provides a comprehensive framework with specific requirements for the development group, the formulation of the healthcare question addressed, the systematic search for the evidence, its critical appraisal, the extraction and the outcome-centered presentation of the evidence, the rating of its quality, strengths and weaknesses, any further considerations relevant for decision-making, and an explicit recommendation statement along with its justification, implementation, and resource aspects. The suggested methodology uses international standards in evidence synthesis, critical appraisal of systematic reviews, rating the quality of evidence, characteristics of recommendations, and guideline development as developed by Cochrane, GRADE (Grading of Recommendations Assessment, Development and Evaluation), AMSTAR (A MeaSurement Tool to Assess systematic Reviews), and AGREE (Appraisal of Guidelines for REsearch & Evaluation). An added distinctive feature of the methodology is to focus on the most up-to-date, most valid evidence and hence to support the development of valid practice recommendations in an efficient way. Practice recommendations generated by such a valid methodology would be generally applicable and promote evidence-based clinical practice globally.
Progressive Tumefactive Demyelination as the Only Result of Extensive Diagnostic Work-Up: A Case Report
Authors: Štourač Pavel , Kolčava Jan , Keřkovský Miloš , Kopřivová Tereza , Křen Leoš , Bednařík Josef
Published: July 2021

Tumefactive demyelinating lesions belong to the rare variants of multiple sclerosis, posing a diagnostic challenge since it is difficult to distinguish them from a neoplasm or other brain lesions and they require a careful differential diagnosis. This contribution presents the case report of a young female with progressive tumefactive demyelinating brain and spinal cord lesions. An extensive diagnostic process including two brain biopsies and an autopsy did not reveal any explanatory diagnosis other than multiple sclerosis. The patient was treated by various disease-modifying treatments without significant effect and died from ascendent infection via ventriculoperitoneal shunt resulting in Staphylococcus aureus meningitis.
Real-World Effectiveness of Natalizumab in Korean Patients With Multiple Sclerosis
Authors: Kim Ki Hoon , Kim Su-Hyun , Park Na Young , Hyun Jae-Won , Kim Ho Jin
Published: July 2021

Background and Purpose: Natalizumab is a highly efficacious disease-modifying therapy for relapsing-remitting multiple sclerosis (MS). Data on the efficacy and safety profile of natalizumab in Asian patients with MS are limited. This study assessed the efficacy and safety of natalizumab in Korean patients with MS in a real-world setting.

Methods: This study enrolled consecutive Korean patients with active relapsing-remitting MS who were treated with natalizumab for at least 6 months between 2015 and 2021. To evaluate the therapeutic outcome of natalizumab, we used the Expanded Disability Status Scale (EDSS) scores and brain magnetic resonance imaging; adverse events were assessed at regular intervals. No evidence of disease activity (NEDA) was defined as no clinical relapse, no worsening of EDSS score, and no radiological activities.

Results: Fourteen subjects with MS were included in the study. The mean age at initiation of natalizumab therapy was 32 years. All patients were positive for anti-John Cunningham virus antibodies before natalizumab administration. The mean annual relapse rate was markedly reduced from 2.7 ± 3.2 before natalizumab therapy to 0.1 ± 0.4 during natalizumab therapy (p = 0.001). Disability was either improved or stabilized after natalizumab treatment in 13 patients (93%). During the 1st year and 2 years after initiating natalizumab, NEDA-3 was achieved in 11/12 (92%) and 9/11 (82%) patients, respectively. No progressive multifocal leukoencephalopathy or other serious adverse events leading to the discontinuation of natalizumab were observed.

Conclusions: Natalizumab therapy showed high efficacy in treating Korean patients with active MS, without unexpected safety problems.
The Differential Effects of Anger and Sadness on Intertemporal Choice: An ERP Study
Authors: Suo Tao , Jia Xuji , Song Xiyan , Liu Lei
Published: July 2021

Previous research has taken a valence-based approach to examine the carryover effects of incidental emotions on intertemporal choices. However, recent studies have begun to explore the effects of specific emotions on intertemporal choices. In this study, we investigated how anger and sadness influenced intertemporal choices using event-related potentials (ERPs). Behavioral results showed that, compared with neutral prime, anger prime was associated with more preference for delayed rewards, whereas sad prime did not change individuals’ choice preference. Specifically, anger prime yielded a shorter response time than sad prime for the difficult-to-select choices. ERP results found that, compared with neutral and sad primes, anger prime elicited larger P1 in the fronto-central and parietal areas, larger P2 in the fronto-central area, and larger P3 in the parietal area during the evaluation stage. These findings suggest that there are differential carryover effects of anger and sadness on intertemporal choice. This study provides enlightenment on the significance of understanding how incidental emotions affect individuals’ intertemporal choices.
Electroacupuncture-Induced Muscular Inflammatory Pain Relief Was Associated With Activation of Low-Threshold Mechanoreceptor Neurons and Inhibition of Wide Dynamic Range Neurons in Spinal Dorsal Horn
Authors: Duan-Mu Cheng-Lin , Zhang Xiao-Ning , Shi Hong , Su Yang-Shuai , Wan Hong-Ye , Wang Yi , Qu Zheng-Yang , He Wei , Wang Xiao-Yu , Jing Xiang-Hong
Published: July 2021

Acupuncture is an effective alternative therapy for pain management. Evidence suggests that acupuncture relieves pain by exciting somatic afferent nerve fibers. However, the mechanism underlying the interaction between neurons in different layers of the spinal dorsal horn induced by electroacupuncture (EA) remains unclear. The aim of this study was to explore the mechanism of EA relieving inflammatory muscle pain, which was associated with activation of the spontaneous firing of low-threshold mechanoreceptor (LTM) neurons and inhibition of wide dynamic range (WDR) neuronal activities in the spinal dorsal horn of rats. Inflammatory muscle pain was induced by injecting complete Freund’s adjuvant into the right biceps femoris muscle. EA with intensity of threshold of A fibers (Ta) in Liangqiu (ST34) muscle considerably inhibited the abnormal spontaneous activities of electromyography (EMG) due to muscle inflammation. While EA with intensity of C-fiber threshold (Tc) increased the abnormal activities of EMG. EA with Ta also ameliorated the imbalance of weight-bearing behavior. A microelectrode array with 750-μm depth covering 32 channels was used to record the neuronal activities of WDR and LTM in different layers of the spinal dorsal horn. The spontaneous firing of LTM neurons was enhanced by EA-Ta, while the spontaneous firing of WDR neurons was inhibited. Moreover, EA-Ta led to a significant inverse correlation between changes in the frequency of WDR and LTM neurons (r = −0.64, p < 0.05). In conclusion, the results indicated that EA could alleviate inflammatory muscle pain, which was associated with facilitation of the spontaneous firing of LTM neurons and inhibition of WDR neuronal activities. This provides a promising evidence that EA-Ta could be applied to relieve muscular inflammatory pain in clinical practice.
Harnessing the Activation of RIG-I Like Receptors to Inhibit Glioblastoma Tumorigenesis
Authors: Bufalieri Francesca , Basili Irene , Di Marcotullio Lucia , Infante Paola
Published: July 2021

Glioblastoma (GB) is an incurable form of brain malignancy in an adult with a median survival of less than 15 months. The current standard of care, which consists of surgical resection, radiotherapy, and chemotherapy with temozolomide, has been unsuccessful due to an extensive inter- and intra-tumoral genetic and molecular heterogeneity. This aspect represents a serious obstacle for developing alternative therapeutic options for GB. In the last years, immunotherapy has emerged as an effective treatment for a wide range of cancers and several trials have evaluated its effects in GB patients. Unfortunately, clinical outcomes were disappointing particularly because of the presence of tumor immunosuppressive microenvironment. Recently, anti-cancer approaches aimed to improve the expression and the activity of RIG-I-like receptors (RLRs) have emerged. These innovative therapeutic strategies attempt to stimulate both innate and adaptive immune responses against tumor antigens and to promote the apoptosis of cancer cells. Indeed, RLRs are important mediators of the innate immune system by triggering the type I interferon (IFN) response upon recognition of immunostimulatory RNAs. In this mini-review, we discuss the functions of RLRs family members in the control of immune response and we focus on the potential clinical application of RLRs agonists as a promising strategy for GB therapy.
Human EEG and Recurrent Neural Networks Exhibit Common Temporal Dynamics During Speech Recognition
Authors: Hashemnia Saeedeh , Grasse Lukas , Soni Shweta , Tata Matthew S.
Published: July 2021

Recent deep-learning artificial neural networks have shown remarkable success in recognizing natural human speech, however the reasons for their success are not entirely understood. Success of these methods might be because state-of-the-art networks use recurrent layers or dilated convolutional layers that enable the network to use a time-dependent feature space. The importance of time-dependent features in human cortical mechanisms of speech perception, measured by electroencephalography (EEG) and magnetoencephalography (MEG), have also been of particular recent interest. It is possible that recurrent neural networks (RNNs) achieve their success by emulating aspects of cortical dynamics, albeit through very different computational mechanisms. In that case, we should observe commonalities in the temporal dynamics of deep-learning models, particularly in recurrent layers, and brain electrical activity (EEG) during speech perception. We explored this prediction by presenting the same sentences to both human listeners and the Deep Speech RNN and considered the temporal dynamics of the EEG and RNN units for identical sentences. We tested whether the recently discovered phenomenon of envelope phase tracking in the human EEG is also evident in RNN hidden layers. We furthermore predicted that the clustering of dissimilarity between model representations of pairs of stimuli would be similar in both RNN and EEG dynamics. We found that the dynamics of both the recurrent layer of the network and human EEG signals exhibit envelope phase tracking with similar time lags. We also computed the representational distance matrices (RDMs) of brain and network responses to speech stimuli. The model RDMs became more similar to the brain RDM when going from early network layers to later ones, and eventually peaked at the recurrent layer. These results suggest that the Deep Speech RNN captures a representation of temporal features of speech in a manner similar to human brain.