bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Spatial Profiling of Individual Glomeruli From Patients With Anti-Neutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis
Authors: Ye Lin , Liu Yu , Zhu Xuejing , Duan Tongyue , Wang Chang , Fu Xiao , Song Panai , Yuan Shuguang , Liu Hong , Sun Lin , Liu Fuyou , Lee Kyung , He John Cijiang , Chen Anqun
Published: March 2022

We previously showed that the rupture of Bowman’s capsule (BC) promotes the progression of crescentic glomerulonephritis by enhancing the entry of CD8+T cells into the glomeruli. In the present study, we utilized digital spatial profiling to simultaneously profile the altered abundances of the messenger RNA (mRNA) transcripts and proteins in the glomerular and periglomerular areas of four biopsy samples of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis (ANCA-GN) and two biopsy specimens of minimal change disease (MCD) controls. The paraffin-embedded biopsy samples were stained with collagen IV, CD45, and SYTO 13 to distinguish the glomeruli with periglomerular infiltration but intact BC, with focal BC rupture, and with extensive rupture of BC and glomeruli without crescent formation and leukocytic infiltration in ANCA-GN. By assessing multiple discrete glomerular areas, we found that the transcript expression levels of the secreted phosphoprotein-1 and its receptor CD44 were upregulated significantly in the glomeruli with more severe ruptures of BC, and their expression levels correlated positively with the fibrotic markers. We also found that both alternative and classic complement pathways were activated in the glomeruli from patients with ANCA-GN. Furthermore, M1 macrophages were involved mostly in the early stage of BC rupture, while M2 macrophages were involved in the late stage and may contribute to the fibrosis process of the crescents. Finally, loss of glomerular cells in ANCA-GN was likely mediated by apoptosis. Our results show that digital spatial profiling allows the comparative analysis of the mRNA and protein profiles in individual glomeruli affected differently by the disease process and the identification of potential novel mechanisms in ANCA-GN.
Celastrol Downmodulates Alpha-Synuclein-Specific T Cell Responses by Mediating Antigen Trafficking in Dendritic Cells
Authors: Ng Lam , Wang Xiaohui , Yang Chuanbin , Su Chengfu , Li Min , Cheung Allen Ka Loon
Published: March 2022

Parkinson’s Disease (PD) is a neurodegenerative disease that affects the elderly. It is associated with motor dysfunction due to the accumulation of misfolded or aggregated fibrillar alpha-synuclein (α-syn) in the mid-brain. Current treatments are mainly focused on relieving the symptoms but are accompanied by side effects and are limited in halting disease progression. Increasing evidence points to peripheral immune cells underlying disease development, especially T cells contributing to α-syn-related neuroinflammation in PD. The onset of these cells is likely mediated by dendritic cells (DCs), whose role in α-syn-specific responses remain less studied. Moreover, Traditional Chinese medicine (TCM)-derived compounds that are candidates to treat PD may alleviate DC-T cell-mediated immune responses. Therefore, our study focused on the role of DC in response to fibrillar α-syn and subsequent induction of antigen-specific T cell responses, and the effect of TCM Curcumin-analog C1 andTripterygium wilfordiiHook F-derived Celastrol. We found that although fibrillar α-syn did not induce significant inflammatory or T cell-mediating cytokines, robust pro-inflammatory T cell responses were found by co-culturing fibrillar α-syn-pulsed DCs with α-syn-specific CD4+T cells. Celastrol, but not C1, reduced the onset of pro-inflammatory T cell differentiation, through promoting interaction of endosomal, amphisomal, and autophagic vesicles with fibrillar α-syn, which likely lead to its degradation and less antigen peptides available for presentation and T cell recognition. In conclusion, regulating the intracellular trafficking/processing of α-syn by DCs can be a potential approach to control the progression of PD, in which Celastrol is a potential candidate to accomplish this.
Combined Single Cell Transcriptome and Surface Epitope Profiling Identifies Potential Biomarkers of Psoriatic Arthritis and Facilitates Diagnosis via Machine Learning
Authors: Liu Jared , Kumar Sugandh , Hong Julie , Huang Zhi-Ming , Paez Diana , Castillo Maria , Calvo Maria , Chang Hsin-Wen , Cummins Daniel D. , Chung Mimi , Yeroushalmi Samuel , Bartholomew Erin , Hakimi Marwa , Ye Chun Jimmie , Bhutani Tina , Matloubian Mehrdad , Gensler Lianne S. , Liao Wilson
Published: March 2022

Early diagnosis of psoriatic arthritis (PSA) is important for successful therapeutic intervention but currently remains challenging due, in part, to the scarcity of non-invasive biomarkers. In this study, we performed single cell profiling of transcriptome and cell surface protein expression to compare the peripheral blood immunocyte populations of individuals with PSA, individuals with cutaneous psoriasis (PSO) alone, and healthy individuals. We identified genes and proteins differentially expressed between PSA, PSO, and healthy subjects across 30 immune cell types and observed that some cell types, as well as specific phenotypic subsets of cells, differed in abundance between these cohorts. Cell type-specific gene and protein expression differences between PSA, PSO, and healthy groups, along with 200 previously published genetic risk factors for PSA, were further used to perform machine learning classification, with the best models achieving AUROC ≥ 0.87 when either classifying subjects among the three groups or specifically distinguishing PSA from PSO. Our findings thus expand the repertoire of gene, protein, and cellular biomarkers relevant to PSA and demonstrate the utility of machine learning-based diagnostics for this disease.
Blockade of Autophagy Prevents the Progression of Hyperuricemic Nephropathy Through Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis
Authors: Hu Yan , Shi Yingfeng , Chen Hui , Tao Min , Zhou Xun , Li Jinqing , Ma Xiaoyan , Wang Yi , Liu Na
Published: March 2022

Hyperuricemia has become a common metabolic disease, and is a risk factor for multiple diseases, including chronic kidney disease. Our recent study indicated that following persistent uric acid stimulation, autophagy was activated in rats of hyperuricemic nephropathy (HN) and facilitated the development of renal fibrosis. Nevertheless, the potential mechanism by which autophagy promoted the progression of HN is still not fully elucidated. Thus, in the current study, we investigated the mechanisms of autophagy inhibition on the development of HN. Our data showed that autophagy was activated in human renal tubular cell lines (HK-2) exposure to uric acid. Inhibition of autophagy with 3-methyladenine (3-MA) and transfected with Beclin-1 siRNA prevented uric acid-induced upregulation of α-SMA, Collagen I and Collagen III in HK-2 cells. Moreover, uric acid upregulated autophagy via promoting the p53 pathway. In vivo, we showed that hyperuricemic injury induced the activation of NLRP3 inflammasome and pyroptosis, as evidenced by cleavage of caspase-1 and caspase-11, activation of gasdermin D (GSDMD) and the release of IL-1β and IL-18. Treatment with autophagy inhibitor 3-MA alleviated aforementioned phenomenon. Stimulation with uric acid in HK-2 cells also resulted in NLRP3 inflammasome activation and pyroptotic cell death, however treatment with 3-MA prevented all these responses. Mechanistically, we showed that the elevation of autophagy and degradation of autophagolysosomes resulted in the release of cathepsin B (CTSB), which is related to the activation of NLRP3 inflammasome. CTSB siRNA can inhibit the activation of NLRP3 inflammasome and pyroptosis. Collectively, our results indicate that autophagy inhibition protects against HN through inhibiting NLRP3 inflammasome-mediated pyroptosis. What’s more, blockade the release of CTSB plays a crucial role in this process. Thus, inhibition of autophagy may be a promising therapeutic strategy for hyperuricemic nephropathy.
NLRP6-Dependent Pyroptosis-Related lncRNAs Predict the Prognosis of Hepatocellular Carcinoma
Authors: Zhang La , Zhang Xiuzhen , Zhao Wei , Xiao Xinyu , Liu Shanshan , Peng Qiling , Jiang Ning , Zhou Baoyong
Published: March 2022

Pyroptosis, a novel pro-inflammatory type of programmed cell death, is involved in the tumorigenesis of various cancers. Recent findings have implicated long non-coding RNAs (lncRNAs) in the serial steps of cancer development. However, the expression and prognostic signatures of pyroptosis-related lncRNAs in hepatocellular carcinoma (HCC) remain largely unknown. Therefore, a pyroptosis-related lncRNA prognostic model was constructed for HCC. Thirty-four pyroptosis-related genes were obtained from previous reviews, and gene expression data were collected from The Cancer Genome Atlas (TCGA) database. Spearman's correlation test was used to identify potential pyroptosis-related lncRNAs. Cox and LASSO regression analyses were used to construct a prognostic model. Subsequently, receiver operating characteristic (ROC) curves were constructed to assess the model's predictive ability for the overall survival (OS) of HCC patients. CytoHubba was used to screen out the potential hub gene, whose expression was verified using clinical samples from HCC patients. Finally, nine pyroptosis-related differentially expressed lncRNAs in HCC were identified, and a prognostic model with four pyroptosis-related lncRNAs was constructed with an area under the ROC curve (AUC) of approximately 0.734. Single-sample gene set enrichment analysis and TCGA revealed different immune infiltration and immune checkpoints between the two risk groups. Moreover, these lncRNAs are closely related to the pyroptosis-related gene, NLRP6, which may be considered a hub gene. NLRP6 was lower-expressed in HCC samples, and patients with lower expression of NLRP6 had the longer OS. In conclusion, NLRP6-dependent pyroptosis-related lncRNAs play important roles in tumor immunity and may be potential predictors and therapeutic targets for HCC.
Academic Half-Day Education Experience in Post-graduate Medical Training: A Scoping Review of Characteristics and Learner Outcomes
Authors: Choe Myong Sun , Huffman Lynne C. , Feldman Heidi M. , Hubner Lauren M.
Published: March 2022

Background

The academic half-day (AHD) has grown in popularity for medical education because it intends to provide learners with uninterrupted, immersive learning time that may promote participant attendance, engagement, and knowledge. Little is known about the extent of use, forms, or effectiveness of AHD in Post-graduate medical education. This scoping review summarizes existing literature and describes the learning outcomes, according to the Kirkpatrick model of learning evaluation, of AHD experiences on Post-graduate medical trainees.

Methods

Authors used Arksey and O'Malley's methodological framework, searching electronic scientific literature databases from the years of 1977–2019 with relevant key terms and identifying 735 papers. Two independent raters completed title/abstract screening and then extracted pertinent data from papers meeting specified criteria.

Results

Authors identified 38 relevant papers published in English, originating from programs in US (n = 19) and Canada (n = 19), spanning 4 disciplines: Medicine (n = 17, 45%), Pediatrics (n = 10, 26%), Critical Care/Surgery (n = 9, 24%), Radiology (n = 2, 5%). A majority (n = 33, 87%) described specific educational experiences; most focused on residents only (n = 27). The educational experiences included various teaching strategies; few were didactics only (n = 4) and most were multi-modal including simulation, case-based learning, problem-based learning, and/or self-directed online study. AHD size ranged from 5 to 364 participants (median 39). AHD length was 1.5–6 h (median 3). Required resources were inconsistently described. When evaluations of the specific educational experience were reported (n = 35 studies), the majority of studies used weak research designs (e.g., one group, pre/post-test, n = 19); few studies used strong research designs (e.g., randomized controlled trial, n = 2). Positive effects of AHD ranged across Kirkpatrick levels 1–3 learner outcomes.

Conclusions

The composition and content of AHD in Post-graduate medical education vary. Few studies of AHD use stringent research designs, and none include learner outcome measures at the highest Kirkpatrick level (i.e., level 4 results/patient outcomes). A consensus definition and further high-quality research on AHD in Post-graduate medical education is needed.
Corticosteroid Treatment Prevents Lipopolysaccharide-Induced Increase of ACE2 and Reduces Fibrin Degradation Products in Bronchoalveolar Lavage Fluid
Authors: Reindl-Schwaighofer Roman , Eskandary Farsad , Bartko Johann , Heinzel Andreas , Jilma Bernd , Hecking Manfred , Schoergenhofer Christian
Published: March 2022

The assessment of systemic corticosteroid effects on intrapulmonary disease biomarkers is challenging. This retrospective evaluation of a human endotoxemia model quantified ACE2 and fibrin degradation product (FDP) concentrations in bronchoalveolar lavage fluid (BALF) samples from a randomized, double-blind, placebo-controlled study (NCT01714427). Twenty-four healthy volunteers received either 2 × 40 mg intravenous dexamethasone or placebo. These doses were administered 12 h apart prior to bronchoscopy-guided intrabronchial lipopolysaccharide (LPS) stimulation (control: saline into the contralateral lung segment). We quantified ACE2 concentration, the Angiotensin-II-to-Angiotensin-1-7 conversion rate as well as FDP in BALF 6 h after LPS instillation. In placebo-treated subjects, LPS instillation increased ACE2 concentrations compared to unstimulated lung segments [1,481 (IQR: 736–1,965) vs. 546 (413–988) pg/mL; p = 0.016]. Dexamethasone abolished the increase in ACE2 concentrations (p=0.13). Accordingly, LPS instillation increased the Angiotensin-II-to-Angiotensin-1-7 conversion capacity significantly in the placebo cohort, indicating increased enzymatic activity (p = 0.012). FDP increased following LPS-instillation [8.9 (2.7–12.2) vs. 6.6 (0.9–9.6) ng/mL, p = 0.025] in the placebo group, while dexamethasone caused a shut-down of fibrinolysis in both lung segments. LPS instillation increased ACE2 concentration, its enzymatic activity and FDP, which was mitigated by systemic dexamethasone treatment. Our results strengthen previously published findings regarding the efficiency of corticosteroids for the treatment of COVID-19-induced acute lung injury.
Antibacterial Effects of Recombinant Endolysins in Disinfecting Medical Equipment: A Pilot Study
Authors: Choi Yoon-Jung , Kim Shukho , Bae Sohyun , Kim Yoonjung , Chang Hyun-Ha , Kim Jungmin
Published: March 2022

Nosocomial infections caused by multidrug-resistant (MDR) bacteria are severe life-threatening factors. Endolysins (lysins) degrade the bacterial cell wall peptidoglycan and may help control pathogens, especially MDR bacteria prevalent in hospital settings. This study was conducted to verify the potential of lysin as disinfectant to kill bacteria contaminating medical devices that cause hospital infections. Eight catheters removed from hospitalized patients were collected and tested for their ability to kill bacteria contaminating the catheters using two lysins, LysSS and CHAP-161. Catheter-contaminating bacterial species were isolated and identified by 16s rRNA sequencing. From the eight catheters, bacteria were cultured from seven catheters, and five bacterial species (Bacillus megaterium, Bacillus muralis, Corynebacterium striatum, Enterococcus faecium, and Staphylococcus epidermidis) were identified. LysSS could inhibit catheter-contaminating bacteria, including C. striatum and S. epidermidis, compared with untreated controls but could not inhibit the growth of E. faecium. CHAP-161 showed more bactericidal effects than LysSS, but could not inhibit the growth of S. epidermidis. This study showed the potential of lysin as an alternative disinfectant for hazardous chemical disinfectants used in hospitals.
Complete Genome Assemblies of All Xanthomonas translucens Pathotype Strains Reveal Three Genetically Distinct Clades
Authors: Goettelmann Florian , Roman-Reyna Veronica , Cunnac Sébastien , Jacobs Jonathan M. , Bragard Claude , Studer Bruno , Koebnik Ralf , Kölliker Roland
Published: March 2022

The Xanthomonas translucens species comprises phytopathogenic bacteria that can cause serious damage to cereals and to forage grasses. So far, the genomic resources for X. translucens were limited, which hindered further understanding of the host–pathogen interactions at the molecular level and the development of disease-resistant cultivars. To this end, we complemented the available complete genome sequence of the X. translucens pv. translucens pathotype strain DSM 18974 by sequencing the genomes of all the other 10 X. translucens pathotype strains using PacBio long-read technology and assembled complete genome sequences. Phylogeny based on average nucleotide identity (ANI) revealed three distinct clades within the species, which we propose to classify as clades Xt-I, Xt-II, and Xt-III. In addition to 2,181 core X. translucens genes, a total of 190, 588, and 168 genes were found to be exclusive to each clade, respectively. Moreover, 29 non-transcription activator-like effector (TALE) and 21 TALE type III effector classes were found, and clade- or strain-specific effectors were identified. Further investigation of these genes could help to identify genes that are critically involved in pathogenicity and/or host adaptation, setting the grounds for the development of new resistant cultivars.
Antibacterial Activity of the Essential Oil From Litsea cubeba Against Cutibacterium acnes and the Investigations of Its Potential Mechanism by Gas Chromatography-Mass Spectrometry Metabolomics
Authors: Chen Jing , Zhang Jianing , Zhu Longping , Qian Chunguo , Tian Hongru , Zhao Zhimin , Jin Lu , Yang Depo
Published: March 2022

Cutibacterium acnes (C. acnes) is an anaerobic Gram-positive bacterium generally considered as a human skin commensal, but is also involved in different infections, such as acne and surgical infections. Although there are a variety of treatments, the side effects and the problem of bacterial drug resistance still limit their clinical usage. In this study, we found that essential oil (EO) distilled from fresh mature Litsea cubeba possessed promising antibacterial activity against C. acnes. In order to elucidate its potential mechanism, bacteriostatic activity test, Live/Dead kit assay, scanning electron microscope (SEM), transmission electron microscope (TEM), and metabolomics were employed. In addition, the content of adenosine triphosphate (ATP) in bacterium and the activities of key enzymes involved in critical metabolic pathways were detected using a variety of biochemical assays. The results showed that EO exhibited significant antibacterial activity against C. acnes at a minimum inhibitory concentration (MIC) of 400 μg/mL and a minimum bactericidal concentration (MBC) of 800 μg/mL, and EO could destroy C. acnes morphology and inhibit its growth. Moreover, results from our study showed that EO had a significant effect on the C. acnes normal metabolism. In total, 86 metabolites were altered, and 34 metabolic pathways related to the carbohydrate metabolism, energy metabolism, amino acid metabolism, as well as cell wall and cell membrane synthesis were perturbed after EO administration. The synthesis of ATP in bacterial cells was also severely inhibited, and the activities of key enzymes of the glycolysis and Wood-Werkman cycle were significantly affected (Pyruvate Carboxylase, Malate Dehydrogenase and Pyruvate kinase activities were decreased, and Hexokinase was increased). Taken together, these results illustrated that the bacteriostatic effect of EO against C. acnes by breaking the bacterial cell morphology and perturbing cell metabolism, including inhibition of key enzyme activity and ATP synthesis. The results from our study may shed new light on the discovery of novel drugs with more robust efficacy.
Genetic Diversity and Population Genetic Structure of Setosphaeria turcica From Sorghum in Three Provinces of China Using Single Nucleotide Polymorphism Markers
Authors: Cui Linkai , Deng Junli , Zhao Linxi , Hu Yanhong , Liu Tingli
Published: March 2022

Setosphaeria turcicais a heterothallic fungus that is the causal agent of northern leaf blight (NLB), which is a devastating foliar disease of sorghum and maize. Despite of its adversary to crop production, little is known about the genetic diversity and population genetic structure of this pathogen from sorghum. In this study, we explored the utilization of single nucleotide polymorphism (SNP) molecular markers and three mating type-specific primers to analyze the genetic diversity, population genetic structure, and mating type distribution of 87S. turcicaisolates that had been collected in sorghum production areas from three provinces, including Henan, Shaanxi, and Shanxi in China. The populations are featured with moderate genetic diversity and relatively equal mating type distribution of MAT1-1 and MAT1-2. The genetic differentiation was significant (p < 0.05) among different populations except those from Henan and Shanxi provinces that showed particularly frequent gene flow between them. Neither the maxinum likelihood phylogenetic tree, nor principal coordinate analysis, nor genetic structure analysis was able to completely separate the three populations. The relatively low genetic distance and high genetic identification were also observed among the three populations. Nevertheless, the genetic variation within populations was the major source of variation as revealed by AMOVA analysis. The findings of this study have improved our current understanding about the genetic diversity, population genetic structure, and the distribution of mating type ofS. turcica, which are useful for unraveling the epidemiology of NLB and developing effective disease management strategies.
Investigation of Tannins Transformation in Sanguisorbae Radix Over Carbonizing by Stir-Frying
Authors: Gu Wei , Wang Hao , Su Man , Wang Yiwei , Xu Fei , Hu Qinglian , Cai Xuyi , Song Jinyun , Tong Huangjin , Qian Yuerong , Zhao Hongyu , Chen Jun
Published: March 2022

Carbonizing by stir-frying (CSF) is the most common technology in botanical folk medicines to enhance the convergence, hemostasis, and antidiarrheal effects. Sanguisorbae Radix (SR), a well-known herbal medicine in China, has extensive therapeutic functions, while charred SR is known as an additional product obtained from SR after CSF. In this study, mass spectrometry was used to investigate the effect of charring on tannins transformation of SR. The findings showed that the content level of tannins in SR decreased significantly after carbonizing process, while their three categories, gallotannins, ellagitannins, and procyanidins, had downward trends in general. Moreover, CSF also induced the polyphenol in SR to release relevant monomers from its origins. Significant amount of hydrolyzable tannins were detected by mass spectrometry, including gallotannins and ellagitannins, suggesting that hydrolysis during CSF yielded gallic and ellagic acid and their derivatives, in addition to sugar moieties. Subsequently, gallic and ellagic acid can further polymerize to form sanguisorbic acid dilactone. The amount of proanthocyanidins, the oligomers of catechin, including procyanidin, procyanidin C2, procyanidin B3, and 3-O-galloylprocyanidin B3, decreased to form catechin and its derivatives, which may further degrade to protocatechualdehyde. Quantitative analysis illustrated that the amount of gallic, pyrogallic, and ellagic acid and methyl gallate, the essential effectors in SR, significantly increased after CSF, with increased ratios of 1.36, 4.28, 10.33, and 4.79, respectively. In contrast, the contents of cathechin and epigallocatechin dropped remarkably with increased ratios of 0.04 and 0.02. Tannins exhibit moderate absorption, while their relevant monomers have a higher bioavailability. Therefore, CSF is proved here to be an effective technique to the release of active monomers from the original polyphenol precursor. This study explored the mechanism by which tannins are transformed upon CSF of SR.
Motor Performance and Skill Acquisition in Oral Motor Training With Exergames: A Pilot Study
Authors: Kumar Abhishek , Munirji Linda , Nayif Sam , Almotairy Nabeel , Grigoriadis Joannis , Grigoriadis Anastasios , Trulsson Mats
Published: March 2022

Objective

To investigate the effects of oral-motor training with exergames on motor performance and motor skill acquisition in two different age groups.

Methods

Thirty-two healthy participants were recruited in the current pilot study and divided equally into two groups (Gen Z and Baby Boomers) according to their age. A pair of electromyographic (EMG) electrodes were placed on the participants’ masseter muscles. The EMG device communicated via Bluetooth with a mobile video game in response to the electromyographic activity of the masseter muscles during clenching. During the experimental session, participants were asked to play a video game in five blocks of 5 min each, with a 3-min break between each time block. The goal of the game was to collect as many coins (game points) as possible and to dodge/avoid upcoming obstacles (game life). Motor performance was assessed by performance scores and the number of game lives. Skill acquisition was measured by task efficiency (ratio of performance scores and number of game lives) across time blocks.

Results

The results of the study showed significantly lower performance scores (p < 0.001), a higher number of game lives (p < 0.001), and lower task efficiency in the Baby Boomer group compared to the Gen Z group. Specifically, the results showed that there was a significant difference in task efficiency between the first and second, third and fourth, fourth- and fifth-time blocks in the Gen Z group (p < 0.002). However, there was only a significant difference between first- and second-time blocks in the Baby Boomer group (p = 1.012), suggesting that skill acquisition in the Baby Boomer group did not change significantly over the course of the time blocks.

Conclusion

The study showed higher motor performance and superior motor skill acquisition with novel exergame training in the Gen Z group compared to the Baby Boomer group. The results of the study indicate that there is an improvement in oral motor skills with short-term training, yet the differences in oral motor skills between the two groups are still evident. The Baby Boomer group, unlike the Gen Z group, did not show robust improvement in task efficiency over the course of the series.
Reinforcement Learning With Vision-Proprioception Model for Robot Planar Pushing
Authors: Cong Lin , Liang Hongzhuo , Ruppel Philipp , Shi Yunlei , Görner Michael , Hendrich Norman , Zhang Jianwei
Published: March 2022

We propose a vision-proprioception model for planar object pushing, efficiently integrating all necessary information from the environment. A Variational Autoencoder (VAE) is used to extract compact representations from the task-relevant part of the image. With the real-time robot state obtained easily from the hardware system, we fuse the latent representations from the VAE and the robot end-effector position together as the state of a Markov Decision Process. We use Soft Actor-Critic to train the robot to push different objects from random initial poses to target positions in simulation. Hindsight Experience replay is applied during the training process to improve the sample efficiency. Experiments demonstrate that our algorithm achieves a pushing performance superior to a state-based baseline model that cannot be generalized to a different object and outperforms state-of-the-art policies which operate on raw image observations. At last, we verify that our trained model has a good generalization ability to unseen objects in the real world.
Thymoquinone in Ocular Neurodegeneration: Modulation of Pathological Mechanisms via Multiple Pathways
Authors: Mahmud Nur Musfirah , Paraoan Luminita , Khaliddin Nurliza , Kamalden Tengku Ain
Published: March 2022

Thymoquinone is a naturally occurring compound and is the major component of Nigella sativa, also known as black seed or black cumin. For centuries thymoquinone has been used especially in the Middle East traditionally to treat wounds, asthma, allergies, fever, headache, cough, hypertension, and diabetes. Studies have suggested beneficial effects of thymoquinone to be attributed to its antioxidant, antibacterial, anti-oxidative stress, anti-inflammatory, and neuroprotective properties. Recently, there has been a surge of interest in thymoquinone as a treatment for neurodegeneration in the brain, such as that seen in Alzheimer’s (AD) and Parkinson’s diseases (PD). In vitro and in vivo studies on animal models of AD and PD suggest the main neuroprotective mechanisms are based on the anti-inflammatory and anti-oxidative properties of thymoquinone. Neurodegenerative conditions of the eye, such as Age-related Macular Degeneration (AMD) and glaucoma share at least in part similar mechanisms of neuronal cell death with those occurring in AD and PD. This review aims to summarize and critically analyze the evidence to date of the effects and potential neuroprotective actions of thymoquinone in the eye and ocular neurodegenerations.
Evaluation of Plasma Neurofilament Light Chain Levels as a Biomarker of Neuronal Injury in the Active and Chronic Phases of Autoimmune Neurologic Disorders
Authors: Kammeyer Ryan , Mizenko Christopher , Sillau Stefan , Richie Alanna , Owens Gregory , Nair Kavita V. , Alvarez Enrique , Vollmer Timothy L. , Bennett Jeffrey L. , Piquet Amanda L.
Published: March 2022

Objective

To evaluate plasma neurofilament light (NfL) levels in autoimmune neurologic disorders (AINDs) and autoimmune encephalitis (AE).

Background

Each particular neural autoantibody syndrome has a different clinical phenotype, making one unifying clinical outcome measure difficult to assess. While this is a heterogeneous group of disorders, the final common pathway is likely CNS damage and inflammation. Defining a biomarker of CNS injury that is easily obtainable through a blood sample and reflects a positive treatment response would be highly advantageous in future therapeutic trials. Measurement of blood concentration of neurofilament light (NfL) chain, however, may provide a biomarker of central nervous system (CNS) injury in AE and other AINDs. Here we provide an initial evaluation of plasma NfL levels in AE as well as other AINDs during active and chronic phases of disease and demonstrate its potential utility as a minimally-invasive biomarker for AE and AINDs.

Design/Methods

Patients were retrospectively identified who were enrolled in the biorepository at the Rocky Mountain MS Center at the University of Colorado, or were prospectively enrolled after initial presentation. Patients had a well-defined AIND and were followed between 2014 and 2021. NfL was tested using the Single Molecule Array (SIMOA) technology. Patients with headaches but without other significant neurologic disease were included as controls.

Results

Twenty-six plasma and 14 CSF samples of patients with AINDs, and 20 plasma control samples stored in the biorepository were evaluated. A positive correlation was found between plasma and CSF NfL levels for patients with an AIND (R2 = 0.83, p < 0.001). Elevated plasma levels of NfL were seen in patients with active AE compared to controls [geometric mean (GM) 51.4 vs. 6.4 pg/ml, p = 0.002]. Patients with chronic symptoms (>6 months since new or worsening symptoms) of AE or cerebellar ataxia (CA) showed a trend toward lower plasma NfL levels (GM 15.1 pg/ml) compared to active AE or CA. Six patients with longitudinal, prospective sampling available demonstrated a trend in decreased plasma NfL levels over time.

Conclusions

Our findings support the use of plasma NfL as a potential minimally-invasive biomarker of CNS injury.
Labyrinthine Fistula in Cholesteatoma Patients: Outcomes of Partial Labyrinthectomy With “Underwater Technique” to Preserve Hearing
Authors: Pace Annalisa , Milani Alessandro , Messineo Daniela , Rossetti Valeria , Cocuzza Salvatore , Maniaci Antonino , Vicini Claudio , Iannella Giannicola , Magliulo Giuseppe
Published: March 2022

Labyrinthine fistula (LF) is one of the most important complications of cholesteatoma and is defined as an abnormal communication between the inner and the middle ear. This study aims to describe our experience with the partial labyrinthectomy evaluating the post-operative hearing results. Twenty-one patients who presented labyrinthine fistula in the semicircular canals were included in the present study. Hearing impairment was present in 48% of patients (10/21). A pre-operative assessment using the Gardner–Robertson hearing classification showed the following: 52%, Class I; and 48%, Class II. A post-surgical Gardner–Robertson hearing classification evidenced the following: 43%, Class I; and 57%, Class II. The presence of LF is usually considered a negative prognostic factor for hearing preservation. The key point of partial labyrinthectomy surgery is the preservation of structures, keeping them wet with Ringer's solution throughout the procedures, and not performing suction that is close to the opened LF. The bony labyrinth is drilled underwater without suction, removing the entire cholesteatoma matrix and quickly plugging the site before and after the LF. This faster plugging of the labyrinth makes it possible to preserve the peri-lymph and the endo-lymph fluid and the hearing function. This study showed that a partial labyrinthectomy is useful for maintaining serviceable hearing in patients with LF.
Age-Related Effects on the Spectrum of Cerebral Visual Impairment in Children With Cerebral Palsy
Authors: Galli Jessica , Loi Erika , Molinaro Anna , Calza Stefano , Franzoni Alessandra , Micheletti Serena , Rossi Andrea , Semeraro Francesco , Fazzi Elisa ,   CP Collaborative Group
Published: March 2022

Background

Cerebral Visual Impairment (CVI) is a very common finding in children affected by Cerebral Palsy (CP). In this paper we studied the characteristics of CVI of a large group of children with CP and CVI, describing their neurovisual profiles according to three different age subgroups (subgroup 1: infants 6 months–2 years; subgroup 2: pre-school age 3–5 years; subgroup 3: school age ≥ 6 years).

Methods

We enrolled 180 subjects (104 males, mean age 66 ± 42.6 months; range 6–192 months) with CP and CVI for the study. We carried out a demographic and clinical data collection, neurological examination, developmental or cognitive assessment, and a video-recorded visual function assessment including an evaluation of ophthalmological characteristics, oculomotor functions, and basic visual functions. In school-aged children, we also performed an evaluation of their cognitive-visual profiles.

Results

There were signs of CVI in all the three subgroups. Subgroup 1 (62 children) and subgroup 2 (50 children) were different for fixation (p = 0.02), visual acuity (p = 0.03) and contrast sensitivity (p < 0.01), being more frequently impaired in younger children. Comparing subgroup 2 with subgroup 3 (68 children), the older children presented more frequently myopia (p = 0.02) while the younger ones esotropia (p = 0.02) and alteration in smooth pursuit (p = 0.03) and saccades (p < 0.01). Furthermore, fixation, smooth pursuit, visual acuity, contrast sensitivity and visual filed (p < 0.01) were more frequently impaired in younger children (subgroup 1) compared to the older ones. Multiple correspondence analysis (MCA) confirmed the different neurovisual profiles according to age: younger children with CP showed more signs of CVI compared to the older ones. 34 out of 68 children belonging to subgroup 3 underwent the cognitive visual evaluation; an impairment of cognitive visual skills was detected in 21 subjects.

Conclusion

Younger children with CP showed more signs of CVI compared to the older ones, likely for the physiological maturation of visual system and mechanisms of neuroplasticity. In this direction, we suggest an early neurovisual evaluation to detect any weak visual functions.
A Unified Software/Hardware Scalable Architecture for Brain-Inspired Computing Based on Self-Organizing Neural Models
Authors: Muliukov Artem R. , Rodriguez Laurent , Miramond Benoit , Khacef Lyes , Schmidt Joachim , Berthet Quentin , Upegui Andres
Published: March 2022

The field of artificial intelligence has significantly advanced over the past decades, inspired by discoveries from the fields of biology and neuroscience. The idea of this work is inspired by the process of self-organization of cortical areas in the human brain from both afferent and lateral/internal connections. In this work, we develop a brain-inspired neural model associating Self-Organizing Maps (SOM) and Hebbian learning in the Reentrant SOM (ReSOM) model. The framework is applied to multimodal classification problems. Compared to existing methods based on unsupervised learning with post-labeling, the model enhances the state-of-the-art results. This work also demonstrates the distributed and scalable nature of the model through both simulation results and hardware execution on a dedicated FPGA-based platform named SCALP (Self-configurable 3D Cellular Adaptive Platform). SCALP boards can be interconnected in a modular way to support the structure of the neural model. Such a unified software and hardware approach enables the processing to be scaled and allows information from several modalities to be merged dynamically. The deployment on hardware boards provides performance results of parallel execution on several devices, with the communication between each board through dedicated serial links. The proposed unified architecture, composed of the ReSOM model and the SCALP hardware platform, demonstrates a significant increase in accuracy thanks to multimodal association, and a good trade-off between latency and power consumption compared to a centralized GPU implementation.
Recent Advances in the Elucidation of Frataxin Biochemical Function Open Novel Perspectives for the Treatment of Friedreich’s Ataxia
Authors: Monfort Beata , Want Kristian , Gervason Sylvain , D’Autréaux Benoit
Published: March 2022

Friedreich’s ataxia (FRDA) is the most prevalent autosomic recessive ataxia and is associated with a severe cardiac hypertrophy and less frequently diabetes. It is caused by mutations in the gene encoding frataxin (FXN), a small mitochondrial protein. The primary consequence is a defective expression of FXN, with basal protein levels decreased by 70–98%, which foremost affects the cerebellum, dorsal root ganglia, heart and liver. FXN is a mitochondrial protein involved in iron metabolism but its exact function has remained elusive and highly debated since its discovery. At the cellular level, FRDA is characterized by a general deficit in the biosynthesis of iron-sulfur (Fe-S) clusters and heme, iron accumulation and deposition in mitochondria, and sensitivity to oxidative stress. Based on these phenotypes and the proposed ability of FXN to bind iron, a role as an iron storage protein providing iron for Fe-S cluster and heme biosynthesis was initially proposed. However, this model was challenged by several other studies and it is now widely accepted that FXN functions primarily in Fe-S cluster biosynthesis, with iron accumulation, heme deficiency and oxidative stress sensitivity appearing later on as secondary defects. Nonetheless, the biochemical function of FXN in Fe-S cluster biosynthesis is still debated. Several roles have been proposed for FXN: iron chaperone, gate-keeper of detrimental Fe-S cluster biosynthesis, sulfide production stimulator and sulfur transfer accelerator. A picture is now emerging which points toward a unique function of FXN as an accelerator of a key step of sulfur transfer between two components of the Fe-S cluster biosynthetic complex. These findings should foster the development of new strategies for the treatment of FRDA. We will review here the latest discoveries on the biochemical function of frataxin and the implication for a potential therapeutic treatment of FRDA.
Ramadan Fasting and NCDs-Example of the Diabetes
Authors: Bencharif Meriem , Sersar Ibrahim , Bentaleb Maroua , Boutata Fatima Zohra , Benabbas Youcef
Published: March 2022

Although Ramadan lasts only for 1 month each year, it can be accompanied by significant changes in: both energy and nutritional intake; in the diet composition; in the working hours; and the usual way of life. The majority of practitioners consume two meals, one after sunset (Iftar) and one before dawn (Sohor). During this month, it is also an opportunity to share a meal with family and friends, a period of highly intensified socialization. In parallel with the nutritional changes brought about by this unique pattern of fasting in Ramadan, other metabolic and physiological changes may occur, such as fluctuations in body weight and/or disturbance in the quantity and quality of the sleep-wake circadian rhythm. In the verses of the Qur'an, the exemption from fasting in certain situations such as illness is clearly stated. Despite this religious tolerance, many faithful who are eligible for the exemption observe the fast of Ramadan either for the spiritual aspect it provides by performing it, by religious guilt or to mark a normalization in the Muslim community for fear of the gaze of others. The world is experiencing an increase in the emergence of non-communicable diseases (NCDs); leading cause of the global mortality. Environmental and behavioral risk factors related to lifestyle, such as smoking, excessive alcohol consumption, unhealthy diet, and sedentarity have a causal association with NCDs. Other factors, such as genetic and physiological factors may also be associated (overweight, high blood pressure, dyslipidemia). Diabetes is one of the highest prevalent NCDs in the world and it continues increasing year by year. This chronic disease can lead to significant potential complications (degenerative, dermatological, and acute) to the patient's health. This requires an individual and appropriate care, both dietetic and therapeutic and over the long term will at best make it possible to sensitize the diabetic patient to the adverse effects related to his disease and thus improve its quality of life. Performing the Fast of Ramadan for a diabetic is a common situation. Diabetes is the only chronic disease widely studied in relation to Ramadan fasting. In the literature, many studies have investigated the effects of Ramadan intermittent fasting on diabetic patients. This article aims to provide a general overview and highlight if there are many effect of Ramadan fasting on diabetes, as an example of a NCDs.
Improvement in Anthropometric Measurements of Malnourished Children by Means of Complementary Food and Nutritional Education in Fars Province, Iran: A Community-Based Intervention
Authors: Shenavar Razieh , Sajjadi Seyedeh Forough , Farmani Azam , Zarmehrparirouy Mina , Azadbakht Leila
Published: March 2022

Background

Childhood malnutrition could have adverse impacts on the growth of child and eventually on fertility and general economic growth, and still, this issue remains a worldwide priority and a concern. This study aimed to evaluate the effectiveness of the national nutritional interventions program on the improvement and nutritional status of malnourished children children aged 6–59 months.

Methods

This community-based intervention study was conducted with 1288 acute and moderately malnourished children aged 6–59 months referred to health centers. Children received combined nutritional education and counseling with the provision of affordable complementary food for 10 months. Anthropometric measurements were assessed monthly according to the standard protocols.

Results

Our results showed the reduction in the risk of malnutrition among children after nutritional interventions for weight-for-height (WHZ) (P < 0.001), height-for-age (HAZ) (P < 0.001), and weight-for-age (WAZ) (P = 0.008). Total malnourished children indicated improvement in HAZ (<-3 SD: OR = 1.10, P = 0.026), WAZ (<-2SD: OR = 1.21, P < 0.001; <-3SD: OR = 1.60, P < 0.001), and WHZ (<-3SD: OR = 1.10, P = 0.030). Controlling potential confounders (socioeconomic status, childrens' birth supine length, and weight) showed a significant amelioration in HAZ (<-2 SD: OR = 6.20, P = 0.020; <-3 SD: OR = 9, P = 0.003) and WAZ (<-2 SD: OR = 5.85, P = 0.010; <-3 SD: OR = 7.50, P = 0.004). In urban areas, significant amelioration was observed in HAZ (<-3 SD: OR = 1.22, P = 0.010) and WAZ (<-2 SD: OR = 1.24, P = 0.003; <-3 SD: OR = 1.64, P < 0.001). In rural, considerable amelioration was observed in WAZ (<-2 SD: OR = 1.20, P = 0.010; <-3 SD: OR = 1.50, P < 0.001) and WHZ (<-3 SD: OR = 1.20, P = 0.020).

Conclusion

Nutritional training and counseling as well as complementary food intervention among the malnourished children significantly improved the nutritional status of children. So community-based intervention is recommended to reduce the malnutrition among children.
Targeting the lncRNA DUXAP8/miR-29a/PIK3CA Network Restores Doxorubicin Chemosensitivity via PI3K-AKT-mTOR Signaling and Synergizes With Inotuzumab Ozogamicin in Chemotherapy-Resistant B-Cell Acute Lymphoblastic Leukemia
Authors: Zhang Li , Zhou Shixia , Zhou Tiejun , Li Xiaoming , Tang Junling
Published: March 2022

Purpose

This study aimed to determine the expression profiles of long non-coding RNA (lncRNA), microRNA (miRNA), and mRNA in chemotherapy-resistant B-cell acute lymphoblastic leukemia (B-ALL).

Methods

LncRNA, miRNA, and mRNA profiles were assessed by RNA-seq in diagnostic bone marrow samples from 6 chemotherapy-resistant and 6 chemotherapy-sensitive B-ALL patients. The lncRNA DUXAP8/miR-29a/PIK3CA signaling network was identified as the most dysregulated in chemoresistant patient samples, and its effect on cellular phenotypes, PI3K-AKT-mTOR signaling, and chemosensitivity of doxorubicin (Dox)-resistant Nalm-6 (N6/ADR), and Dox-resistant 697 (697/ADR) cells were assessed. Furthermore, its synergy with inotuzumab ozogamicin treatment was investigated.

Results

1,338 lncRNAs, 75 miRNAs, and 1620 mRNAs were found to be dysregulated in chemotherapy-resistant B-ALL in comparison to chemotherapy-sensitive B-ALL patient samples. Through bioinformatics analyses and RT-qPCR validation, the lncRNA DUXAP8/miR-29a/PIK3CA network and PI3K-AKT-mTOR signaling were identified as significantly associated with B-ALL chemotherapy resistance. In N6/ADR and 697/ADR cells, LncRNA DUXAP8 overexpression and PIK3CA overexpression induced proliferation and inhibited apoptosis, and their respective knockdowns inhibited proliferation, facilitated apoptosis, and restored Dox chemosensitivity. MiR-29a was shown to affect the lncRNA DUXAP8/PIK3CA network, and luciferase reporter gene assay showed direct binding between lncRNA DUXAP8 and miR-29a, as well as between miR-29a and PIK3CA. Targeting lncRNA DUXAP8/miR-29a/PIK3CA network synergized with inotuzumab ozogamicin’s effect on N6/ADR and 697/ADR cells.

Conclusion

Targeting the lncRNA DUXAP8/miR-29a/PIK3CA network not only induced an apoptotic effect on Dox-resistant B-ALL and restored Dox chemosensitivity via PI3K-AKT-mTOR signaling but also showed synergism with inotuzumab ozogamicin treatment.