bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature-Dependent Electrochemical Stability Window of Bis(trifluoromethanesulfonyl)imide and Bis(fluorosulfonyl)imide Anion Based Ionic Liquids
Authors: Lethesh Kallidanthiyil Chellappan , Bahaa Ahmed , Abdullah Mariam , Bamgbopa Musbaudeen O. , Susantyoko Rahmat Agung
Published: June 2022

The electrochemical stability of 22 commercially available hydrophobic ionic liquids was measured at different temperatures (288.15, 298.15, 313.15, 333.15 and 358.15 K), to systematically investigate ionic liquids towards electrolytes for supercapacitors in harsh weather conditions. Bis(trifluoromethanesulfonyl)imide and bis(fluorosulfonyl)imide anions in combination with 1-Butyl-1-methylpyrrolidinium, 1-Ethyl-3-methylimidazolium, N-Ethyl-N, N-dimethyl-N(2methoxyethyl)ammonium, 1-Methyl-1-(2-methoxyethyl)pyrrolidinium, N-Pentyl-N-methylpyrrolidinium, N, N-Diethyl-N-methyl-N-propylammonium, N, N-Dimethyl-N-ethyl-N-benzyl ammonium, N, N-Dimethyl-N-Ethyl-N-phenylethylammonium, N-Butyl-N-methylpiperidinium, 1-Methyl-1-propylpiperidinium, N-Tributyl-N-methylammonium, N-Trimethyl-N-butylammonium, N-Trimethyl-N-butylammonium, N-Trimethyl-N-propylammonium, N-Propyl-N-methylpyrrolidinium cations were selected for the study. Linear regression with a numerical model was used in combination with voltammetry experiments to deduce the temperature sensitivity of both anodic and cathodic potential limits (defining the electrochemical stability window), in addition to extrapolating results to 283.15 and 363.15 K. We evaluated the influence of the cations, anions, and the presence of functional groups on the observed electrochemical stability window which ranged from 4.1 to 6.1 V.
Simultaneous Electrochemical Determination of Chlorzoxazone and Diclofenac on an Efficient Modified Glassy Carbon Electrode by Lanthanum Oxide@ Copper(I) Sulfide Composite
Authors: Baniahmad Bahar , Hassani Nadiki Hadi , Jahani Shohreh , Nezamabadi-Pour Najmeh , Toolabi Ali , Foroughi Mohammad Mehdi
Published: June 2022

This study synthesized a La2O3@snowflake-like Cu2S composite to fabricate an electrochemical sensor for sensitively simultaneous detection of diclofenac and chlorzoxazone exploiting an easy hydrothermal approach, followed by analysis with XRD, FE-SEM, and EDX methods. According to voltammetric studies, the electrocatalytic diclofenac and chlorzoxazone oxidations on the electrode modified with La2O3@SF-L Cu2S composites were increased, with greater oxidation currents, as well as the oxidation potential was significantly decreased due to synergetic impact of La2O3@SF-L Cu2S composites when compared with the pure SF-L Cu2S NS-modified electrode. The differential pulse voltammetry findings showed wide straight lines (0.01–900.0 μM) for La2O3 NP@SF-L Cu2S NS-modified electrode with a limit of detection (LOD) of 1.7 and 2.3 nM for the detection of diclofenac and chlorzoxazone, respectively. In addition, the limit of quantification was calculated to be 5.7 and 7.6 nM for diclofenac and chlorzoxazone, respectively. The diffusion coefficient was calculated to be 1.16 × 10−5and 8.4 × 10−6 cm2/s for diclofenac and chlorzoxazone oxidation on the modified electrode, respectively. Our proposed electrode was examined for applicability by detecting diclofenac and chlorzoxazone in real specimens.
Safety and Feasibility of Rotational Atherectomy for Retrograde Recanalization of Chronically Occluded Coronary Arteries
Authors: Wang Jing , Huang Junlin , Yakubu Abdul-Subulr , Wu Kaize , Huang Zehan , Zhong Zhian , Liao Hongtao , Zhang Bin
Published: June 2022

Objective

To evaluate the safety and feasibility of rotational atherectomy (RA) in retrograde chronic total occlusion percutaneous coronary intervention (CTO-PCI) by analyzing immediate and long-term outcomes.

Background

Recent evidence supports the safety and feasibility of RA in CTO-PCI. However, few studies have focused on the use of RA in a retrograde approach to percutaneous revascularization of chronic total occlusion (CTO) lesions and information on long-term outcomes is lacking.

Methods

A total of 329 patients who underwent retrograde CTO-PCI, out of 1496 consecutive CTO-PCI patients from April 2017 to July 2020, were retrospectively recruited from the 2nd Cardiology Department of the Guangdong Provincial People's Hospital. 16 patients underwent RA (RA group) whilst 313 did not (non-RA group).

Results

Technical (87.5% vs. 87.5) and procedural (85.9% vs. 87.5) success rates were similar between both groups. There was no difference concerning major procedural complications between groups (12.5% vs. 19.2%; p > 0.75). No in-hospital MACCEs was recorded in the RA group while there were eight MACCEs in the non-RA group (p > 0.99). In the RA group, 2 cases recorded perforation (1 target vessel perforation case and 1 branch vessel perforation), and 55 cases of vessel perforations/dissections were recorded in non-RA group including 18 target vessel perforations, 2 branch vessel perforations, 35 collateral vessel perforations (one patient died from cardiac tamponade). No difference was found in terms of the perforation rate between the two groups (p > 0.99). Over a mean follow-up period of 26.47 ± 14.46 months, use of RA in retrograde CTO-PCI did not result in an increased mortality rate [hazard ratio (HR) 1.58, 95% confidence interval (CI), 0.31–8.21, p = 0.65], major adverse cardiac and cerebral events (HR 0.99, 95% CI 0.35–2.79, p = 0.99) or overall rehospitalization rate (HR 1.27, 95% CI 0.44–3.67, p = 0.67). Adjusted Kaplan–Meier curves according to Cox regression model suggested several predictors influencing the all-cause mortality, cardiovascular mortality, MACCEs, stroke rate, non-fatal myocardial infarction, target vessel recanalization rate and rehospitalization rate in the comparison.

Conclusions

Our study demonstrates that the in-hospital outcomes and long-term follow up events were the same between RA and non-RA retrograde CTO-PCI patients. RA offered an option for skillful operators in difficult cases when the lesion was severely calcified in retrograde CTO-PCI.
Deciphering Pro-angiogenic Transcription Factor Profiles in Hypoxic Human Endothelial Cells by Combined Bioinformatics and in vitro Modeling
Authors: Schmidt Arne , Fuchs Maximilian , Stojanović Stevan D. , Liang Chunguang , Schmidt Kevin , Jung Mira , Xiao Ke , Weusthoff Jan , Just Annette , Pfanne Angelika , Distler Jörg H. W. , Dandekar Thomas , Fiedler Jan , Thum Thomas , Kunz Meik
Published: June 2022

Background

Constant supply of oxygen is crucial for multicellular tissue homeostasis and energy metabolism in cardiac tissue. As a first response to acute hypoxia, endothelial cells (ECs) promote recruitment and adherence of immune cells to the dysbalanced EC barrier by releasing inflammatory mediators and growth factors, whereas chronic hypoxia leads to the activation of a transcription factor (TF) battery, that potently induces expression of growth factors and cytokines including platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). We report a hypoxia-minded, targeted bioinformatics approach aiming to identify and validate TFs that regulate angiogenic signaling.

Results

A comprehensive RNA-Seq dataset derived from human ECs subjected to normoxic or hypoxic conditions was selected to identify significantly regulated genes based on (i) fold change (normoxia vs. hypoxia) and (ii) relative abundancy. Transcriptional regulation of this gene set was confirmed via qPCR in validation experiments where HUVECs were subjected to hypoxic conditions for 24 h. Screening the promoter and upstream regulatory elements of these genes identified two TFs, KLF5 and SP1, both with a potential binding site within these regions of selected target genes. In vitro, siRNA experiments confirmed SP1- and KLF5-mediated regulation of identified hypoxia-sensitive endothelial genes. Next to angiogenic signaling, we also validated the impact of TFs on inflammatory signaling, both key events in hypoxic sensing. Both TFs impacted on inflammatory signaling since endogenous repression led to increased NF-κB signaling. Additionally, SP1 silencing eventuated decreased angiogenic properties in terms of proliferation and tube formation.

Conclusion

By detailed in silico analysis of promoter region and upstream regulatory elements for a list of hypoxia-sensitive genes, our bioinformatics approach identified putative binding sites for TFs of SP or KLF family in vitro. This strategy helped to identify TFs functionally involved in human angiogenic signaling and therefore serves as a base for identifying novel RNA-based drug entities in a therapeutic setting of vascularization.
Artificial Intelligence in Coronary CT Angiography: Current Status and Future Prospects
Authors: Liao Jiahui , Huang Lanfang , Qu Meizi , Chen Binghui , Wang Guojie
Published: June 2022

Coronary heart disease (CHD) is the leading cause of mortality in the world. Early detection and treatment of CHD are crucial. Currently, coronary CT angiography (CCTA) has been the prior choice for CHD screening and diagnosis, but it cannot meet the clinical needs in terms of examination quality, the accuracy of reporting, and the accuracy of prognosis analysis. In recent years, artificial intelligence (AI) has developed rapidly in the field of medicine; it played a key role in auxiliary diagnosis, disease mechanism analysis, and prognosis assessment, including a series of studies related to CHD. In this article, the application and research status of AI in CCTA were summarized and the prospects of this field were also described.
Biomarkers of Volume Overload and Edema in Heart Failure With Reduced Ejection Fraction
Authors: Chiorescu Roxana Mihaela , Lazar Roxana-Daiana , Buksa Sándor-Botond , Mocan Mihaela , Blendea Dan
Published: June 2022

From a pathogenetic point of view, heart failure (HF) is characterized by the activation of several neurohumoral pathways with a role in maintaining the cardiac output and the adequate perfusion pressure in target organs and tissues. Decreased cardiac output in HF with reduced ejection fraction causes activation of the sympathetic nervous system, the renin angiotensin aldosterone system, arginine-vasopressin system, natriuretic peptides, and endothelin, all of which cause water and salt retention in the body. As a result, patients will present clinically as the main symptoms: dyspnea and peripheral edema caused by fluid redistribution to the lungs and/or by fluid overload. By studying these pathophysiological mechanisms, biomarkers with a prognostic and therapeutic role in the management of edema were identified in patients with HF with low ejection fraction. This review aims to summarize the current data from the specialty literature of such biomarkers with a role in the pathogenesis of edema in HF with low ejection fraction. These biomarkers may be the basis for risk stratification and the development of new therapeutic means in the treatment of edema in these patients.
High P-T Calcite-Aragonite Phase Transitions Under Hydrous and Anhydrous Conditions
Authors: Zhao Xia , Zheng Zhi , Chen Jiangzhi , Gao Yue , Sun Jianhui , Hou Xue , Xiong Mengjun , Mei Shenghua
Published: June 2022

The subduction of calcite into deep Earth and subsequent phase change are important for global carbon cycle. However, the study of the phase boundary between calcite and aragonite under high P-T conditions is insufficient due to sparse existing phase points and narrow pressure range. In addition, the impact of aqueous fluid on the phase transition requires further investigation. In this work, the calcite-aragonite phase transitions in both anhydrous and hydrous conditions were studied using diamond anvil cell (DAC) with in-situ Raman spectroscopy. In the anhydrous condition, investigations were conducted up to 12 GPa and 400°C and only the solid recrystallization-reconstructive (SRR) phase transition was observed. The calcite-aragonite boundary shows a convex upward curve with the minimum transformation temperature at around 150°C and a wide transformation pressure range from 1 to 12 GPa, consistent with the molar volume change between aragonite and calcite-I/II/III/IIIb. In the hydrous condition, both the SRR phase transition and dissolution-precipitation-dehydration (DPD) phase transition were observed under different heating conditions, and in the DPD phase transition ikaite serves as an intermediate phase precipitated from dissolved calcite and then dehydrates into aragonite. Our results suggest the phase transition of calcite-aragonite in the subduction zone, where the SRR phase transition can exist in slabs under wide P-T conditions (1–2 GPa and 160–400°C), and the DPD process can only occur under lower P-T conditions (less than 1.5 GPa and 110°C).
Jiangtang Tongmai Prescription Reduced Diabetic Lung Injury Through SnoN and TGF-β1/Smads Signaling Pathway
Authors: Ding Nian , Zheng Chenghong
Published: June 2022

By establishing a rat diabetes model in rats with intervening treatment by Jiangtang Tongmai Prescription (JTTMP), this study explored the restorative pairing effect of JTTMP on diabetic lung injury. The model of type II diabetes model was used to establish the rat diabetes model, using a high-fat diet and streptozotocin (STZ) induction. Different doses of JTTMP and metformin were administered as a therapeutic to intervene, and blood was collected to assess the blood glucose level of each group of rats. HE (Hematoxylin and eosin (H&E) staining was performed to detect the morphological changes in rat lung tissue and enzyme-linked immunoassay ELISA was used to detect and quantify the expression of interleukin (IL)-6, TNF tumor necrosis factor-ɑa, and IL-1β in serum and the lung tissue of each group of rats. The level expression of TGF-β1 [transforming growth factor (TGF)-β1), SnoN (transcriptional co-repressor Ski-N terminal (SnoN)], Smad2, Smad3, Smad7, and other signaling pathway proteins were assessed by Western blot. In comparison with the normal control (NC) group, rats in the diabetes model (DM) group lost weight and showed significantly increased blood sugar levels. The levels of TGF-β1 and Smad2/3 were increased in the DM group but Smad7 decreased. After 8 weeks of JTTMP intervention, the level of TGF-β1 and Smad2/3 decreased but Smad7 increased, blood sugar decreased significantly and the expression of inflammatory factors in lung tissue decreased. Therefore, JTTMP may activate SnoN and the downstream TGF-β1/Smads signaling pathway to repair diabetic lung injury, which suggests its application has potential for future clinical treatment of diabetes with lung injury.
Association of Famine Exposure on the Changing Clinical Phenotypes of Primary Hyperparathyroidism in 20 years
Authors: Yuan Tian-jiao , Yang Yu-ying , Zhu Min-ting , He Yang , Zhao Lin , Zhou Wen-zhong , Su Ting-wei , Zhao Hong-yan , Sun Li-hao , Tao Bei , Liu Jian-min
Published: June 2022

Background & Aims

Primary hyperparathyroidism(PHPT) has been evolving into a milder asymptomatic disease. No study has assessed the association between famine exposure and such a shift. We aim to explore the effects of China’s Great Famine exposure on the changing pattern of PHPT phenotypes.

Methods

750 PHPT patients diagnosed from 2000 to 2019 were studied. The clinical presentations were compared between them in recent 10 years (2010-2019) and previous 10 years (2000-2009). Participants were then categorized into fetal, childhood, adolescent, adult exposure, and unexposed groups. Logistic regression was used to estimate the odds ratios (ORs) and confidence intervals (CIs) of famine exposure as factors contributing to the changes in the clinical presentations of PHPT.

Results

Serum levels of PTH, albumin-corrected Ca, tumor size, eGFR, BMDs (all P<0.001), and clinical symptoms became milder in recent 10 years. Famine exposure (72.6% vs 58.4%, P<0.001), especially the adult exposure (18.8% vs 4.1%, P<0.001)was significant less in recent 10 years. The ORs (95%CIs) of having upper 3rd tertile PTH were 2.79(1.34,5.8), 2.07(1.04,4.11), 3.10(1.15,8.38) and 8.85(2.56,30.56) for patients with fetal, childhood, adolescent and adult famine exposure, respectively. The ORs (95%CIs) of upper 3rd tertile albumin-corrected Ca and upper 3rd tertile of tumor size was 4.78(1.39, 16.38) and 4.07(1.12,14.84) for participants with adult famine exposure, respectively. All these associations were independent of age, sex, disease duration and other confounders.

Conclusions

The clinical manifestations of PHPT in China continue to be milder. Exposure to famine is associated with PHPT. Less famine exposure might be responsible for the mile form of PHPT in recent years.
Case Report: A Novel EIF2B3 Pathogenic Variant in Central Nervous System Hypomyelination/Vanishing White Matter
Authors: Wongkittichote Parith , Mar Soe Soe , McKinstry Robert C. , Nguyen Hoanh
Published: June 2022

Leukodystrophies are a group of heterogeneous disorders affecting brain myelin. Among those, childhood ataxia with central nervous system hypomyelination/vanishing white matter (CACH/VWM) is one of the more common inherited leukodystrophies. Pathogenic variants in one of the genes encoding five subunits of EIF2B are associated with CACH/VWM. Herein, we presented a case of CACH/VWM who developed ataxia following a minor head injury. Brain magnetic resonance imaging showed extensive white matter signal abnormality. Diagnosis of CACH/VWM was confirmed by the presence of compound heterozygous variants in EIF2B3: the previously known pathogenic variant c c.260C>T (p.Ala87Val) and the novel variant c.673C>T (p.Arg225Trp). Based on the American College of Medical Genetics (ACMG) recommendations, we classified p.Arg225Trp as likely pathogenic. We report a novel variant in a patient with CACH/VWM and highlight the importance of genetic testing in patients with leukodystrophies.
Transcriptome Profiling and Network Analysis Provide Insights Into the Pathogenesis of Vulvar Lichen Sclerosus
Authors: Wang Lingyan , Lv Qingqing , Guo Jiayi , Wang Jianwei , Pan Jing
Published: June 2022

Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis that affects female anogenital skin. Although VLS is considered a T cell-mediated autoimmune disease, the diagnosis criteria, molecular mechanism, and universally accepted therapies for this disease remain largely unresolved. To explore disease pathogenesis and potential biomarkers, we performed an RNA-Seq-based transcriptome analysis to profile the gene expression of VLS lesions. Differentially expressed gene (DEG) analysis revealed profound changes in expressions of coding genes, microRNAs, and long non-coding RNAs. Pathway and network analysis suggested that T cell activation-associated genes, including CD3G, CD3D, CD8B, LAT, LCK, ZAP70, CCR5, CXCR3, CXCL9, CXCL10, and CXCL11, were highly expressed in VLS, while NR4A family genes (NR4A1, NR4A2, NR4A3), whose coding products inhibit T cell activity, were significantly downregulated, suggesting heightened T cell response in VLS. Neutrophil chemoattractant genes CXCL1, CXCL2, CXCL3, CXCL8, and their cognate receptor CXCR2 were downregulated, suggesting dampened neutrophil activity. We also found the downregulation of genes involved in cell cycle progression, including cyclins (CCNB1, CCNB2, CCNL1, CCNE1, and CCNK) and centrosome factors (CENPA, CENPE, CENPF, and CENPN), while microRNA-203a and let-7, microRNAs known to inhibit cell growth, were found to be upregulated. These data collectively indicate that cell proliferation in VLS is compromised. In sum, these findings comprehensively deciphered key regulatory genes and networks in VLS, which could further our understanding of disease mechanisms and point toward therapeutic strategies.
SARS-CoV-2 Omicron Variants Reduce Antibody Neutralization and Acquire Usage of Mouse ACE2
Authors: Wang Ruoke , Zhang Qi , Zhang Rui , Aw Zhen Qin , Chen Peng , Wong Yi Hao , Hong Junxian , Ju Bin , Shi Xuanling , Ding Qiang , Zhang Zheng , Chu Justin Jang Hann , Zhang Linqi
Published: June 2022

Striking number of mutations found in the spike protein of recently emerged SARS-CoV-2 Omicron subvariants BA.1, BA.2, BA.3 and BA.4/5 has raised serious concerns regarding the escape from current antibody therapies and vaccine protection. Here, we conducted comprehensive analysis on the extent of two major Omicron lineages BA.1/BA.1.1 and BA.2 to escape neutralization from the therapeutic antibodies approved by the regulatory authorities and convalescent plasma from SARS-CoV-2 patients infected during initial wave of pandemic in early 2020. We showed that Omicron BA.1/BA.1.1 were the most resistant in both magnitude and breadth against antibodies and convalescent plasma, followed by Beta, BA.2, Gamma, Delta and Alpha. While the majority of therapeutic antibodies lost binding and neutralization to Omicron variants, BRII combo (BRII-196 + BRII-198), S309, and AZ combo (COV2-2196 + COV2-2130) maintained neutralization despite of reduction due to either conserved epitope or combinational effect between the two designated antibodies. A single intraperitoneal injection of BRII combo as a prophylactic treatment protected animals from Omicron infection. Treated animals manifested normal body weight, survived infection up to 14 days, undetectable levels of infectious viruses in the lungs, and reduced lung pathology compared to the controls. Analyzing ACE2 from diverse host species showed that Omicron variants acquired ability to use mouse ACE2 for entry. These results demonstrate major antigenic shifts and potentially broadening the host range of two major Omicron lineages BA.1/BA.1.1 and BA.2, posing serious challenges to current antibody therapies and vaccine protection as well as increasing danger of spillover into the wildlife.
Immunogenicity of Monoclonal Antibodies and the Potential Use of HLA Haplotypes to Predict Vulnerable Patients
Authors: Mosch Romy , Guchelaar Henk-Jan
Published: June 2022

The use of monoclonal antibodies (mAbs) in the clinic has successfully expanded to treatment of cancer, viral infections, inflammations, and other indications. However, some of the classes of mAbs that are used in the clinic show the formation of anti-drug antibodies (ADAs) leading to loss of efficacy. This review describes ADA formation for the various mAbs, and its clinical effect. Lastly, this review considers the use of HLA-haplotypes as biomarkers to predict vulnerability of patients sensitive to formation of ADAs.
The Specific Alteration of Gut Microbiota in Diabetic Kidney Diseases—A Systematic Review and Meta-Analysis
Authors: Wang Yuwei , Zhao Jin , Qin Yunlong , Yu Zixian , Zhang Yumeng , Ning Xiaoxuan , Sun Shiren
Published: June 2022

Background

Emerging evidence indicates that gut dysbiosis is involved in the occurrence and development of diabetic kidney diseases (DKD). However, the key microbial taxa closely related to DKD have not been determined.

Methods

PubMed, Web of Science, Cochrane, Chinese Biomedical Databases, China National Knowledge Internet, and Embase were searched for case-control or cross-sectional studies comparing the gut microbiota of patients with DKD and healthy controls (HC) from inception to February 8, 2022, and random/fixed-effects meta-analysis on the standardized mean difference (SMD) were performed for alpha diversity indexes between DKD and HC, and beta diversity indexes and the relative abundance of gut microbiota were extracted and summarized qualitatively.

Results

A total of 16 studies (578 patients with DKD and 444 HC) were included. Compared to HC, the bacterial richness of patients with DKD was significantly decreased, and the diversity indexes were decreased but not statistically, companying with a distinct beta diversity. The relative abundance of phylum Proteobacteria, Actinobacteria, and Bacteroidetes, family Coriobacteriaceae, Enterobacteriaceae, and Veillonellaceae, genus Enterococcus, Citrobacter, Escherichia, Klebsiella, Akkermansia, Sutterella, and Acinetobacter, and species E. coli were enriched while that of phylum Firmicutes, family Lachnospiraceae, genus Roseburia, Prevotella, and Bifidobacterium were depleted in patients with DKD.

Conclusions

The gut microbiota of patients with DKD may possess specific features characterized by expansion of genus Escherichia, Citrobacter, and Klebsiella, and depletion of Roseburia, which may contribute most to the alterations of their corresponding family and phylum taxa, as well as the bacterial diversity and composition. These microbial taxa may be closely related to DKD and serve as promising targets for the management of DKD.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42021289863.
Causal Relationship Between Sleep Traits and Risk of Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study
Authors: Sang Ni , Gao Rui-Chen , Zhang Meng-Yao , Wu Zhen-Zhen , Wu Zhen-Gang , Wu Guo-Cui
Published: June 2022

A correlation between sleep and systemic lupus erythematosus (SLE) has been observed in a number of prior investigations. However, little is known regarding the potential causative relationship between them. In this study, we selected genetic instruments for sleep traits from pooled data from published genome-wide association studies (GWAS). Independent genetic variants associated with six sleep-related traits (chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, and daytime sleepiness) were selected as instrumental variables. A two-sample Mendelian randomization (TSMR) study was first conducted to assess the causal relationship between sleep traits and SLE (7219 cases versus 15,991 controls). The reverse MR analysis was then used to infer the causal relationship between SLE and sleep traits. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were applied to perform the primary MR analysis. MR Egger regression and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were used to detect horizontal pleiotropy, and Cochran’s Q was used to detect heterogeneity. In studies of the effect of sleep traits on SLE risk, the IVW method demonstrated no causal relationship between chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, daytime sleepiness and SLE risk. The remaining three methods agreed with the results of IVW. In studies of the effect of SLE on the risk of sleep traits, neither IVW, MR Egger, Weighted median, nor Weighted mode methods provided evidence of a causal relationship between SLE and the risk of sleep traits. Overall, our study found no evidence of a bidirectional causal relationship between genetically predicted sleep traits and SLE.
Case Report: Secondary Hemophagocytic Lymphohistiocytosis (sHLH) and Candida auris Fungemia in Post-acute COVID-19 Syndrome: A Clinical Challenge
Authors: Gautam Sachin , Sharma Gaurav , Singla Sumeet , Garg Sandeep
Published: June 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a disease (COVID-19) with multisystem involvement. The world is now entering a phase of post-COVID-19 manifestations in this pandemic. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event triggered by viral infections, including SARS-CoV-2. Both Multisystem Inflammatory Syndrome-Adults (MIS-A) and Cytokine Storm Syndrome (CSS) are considered close differentials of sHLH and add to the spectrum of Post-acute COVID-19 syndrome (PACS). In this report, we presented the case of a middle-aged Asian man who was initially discharged upon recovery from severe COVID-19 infection after 17 days of hospitalization to a private institute and later came to our hospital 13 days post-discharge. Here, he was diagnosed with sHLH, occurring as an extension of CSS, with delayed presentation falling within the spectrum of PACS. The diagnosis of sHLH was made holistically with the HLH-2004 criteria. Our patient initially responded to intravenous immunoglobulin (IVIG) and dexamethasone, later complicated by disseminated Candida auris infection and had a fatal outcome. Though many cases of HLH during active COVID-19 and a few cases post COVID-19 recovery have been reported, based on H-score, which has limitations as a diagnostic tool. We report the first case report of post-COVID-19 sHLH using the HLH-2004 criteria, complicated by disseminated Candidemia, emphasizing that the care of patients with COVID-19 does not conclude at the time of hospital discharge. We highlight the importance of surveillance in the post-COVID phase for early detection of sHLH which may predispose to fatal opportunistic infections (OIs).
Metaomics in Clinical Laboratory: Potential Driving Force for Innovative Disease Diagnosis
Authors: Wang Liang , Li Fen , Gu Bin , Qu Pengfei , Liu Qinghua , Wang Junjiao , Tang Jiawei , Cai Shubin , Zhao Qi , Ming Zhong
Published: June 2022

Currently, more and more studies suggested that reductionism was lack of holistic and integrative view of biological processes, leading to limited understanding of complex systems like microbiota and the associated diseases. In fact, microbes are rarely present in individuals but normally live in complex multispecies communities. With the recent development of a variety of metaomics techniques, microbes could be dissected dynamically in both temporal and spatial scales. Therefore, in-depth understanding of human microbiome from different aspects such as genomes, transcriptomes, proteomes, and metabolomes could provide novel insights into their functional roles, which also holds the potential in making them diagnostic biomarkers in many human diseases, though there is still a huge gap to fill for the purpose. In this mini-review, we went through the frontlines of the metaomics techniques and explored their potential applications in clinical diagnoses of human diseases, e.g., infectious diseases, through which we concluded that novel diagnostic methods based on human microbiomes shall be achieved in the near future, while the limitations of these techniques such as standard procedures and computational challenges for rapid and accurate analysis of metaomics data in clinical settings were also examined.
Structure Characterization of Escherichia coli Pseudouridine Kinase PsuK
Authors: Li Xiaojia , Li Kangjie , Guo Wenting , Wen Yan , Meng Chunyan , Wu Baixing
Published: June 2022

Pseudouridine (Ψ) is one of the most abundant RNA modifications in cellular RNAs that post-transcriptionally impact many aspects of RNA. However, the metabolic fate of modified RNA nucleotides has long been a question. A pseudouridine kinase (PsuK) and a pseudouridine monophosphate glycosylase (PsuG) in Escherichia coli were first characterized as involved in pseudouridine degradation by catalyzing the phosphorylation of pseudouridine to pseudouridine 5′-phosphate (ΨMP) and further hydrolyzing 5′-ΨMP to produce uracil and ribose 5′-phosphate. Recently, their homolog proteins in eukaryotes were also identified, which were named PUKI and PUMY in Arabidopsis. Here, we solved the crystal structures of apo-EcPsuK and its binary complex with Ψ or N1-methyl-pseudouridine (m1Ψ). The structure of EcPsuK showed a homodimer conformation assembled by its β-thumb region. EcPsuK has an appropriate binding site with a series of hydrophilic and hydrophobic interactions for Ψ. Moreover, our complex structure of EcPsuK-m1Ψ suggested the binding pocket has an appropriate capacity for m1Ψ. We also identified the monovalent ion-binding site and potential ATP-binding site. Our studies improved the understanding of the mechanism of Ψ turnover.
Genetic Variants Associated With Subjective Cognitive Decline in Patients With Migraine
Authors: Yeh Po-Kuan , Liang Chih-Sung , Tsai Chia-Lin , Lin Yu-Kai , Lin Guan-Yu , Tsai Chia-Kuang , Tsai Ming-Chen , Liu Yi , Tai Yueh-Ming , Hung Kuo-Sheng , Yang Fu-Chi
Published: June 2022

The genetic association between subjective cognitive decline (SCD) and migraine comorbidity remains unclear. Furthermore, single nucleotide polymorphisms (SNP) associated with SCD have not been identified previously. Migraineurs were genotyped using an Affymetrix array. The correlation between different SNP variants in migraineurs with or without SCD and non-migraine controls was investigated. Migraineurs with or without SCD were further divided for the analysis of relevant SNP variants linked to migraine with aura (MA), migraine without aura (MoA), episodic migraine (EM), and chronic migraine (CM). Significant connectivity between SNPs and clinical indices in migraineurs and non-migraine controls with SCD were assessed using multivariate regression analysis. The rs144191744 SNP was found in migraineurs (p = 3.19E-08), EM (p = 1.34E-07), and MoA(p = 7.69E-07) with and without SCD. The T allele frequency for rs144191744 in TGFBR3 was 0.0054 and 0.0445 in migraineurs with and without SCD (odds ratio, 0.12), respectively. rs2352564, rs6089473 in CDH4, rs112400385 in ST18, rs4488224 and rs17111203 in ARHGAP29 SNPs were found, respectively, in non-migraineurs (p = 4.85E-06, p = 8.28E-06), MoA (p = 3.13E-07), and CM subgroups (p = 1.05E-07, 6.24E-07) with and without SCD. Rs144191744 closely relates to SCD with the all-migraine group and the EM and MoA subgroups. In conclusion, rs144191744 in TGFBR3 was significantly associated with SCD in migraineurs, especially in the EM, MoA, and female patient subgroups. Furthermore, three SNPs (rs112400385, rs4488224, and rs17111203) were associated with SCD in migraineurs but not in non-migraine controls.
Harmonization of Multicenter Cortical Thickness Data by Linear Mixed Effect Model
Authors: Kim SeungWook , Kim Sung-Woo , Noh Young , Lee Phil Hyu , Na Duk L. , Seo Sang Won , Seong Joon-Kyung
Published: June 2022

Objective

Analyzing neuroimages being useful method in the field of neuroscience and neurology and solving the incompatibilities across protocols and vendors have become a major problem. We referred to this incompatibility as “center effects,” and in this study, we attempted to correct such center effects of cortical feature obtained from multicenter magnetic resonance images (MRIs).

Methods

For MRI of a total of 4,321 multicenter subjects, the harmonized w-score was calculated by correcting biological covariates such as age, sex, years of education, and intercranial volume (ICV) as fixed effects and center information as a random effect. Afterward, we performed classification tasks using principal component analysis (PCA) and linear discriminant analysis (LDA) to check whether the center effect was successfully corrected from the harmonized w-score.

Results

First, an experiment was conducted to predict the dataset origin of a random subject sampled from two different datasets, and it was confirmed that the prediction accuracy of linear mixed effect (LME) model-based w-score was significantly closer to the baseline than that of raw cortical thickness. As a second experiment, we classified the data of the normal and patient groups of each dataset, and LME model-based w-score, which is biological-feature-corrected values, showed higher classification accuracy than the raw cortical thickness data. Afterward, to verify the compatibility of the dataset used for LME model training and the dataset that is not, intraobject comparison and w-score RMSE calculation process were performed.

Conclusion

Through comparison between the LME model-based w-score and existing methods and several classification tasks, we showed that the LME model-based w-score sufficiently corrects the center effects while preserving the disease effects from the dataset. We also showed that the preserved disease effects have a match with well-known disease atrophy patterns such as Alzheimer’s disease or Parkinson’s disease. Finally, through intrasubject comparison, we found that the difference between centers decreases in the LME model-based w-score compared with the raw cortical thickness and thus showed that our model well-harmonizes the data that are not used for the model training.
Impact of Parkinson’s Disease on Functional Mobility at Different Stages
Authors: Mollà-Casanova Sara , Pedrero-Sánchez Jose , Inglés Marta , López-Pascual Juan , Muñoz-Gómez Elena , Aguilar-Rodríguez Marta , Sempere-Rubio Nuria , Serra-Añó Pilar
Published: June 2022

Introduction

Specific functional assessments to determine the progression of Parkinson’s Disease (PD) are important to slow down such progression and better plan rehabilitation. This study aimed to explore possible differences in the performance of different functional tasks included in a mobility test using sensors embedded in an Android device, in people at different PD stages.

Materials and Methods

Eighty-seven participants with PD agreed to participate in this cross-sectional study. They were assessed once using an inertial sensor and variables related to functional status were recorded (i.e., MLDisp, APDisp, DispA, Vrange, MLRange, PTurnSit, PStand, TTime, and RTime).

Results

There was significant impairment of the vertical range during gait between stages I and II. Further, when stages II and III were compared, the sit-to-stand power was significantly impaired, and the total time required to complete the test increased significantly (p < 0.05). Even more significant differences were obtained when stages I and III were compared, in particular, dysfunction in postural control, vertical range, sit to stand power and total time. Finally, there were no significant differences between stages in the medial-lateral displacements and reaction time (p > 0.05).

Conclusion

Functional mobility becomes more significantly impaired in the PD population as the PD stages progress. This implies impaired postural control, decreased ability to sit down or stand up from a chair, increased metabolic cost during walking, and overall slowing-down of motor function.
Single-Nucleus RNA-seq of Normal-Appearing Brain Regions in Relapsing-Remitting vs. Secondary Progressive Multiple Sclerosis: Implications for the Efficacy of Fingolimod
Authors: Kihara Yasuyuki , Zhu Yunjiao , Jonnalagadda Deepa , Romanow William , Palmer Carter , Siddoway Benjamin , Rivera Richard , Dutta Ranjan , Trapp Bruce D. , Chun Jerold
Published: June 2022

Multiple sclerosis (MS) is an immune-mediated demyelinating disease that alters central nervous system (CNS) functions. Relapsing-remitting MS (RRMS) is the most common form, which can transform into secondary-progressive MS (SPMS) that is associated with progressive neurodegeneration. Single-nucleus RNA sequencing (snRNA-seq) of MS lesions identified disease-related transcriptomic alterations; however, their relationship to non-lesioned MS brain regions has not been reported and which could identify prodromal or other disease susceptibility signatures. Here, snRNA-seq was used to generate high-quality RRMS vs. SPMS datasets of 33,197 nuclei from 8 normal-appearing MS brains, which revealed divergent cell type-specific changes. Notably, SPMS brains downregulated astrocytic sphingosine kinases (SPHK1/2) – the enzymes required to phosphorylate and activate the MS drug, fingolimod. This reduction was modeled with astrocyte-specific Sphk1/2 null mice in which fingolimod lost activity, supporting functionality of observed transcriptomic changes. These data provide an initial resource for studies of single cells from non-lesioned RRMS and SPMS brains.
NeoRS: A Neonatal Resting State fMRI Data Preprocessing Pipeline
Authors: Enguix Vicente , Kenley Jeanette , Luck David , Cohen-Adad Julien , Lodygensky Gregory Anton
Published: June 2022

Resting state functional MRI (rsfMRI) has been shown to be a promising tool to study intrinsic brain functional connectivity and assess its integrity in cerebral development. In neonates, where functional MRI is limited to very few paradigms, rsfMRI was shown to be a relevant tool to explore regional interactions of brain networks. However, to identify the resting state networks, data needs to be carefully processed to reduce artifacts compromising the interpretation of results. Because of the non-collaborative nature of the neonates, the differences in brain size and the reversed contrast compared to adults due to myelination, neonates can’t be processed with the existing adult pipelines, as they are not adapted. Therefore, we developed NeoRS, a rsfMRI pipeline for neonates. The pipeline relies on popular neuroimaging tools (FSL, AFNI, and SPM) and is optimized for the neonatal brain. The main processing steps include image registration to an atlas, skull stripping, tissue segmentation, slice timing and head motion correction and regression of confounds which compromise functional data interpretation. To address the specificity of neonatal brain imaging, particular attention was given to registration including neonatal atlas type and parameters, such as brain size variations, and contrast differences compared to adults. Furthermore, head motion was scrutinized, and motion management optimized, as it is a major issue when processing neonatal rsfMRI data. The pipeline includes quality control using visual assessment checkpoints. To assess the effectiveness of NeoRS processing steps we used the neonatal data from the Baby Connectome Project dataset including a total of 10 neonates. NeoRS was designed to work on both multi-band and single-band acquisitions and is applicable on smaller datasets. NeoRS also includes popular functional connectivity analysis features such as seed-to-seed or seed-to-voxel correlations. Language, default mode, dorsal attention, visual, ventral attention, motor and fronto-parietal networks were evaluated. Topology found the different analyzed networks were in agreement with previously published studies in the neonate. NeoRS is coded in Matlab and allows parallel computing to reduce computational times; it is open-source and available on GitHub (https://github.com/venguix/NeoRS). NeoRS allows robust image processing of the neonatal rsfMRI data that can be readily customized to different datasets.
Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model
Authors: Oria Marc , Pathak Bedika , Li Zhen , Bakri Kenan , Gouwens Kara , Varela Maria Florencia , Lampe Kristin , Murphy Kendall P. , Lin Chia-Ying , Peiro Jose L.
Published: June 2022

During embryonic spinal cord development, neural progenitor cells (NPCs) generate three major cell lines: neurons, oligodendrocytes, and astrocytes at precise times and locations within the spinal cord. Recent studies demonstrate early astrogenesis in animal models of spina bifida, which may play a role in neuronal dysfunction associated with this condition. However, to date, the pathophysiological mechanisms related to this early astrocytic response in spina bifida are poorly understood. This study aimed to characterize the development of early astrogliosis over time from Pax6+, Olig2+, or Nkx2.2+ NPCs using a retinoic acid-induced spina bifida rat model. At three gestational ages (E15, E17, and E20), spinal cords from fetuses with retinoic acid-induced spina bifida, their healthy sibling controls, or fetuses treated with the vehicle control were analyzed. Results indicated that premature astrogliosis and astrocytic activation were associated with an altered presence of Pax6+, Olig2+, and Nkx2.2+ NPCs in the lesion compared to the controls. Finally, this response correlated with an elevation in genes involved in the Notch-BMP signaling pathway. Taken together, changes in NPC patterning factor expression with Notch-BMP signaling upregulation may be responsible for the altered astrogenesis patterns observed in the spinal cord in a retinoic acid-induced spina bifida model.
Development of Formulas for Calculating L3 Skeletal Muscle Mass Index and Visceral Fat Area Based on Anthropometric Parameters
Authors: Ji Wei , Liu XiangLiang , Zhang Yiqun , Zhao Yixin , He YuWei , Cui JiuWei , Li Wei
Published: June 2022

Background

The anthropometric index is not accurate but shows a great advantage in accessibility. Simple body composition formulas should be investigated before proceeding with the universal nutrition screening.

Materials and Methods

Clinical data of patients with a malignant tumor of the digestive system were collected. SliceOmatic 5.0 software (TOMOVISION, Canada) was used to analyze abdominal CT images and taken as references. A linear regression analysis was adopted to establish the formula for calculating skeletal muscle index (SMI) and visceral fat area (VFA). In addition, the relweights function was adopted to measure the contribution of each variable.

Results

In total, 344 patients were divided into the training set and 134 patients into the validation set. The selected formulas were SMI.pre = 0.540 × weight (kg) – 0.559 × height (cm) – 13.877 × sex (male = 1, female = 2) + 123.583, and VFA.pre = 5.146 × weight (kg) – 2.666 × height (cm) + 1.436 × age (year) + 134.096, of which the adjusted R2 were 0.597 and 0.581, respectively. The “weight” explained more than 80% of R2 in the prediction of VFA. In addition, “sex” occupied approximately 40% of R2 in the prediction of SMI. The paired t-test showed no significant difference between the real measured indices and the predicting ones (p = 0.123 for SMI and p = 0.299 for VFA). The logistic regression analysis exhibited similar diagnostic efficacy of the real measured parameters and formulas.

Conclusion

The SMI and VFA formulas were developed through basic indices, such as weight, height, sex, and age. According to the contribution of each variable, weight should always be focused on preserving appropriate muscle and adipose tissue.
An Endemic Plant of the Mediterranean Area: Phytochemical Characterization of Strawberry Tree (Arbutus unedo L.) Fruits Extracts at Different Ripening Stages
Authors: Scarano Pierpaolo , Guida Rosa , Zuzolo Daniela , Tartaglia Maria , Prigioniero Antonello , Postiglione Alessia , Pinto Gabriella , Illiano Anna , Amoresano Angela , Schicchi Rosario , Geraci Anna , Sciarrillo Rosaria , Guarino Carmine
Published: June 2022

This work focused on the extraction, quantification, and characterization of bioactive compounds of Arbutus unedo L. fruits, comparing the results obtained from the different ripening states. Extractions were performed by different methods (such as maceration extraction and ultrasonic extraction) and food grade solvents (aqueous and hydroalcoholic solvents) in each of the all ripening states (four states considered, associated with four different colors, i.e., green, yellow, orange, and red). The presence of (poly)phenols was quantified and characterized, and scavenging activity was determined by the Folin–Ciocâlteu reagent and the DPPH method, respectively. The content of bioactive compounds was characterized by LC-MS/MS, such as multiple reaction monitoring (MRM) mass spectrometry. The results showed that ultrasound-assisted extraction (UAE) performed better than maceration extraction; ethanol–water mixture extracts showed a more positive effect than the use of aqueous extracts regarding the content of total phenolic compounds. Overall, the total phenolic compounds in the EtOH:H2O mixture at a ratio of 7:3 (v:v) were higher than that of the other solvents for both extraction methods. Some bioactive molecules were characterized for the first time in the extracts of A. unedo. The chemical profile of the strawberry tree extracts depended on the degree of fruit ripeness. The results suggest that A. unedo fruits may be of great interest for food and nutraceutical applications.