bluuebunny/crossref_metadata_2025_split huggingface dataset:
Veno-Venous Extracorporeal Membrane Oxygenation in Minipigs as a Robust Tool to Model Acute Kidney Injury: Technical Notes and Characteristics
Authors: Szabó-Biczók Antal , Varga Gabriella , Varga Zoltán , Bari Gábor , Vigyikán Gyöngyvér , Gajda Ámos , Vida Noémi , Hodoniczki Ádám , Rutai Attila , Juhász László , Nászai Anna , Gyöngyösi Máté , Turkevi-Nagy Sándor , Érces Dániel , Boros Mihály 
Published: April 2022

ObjectiveVeno-venous extracorporeal membrane oxygenation (vv-ECMO) can save lives in severe respiratory distress, but this innovative approach has serious side-effects and is accompanied by higher rates of iatrogenic morbidity. Our aims were, first, to establish a large animal model of vv-ECMO to study the pathomechanism of complications within a clinically relevant time frame and, second, to investigate renal reactions to increase the likelihood of identifying novel targets and to improve clinical outcomes of vv-ECMO-induced acute kidney injury (AKI).MethodsAnesthetized Vietnamese miniature pigs were used. After cannulation of the right jugular and femoral veins, vv-ECMO was started and maintained for 24 hrs. In Group 1 (n = 6) ECMO was followed by a further 6-hr post-ECMO period, while (n = 6) cannulation was performed without ECMO in the control group, with observation maintained for 30 h. Systemic hemodynamics, blood gas values and hour diuresis were monitored. Renal artery flow (RAF) was measured in the post-ECMO period with an ultrasonic flowmeter. At the end of the experiments, renal tissue samples were taken for histology to measure myeloperoxidase (MPO) and xanthine oxidoreductase (XOR) activity and to examine mitochondrial function with high-resolution respirometry (HRR, Oroboros, Austria). Plasma and urine samples were collected every 6 hrs to determine neutrophil gelatinase-associated lipocalin (NGAL) concentrations.ResultsDuring the post-ECMO period, RAF dropped (96.3 ± 21 vs. 223.6 ± 32 ml/min) and, similarly, hour diuresis was significantly lower as compared to the control group (3.25 ± 0.4 ml/h/kg vs. 4.83 ± 0.6 ml/h/kg). Renal histology demonstrated significant structural damage characteristic of ischemic injury in the tubular system. In the vv-ECMO group NGAL levels, rose significantly in both urine (4.24 ± 0.25 vs. 2.57 ± 0.26 ng/ml) and plasma samples (4.67 ± 0.1 vs. 3.22 ± 0.2 ng/ml), while tissue XOR (5.88 ± 0.8 vs. 2.57 ± 0.2 pmol/min/mg protein) and MPO (11.93 ± 2.5 vs. 4.34 ± 0.6 mU/mg protein) activity was elevated. HRR showed renal mitochondrial dysfunction, including a significant drop in complex-I-dependent oxidative capacity (174.93 ± 12.7 vs. 249 ± 30.07 pmol/s/ml).ConclusionSignificantly decreased renal function with signs of structural damage and impaired mitochondrial function developed in the vv-ECMO group. The vv-ECMO-induced acute renal impairment in this 30-hr research protocol provides a good basis to study the pathomechanism, biomarker combinations or possible therapeutic possibilities for AKI.
Fibrinogen A Alpha-Chain Amyloidosis in Two Chinese Patients
Authors: Li Zhen-Yu , Wang Shuang , Li Dan-Yang , Liu Dan , Wang Su-Xia , Yu Xiao-Juan , Liu Gang , Zhou Fu-De , Zhao Ming-Hui 
Published: April 2022

ObjectivesFibrinogen A alpha-chain amyloidosis (AFib amyloidosis) is the most common form of hereditary renal amyloidosis in the United Kingdom and Europe, but has rarely been reported in Asia. In this study, we reported two AFib amyloidosis patients in China, reviewing the literature and summarizing main characteristics of AFib amyloidosis in Asia.MethodsTwo unrelated Chinese patients were diagnosed with AFib amyloidosis by clinical presentation, renal biopsy, mass spectrometry and DNA sequencing in Peking University First Hospital of China from 2014 to 2016.ResultsBoth of the patients presented with proteinuria, edema and hypertension. Renal biopsies of two patients showed extensive amyloid deposits (Congo red positive) in glomeruli, and focal tubulointerstitial amyloid deposits was also found in patient 1. Besides, hepatic involvement of amyloidosis has been detected by liver biopsy in patient 1. By electron microscopy, randomly arranged fibrils in a diameter of 8–12 nm was identified in mesangial matrix and subendothelial area of glomeruli. Immunohistochemistry demonstrated amyloid deposits were strongly positive for fibrinogen Aα in glomeruli and positive for LECT2 in the interstitium of renal medulla and the liver in Patient 1. Unevenly positive staining for both fibrinogen Aα and ApoA-I were found in Patient 2. Fibrinogen Aα was the most abundant amyloidogenic protein in both patients identified by laser microdissection and mass spectrometry-based proteomic analysis. Genetic analysis revealed the fibrinogen A a-chain gene (FGA) mutation in both patients, including a new deletion mutation [c.1639delA (p.Arg547Glyfs*21; NM_000508)] in Patient 2. Genetic analysis of the LECT2 gene in patient 1 revealed a codon change from ATC to GTC at position 172 [c.172A&gt;G (p.Ile58Val; NM_002302)], which is a common polymorphism (SNP rs31517) in all ALECT2 amyloidosis patients.ConclusionsWe reported two AFib amyloidosis patients in China, one of them coexisted with ALECT2 amyloidosis simultaneously.
Case Report: The First Reported Concurrence of Wilson Disease and Bilateral Retinitis Pigmentosa
Authors: Ye Zifan , Jia Xiuhua , Liu Xin , Zhang Qi , Wang Kaijun , Chen Min 
Published: April 2022

BackgroundWilson disease (WD) and retinitis pigmentosa (RP) are common genetic disorders in clinical practice, however, the concurrence of WD and RP has never been reported before. WD occurs due to mutations that cause copper metabolic abnormalities; in turn, change in copper metabolism has been suggested to be related with RP. Here, we report the first case of concurrent WD and bilateral RP, and investigate possible pathogenesis to illuminate whether the two genetic disorders are causality or coincidence.Case PresentationThe patient was a 43-year-old Chinese female diagnosed with WD 12 years ago. She had suffered from night blindness since childhood and faced diminution of bilateral vision within 10 years, for which she was referred to our Eye Center during hospitalization for routine copper excretion treatment. The ceruloplasmin, skull magnetic resonance imaging (MRI), and abdominal ultrasound results accorded with hepatolenticular degeneration. Ocular examinations revealed corneal Kayser-Fleischer (K-F) ring, sunflower-like cataract, retinal osteocyte-like pigmentation, bilateral atrophy of outer retina, cystoid macular edema (CME), and tubular vision in both eyes. Phacoemulsification combined with intraocular lens implantation was performed in the right and left eye, but there was limited improvement in her visual acuity. Whole exome sequencing (WES) detected a deleterious homozygous mutation in the ATP7B gene related to WD, and a homozygous mutation in the CNGA1 gene very likely to cause RP.ConclusionsWe reported the first case of concurrent WD and RP. WES detected two pathogenic gene mutations, ATP7B and CNGA1. Though we cannot completely rule out a causal effect of WD-related abnormal copper metabolism with RP, we speculate that the two gene mutations lead to the coincidence of the two genetic disorders, respectively.
Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects
Authors: Bukowska-Olech Ewelina , Sowińska-Seidler Anna , Larysz Dawid , Gawliński Paweł , Koczyk Grzegorz , Popiel Delfina , Gurba-Bryśkiewicz Lidia , Materna-Kiryluk Anna , Adamek Zuzanna , Szczepankiewicz Aleksandra , Dominiak Paweł , Glista Filip , Matuszewska Karolina , Jamsheer Aleksander 
Published: April 2022

Background: Craniosynostosis (CS) represents a highly heterogeneous genetic condition whose genetic background has not been yet revealed. The abnormality occurs either in isolated form or syndromic, as an element of hundreds of different inborn syndromes. Consequently, CS may often represent a challenging diagnostic issue.Methods: We investigated a three-tiered approach (karyotyping, Sanger sequencing, followed by custom gene panel/chromosomal microarray analysis, and exome sequencing), coupled with prioritization of variants based on dysmorphological assessment and description in terms of human phenotype ontology. In addition, we have also performed a statistical analysis of the obtained clinical data using the nonparametric test χ2.Results: We achieved a 43% diagnostic success rate and have demonstrated the complexity of mutations’ type harbored by the patients, which were either chromosomal aberrations, copy number variations, or point mutations. The majority of pathogenic variants were found in the well-known CS genes, however, variants found in genes associated with chromatinopathies or RASopathies are of particular interest.Conclusion: We have critically summarized and then optimised a cost-effective diagnostic algorithm, which may be helpful in a daily diagnostic routine and future clinical research of various CS types. Moreover, we have pinpointed the possible underestimated co-occurrence of CS and intellectual disability, suggesting it may be overlooked when intellectual disability constitutes a primary clinical complaint. On the other hand, in any case of already detected syndromic CS and intellectual disability, the possible occurrence of clinical features suggestive for chromatinopathies or RASopathies should also be considered.
AD Resemblance Atrophy Index of Brain Magnetic Resonance Imaging in Predicting the Progression of Mild Cognitive Impairment Carrying Apolipoprotein E-ε4 Allele
Authors: Mai Yingren , Cao Zhiyu , Xu Jiaxin , Yu Qun , Yang Shaoqing , Tang Jingyi , Zhao Lei , Fang Wenli , Luo Yishan , Lei Ming , Mok Vincent C. T. , Shi Lin , Liao Wang , Liu Jun ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2022

Background and ObjectiveEarly identification is important for timely Alzheimer’s disease (AD) treatment. Apolipoprotein E ε4 allele (APOE-ε4) is an important genetic risk factor for sporadic AD. The AD-Resemblance Atrophy Index (RAI)—a structural magnetic resonance imaging-derived composite index—was found to predict the risk of progression from mild cognitive impairment (MCI) to AD. Therefore, we investigated whether the AD-RAI can predict cognitive decline and progression to AD in patients with MCI carrying APOE ε4.MethodsWe included 733 participants with MCI from the Alzheimer’s Disease Neuroimaging Initiative Database (ADNI). Their APOE genotypes, cognitive performance, and levels of AD-RAI were assessed at baseline and follow-up. Linear regression models were used to test the correlations between the AD-RAI and baseline cognitive measures, and linear mixed models with random intercepts and slopes were applied to investigate whether AD-RAI and APOE-ε4 can predict the level of cognitive decline. Cox proportional risk regression models were used to test the association of AD-RAI and APOE status with the progression from MCI to AD.ResultsThe baseline AD-RAI was higher in the MCI converted to AD group than in the MCI stable group (P &lt; 0.001). The AD-RAI was significantly correlated with cognition, and had a synergistic effect with APOE-ε4 to predict the rate of cognitive decline. The AD-RAI predicted the risk and timing of MCI progression to AD. Based on the MCI population carrying APOE-ε4, the median time to progression from MCI to AD was 24 months if the AD-RAI &gt; 0.5, while the median time to progression from MCI to AD was 96 months for patients with an AD-RAI ≤ 0.5.ConclusionThe AD-RAI can predict the risk of progression to AD in people with MCI carrying APOE ε4, is strongly correlated with cognition, and can predict cognitive decline.
Clinical Features and Genetic Spectrum of Patients With Clinically Suspected Hereditary Progressive Spastic Paraplegia
Authors: Shi Yuzhi , Wang An , Chen Bin , Wang Xingao , Niu Songtao , Li Wei , Li Shaowu , Zhang Zaiqiang 
Published: April 2022

Background and PurposeA variety of hereditary diseases overlap with neurological phenotypes or even share genes with hereditary spastic paraplegia (HSP). The aim of this study was to determine the clinical features and genetic spectrum of patients with clinically suspected HSPs.MethodsA total of 52 patients with clinically suspected HSPs were enrolled in this study. All the patients underwent next-generation sequencing (NGS) and triplet repeat primed PCR to screen for the dynamic mutations typical of spinocerebellar ataxia (SCA). Multiplex ligation-dependent probe amplification (MLPA) was further conducted in patients with no causative genetic mutations detected to examine for large deletions and duplications in genes of SPAST, ATL1, REEP1, PGN, and SPG11. Clinical characteristics and findings of brain MRI were analyzed in patients with definite diagnoses.ResultsThe mean age of the patients studied was 36.90 ± 14.57 years. 75% (39/52) of patients manifested a phenotype of complex form of HSPs. A genetic diagnosis was made in 51.9% (27/52) of patients, of whom 40.3% (21/52) of patients had mutations in HSPs genes (SPG4/SPG6/SPG8/SPG11/SPG15/SPG78/SPG5A) and 11.5% (6/52) of patients had mutations in SCAs genes (SCA3/SCA17/SCA28). SPG4 and SPG11 were the most common cause of pure form of HSPs (5/6, 83.3%) and complex form of HSPs (5/15, 33.3%), respectively. Gait disturbance was the most common initial symptom in both the patients with HSPs (15/21) and in patients with SCAs (5/6). Dysarthria and cerebellar ataxia were detected in 28.5% (6/21) and 23.8% (5/21) of patients with HSPs, respectively, and were the most common symptoms in addition to progressive weakness and spasticity of the lower limbs. Cerebellar atrophy was seen on the brain MRI of patients with SPG5A, SCA3, and SCA28.ConclusionCausative genetic mutations were identified in 51.9% of patients with clinically suspected HSPs by NGS and triplet repeat primed PCR. A final diagnosis of HSPs or SCAs was made in 40.3% and 11.5% of patients, respectively. The clinical manifestations and neuroimaging findings overlapped between patients with HSPs and patients with SCAs. Dynamic mutations should be screened in patients with clinically suspected HSPs, especially in those with phenotypes of complex form of HSPs.
The Effect and Optimal Parameters of Repetitive Transcranial Magnetic Stimulation on Poststroke Dysphagia: A Meta-Analysis of Randomized Controlled Trials
Authors: Qiao Jia , Ye Qiu-ping , Wu Zhi-min , Dai Yong , Dou Zu-lin 
Published: April 2022

ObjectiveThe objectives of the study were to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment for poststroke dysphagia (PSD) and explore the optimal stimulation parameters.MethodThe databases of Medline, Embase, Web of Science, and Cochrane Library were searched from the establishment to June 2021. All randomized controlled trials about rTMS treatment for PSD were enrolled. Dysphagia Grade (DG) and Penetration Aspiration Scale (PAS) were applied as the major dysphagia severity rating scales to evaluate the outcomes.ResultsA total of 12 clinical randomized controlled studies were included in our study. The summary effect size indicated that rTMS had a positive effect on PSD (SMD = −0.67, p &lt; 0.001). The subgroup analysis for treatment duration and different stroke stages showed significant differences (treatment duration &gt;5 days: SMD = −0.80, p &lt; 0.001; subacute phase after stroke: SMD = −0.60, p &lt; 0.001). Furthermore, no significant differences were observed among the other stimulation parameter subgroups (including stimulation frequency, location, and a single stimulation time) (p &gt; 0.05).ConclusionrTMS is beneficial to the recovery of PSD patients, while an intervention of more than 5 days and in the subacute phase after stroke might bring new strategies and rational therapeutics to the treatment of PSD.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022299469.
Validation of a Visually Aided Dietary Assessment Tool to Estimate Dietary Intake in an Adult Swiss Population
Authors: Nève Gilles , Bur Laura , Lampert Ladina , Höchsmann Christoph , Brombach Christine , Steinemann Nina , Schmidt-Trucksäss Arno 
Published: April 2022

BackgroundAccurately assessing dietary intake is crucial for understanding how diet affects a person’s health. In large cohorts, paper-based dietary assessment tools (DAT) such as food recalls or food frequency questionnaires have emerged as valid tools with a low burden for participants.ObjectiveTo validate a visually aided DAT for use in studies with Swiss adults against the gold standard of a weighed 7-day food record (7 d-FR).DesignFifty-one adults (n = 24 women, n = 27 males) participated in the study and were recruited within two age groups (20–40 and 50–70 y). Each participant filled out the visually aided DAT, then the 7 d-FR. The DAT was compared to the 7 d-FR for total energy intake, macronutrients, sugar, water, and portions of fruits and vegetables. Pearson correlation and Bland–Altman analyses were used for statistical analyses.ResultsTotal correlations ranged from 0.288 (sugar, p &lt; 0.05) to 0.729 (water, p &lt; 0.01). The older age group showed higher correlations for total energy intake, protein, fats, carbohydrates, and sugar, but not for water (p &lt; 0.05). Correlations were moderate at r &gt; 0.5, whereas only water and protein reached those values in the young group. Both groups overestimated total calories in kcal (+14.0%), grams of protein (+ 44.6%), fats (+36.3%), and portions of fruits and vegetables (+16.0%) but strongly underestimated sugar intake (−50.9%).ConclusionThis DAT showed that all macronutrients and total energy intake were estimated more accurately by the older age group and therefore might be adequate to capture dietary habits in older Swiss adults.
High Dietary Salt Intake Is Associated With Histone Methylation in Salt-Sensitive Individuals
Authors: Liao Yueyuan , Chu Chao , Yan Yu , Wang Dan , Ma Qiong , Gao Ke , Sun Yue , Hu Jiawen , Zheng Wenling , Mu Jianjun 
Published: April 2022

BackgroundHigh salt diet is one of the important risk factors of hypertension and cardiovascular diseases. Increasingly strong evidence supports epigenetic mechanisms' significant role in hypertension. We aimed to explore associations of epigenetics with high salt diet, salt sensitivity (SS), and SS hypertension.MethodsWe conducted a dietary intervention study of chronic salt loading in 339 subjects from northern China in 2004 and divided the subjects into different salt sensitivity phenotypes. A total of 152 participants were randomly selected from the same cohort for follow-up in 2018 to explore the effect of a high-salt diet on serum monomethylation of H3K4 (H3K4me1), histone methyltransferase Set7, and lysine-specific demethylase 1 (LSD-1).ResultsAmong SS individuals, the blood pressure (SBP: 140.8 vs. 132.9 mmHg; MAP: 104.2 vs. 98.7 mmHg) and prevalence of hypertension (58.8 vs. 32.8%) were significantly higher in high salt (HS) diet group than in normal salt (NS) diet group, but not in the salt-resistant (SR) individuals (P &gt; 0.05). Serum H3K4me1 level (287.3 vs. 179.7 pg/ml, P &lt; 0.05) significantly increased in HS group of SS individuals, but not in SR individuals. We found daily salt intake in SS individuals was positively correlated with serum H3K4me1 (r = 0.322, P = 0.005) and Set7 (r = 0.340, P = 0.005) levels after adjusting for age and gender, but not with LSD-1 (r = −0.137, P = 0.251). In addition, positive correlation between the serum H3K4me1 level and Set7 level (r = 0.326, P = 0.007) was also found in SS individuals. These correlations were not evident in SR individuals.ConclusionOur study indicates that high salt diet increases the serum H3K4me1 and Set7 levels in SS individuals.
Effect of a High Protein, Low Glycemic Index Dietary Intervention on Metabolic Dysfunction-Associated Fatty Liver Disease: A Randomized Controlled Trial
Authors: Sun Ping , Huang Liping , Shuai Ping , Wan Zhengwei , Liu Yingying , Xue Jianqiang , Liu Yuping 
Published: April 2022

Background:Metabolic dysfunction-associated fatty liver disease (MAFLD) affects people at an increasingly younger age. The primary treatment for patients with MAFLD is diet-induced weight loss; however, excessive dieting is poorly effective.ObjectivesThe aim of this trial was to evaluate whether a high protein and low glycemic index (HPLG) dietary intervention would result in improvement of controlled attenuation parameter (CAP) and related metabolic markers in MAFLD.MethodsA 12-week controlled, parallel-group, randomized intervention trial was performed. A number of 63 participants with MAFLD were enrolled and randomized between the HPLG dietary group and the balanced diet control group. Both diets had the same hypocaloric level and were prescribed ad libitum within food limit lists. The primary outcome was CAP. The main secondary outcomes were weight loss and improvement of metabolism-related indexes at week 12 after the program initiation.ResultsA total of 59 participants completed the intervention and were included in the final analysis. The mean age was 39.3 ± 8.9 years and 66.1% were men. In this trial, protein and carbohydrate intakes were significantly higher and lower, respectively, in the HPLG group compared to controls (p &lt; 0.001). At week 12, CAP was significantly reduced in both groups (p &lt; 0.001). However, a significantly greater reduction in liver fat was observed in the HPLG group compared to the control group (p = 0.011), with mean relative reductions of 30.90 dB/m (95% CI, 21.53 to 40.26, p &lt; 0.001) and 15.43 dB/m (95% CI, 7.57 to 23.30, p &lt; 0.001), respectively. From baseline to week 12, a significantly greater loss in bodyweight was recorded in participants in the HPLG group (6.52 kg; 95% CI, 5.50 to 7.54, p &lt; 0.001) compared to control subjects (2.00 kg; 95% CI, 0.89 to 3.11, p = 0.001). Moreover, body fat percentage in the HPLG group was significantly reduced compared with the control group (p = 0.002). Within-group improvements in visceral fat, blood pressure, cardiovascular risk factors, and blood glucose-related indicators were detected in patients with MAFLD assigned to the HPLG diet (p &lt; 0.05), but not in those prescribed the control diet (p &gt; 0.05).ConclusionUnder our experimental conditions, and compared to the traditional balanced diet, an HPLG diet led to a significant CAP remission, bodyweight or fat reduction, and improvement of metabolic markers in patients with MAFLD.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03972631.