bluuebunny/crossref_metadata_2025_split huggingface dataset:
STAT3 gain-of-function is not responsible for low total IgE levels in patients with autoimmune chronic spontaneous urticaria
Authors: Sauer Merle , Scheffel Jörg , Frischbutter Stefan , Mahnke Niklas , Maurer Marcus , Burmeister Thomas , Krause Karoline , Metz Martin 
Published: July 2022

BackgroundThe pathogenesis of chronic spontaneous urticaria (CSU) has not been clarified entirely. Type IIb autoimmune chronic spontaneous urticaria (CSUaiTIIb) is a distinct subtype of CSU that is often difficult to treat and is connected to low levels of total IgE. Previous findings indicate that an enhanced signal transducer and activator of transcription 3 (STAT3) may be responsible for reduced IgE serum levels.ObjectiveOur aim was to investigate a possible underlying gain-of-function mutation or activating polymorphism in STAT3 that could be responsible for the low levels of IgE in patients with CSUaiTIIb.MethodsWe included 10 patients with CSUaiTIIb and low levels of IgE and sequenced selected single nucleotide polymorphisms (SNP) in STAT3 associated with common autoimmune diseases. Exon sequencing was performed for the most relevant exons of STAT3. To test for a gain-of-function of STAT3, we performed a phospho-specific flow cytometry analysis of STAT3 in peripheral blood mononuclear cells before and after stimulation with interleukin-6.ResultsNo differences were found in the prevalence of the tested SNPs between our patients and a control population. Moreover, we could not find any mutations or variants on the tested exons of STAT3. The function of STAT3 was also not altered in our patients.ConclusionIn total, we could not find any evidence for our hypothesis that low IgE in patients with CSUaiTIIb is linked to mutations in STAT3 or altered activity of STAT3. Thus, it remains to be discovered what causes the low serum levels of IgE in patients with CSUaiTIIb.
Low-dose mycophenolate mofetil improves survival in a murine model of Staphylococcus aureus sepsis by increasing bacterial clearance and phagocyte function
Authors: Alby-Laurent Fanny , Belaïdouni Nadia , Blanchet Benoit , Rousseau Christophe , Llitjos Jean-François , Sanquer Sylvia , Mira Jean-Paul , Pène Frédéric , Toubiana Julie , Chiche Jean-Daniel 
Published: July 2022

Regulators of TLRs signaling pathways play an important role in the control of the pro-inflammatory response that contributes to sepsis-induced tissue injury. Mycophenolate mofetil, an immunosuppressive drug inhibiting lymphocyte proliferation, has been reported to be a regulator of TLRs signaling pathways. Whether MMF used at infra-immunosuppressive doses has an impact on survival and on innate immune response in sepsis is unknown.C57BL/6J mice were infected intraperitoneally with 108 CFU Staphylococcus aureus, and treated or not with low-dose of MMF (20mg/kg/day during 4 days). Survival rate and bacterial clearance were compared. Cytokine levels, quantitative and qualitative cellular responses were assessed. S. aureus – infected mice treated with MMF exhibited improved survival compared to non-treated ones (48% vs 10%, p&lt;0.001). With the dose used for all experiments, MMF did not show any effect on lymphocyte proliferation. MMF treatment also improved local and systemic bacterial clearance, improved phagocytosis activity of peritoneal macrophages resulting in decreased inflammatory cytokines secretion. MMF-treated mice showed enhanced activation of NF-κB seemed with a suspected TLR4-dependent mechanism. These results suggest that infra-immunosuppressive doses of MMF improve host defense during S. aureus sepsis and protects infected mice from fatal outcome by regulating innate immune responses. The signaling pathways involved could be TLR4-dependent. This work brings new perspectives in pathogenesis and therapeutic approaches of severe infections.
First-Principles Study of Metal Impurities in Silicon Carbide: Structural, Magnetic, and Electronic Properties
Authors: Zhang Lin , Cui Zhen 
Published: July 2022

The configurations of 10 types of metal-doped silicon carbide (SiC) systems were investigated by the first-principles calculations. The dopants include eight types of 3d-series transition metal atoms, one semi-metal Ge atom, and one other metal Al atom. For all the metal-doped SiC systems, the steadiest doping sites are fixed at the substituted Si site, while the Ti-SiC system exhibits the most potent binding activity. The properties of these new systems vary with the doping atoms. The SiC- and Al-SiC systems convert to magnetic metals. The Ti- and Ge-SiC systems remain non-magnetic semiconductors, while the V-, Cr-, Mn-, Fe-, Co-, and Zn-SiC systems turn into magnetic semiconductors with magnetic moments related to the valence electron number of dopants. Partial charge transfers from the metal atoms to the adjacent C atoms accompanied the change in the electron-emitting capacity of the new systems. The work function achieves the minimum of 3.439 eV in the Co-SiC system, just 71.6% of the original SiC system. Our analysis indicates that the potent binding energy of the Ti-SiC system is due to the complete bonding states between the transition metal Ti and the adjacent C atoms. The magnetism evolution in semiconducting metal-doped SiC is attributed to the occupation mode of the hybridization orbitals nearby the Fermi level, which are determined by the coupling of the 3d orbital of transition metal atoms and the defect states of the vacancy atoms. The adjustable magnetic and electronic properties of the metal-doped SiC systems provide a flexible method in designing more suitable SiC-based spintronics and field electron-emitting devices.
Use of failure mode and effect analysis to reduce patient safety risks in purchasing prescription drugs from online pharmacies in China
Authors: Hu Qinyuan , Hu Haiyao , Hu Ming , Zhang Jun , Gou Liangwen , Shi Shuping , Zhou Jingyi , Zhou Naitong , Huang Zhen 
Published: July 2022

BackgroundOnline pharmacies have gradually penetrated the market, but pose risks to patients' health. Failure Mode and Effect Analysis (FMEA) is an effective and reliable method for reducing pharmacy and medication risks. The purpose of this study was to conduct a prospective risk analysis of the process of purchasing prescription drugs from online pharmacies in China to guarantee drug quality and patient safety.MethodsThe FMEA was performed at Sichuan University, China. A multidisciplinary team was assembled comprising a leader, four regulators, four pharmacists, two experts, etc. The process was composed of eight subprocesses: searching for prescription drugs, submitting medication requirements, completing patient information forms, dispensing, delivering, etc. Brainstorming was used to identify and prioritize failure modes, propose corrective actions, and reduce risks. Risk priority numbers were the main criterion and were obtained by multiplying three scores: severity, occurrence and detectability, which were scored by the team The team proposed corrective actions for each selected failure mode.ResultsA total of forty-one potential failure modes were identified, and the causes, effects, and corrective actions of the 30 top failure modes were analyzed. The highest risk value was assigned to “photocopies of paper prescriptions uploaded were reused by patients.” Three failure modes for the S value of 5 were: “drugs are eroded and polluted by moisture or insects in the process of transportation,” “the qualification information of the pharmacies were absent or fake,” and “pharmacists fail to check prescriptions in accordance with Prescription Administrative Regulation.” Of the top failure modes, 36.67% were from Step 5, delivering the drug. After taking corrective measures to control risks, the risks reduced by 69.26%.ConclusionThe results of this study proves that the FMEA is a valuable tool for identifying and prioritizing the risks inherent in online pharmacies. This study shows that there are many potential risks in the process of purchasing prescription drugs from online pharmacies, especially in the drug delivery stage. Enhanced training and the introduction of smart devices may minimize risks. Online pharmacies and Chinese regulators should consider these findings for risk mitigation and the improvement of regulations pertaining to online pharmacies.
Nitrate exposure reprograms hepatic amino acid and nutrient sensing pathways prior to exercise: A metabolomic and transcriptomic investigation in zebrafish (Danio rerio)
Authors: Keller Rosa M. , Beaver Laura M. , Prater Mary C. , Truong Lisa , Tanguay Robyn L. , Stevens Jan F. , Hord Norman G. 
Published: July 2022

Scope: Nitrate supplementation is a popular ergogenic aid that improves exercise performance by reducing oxygen consumption during exercise. We investigated the effect of nitrate exposure and exercise on metabolic pathways in zebrafish liver.Materials and methods: Fish were exposed to sodium nitrate (606.9 mg/L), or control water, for 21 days and analyzed at intervals during an exercise test. We utilized untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and measured gene expression of 24 genes central to energy metabolism and redox signaling.Results: We observed a greater abundance of metabolites involved in endogenous nitric oxide (NO) metabolism and amino acid metabolism in nitrate-treated liver at rest, compared to rested controls. In the absence of exercise, nitrate treatment upregulated expression of genes central to nutrient sensing (pgc1a), protein synthesis (mtor) and purine metabolism (pnp5a and ampd1) and downregulated expression of genes involved in mitochondrial fat oxidation (acaca and cpt2).Conclusion: Our data support a role for sub-chronic nitrate treatment in the improvement of exercise performance, in part, by improving NO bioavailability, sparing arginine, and modulating hepatic gluconeogenesis and glycolytic capacity in the liver.
Effects of combined cognitive and physical intervention on enhancing cognition in older adults with and without mild cognitive impairment: A systematic review and meta-analysis
Authors: Han Kaiyue , Tang Zhiqing , Bai Zirong , Su Wenlong , Zhang Hao 
Published: July 2022

BackgroundCombined cognitive and physical intervention is commonly used as a non-pharmacological therapy to improve cognitive function in older adults, but it is uncertain whether combined intervention can produce stronger cognitive gains than either single cognitive or sham intervention. To address this uncertainty, we performed a systematic review and meta-analysis to evaluate the effects of combined intervention on cognition in older adults with and without mild cognitive impairment (MCI).MethodsWe systematically searched eight databases for relevant articles published from inception to November 1, 2021. Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) were used to compare the effects of the combined intervention with a single cognitive or sham intervention on cognition in older adults with and without MCI aged ≥ 50 years. We also searched Google Scholar, references of the included articles, and relevant reviews. Two independent reviewers performed the article screening, data extraction, and bias assessment. GRADEpro was used to rate the strength of evidence, and RevMan software was used to perform the meta-analysis.ResultsSeventeen studies were included in the analysis, comprising eight studies of cognitively healthy older adults and nine studies of older adults with MCI. The meta-analysis showed that the combined intervention significantly improved most cognitive functions and depression (SMD = 0.99, 95% CI 0.54–1.43, p &lt; 0.0001) in older adults compared to the control groups, but the intervention effects varied by cognition domains. However, there was no statistically significant difference in the maintenance between the combined and sham interventions (SMD = 1.34, 95% CI −0.58–3.27, p = 0.17). The subgroup analysis also showed that there was no statistical difference in the combined intervention to improve global cognition, memory, attention, and executive function between cognitive healthy older adults and older adults with MCI.ConclusionsCombined intervention improves cognitive functions in older adults with and without MCI, especially in global cognition, memory, and executive function. However, there was no statistical difference in the efficacy of the combined intervention to improve cognition between cognitive healthy older adults and older adults with MCI. Moreover, the maintenance of the combined intervention remains unclear due to the limited follow-up data and high heterogeneity. In the future, more stringent study designs with more follow-ups are needed further to explore the effects of combined intervention in older adults.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42021292490.
Cognitive impairment in the population-based ural very old study
Authors: Bikbov Mukharram M. , Kazakbaeva Gyulli M. , Iakupova Ellina M. , Panda-Jonas Songhomitra , Fakhretdinova Albina A. , Tuliakova Azaliia M. , Rusakova Iuliia A. , Jonas Jost B. 
Published: July 2022

BackgroundDespite its marked importance in public health, the prevalence of cognitive impairment (CI) and its associated factors have only rarely been examined in old populations in general or in Russia at all.ObjectiveTo assess CI prevalence and its determinants in a very elderly population in Russia.Materials and methodsThe population-based Ural Very Old Study, conducted in rural and urban region in Bashkortostan/Russia, included 1,526 (81.1%) out of 1,882 eligible individuals aged 85+ years. A series of medical examinations including the Mini-Mental State Examination (MMSE) for the assessment of CI was performed.ResultsMini-Mental State Examination data were available for 1,442 (94.5%) individuals (mean age: 88.3 ± 2.9 years; range: 85–103 years). The median MMSE score was 24 (interquartile range: 19, 27). Prevalence of any CI (MMSE score &lt; 24 points) was 701/1,442 [48.6%; 95% confidence interval (CI): 46.0, 51.2]. Prevalence of mild, moderate and severe CI (MMSE score 19–23 points, 10–18 points, and ≤9 points, respectively) was 357/1,442 (24.8%; 95% CI: 22.5, 27.0), 246/1,442 (17.1%; 95% CI: 15.1, 19.0), and 98/1,442 (6.8%; 95% CI: 5.5, 8.1), resp. A lower MMSE score correlated (regression coefficient r2: 0.31) with older age (beta: −0.13; P &lt; 0.001), rural region of habitation (beta: 0.15; P &lt; 0.001), lower level of education (beta: 0.19; P &lt; 0.001), higher depression score (beta: −0.33; P &lt; 0.001) (or alternatively, higher prevalence of hearing loss (beta: −0.10; P = 0.001), worse visual acuity (beta: −0.10; P = 0.001), and lower physical activity (beta: 0.06; P = 0.04).ConclusionIn this elderly study population from rural and urban Russia, prevalence of any, mild, moderate and severe CI was 48.6, 24.8, 17.1, and 6.8%, resp. Besides medical and lifestyle factors, vision and hearing impairment were major factors associated with CI.
Phase-dependent Brain Activation of the Frontal and Parietal Regions During Walking After Stroke - An fNIRS Study
Authors: Lim Shannon B. , Yang Chieh-ling , Peters Sue , Liu-Ambrose Teresa , Boyd Lara A. , Eng Janice J. 
Published: July 2022

BackgroundRecovery of walking post-stroke is highly variable. Accurately measuring and documenting functional brain activation characteristics during walking can help guide rehabilitation. Previous work in this area has been limited to investigations of frontal brain regions and have not utilized recent technological and analytical advances for more accurate measurements. There were three aims for this study: to characterize the hemodynamic profile during walking post-stroke, to investigate regional changes in brain activation during different phases of walking, and to related brain changes to clinical measures.MethodsFunctional near-infrared spectroscopy (fNIRS) along the pre-frontal, premotor, sensorimotor, and posterior parietal cortices was used on twenty individuals greater than six months post-stroke. Individual fNIRS optodes were digitized and used to estimate channel locations on each participant and short separation channels were used to control for extracerebral hemodynamic changes. Participants walked at their comfortable pace several times along a hallway while brain activation was recorded. Exploratory cluster analysis was conducted to determine if there was a link between brain activation and clinical measures.ResultsSustained activation was observed in the pre-frontal cortex with the ipsilesional hemisphere showing greater activation compared to the contralesional side. Sensorimotor cortex was active during the early, acceleration stage of walking only. Posterior parietal cortex showed changes in activation during the later, steady-state stage of walking. Faster gait speeds also related to increased activation in contralesional sensorimotor and posterior parietal cortices. Exploratory analysis clustered participants into two distinct groups based on their brain activation profiles and generally showed that individuals with greater activation tended to have better physical outcomes.ConclusionsThese findings can guide future research for obtaining adequate power and determining factors that can be used as effect modifiers to reduce inter-subject variability. Overall, this is the first study to report specific oxygenated and deoxygenated hemoglobin changes in frontal to parietal regions during walking in the stroke population. Our results shed light on the importance of measuring brain activation across the cortex and show the importance of pre-frontal, sensorimotor, and posterior parietal cortices in walking after a stroke.
Protocol and Preliminary Results of the Establishment of Intracranial Aneurysm Database for Artificial Intelligence Application Based on CTA Images
Authors: You Wei , Sun Yong , Feng Junqiang , Wang Zhiliang , Li Lin , Chen Xiheng , Lv Jian , Tang Yudi , Deng Dingwei , Wei Dachao , Gui Siming , Liu Xinke , Liu Peng , Jin Hengwei , Ge Huijian , Zhang Yanling 
Published: July 2022

Background and PurposeUnruptured intracranial aneurysms (UIAs) are increasingly being detected in clinical practice. Artificial intelligence (AI) has been increasingly used to assist diagnostic techniques and shows encouraging prospects. In this study, we reported the protocol and preliminary results of the establishment of an intracranial aneurysm database for AI application based on computed tomography angiography (CTA) images.MethodsThrough a review of picture archiving and communication systems, we collected CTA images of patients with aneurysms between January 2010 and March 2021. The radiologists performed manual segmentation of all diagnosed aneurysms on subtraction CTA as the basis for automatic aneurysm segmentation. Then, AI will be applied to two stages of aneurysm treatment, namely, automatic aneurysm detection and segmentation model based on the CTA image and the aneurysm risk prediction model.ResultsThree medical centers have been included in this study so far. A total of 3,190 cases of CTA examinations with 4,124 aneurysms were included in the database. All identified aneurysms from CTA images that enrolled in this study were manually segmented on subtraction CTA by six readers. We developed a structure of 3D-Unet for aneurysm detection and segmentation in CTA images. The algorithm was developed and tested using a total of 2,272 head CTAs with 2,938 intracranial aneurysms. The recall and false positives per case (FP/case) of this model for detecting aneurysms were 0.964 and 2.01, and the Dice values for aneurysm segmentation were 0.783.ConclusionThis study introduces the protocol and preliminary results of the establishment of the intracranial aneurysm database for AI applications based on CTA images. The establishment of a multicenter database based on CTA images of intracranial aneurysms is the basis for the application of AI in the diagnosis and treatment of aneurysms. In addition to segmentation, AI should have great potential for aneurysm treatment and management in the future.
Altered resting-state functional connectivity of insula in children with primary nocturnal enuresis
Authors: Zhong Shaogen , Shen Jiayao , Wang Mengxing , Mao Yi , Du Xiaoxia , Ma Jun 
Published: July 2022

ObjectivePrimary nocturnal enuresis (PNE) is a common developmental condition in school-aged children. The objective is to better understand the pathophysiology of PNE by using insula-centered resting-state functional connectivity (rsFC).MethodsWe recruited 66 right-handed participants in our analysis, 33 with PNE and 33 healthy control (HC) children without enuresis matched for gender and age. Functional and structural MRI data were obtained from all the children. Seed-based rsFC was used to examine differences in insular functional connectivity between the PNE and HC groups. Correlation analyses were carried out to explore the relationship between abnormal insula-centered functional connectivity and clinical characteristics in the PNE group.ResultsCompared with HC children, the children with PNE demonstrated decreased left and right insular rsFC with the right medial superior frontal gyrus (SFG). In addition, the bilateral dorsal anterior insula (dAI) seeds also indicated the reduced rsFC with right medial SFG. Furthermore, the right posterior insula (PI) seed showed the weaker rsFC with the right medial SFG, while the left PI seed displayed the weaker rsFC with the right SFG. No statistically significant correlations were detected between aberrant insular rsFC and clinical variables (e.g., micturition desire awakening, bed-wetting frequency, and bladder volume) in results without global signal regression (GSR) in the PNE group. However, before and after setting age as a covariate, significant and positive correlations between bladder volume and the rsFC of the left dAI with right medial SFG and the rsFC of the right PI with right medial SFG were found in results with GSR in the PNE group.ConclusionTo the best of our knowledge, this study explored the rsFC patterns of the insula in children with PNE for the first time. These results uncovered the abnormal rsFC of the insula with the medial prefrontal cortex without and with GSR in the PNE group, suggesting that dysconnectivity of the salience network (SN)-default mode network (DMN) may involve in the underlying pathophysiology of children with PNE. However, the inconsistent associations between bladder volume and dysconnectivity of the SN-DMN in results without and with GSR need further studies.