bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure Detection in Deep Neural Networks for Medical Imaging
Authors: Ahmed Sabeen , Dera Dimah , Hassan Saud Ul , Bouaynaya Nidhal , Rasool Ghulam
Published: July 2022

Deep neural networks (DNNs) have started to find their role in the modern healthcare system. DNNs are being developed for diagnosis, prognosis, treatment planning, and outcome prediction for various diseases. With the increasing number of applications of DNNs in modern healthcare, their trustworthiness and reliability are becoming increasingly important. An essential aspect of trustworthiness is detecting the performance degradation and failure of deployed DNNs in medical settings. The softmax output values produced by DNNs are not a calibrated measure of model confidence. Softmax probability numbers are generally higher than the actual model confidence. The model confidence-accuracy gap further increases for wrong predictions and noisy inputs. We employ recently proposed Bayesian deep neural networks (BDNNs) to learn uncertainty in the model parameters. These models simultaneously output the predictions and a measure of confidence in the predictions. By testing these models under various noisy conditions, we show that the (learned) predictive confidence is well calibrated. We use these reliable confidence values for monitoring performance degradation and failure detection in DNNs. We propose two different failure detection methods. In the first method, we define a fixed threshold value based on the behavior of the predictive confidence with changing signal-to-noise ratio (SNR) of the test dataset. The second method learns the threshold value with a neural network. The proposed failure detection mechanisms seamlessly abstain from making decisions when the confidence of the BDNN is below the defined threshold and hold the decision for manual review. Resultantly, the accuracy of the models improves on the unseen test samples. We tested our proposed approach on three medical imaging datasets: PathMNIST, DermaMNIST, and OrganAMNIST, under different levels and types of noise. An increase in the noise of the test images increases the number of abstained samples. BDNNs are inherently robust and show more than 10% accuracy improvement with the proposed failure detection methods. The increased number of abstained samples or an abrupt increase in the predictive variance indicates model performance degradation or possible failure. Our work has the potential to improve the trustworthiness of DNNs and enhance user confidence in the model predictions.
Genetic Configuration of Genomic Resistance Islands in Acinetobacter baumannii Clinical Isolates From Egypt
Authors: Hamed Samira M. , Hussein Amira F. A. , Al-Agamy Mohamed H. , Radwan Hesham H. , Zafer Mai M.
Published: July 2022

In Acinetobacter baumannii (A. baumannii), a wide repertoire of resistance genes is often carried within genomic resistance islands (RIs), particularly in high-risk global clones (GCs). As the first in Egypt, the current study aimed at exploring the diversity and genetic configuration of RIs in the clinical isolates of A. baumannii. For this purpose, draft genomes of 18 isolates were generated by Illumina sequencing. Disk diffusion susceptibility profiling revealed multidrug resistance (MDR) and extensive drug resistance (XDR) phenotypes in 27.7 and 72.2%, respectively. The highest susceptibility was noted for tigecycline (100.0%) followed by colistin (94.4%), for which an MIC50 of 0.25 μg/ml was recorded by the broth microdilution assay. Sequence typing (ST) showed that the majority of the isolates belonged to high-risk global clones (GC1, GC2, and GC9). A novel Oxford sequence type (ST2329) that also formed a novel clonal complex was submitted to the PubMLST database. A novel blaADC variant (blaADC−258) was also identified in strain M18 (ST85Pas/1089Oxf). In addition to a wide array of resistance determinants, whole-genome sequencing (WGS) disclosed at least nine configurations of genomic RIs distributed over 16/18 isolates. GC2 isolates accumulated the largest number of RIs (three RIs/isolate) followed by those that belong to GC1 (two RIs/isolate). In addition to Tn6022 (44.4%), the comM gene was interrupted by AbaR4 (5.5%) and three variants of A. baumanniigenomic resistance island 1(AbGRI)-type RIs (44.4%), including AbaR4b (16.6%) and two novel configurations of AbGRI1-like RIs (22.2%). Three of which (AbaR4, AbaR4b, and AbGRI1-like-2) carried blaOXA−23 within Tn2006. With less abundance (38.8%), IS26-bound RIs were detected exclusively in GC2 isolates. These included a short version of AbGRI2 (AbGRI2-15) carrying the genes blaTEM−1 and aphA1 and two variants of AbGRI3 RIs carrying up to seven resistance genes [mphE-msrE-armA-sul1-aadA1-catB8-aacA4]. Confined to GC1 (22.2%), sulfonamide resistance was acquired by an ISAba1 bracketed GIsul2 RI. An additional RI (RI-PER-7) was also identified on a plasmid carried by strain M03. Among others, RI-PER-7 carried the resistance genes armA and blaPER−7. Here, we provided a closer view of the diversity and genetic organization of RIs carried by a previously unexplored population of A. baumannii.
Study of CD27, CD38, HLA-DR and Ki-67 immune profiles for the characterization of active tuberculosis, latent infection and end of treatment
Authors: Díaz-Fernández Sergio , Villar-Hernández Raquel , Stojanovic Zoran , Fernández Marco , Galvão Maria Luiza De Souza , Tolosa Guillermo , Sánchez-Montalva Adrián , Abad Jorge , Jiménez-Fuentes María Ángeles , Safont Guillem , Romero Iris , Sabrià Josefina , Prat Cristina , Domínguez Jose , Latorre Irene
Published: July 2022

Background

Current blood-based diagnostic tools for TB are insufficient to properly characterize the distinct stages of TB, from the latent infection (LTBI) to its active form (aTB); nor can they assess treatment efficacy. Several immune cell biomarkers have been proposed as potential candidates for the development of improved diagnostic tools.

Objective

To compare the capacity of CD27, HLA-DR, CD38 and Ki-67 markers to characterize LTBI, active TB and patients who ended treatment and resolved TB.

Methods

Blood was collected from 45 patients defined according to clinical and microbiological criteria as: LTBI, aTB with less than 1 month of treatment and aTB after completing treatment. Peripheral blood mononuclear cells were stimulated with ESAT-6/CFP-10 or PPD antigens and acquired for flow cytometry after labelling with conjugated antibodies against CD3, CD4, CD8, CD27, IFN-γ, TNF-α, CD38, HLA-DR, and Ki-67. Conventional and multiparametric analyses were done with FlowJo and OMIQ, respectively.

Results

The expression of CD27, CD38, HLA-DR and Ki-67 markers was analyzed in CD4+ T-cells producing IFN-γ and/or TNF-α cytokines after ESAT-6/CFP-10 or PPD stimulation. Within antigen-responsive CD4+ T-cells, CD27− and CD38+ (ESAT-6/CFP-10-specific), and HLA-DR+ and Ki-67+ (PPD- and ESAT-6/CFP-10-specific) populations were significantly increased in aTB compared to LTBI. Ki-67 demonstrated the best discriminative performance as evaluated by ROC analyses (AUC > 0.9 after PPD stimulation). Data also points to a significant change in the expression of CD38 (ESAT-6/CFP-10-specific) and Ki-67 (PPD- and ESAT-6/CFP-10-specific) after ending the anti-TB treatment regimen. Furthermore, ratio based on the CD27 median fluorescence intensity in CD4+ T-cells over Mtb-specific CD4+ T-cells showed a positive association with aTB over LTBI (ESAT-6/CFP-10-specific). Additionally, multiparametric FlowSOM analyses revealed an increase in CD27 cell clusters and a decrease in HLA-DR cell clusters within Mtb-specific populations after the end of treatment.

Conclusion

Our study independently confirms that CD27−, CD38+, HLA-DR+ and Ki-67+ populations on Mtb-specific CD4+ T-cells are increased during active TB disease. Multiparametric analyses unbiasedly identify clusters based on CD27 or HLA-DR whose abundance can be related to treatment efficacy. Further studies are necessary to pinpoint the convergence between conventional and multiparametric approaches.
Progressive microbial adaptation of the bovine rumen and hindgut in response to a step-wise increase in dietary starch and the influence of phytogenic supplementation
Authors: Ricci Sara , Pacífico Cátia , Castillo-Lopez Ezequias , Rivera-Chacon Raul , Schwartz-Zimmermann Heidi E. , Reisinger Nicole , Berthiller Franz , Zebeli Qendrim , Petri Renee M.
Published: July 2022

Microbial composition and activity in the gastrointestinal tract (GIT) of cattle has important implications for animal health and welfare, driving the focus of research toward ways to modify their function and abundance. However, our understanding of microbial adaption to nutritional changes remains limited. The aim of this study was to examine the progressive mechanisms of adaptation in the rumen and hindgut of cattle receiving increasing amounts of starch with or without dietary supplementation of a blended phytogenic feed additive (PFA; containing menthol, thymol and eugenol). We used 16S rRNA gene amplicon sequencing to assess the microbial composition and predicted metabolic pathways in ruminal solid and liquid digesta, and feces. Furthermore, we employed targeted liquid chromatography-mass spectrometry methods to evaluate rumen fluid metabolites. Results indicated a rapid microbial adaptation to diet change, starting on the second day of starch feeding for the particle associated rumen liquid (PARL) microbes. Solid rumen digesta- and feces-associated microbes started changing from the following day. The PARL niche was the most responsive to dietary changes, with the highest number of taxa and predicted pathways affected by the increase in starch intake, as well as by the phytogenic supplementation. Despite the differences in the microbial composition and metabolic potential of the different GIT niches, all showed similar changes toward carbohydrate metabolism. Metabolite measurement confirmed the high prevalence of glucose and volatile fatty acids (VFAs) in the rumen due to the increased substrate availability and metabolic activity of the microbiota. Families Prevotellaceae, Ruminococcaceae and Lachnospiraceae were found to be positively correlated with carbohydrate metabolism, with the latter two showing wide-ranging predicted metabolic capabilities. Phytogenic supplementation affected low abundant taxa and demonstrated the potential to prevent unwanted implications of feeding high-concentrate diet, such as reduction of microbial diversity. The inclusion of 50% concentrate in the diet caused a major shift in microbial composition and activity in the GIT of cattle. This study demonstrated the ability of microorganisms in various GIT niches to adjust differentially, yet rapidly, to changing dietary conditions, and revealed the potential beneficial effects of supplementation with a PFA during dietary adaptation.
Molecular characterization of extended spectrum cephalosporin resistant Escherichia coli isolated from livestock and in-contact humans in Southeast Nigeria
Authors: Olorunleke Solomon O. , Kirchner Miranda , Duggett Nicholas , AbuOun Manal , Okorie-Kanu Onyinye J. , Stevens Kim , Card Roderick M. , Chah Kennedy Foinkfu , Nwanta John A. , Brunton Lucy A. , Anjum Muna F.
Published: July 2022

The rise in antimicrobial resistance (AMR) in bacteria is reducing therapeutic options for livestock and human health, with a paucity of information globally. To fill this gap, a One-Health approach was taken by sampling livestock on farms (n = 52), abattoir (n = 8), and animal markets (n = 10), and in-contact humans in Southeast Nigeria. Extended spectrum cephalosporin (ESC)-resistant (ESC-R) Escherichia coli was selectively cultured from 975 healthy livestock faecal swabs, and hand swabs from in-contact humans. Antimicrobial susceptibility testing (AST) was performed on all ESC-R E. coli. For isolates showing a multi-drug resistance (MDR) phenotype (n = 196), quantitative real-time PCR (qPCR) was performed for confirmation of extended-spectrum β-lactamase (ESBL) and carbapenemase genes. Whole-genome sequencing (WGS) was performed on a subset (n = 157) for detailed molecular characterisation. The results showed ESC-R E. coli was present in 41.2% of samples, with AST results indicating 48.8% of isolates were phenotypically MDR. qPCR confirmed presence of ESBL genes, with blaCTX-M present in all but others in a subset [blaTEM (62.8%) and blaSHV (0.5%)] of isolates; none harboured transferable carbapenemase genes. Multi-locus sequence typing identified 34 Sequence Types (ST) distributed among different sampling levels; ST196 carrying blaCTX-M-55 was predominant in chickens. Large numbers of single nucleotide polymorphisms (SNPs) in the core genome of isolates, even within the same clade by phylogenetic analysis, indicated high genetic diversity. AMR genotyping indicated the predominant blaCTX-M variant was blaCTX-M-15 (87.9%), although blaCTX-M-55, blaCTX-M-64, and blaCTX-M-65 were present; it was notable that blaCTX-M-1, common in livestock, was absent. Other predominant AMR genes included: sul2, qnrS1, strB, blaTEM-1b, tetA-v2, and dfrA14, with prevalence varying according to host livestock species. A blaCTX-M-15 harbouring plasmid from livestock isolates in Ebonyi showed high sequence identity to one from river/sewage water in India, indicating this ESBL plasmid to be globally disseminated, being present beyond the river environment. In conclusion, ESC-R E. coli was widespread in livestock and in-contact humans from Southeast Nigeria. WGS data indicated the isolates were genetically highly diverse, probably representing true diversity of wild type E. coli; they were likely to be MDR with several harbouring blaCTX-M-15. Surprisingly, human isolates had highest numbers of AMR genes and pigs the least.
Diversity and composition of soil bacteria between abandoned and selective-farming farmlands in an antimony mining area
Authors: Duan Renyan , Du Yihuan , Chen Zhiwei , Zhang Yaqi , Hu Wei , Yang Li , Xiang Guohong , Luo Yucai
Published: July 2022

Background and aims

Land abandonment and selective farming are two common management methods to restore the soil conditions of low-pollution farmland in mining areas. The soil bacterial community plays an important role in farmland soil restoration; however, few studies have compared the composition and diversity of soil bacteria between the abandoned farmlands (AFS) and selective-farming farmlands (FFS). Here, the effects of AFS and FFS on soil properties and bacterial diversity were evaluated in an antimony (Sb) mining area in southern China. This study aimed to identify effective land management methods in terms of positive or negative changes in soil environment and bacterial diversity.

Methods

16S rRNA high-throughput sequencing was used to compare the diversity and composition of soil bacteria between AFS and FFS in the Xikuangshan (the largest Sb mine in the world).

Results

Compared to AFS, FFS had higher Sb concentration and nutritional properties (e.g., available N, P, and K) and lower Zn concentration (p < 0.05). The bacterial alpha diversity including Chao1 index, Simpson index, Shannon index and Pielou−e index in FFS was higher than AFS (p < 0.05). At the phylum level, FFS had higher relative abundances of Chloroflexi, Acidobacteria, Gemmatimonadetes, and Rokubacteria, and lower relative abundances of Firmicutes, Actinobacteria, and Bacteroidetes. At the genus level, FFS had higher relative abundances of Acidothermus, Haliangium, and Rokubacteriales, and lower relative abundances of Bacillus, Rhodococcus, Sphingomonas, and 67-14. Redundancy analysis indicated that soil heavy metal content and soil fertility were closely correlated with the soil bacterial community. Altogether, selective farming of low-pollution farmland in the mining area can improve soil properties and soil bacterial diversity.
Family 1 glycosyltransferases (GT1, UGTs) are subject to dilution-induced inactivation and low chemo stability toward their own acceptor substrates
Authors: Teze David , Bidart Gonzalo Nahuel , Welner Ditte Hededam
Published: July 2022

Glycosylation reactions are essential but challenging from a conventional chemistry standpoint. Conversely, they are biotechnologically feasible as glycosyltransferases can transfer sugar to an acceptor with perfect regio- and stereo-selectivity, quantitative yields, in a single reaction and under mild conditions. Low stability is often alleged to be a limitation to the biotechnological application of glycosyltransferases. Here we show that these enzymes are not necessarily intrinsically unstable, but that they present both dilution-induced inactivation and low chemostability towards their own acceptor substrates, and that these two phenomena are synergistic. We assessed 18 distinct GT1 enzymes against three unrelated acceptors (apigenin, resveratrol, and scopoletin—respectively a flavone, a stilbene, and a coumarin), resulting in a total of 54 enzymes: substrate pairs. For each pair, we varied catalyst and acceptor concentrations to obtain 16 different reaction conditions. Fifteen of the assayed enzymes (83%) displayed both low chemostability against at least one of the assayed acceptors at submillimolar concentrations, and dilution-induced inactivation. Furthermore, sensitivity to reaction conditions seems to be related to the thermal stability of the enzymes, the three unaffected enzymes having melting temperatures above 55°C, whereas the full enzyme panel ranged from 37.4 to 61.7°C. These results are important for GT1 understanding and engineering, as well as for discovery efforts and biotechnological use.
NPC1 Deficiency Contributes to Autophagy-Dependent Ferritinophagy in HEI-OC1 Auditory Cells
Authors: Liang Lihong , Wang Hongshun , Yao Jun , Wei Qinjun , Lu Yajie , Wang Tianming , Cao Xin
Published: July 2022

Niemann–Pick type C disease (NPCD) is a rare genetic syndrome characterized by cholesterol accumulation in multiple organelles. NPCD is mainly caused by gene deficiency of NPC intracellular cholesterol transporter 1 (NPC1). It has been reported that some of the NPCD patients exhibit clinical features of progressive hearing loss at high frequency and iron disorder, but the underlying relationship is unknown. A recent study has reported that ferroptosis contributes to the impairment of cochlear hair cells that are related to sensory hearing. In this study, we generated NPC1-deficient HEI-OC1 cells to show the effect of NPC1 deficiency on cochlear outer hair cells. We found that NPC1 deficiency enhances autophagy-dependent ferritinophagy to release Fe (II). Our work provides important insights into the effect of NPC1 deficiency in auditory cells, indicating that it induces ferroptosis and results in hearing loss.
Instrumental Activities of Daily Living by Subjective and Objective Measures: The Impact of Depression and Personality
Authors: Numbers Katya , Jang Sujin , Brodaty Henry , Sachdev Perminder S. , Draper Brian , Reppermund Simone
Published: July 2022

Objective

Previous research shows that depression and personality are independently associated with self- and informant-reports of the ability to perform instrumental activities of daily living (IADLs). However, less is known about the association between depression and personality and performance-based measures of IADLs. We aimed to determine how depression and personality predict self-and informant-reports of IADL compared to performance-based measures of IADLs in a sample of older adults with normal cognition (NC) and Mild Cognitive Impairment (MCI).

Methods

Participants consisted of 385 older adults with NC (n = 235), or a diagnosis of MCI (n = 150), aged between 76 and 99-years from the Sydney Memory and Ageing Study. Participants underwent comprehensive neuropsychological and clinical assessments to determine global cognition and clinical diagnoses. Personality traits were measured by the NEO Five-Factor Inventory (NEO-FFI) and depression by the Geriatric Depression Scale (GDS). Subjective IADLs were self- and informant-reported Bayer Activities of Daily Living (B-ADL) scales and objective IADL was the Sydney Test of Activities of Daily Living in Memory Disorders (STAM). Linear regressions examined the relationship between depression and personality and the three types of IADL measures, controlling for all covariates and global cognition.

Results

Participant-reported IADL, although associated with global cognition, was more strongly associated with GDS and NEO-FFI scores (conscientiousness and neuroticism). Informant-reported IADL was strongly associated with both global cognition and participants’ GDS scores. STAM scores were not associated with participants’ GDS or NEO-FFI scores; instead, they were predicted by demographics and global cognition.

Conclusion

These results suggest that performance-based measures of IADL may provide more objective and reliable insight into an individual’s underlying functional ability and are less impacted by the participants’ mood and personality compared to subjectively reported IADL. We argue that performance-based IADL measures are preferable when trying to accurately assess everyday functional ability and its relationship to cognitive status. Where performance-based measures are not available (e.g., in some clinical settings), informant ratings should be sought as they are less influenced by the participant’s personality and mood compared to self-reports.
Exploring the effects of peripheral sensibility on visuospatial and postural capacities during goal-directed movements in long-term Tai Chi practitioners
Authors: Shao Zhufeng , Li Li , Mao Min , Sun Wei , Zhang Cui , Song Qipeng
Published: July 2022

Background

Falls are directly related to visuospatial ability and postural stability. Perturbations of upper body movements pose a challenge to older adults and may cause falls. This study investigated visuospatial ability and postural stability during goal-directed upper body movements between the Tai Chi and control groups and tried to connect them with their sensations.

Materials and methods

Thirty-seven older adults were recruited to perform the touch (TT) and blind touch (BTT) tasks. The target positioning error (TPE), ankle proprioception, tactile sensation, time to stabilization (TTS), and maximum displacement (Dmax) of the center of pressure trajectory were compared between the groups during the tasks. The relationships of visuospatial ability and postural stability to proprioception and tactile sensation were investigated.

Results

Dmax in the mediolateral (DmaxML) direction decreased during BTT compared to TT among the Tai Chi group but not the control group. Compared to the control group, less Dmax in the anterio-posterior (DmaxAP) direction, and shorter TTS in AP/ML (TTSAP/TTSML) directions were observed among the Tai Chi group. Compared to TT, DmaxAP decreased during the BTT. The Tai Chi group had less TPE in the vertical (TPEV) direction and in three-dimensional space. Among the Tai Chi group, TPEV, TTSML, and DmaxAP were correlated to their proprioception during plantarflexion; TTSAP was correlated to tactile sensation at the great toe during the TT and BTT; DmaxAP was correlated to tactile sensation at the great toe during the TT. Among the control group, TTSML was correlated to ankle proprioception during dorsiflexion and plantarflexion during the BTT.

Conclusion

Long-term Tai Chi practitioners exhibited superior visuospatial ability and postural stability during goal-directed upper body movements, which was associated with sensitive proprioception and tactile sensation.
Dysfunction of Emotion Regulation in Mild Cognitive Impairment Individuals Combined With Depressive Disorder: A Neural Mechanism Study
Authors: Liu Meng , Ma Jing , Fu Chang-Yong , Yeo Janelle , Xiao Sha-Sha , Xiao Wei-Xin , Li Ren-Ren , Zhang Wei , Xie Zeng-Mai , Li Ying-Jie , Li Yun-Xia
Published: July 2022

Depression increases the risk of progression from mild cognitive impairment (MCI) to dementia, where impaired emotion regulation is a core symptom of depression. However, the neural mechanisms underlying the decreased emotion regulation in individuals with MCI combined with depressive symptoms are not precise. We assessed the behavioral performance by emotion regulation tasks and recorded event-related electroencephalography (EEG) signals related to emotion regulation tasks simultaneously. EEG analysis, including event-related potential (ERP), event-related spectral perturbation (ERSP), functional connectivity and graph theory, was used to compare the difference between MCI individuals and MCI depressed individuals in behavioral performance, the late positive potential (LPP) amplitudes, neural oscillations and brain networks during the processing of emotional stimuli. We found that MCI depressed individuals have negative preferences and are prone to allocate more attentional resources to negative stimuli. Results suggested that theta and alpha oscillations activity is increased, and gamma oscillations activity is decreased during negative stimulus processing in MCI depressed individuals, thus indicating that the decreased emotion regulation in MCI depressed individuals may be associated with enhanced low-frequency and decreased high-frequency oscillations activity. Functional connectivity analysis revealed a decrease in functional connectivity in the left cerebral hemisphere of the alpha band and an increase in functional connectivity in the right cerebral hemisphere of the alpha band in MCI depressed individuals. Graph theory analysis suggested that global network metrics, including clustering coefficients and disassortative, decreased, while nodal and modular network metrics regarding local nodal efficiency, degree centrality, and betweenness centrality were significantly increased in the frontal lobe and decreased in the parieto-occipital lobe, which was observed in the alpha band, further suggesting that abnormal alpha band network connectivity may be a potential marker of depressive symptoms. Correlational analyses showed that depressive symptoms were closely related to emotion regulation, power oscillations and functional connectivity. In conclusion, the dominant processing of negative stimuli, the increased low-frequency oscillations activity and decreased high-frequency activity, so as the decrease in top-down information processing in the frontal parieto-occipital lobe, results in the abnormality of alpha-band network connectivity. It is suggested that these factors, in turn, contribute to the declined ability of MCI depressed individuals in emotion regulation.
Atrial cardiopathy and cognitive impairment
Authors: Myers Sarah J. , Jiménez-Ruiz Amado , Sposato Luciano A. , Whitehead Shawn N.
Published: July 2022

Cognitive impairment involves complex interactions between multiple pathways and mechanisms, one of which being cardiac disorders. Atrial cardiopathy (AC) is a structural and functional disorder of the left atrium that may be a substrate for other cardiac disorders such as atrial fibrillation (AF) and heart failure (HF). The association between AF and HF and cognitive decline is clear; however, the relationship between AC and cognition requires further investigation. Studies have shown that several markers of AC, such as increased brain natriuretic peptide and left atrial enlargement, are associated with an increased risk for cognitive impairment. The pathophysiology of cognitive decline in patients with AC is not yet well understood. Advancing our understanding of the relationship between AC and cognition may point to important treatable targets and inform future therapeutic advancements. This review presents our current understanding of the diagnosis of AC, as well as clinical characteristics and potential pathways involved in the association between AC and cognitive impairment.
Alzheimer’s disease and epilepsy: The top 100 cited papers
Authors: Zhang Gui-Fen , Gong Wen-Xin , Xu Zheng-Yan-Ran , Guo Yi
Published: July 2022

Background

Alzheimer’s disease (AD) is one of the common neurodegenerative diseases, which often coexists with epilepsy. It is very significant to study the treatment options and the relationship between AD and epilepsy.

Aims

The purpose of this study was to analyze the top 100 cited papers about AD and epilepsy using bibliometrics, and to describe the current situation and predict research hot spots.

Methods

Top 100 papers were obtained from the Web of Science Core Collection (WoSCC). The WoSCC was used to analyze the author, institution, country, title, keywords, abstract, citation, subject category, publication year, impact factor (IF), and other functions. SPSS25 software was used for statistical analysis and CiteSpace V.5.7.R2 was used to visualize the information through collaborative networks.

Results

The number of publications gradually increased from 2000 to 2021. The total citation count for the top 100 papers ranged from 15 to 433(mean = 67.43). The largest number of papers were published in 2016 (n = 11). Meanwhile, USA (centrality: 0.93) and Columbia University (centrality: 0.06) were the most influential research country and institutions, respectively. The top contributing journals was Journal of Alzheimer’s Disease (8%). The IF for journals ranged from 1.819 to 53.44. A network analysis of the author’s keywords showed that “beta” (centrality: 0.39), “amyloid beta” (centrality: 0.29), “hyperexcitability” (centrality: 0.29) and “disease” (centrality: 0.29) had a high degree of centrality.

Conclusion

AD and epilepsy have been intensively studied in the past few years. The relationships, mechanisms and treatment of AD and epilepsy will be subjects of active research hotpots in future. These findings provide valuable information for clinicians and scientists to identify new perspectives with potential collaborators and cooperative countries.
Signal transmission in mature mammalian vestibular hair cells
Authors: Spaiardi Paolo , Marcotti Walter , Masetto Sergio , Johnson Stuart L.
Published: July 2022

The maintenance of balance and gaze relies on the faithful and rapid signaling of head movements to the brain. In mammals, vestibular organs contain two types of sensory hair cells, type-I and type-II, which convert the head motion-induced movement of their hair bundles into a graded receptor potential that drives action potential activity in their afferent fibers. While signal transmission in both hair cell types involves Ca2+-dependent quantal release of glutamate at ribbon synapses, type-I cells appear to also exhibit a non-quantal mechanism that is believed to increase transmission speed. However, the reliance of mature type-I hair cells on non-quantal transmission remains unknown. Here we investigated synaptic transmission in mammalian utricular hair cells using patch-clamp recording of Ca2+ currents and changes in membrane capacitance (ΔCm). We found that mature type-II hair cells showed robust exocytosis with a high-order dependence on Ca2+ entry. By contrast, exocytosis was approximately 10 times smaller in type-I hair cells. Synaptic vesicle exocytosis was largely absent in mature vestibular hair cells of CaV1.3 (CaV1.3−/−) and otoferlin (Otof−/−) knockout mice. Even though Ca2+-dependent exocytosis was small in type-I hair cells of wild-type mice, or absent in CaV1.3−/− and Otof−/−mice, these cells were able to drive action potential activity in the postsynaptic calyces. This supports a functional role for non-quantal synaptic transmission in type-I cells. The large vesicle pools in type-II cells would facilitate sustained transmission of tonic or low-frequency signals. In type-I cells, the restricted vesicle pool size, together with a rapid non-quantal mechanism, could allow them to sustain high-frequency phasic signal transmission at their specialized large calyceal synapses.
Protein quality control of N-methyl-D-aspartate receptors
Authors: Benske Taylor M. , Mu Ting-Wei , Wang Ya-Juan
Published: July 2022

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated cation channels that mediate excitatory neurotransmission and are critical for synaptic development and plasticity in the mammalian central nervous system (CNS). Functional NMDARs typically formviathe heterotetrameric assembly of GluN1 and GluN2 subunits. Variants withinGRINgenes are implicated in various neurodevelopmental and neuropsychiatric disorders. Due to the significance of NMDAR subunit composition for regional and developmental signaling at synapses, properly folded receptors must reach the plasma membrane for their function. This review focuses on the protein quality control of NMDARs. Specifically, we review the quality control mechanisms that ensure receptors are correctly folded and assembled within the endoplasmic reticulum (ER) and trafficked to the plasma membrane. Further, we discuss disease-associated variants that have shown disrupted NMDAR surface expression and function. Finally, we discuss potential targeted pharmacological and therapeutic approaches to ameliorate disease phenotypes by enhancing the expression and surface trafficking of subunits harboring disease-associated variants, thereby increasing their incorporation into functional receptors.
Dopamine-Mediated Major Depressive Disorder in the Neural Circuit of Ventral Tegmental Area-Nucleus Accumbens-Medial Prefrontal Cortex: From Biological Evidence to Computational Models
Authors: Li Yuanxi , Zhang Bing , Pan Xiaochuan , Wang Yihong , Xu Xuying , Wang Rubin , Liu Zhiqiang
Published: July 2022

Major depressive disorder (MDD) is a serious psychiatric disorder, with an increasing incidence in recent years. The abnormal dopaminergic pathways of the midbrain cortical and limbic system are the key pathological regions of MDD, particularly the ventral tegmental area- nucleus accumbens- medial prefrontal cortex (VTA-NAc-mPFC) neural circuit. MDD usually occurs with the dysfunction of dopaminergic neurons in VTA, which decreases the dopamine concentration and metabolic rate in NAc/mPFC brain regions. However, it has not been fully explained how abnormal dopamine concentration levels affect this neural circuit dynamically through the modulations of ion channels and synaptic activities. We used Hodgkin-Huxley and dynamical receptor binding model to establish this network, which can quantitatively explain neural activity patterns observed in MDD with different dopamine concentrations by changing the kinetics of some ion channels. The simulation replicated some important pathological patterns of MDD at the level of neurons and circuits with low dopamine concentration, such as the decreased action potential frequency in pyramidal neurons of mPFC with significantly reduced burst firing frequency. The calculation results also revealed that NaP and KS channels of mPFC pyramidal neurons played key roles in the functional regulation of this neural circuit. In addition, we analyzed the synaptic currents and local field potentials to explain the mechanism of MDD from the perspective of dysfunction of excitation-inhibition balance, especially the disinhibition effect in the network. The significance of this article is that we built the first computational model to illuminate the effect of dopamine concentrations for the NAc-mPFC-VTA circuit between MDD and normal groups, which can be used to quantitatively explain the results of existing physiological experiments, predict the results for unperformed experiments and screen possible drug targets.
Longitudinal imaging of individual olfactory sensory neurons in situ
Authors: Zak Joseph D.
Published: July 2022

Olfactory sensory neurons are found deep within the nasal cavity at a spatially restricted sheet of sensory epithelium. Due to their location behind the nasal turbinates, accessing these cells for physiological measurements in living animals is challenging, and until recently, not possible. As a further complication, damage to the overlying bone on the dorsal surface of the snout disrupts the negative pressure distribution throughout the nasal cavities, which fundamentally alters how odorants are delivered to the sensory epithelium and the inherent mechanosensory properties of olfactory sensory neurons in live animals. The approach described here circumvents these limitations and allows for optical access to olfactory sensory neurons in mice across time scales ranging from days to months.
SARS-CoV-2 neutralizing antibody response after three doses of mRNA1273 vaccine and COVID-19 in hemodialysis patients
Authors: Wang Xiaoling , Han Maggie , Fuentes Lemuel Rivera , Thwin Ohnmar , Grobe Nadja , Wang Kevin , Wang Yuedong , Kotanko Peter
Published: July 2022

Background

In hemodialysis patients, a third vaccination is frequently administered to augment protection against coronavirus disease 2019 (COVID-19). However, the newly emerged B.1.1.159 (Omicron) variant may evade vaccinal protection more easily than previous strains. It is of clinical interest to better understand the neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants after booster vaccine or COVID-19 infection in these mostly immunocompromised patients.

Methods

Hemodialysis patients from four dialysis centers were recruited between June 2021 and February 2022. Each patient provided a median of six serum samples. SARS-CoV-2 neutralizing antibodies (nAbs) against wild type (WT) or Omicron were measured using the GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit.

Results

Forty-two patients had three doses of mRNA1273. Compared to levels prior to the third dose, nAb-WT increased 18-fold (peak at day 23) and nAb-Omicron increased 23-fold (peak at day 24) after the third dose. Peak nAb-WT exceeded peak nAb-Omicron 27-fold. Twenty-one patients had COVID-19 between December 24, 2021, and February 2, 2022. Following COVID-19, nAb-WT and nAb-Omicron increased 12- and 40-fold, respectively. While levels of vaccinal and post-COVID nAb-WT were comparable, post-COVID nAb-Omicron levels were 3.2 higher than the respective peak vaccinal nAb-Omicron. Four immunocompromised patients having reasons other than end-stage kidney disease have very low to no nAb after the third dose or COVID-19.

Conclusions

Our results suggest that most hemodialysis patients have a strong humoral response to the third dose of vaccination and an even stronger post-COVID-19 humoral response. Nevertheless, nAb levels clearly decay over time. These findings may inform ongoing discussions regarding a fourth vaccination in hemodialysis patients.
Risk Factors for Recurrence of Intracranial Aneurysm After Coil Embolization: A Meta-Analysis
Authors: Jin Ji , Guo Geng , Ren Yeqing , Yang Biao , Wu Yongqiang , Wang Shule , Sun Yanqi , Wang Xiaogang , Wang Yuxiao , Zheng Jianzhong
Published: July 2022

Intracranial aneurysm is a severe cerebral disorder involving complicated risk factors and endovascular coiling is a common therapeutic selection for intracranial aneurysm. The recurrence is a clinical challenge in intracranial aneurysms after coil embolization. With this study, we provided a meta-analysis of the risk factors for the recurrence of intracranial aneurysm after coil embolization. Nine studies were included with a total of 1,270 studies that were retrieved from the database. The sample size of patients with intracranial aneurysms ranged from 241 to 3,530, and a total of 9,532 patients were included in the present meta-analysis. The intracranial aneurysms that occurred in middle cerebral artery (MCA) (OR = 1.09, 95% CI: 1.03–1.16, P = 0.0045) and posterior circulation (OR = 2.01, 95% CI: 1.55–2.60, P = 0.000) presented the significantly higher risk of recurrence after coil embolization. Meanwhile, intracranial aneurysms of size > 7 mm (OR = 5.38, 95%CI: 3.76–7.70, P = 0.000) had a significantly higher risk of recurrence after coil embolization. Moreover, ruptured aneurysm (OR = 2.86, 95% CI: 2.02–4.04, P = 0.000) and subarachnoid hemorrhage (SAH) (OR = 1.57, 95% CI: 1.20–2.06, P = 0.001) was positively correlated with the risk of recurrence after coil embolization. In conclusion, this meta-analysis identified the characteristics of intracranial aneurysms with MCA, posterior circulation, size > 7 mm, ruptured aneurysm, and SAH as the risk factors of recurrence after coil embolization for intracranial aneurysms.
The effects of stroke on weight transfer before voluntary lateral and forward steps
Authors: Lanza Marcel Bahia , Gray Vicki L.
Published: July 2022

There is a higher rate of falls in the first year after a stroke, and the ability to step in different directions is essential for avoiding a fall and navigating small spaces where falls commonly occur. The lateral transfer of weight is important for stabilizing the body before initiating a step. Hence, understanding the ability to control lateral weight transfer (WT) in different step directions might help understand falls in individuals with stroke. The present study aimed to compare the WT characteristics (onset time, duration, mediolateral center of pressure (ML COP) velocity, and ML COP displacement) and hip abduction torque preceding a lateral and forward voluntary step between individuals with stroke (paretic and non-paretic leg) and controls. Twenty individuals with stroke and ten controls performed voluntary choice reaction tests in the lateral and forward directions. Ten trials (five on each side—right and left) were performed for each step direction. The overall primary findings were that (1) the WT before a lateral step was shorter and initiated earlier, with a larger ML COP displacement and greater hip abductor torque in the stepping leg than the forward step, (2) there was greater hip abductor produced in the stance leg before a forward step than a lateral step, (3) the WT before the lateral step took longer to initiate and was slower to execute in individuals with stroke regardless of the leg (4) the WT before the forward step had more differences in the paretic than the non-paretic leg. Thus, for the first time, it was shown that the WT characteristics and hip abduction torque during the WT are different according to step direction and also appear to be impaired in individuals with stroke. These results have implications for understanding the direction that individuals with stroke are more susceptible to being unable to recover balance and are at risk of falling.
Essential tremor patients experience significant burden beyond tremor: A systematic literature review
Authors: Gerbasi Margaret E. , Nambiar Shruti , Reed Spencer , Hennegan Kalin , Hadker Nandini , Eldar-Lissai Adi , Cosentino Stephanie
Published: July 2022

Background

Essential tremor (ET) is among the most common movement disorders in adults. While ET is diagnosed and primarily characterized by the presence of tremor, it also can impact cognition, sleep, mood, and motor functioning more broadly. The manifestations of ET can have various consequences, including difficulty with activities of daily living (ADL), embarrassment, and overall decline in health-related quality of life, which have not been fully explored in prior studies.

Objective

We performed a systematic literature review to comprehensively characterize the burden experienced by patients with ET from the clinical and humanistic perspectives, focusing on outcomes beyond tremor.

Methods

This systematic literature review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches in PubMed, Embase, and Cochrane Library identified original, observational studies of the clinical and humanistic burden in adult patients with ET published in English between 2010 and 2020. Studies assessing epidemiology, treatment patterns, or disease management were excluded. Search results were screened according to pre-determined eligibility criteria. Data from included studies were collected, independently verified, and qualitatively synthesized.

Results

Following the screening of 2,303 records and 145 full-text articles, 39 studies were identified. There was significant heterogeneity in study designs, statistical approaches, and patient cohorts across the included studies. Patients with ET in these studies exhibited more severe disabilities and reduced independence compared to healthy individuals, and they often struggled to perform ADL and relied on caregivers for physical and emotional support. Patients also experienced various issues with movement and balance, increased risk of falls, depression, anxiety, poor sleep quality, and psychosocial consequences including embarrassment, apathy, and enfeeblement.

Conclusion

A systematic literature review of non-tremor manifestations and/or consequences of ET identified far-reaching negative impacts on patients' ability to function independently and revealed accompanying psychosocial effects, including social fear and embarrassment. The reduced function and psychosocial deficits observed in patients with ET result in significant clinical and humanistic burdens, decreasing quality of life. Future studies should evaluate this condition beyond the tremor itself to provide an improved understanding of the multi-dimensional burden of the disease, thereby highlighting the need to diagnose and appropriately manage patients with ET.
High Actin Expression in Thrombus of Acute Ischemic Stroke Can Be a Biomarker of Atherothrombotic Origin Stroke
Authors: Wang Rongyu , Wang Zhiqiang , Jiang Lianyan , Gu Gangfeng , Zheng Bo , Xian Liulin , Zhang Yaodan , Wang Jian
Published: July 2022

Background

As the treatment target, the imaging information and histologic characteristics of the thrombus may differ according to the stroke subtype. This study aimed to provide the correlative study of stroke etiology with the non-contrast CT, and histological composition of retrieved clots in acute ischemic stroke (AIS).

Materials and Methods

A total of 94 patients with AIS who underwent the endovascular treatment with successfully retrieved clots from January 2017 to October 2020 were enrolled in the present study. Histological analysis was performed using hematoxylin and eosin (H&E) staining and immunostaining with CD3, CD20, CD105, and actin antibodies. CT obtained at the patients' admission was to measure the attenuation and volume of all thrombus.

Results

A total of 94 subjects were included in this study. Fifty-six patients were classified as cardioembolic (CE), and 38 were classified with large-artery atherosclerosis (LAA). The subjects with LAA tend to exhibit higher actin and CD105 levels, and lower Hounsfield Unit (HU) values than subjects with CE. After adjusting for confounders, the actin was positively correlated with CD105 but not with HU values. Logistics regression shows actin was valuable for the prediction of LAA (OR, 1.148; 95% CI, 1.075–1.227; p < 0.001), even adjusted for age, sex, and intervention type (OR, 1.129; 95% CI, 1.048–1.216; p = 0.001), CT density and CD105 (OR, 1.161; 95% CI, 1.056–1.277; p = 0.002). Actin levels have a strong accuracy in differentiating LAA from CE, especially combined with CT density and CD105, which yielded a sensitivity of 63.2%, a specificity of 89.3%, with the area under the curve (AUC) at 0.821 (95% CI, 0.731–0.912).

Conclusion

Our findings suggest that actin's level was a major factor differentiating atherothrombotic origin strokes from the cardioembolic stroke.

Clinical Trial Registration

ChiCTR2100051173.