bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection Against Post-resuscitation Acute Kidney Injury by N-Acetylcysteine via Activation of the Nrf2/HO-1 Pathway
Authors: Wang Shiwei , Liu Guoxiang , Jia Tianyuan , Wang Changsheng , Lu Xiaoye , Tian Lei , Yang Qian , Zhu Changqing 
Published: May 2022

Background and ObjectiveAcute kidney injury (AKI), the common complication after cardiopulmonary resuscitation (CPR), seriously affects the prognosis of cardiac arrest (CA) patients. However, there are limited studies on post-resuscitation AKI. In addition, it has been demonstrated that N-acetylcysteine (N-AC) as an ROS scavenger, has multiorgan-protective effects on systemic and regional ischaemia-reperfusion injuries. However, no studies have reported its protective effects against post-resuscitation AKI and potential mechanisms. This study aimed to clarify the protective effects of N-AC on post-resuscitation AKI and investigate whether its potential mechanism was mediated by activating Nrf-2/HO-1 pathway in the kidney.MethodsWe established cardiac arrest models in rats. All animals were divided into four groups: the sham, control, N-AC, and ZnPP groups. Animals in each group except for the ZnPP group were assigned into two subgroups based on the survival time: 6 and 48 h. The rats in the control, N-AC, and ZnPP groups underwent induction of ventricular fibrillation (VF), 8 min untreated VF and cardiopulmonary resuscitation. Renal function indicators, were detected using commercial kits. Renal pathologic changes were assessed by haematoxylin–eosin (HE) staining. Oxidative stress and inflammatory responses were measured using the corresponding indicators. Apoptosis was evaluated using terminal uridine nick-end labeling (TUNEL) staining, and expression of proteins associated with apoptosis and the Nrf-2/HO-1 pathway was measured by western blotting.ResultsN-AC inhibited post-resuscitation AKI. We observed that N-AC reduced the levels of biomarkers of renal function derangement; improved renal pathological changes; and suppressed apoptosis, oxidative stress, and inflammatory response. Additionally, the production of ROS in the kidneys markedly decreased by N-AC. More importantly, compared with the control group, N-AC further upregulated the expression of nuclear Nrf2 and endogenous HO-1 in N-AC group. However, N-AC-determined protective effects on post-resuscitation AKI were markedly reversed after pretreatment of the HO-1 inhibitor zinc protoporphyrin (ZnPP).ConclusionsN-AC alleviated renal dysfunction and prolonged survival in animal models of CA. N-AC partially exerts beneficial renal protection via activation of the Nrf-2/HO-1 pathway. Altogether, all these findings indicated that N-AC as a common clinical agent, may have the potentially clinical utility to improve patients the outcomes in cardiac arrest.
Time-Controlled Adaptive Ventilation Does Not Induce Hemodynamic Impairment in a Swine ARDS Model
Authors: Lescroart Mickael , Pequignot Benjamin , Bitker Laurent , Pina Héloïse , Tran N'Guyen , Hébert Jean-Louis , Richard Jean-Christophe , Lévy Bruno , Koszutski Matthieu 
Published: May 2022

BackgroundThe current standard of care during severe acute respiratory distress syndrome (ARDS) is based on low tidal volume (VT) ventilation, at 6 mL/kg of predicted body weight. The time-controlled adaptive ventilation (TCAV) is an alternative strategy, based on specific settings of the airway pressure release ventilation (APRV) mode. Briefly, TCAV reduces lung injury, including: (1) an improvement in alveolar recruitment and homogeneity; (2) reduction in alveolar and alveolar duct micro-strain and stress-risers. TCAV can result in higher intra-thoracic pressures and thus impair hemodynamics resulting from heart-lung interactions. The objective of our study was to compare hemodynamics between TCAV and conventional protective ventilation in a porcine ARDS model.MethodsIn 10 pigs (63–73 kg), lung injury was induced by repeated bronchial saline lavages followed by 2 h of injurious ventilation. The animals were then randomized into two groups: (1) Conventional protective ventilation with a VT of 6 mL/kg and PEEP adjusted to a plateau pressure set between 28 and 30 cmH2O; (2) TCAV group with P-high set between 27 and 29 cmH2O, P-low at 0 cmH2O, T-low adjusted to terminate at 75% of the expiratory flow peak, and T-high at 3–4 s, with I:E &gt; 6:1.ResultsBoth lung elastance and PaO2:FiO2 were consistent with severe ARDS after 2 h of injurious mechanical ventilation. There was no significant difference in systemic arterial blood pressure, pulmonary blood pressure or cardiac output between Conventional protective ventilation and TCAV. Levels of total PEEP were significantly higher in the TCAV group (p &lt; 0.05). Driving pressure and lung elastance were significantly lower in the TCAV group (p &lt; 0.05).ConclusionNo hemodynamic adverse events were observed in the TCAV group compared as to the standard protective ventilation group in this swine ARDS model, and TCAV appeared to be beneficial to the respiratory system.
Immune-Mediated Thrombotic Thrombocytopenic Purpura Following mRNA-Based COVID-19 Vaccine BNT162b2: Case Report and Mini-Review of the Literature
Authors: Buetler Vanessa Alexandra , Agbariah Nada , Schild Deborah Pia , Liechti Fabian D. , Wieland Anna , Andina Nicola , Hammann Felix , Kremer Hovinga Johanna A. 
Published: May 2022

IntroductionAn increasing number of case reports have associated vaccinations against coronavirus disease 2019 (COVID-19) with immune-mediated thrombotic thrombocytopenic purpura (iTTP), a very rare but potentially life-threatening thrombotic microangiopathy, which leads to ischemic organ dysfunction. Thrombus formation in iTTP is related to a severe deficiency of the specific von Willebrand-factor-cleaving protease ADAMTS13 due to ADAMTS13 autoantibodies.MethodsWe present a case of iTTP following exposure to the mRNA-based COVID-19 vaccine BNT162b2 (Comirnaty®, Pfizer-BioNTech). In addition, we review previously reported cases in the literature and assess current evidence.ResultsApart from our case, twenty cases of iTTP occurring after COVID-19 vaccination had been published until the end of November 2021. There were 11 male and 10 female cases; their median age at diagnosis was 50 years (range 14–84 years). Five patients (24%) had a preexisting history of iTTP. Recombinant adenoviral vector-based vaccines were involved in 19%, mRNA-based vaccines in 81%. The median onset of symptoms after vaccination was 12 days (range 5–37), with 20 cases presenting within 30 days. Treatment included therapeutic plasma exchange in all patients. Additional rituximab, caplacizumab, or both these treatments were given in 43% (9/21), 14% (3/21), and 24% (5/21) of cases, respectively. One patient died, despite a prolonged clinical course in one patient, all surviving patients were in clinical remission at the end of the observational period.ConclusionClinical features of iTTP following COVID-19 vaccination were in line with those of pre-pandemic iTTP. When timely initiated, an excellent response to standard treatment was seen in all cases. ADAMTS13 activity should be determined pre-vaccination in patients with a history of a previous iTTP episode. None of the reported cases met the WHO criteria for assessing an adverse event following immunization (AEFI) as a consistent causal association to immunization. Further surveillance of safety data and additional case-based assessment are needed.
Intracranial Aneurysms Induced by RUNX1 Through Regulation of NFKB1 in Patients With Hypertension-An Integrated Analysis Based on Multiple Datasets and Algorithms
Authors: Li Yang , Zhang Zhen , Liu Donghua 
Published: May 2022

ObjectiveThe purpose of this study was to identify potential therapeutic targets by examining the hub genes contributing to progression of intracranial aneurysm (IA) in patients with hypertension.MethodsThe bulk RNA sequencing (RNA-seq) datasets of hypertension and IA were obtained from the Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo) database. These data were then used to calculate disease-related differentially expressed genes (DEGs) at the individual level. An scRNA-seq dataset of patients with abdominal aortic aneurysms (AAA) was used to analyze monocyte/macrophage-related DEGs. On the basis of the DEG data related to monocytes and macrophages, a TF-genes network has been developed. Hub genes and core sub-networks have also been identified. Furthermore, the key genes have been validated in an external cohort.ResultsFrom combined monocyte and macrophage-derived DEGs from abdominal aortic aneurysms, five hub DEGs were detected, including IFI30, SERPINE1, HMOX1, IL24, and RUNX1. A total of 57 genes were found in the IA bulk RNA-seq dataset. A support vector machine-recursive feature elimination algorithm (SVM-RFE) was applied to further screen the seven genes (RPS4Y1, DDX3Y, RUNX1, CLEC10A, PLAC8, SLA, and LILRB3). RUNX1 was the hub gene that regulated NFKB1 in the monocyte/macrophage-related network. And RUNX1 is implicated in IA progression by regulating hematopoietic stem cell differentiation and abnormal platelet production, according to gene set enrichment analysis.ConclusionAmong patients with hypertension, RUNX1 in monocytes and macrophages was associated with a higher risk of IA through its regulation of NFKB1.
The Role of Neck Input in Producing Corrective Saccades in the Head Impulse Test
Authors: Iwasaki Shinichi , Kamogashira Teru , Fujimoto Chisato , Kabaya Kayoko , Kinoshita Makoto , Yamasoba Tatsuya 
Published: May 2022

BackgroundThe head impulse test is a valuable clinical test that can help identify peripheral vestibular dysfunction by observing corrective saccades that return the eyes to the target of interest. Corrective saccades have been classified as covert if the onset occurs before the end of the head impulse and as overt if they occur afterwards. However, the mechanism that trigger these saccades remain unclear.ObjectiveThe objective of this study was to examine the role of neck input in generating overt as well as covert saccades.MethodsSixteen patients (9 males and 7 females: age 35-80 years, average 62.7 years old) who showed corrective saccades during the head impulse test were included. Twelve patients had unilateral vestibular dysfunction, and 4 patients had bilateral vestibular dysfunction. Patients underwent both the head impulse test (HIT) and the body impulse test (BIT) in a randomized order. While the head is rotated horizontally in HIT, the body is rotated horizontally in BIT. During BIT, the neck is fixed by a cervical collar (neck lock extrication collar) to reduce somatosensory input from the neck. The head movements and eye movements were recorded and analyzed by the video HIT recording system.ResultsIn all 16 patients, corrective saccades were observed in HIT as well as in BIT. While there were no significant differences in peak head velocities between HIT and BIT (p = 0.33, paired t-test), the VOR gain in BIT was significantly smaller than that in HIT (p = 0.011, paired t-test). The number of overt saccades per trial in BIT was significantly decreased compared to that in HIT (p &lt; 0.001, paired t-test) whereas there were no significant differences in the number of covert saccades between the two tests. The proportion of overt saccades among all corrective saccades in BIT was significantly lower than the proportion in HIT (p &lt; 0.001, paired t-test).ConclusionsSomatosensory input from the neck contributes to the generation of overt saccades and reinforces the vestibulo-ocular reflex complementing the retinal slip during high frequency head movements.
SHROOM4 Variants Are Associated With X-Linked Epilepsy With Features of Generalized Seizures or Generalized Discharges
Authors: Bian Wen-Jun , Li Zong-Jun , Wang Jie , Luo Sheng , Li Bing-Mei , Gao Liang-Di , He Na , Yi Yong-Hong 
Published: May 2022

ObjectiveSHROOM4 gene encodes an actin-binding proteins, which plays an important role in cytoskeletal architecture, synaptogenesis, and maintaining gamma-aminobutyric acid receptors-mediated inhibition. SHROOM4 mutations were reported in patients with the Stocco dos Santos type of X-linked syndromic intellectual developmental disorder (SDSX; OMIM# 300434). In this study, we investigated the association between SHROOM4 and epilepsy.MethodsTrios-based whole-exome sequencing was performed in a cohort of 320 cases with idiopathic generalized epilepsy or idiopathic partial epilepsy. Protein modeling was used to assess the damaging effects of variations.ResultsSix hemizygous missense SHROOM4 variants, including c.13C &gt; A/p. Pro5Thr, c.3236C &gt; T/p.Glu1079Ala, c.3581C &gt; T/p.Ser1194Leu, c.4288C &gt; T/p.Arg1430Cys, c.4303G &gt; A/p.Val1435Met, c.4331C &gt; T/p.Pro1444Leu, were identified in six cases with idiopathic epilepsy without intellectual disability. All patients presented with features of generalized seizures or generalized discharges. These hemizygous variants had no or extremely low allele frequencies in controls and showed statistically higher frequency in the case cohort than controls. All variants were predicted to alter hydrogen bond with surrounding amino acids or decreased protein stability. The SHROOM4 variants reported in patients with SDSX were mostly destructive or duplicative variants; in contrast, the SHROOM4 variants were all missense variants, suggesting a potential genotype-phenotype correlation. The two missense variants associated with SDSX were located in the middle of SHROOM4 protein, whereas variants associated with idiopathic epilepsy were located around the N-terminal PDZ domain and the C-terminal ASD2 domain.SignificanceSHROOM4 was potentially a candidate pathogenic gene of idiopathic epilepsy without intellectual disability. The genotype-phenotype correlation and sub-regional effect helps understanding the mechanism underlying phenotypic variation.
Cigarette Smoke Exposure Induces Neurocognitive Impairments and Neuropathological Changes in the Hippocampus
Authors: Dobric Aleksandar , De Luca Simone N. , Seow Huei Jiunn , Wang Hao , Brassington Kurt , Chan Stanley M. H. , Mou Kevin , Erlich Jonathan , Liong Stella , Selemidis Stavros , Spencer Sarah J. , Bozinovski Steven , Vlahos Ross 
Published: May 2022

Background and ObjectiveNeurocognitive dysfunction is present in up to ∼61% of people with chronic obstructive pulmonary disease (COPD), with symptoms including learning and memory deficiencies, negatively impacting the quality of life of these individuals. As the mechanisms responsible for neurocognitive deficits in COPD remain unknown, we explored whether chronic cigarette smoke (CS) exposure causes neurocognitive dysfunction in mice and whether this is associated with neuroinflammation and an altered neuropathology.MethodsMale BALB/c mice were exposed to room air (sham) or CS (9 cigarettes/day, 5 days/week) for 24 weeks. After 23 weeks, mice underwent neurocognitive tests to assess working and spatial memory retention. At 24 weeks, mice were culled and lungs were collected and assessed for hallmark features of COPD. Serum was assessed for systemic inflammation and the hippocampus was collected for neuroinflammatory and structural analysis.ResultsChronic CS exposure impaired lung function as well as driving pulmonary inflammation, emphysema, and systemic inflammation. CS exposure impaired working memory retention, which was associated with a suppression in hippocampal microglial number, however, these microglia displayed a more activated morphology. CS-exposed mice showed changes in astrocyte density as well as a reduction in synaptophysin and dendritic spines in the hippocampus.ConclusionWe have developed an experimental model of COPD in mice that recapitulates the hallmark features of the human disease. The altered microglial/astrocytic profiles and alterations in the neuropathology within the hippocampus may explain the neurocognitive dysfunction observed during COPD.
NSAID Treatment Before and on the Early Onset of Acute Kidney Injury Had an Opposite Effect on the Outcome of Patients With AKI
Authors: Wang Hai , Liu Tong , Li Qinglin , Cui Ruixia , Fan Xueying , Tong Yingmu , Ma Shuzhen , Liu Chang , Zhang Jingyao 
Published: May 2022

Background: NSAIDs are one of the most frequently used medications and a risk factor for AKI. However, the optimal time of NSAIDs in patients with AKI is unknown.Methods: A secondary analysis of a multicenter, randomized clinical trial including adult inpatients with acute kidney injury was performed. Univariate, multivariate, and subgroup analyses were used to explore the impact of NSAIDs during the early onset of AKI on the outcome of patients with AKI.Results: A total of 6,030 patients with AKI were enrolled in the study. Following are the findings of the multi-factor analysis: NSAID treatments within 72 and 24 h before the onset of AKI were not associated with AKI progression, dialysis, or discharge from dialysis; only NSAID treatment within the 24-h onset of AKI was associated with these outcomes, and their OR values were independently 1.50 (95% CI: 1.02–2.19, p = 0.037), 4.20 (95% CI: 1.47–11.97, p = 0.007), and 0.71 (95% CI: 0.54–0.92, p = 0.011); only NSAID treatment within the 24-h onset of AKI would decrease the 14-day mortality, and the OR value was 0.52 (95% CI: 0.33–0.82, p = 0.005). The subgroup analysis revealed that in patients with age ≥65 years, CKD (chronic kidney disease), congestive heart failure, hypertension, and liver disease, NSAID treatments within the 24-h onset of AKI would deteriorate the outcome of patients with AKI.Conclusion: Before an early onset of AKI, NSAID treatment might be safe, but during the onset of AKI, even early NSAID treatment would deteriorate the outcome of patients with AKI.
Membrane Attack Complex C5b-9 Promotes Renal Tubular Epithelial Cell Pyroptosis in Trichloroethylene-Sensitized Mice
Authors: Wang Feng , Huang Meng , Wang Yican , Hong Yiting , Zang Dandan , Yang Chunjun , Wu Changhao , Zhu Qixing 
Published: May 2022

Trichloroethylene (TCE), a commonly used organic solvent, is known to cause trichloroethylene hypersensitivity syndrome (THS), also called occupational medicamentosa–like dermatitis due to TCE (OMDT) in China. OMDT patients presented with severe inflammatory kidney damage, and we have previously shown that the renal damage is related to the terminal complement complex C5b-9. Here, we sought to determine whether C5b-9 participated in TCE-induced immune kidney injury by promoting pyroptosis, a new form of programed cell death linked to inflammatory response, with underlying molecular mechanisms involving the NLRP3 inflammasome. A BALB/c mouse-based model of OMDT was established by dermal TCE sensitization in the presence or absence of C5b-9 inhibitor (sCD59-Cys, 25μg/mouse) and NLRP3 antagonist (MCC950, 10 mg/kg). Kidney histopathology, renal function, expression of inflammatory mediators and the pyroptosis executive protein gasdermin D (GSDMD), and the activation of pyroptosis canonical NLRP3/caspase-1 pathway were examined in the mouse model. Renal tubular damage was observed in TCE-sensitized mice. GSDMD was mainly expressed on renal tubular epithelial cells (RTECs). The caspase-1–dependent canonical pathway of pyroptosis was activated in TCE-induced renal damage. Pharmacological inhibition of C5b-9 could restrain the caspase-1–dependent canonical pathway and rescued the renal tubular damage. Taken together, our results demonstrated that complement C5b-9 plays a central role in TCE-induced immune kidney damage, and the underlying mechanisms involve NLRP3-mediated pyroptosis.
Persistence and Adherence to Biologics in Patients with Psoriasis in Taiwan: A New Biologics User Cohort Study
Authors: Huang Yu-Huei , Tang Chao-Hsiun , Goh Choo Hua , Chang Chia-Li , Qiu Hong , Yang Ya-Wen , Saadoun Carine , Chang Chia-Ling , Liu Yanfang 
Published: May 2022

Background: Biologics are used to treat moderate-to-severe psoriasis, and persistence to biologics may reflect clinical effectiveness. Limited information describing how biologics are used in patients with moderate-to-severe psoriasis in Asian countries is available. We conducted a population-based, retrospective, new user cohort study using the National Health Insurance Research Database (NHIRD) in Taiwan to assess treatment persistence and adherence to biologics.Methods: Adults with a diagnosis of psoriasis between 01 January 2015 and 31 December 2017 were identified in the NHIRD (ICD-9-CM 696.1; ICD-10 L40.0). New users were patients who initiated treatment with etanercept, adalimumab, ustekinumab or secukinumab between 01 January 2015 and 31 December 2017. All eligible patients were followed until 31 December 2018, death or disenrollment. Kaplan-Meier analysis was conducted to estimate persistence of treatment for index biologics. A Cox-proportional hazard regression model was used to compare risks of biologic discontinuation between biologic groups. Adjustments for potential confounding factors (age, gender and Charlson comorbidity index score) were made in the Cox model.Results: There were 1,397 new biologic users with psoriasis during the study period. The ratio men:women was approximately 4:1. Mean age of patients ranged from 44.6 to 47.7 years across exposure groups. The 1-year/2-years persistence rates were 94.2%/84.9% for ustekinumab, 96.2%/not calculated (due to too few patients at year 2) for secukinumab, 66.0%/29.9% for etanercept, and 59.8%/40.3% for adalimumab. The risk of discontinuation was significantly lower in patients initiating ustekinumab compared with adalimumab (hazard ratio adjusted for age, sex and co-morbidities 0.289, 95%CI 0.247–0.339, p &lt; 0.0001). Drug survival was significantly higher for ustekinumab compared with adalimumab and etanercept (log-rank test p &lt; 0.0001). The proportions of patients with 1-year/2-years medication possession ratios of ≥80% were 95.3%/92.0% for ustekinumab, 98.1%/not calculated for secukinumab, 89.4%/83.1% for etanercept, and 70.8%/59.4% for adalimumab.Limitations: Clinical improvement and response to treatment data were not available.Conclusion: There was relatively high persistence amongst biologic users with psoriasis in Taiwan. There is a trend towards greater persistence of ustekinumab compared to other biologics, the magnitude of which depends on the treatment gap used for its calculation. This study provides real-world evidence that may facilitate optimal treatment choice.
The Chain-Mediation Pathway of Social Avoidance to Depression in College Students Is Regulated by Self-Esteem
Authors: Yuan Ye , Jiang Suhua , Wen Xi , Han Zhong , Wu Daili , Wang Xuanping , Ye Tingyang , Hu Yimin , Jeong Jaesik , Xiang Min 
Published: May 2022

ObjectiveHere, we investigated the relationship between social avoidance and depression in college students, explored the mediating roles of loneliness and trust, and the regulatory role of self-esteem, to provide a theoretical intervention approach based on internal mechanisms.MethodsUsing a simple random overall sampling method, 1,021 college students were investigated using self-rating depression, social avoidance and distress, loneliness, interpersonal trust and self-esteem scales.ResultsThere was a significant positive correlation between social avoidance and depression. Loneliness and interpersonal trust played chain-mediating roles between social avoidance and depression. The influence of social avoidance on interpersonal trust was regulated by self-esteem. Specifically, the social avoidance level of the low self-esteem group was more likely to be affected by interpersonal trust issues.ConclusionSocial avoidance not only directly affects college students’ depression, it also has indirect effects through interpersonal trust and loneliness. Thus, interpersonal trust and loneliness have chain-mediating effects between social avoidance and depression in college students, and self-esteem regulates the mediation process.