bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of renal function on the diagnostic performance of plasma biomarkers for Alzheimer’s disease
Authors: Zhang Bin , Zhang Cheng , Wang YuYe , Chen LeiAn , Qiao YaNan , Wang Yu , Peng DanTao ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2023

BackgroundSeveral blood-based biomarkers are promising to be used in the diagnosis of Alzheimer’s disease (AD) including Aβ42/40, p-tau181, and neurofilament light (NfL). The kidney is associated with the clearance of proteins. It is crucial to evaluate the effect of renal function on the diagnostic performance of these biomarkers before clinical implementation, which is important for the establishment of reference ranges and the interpretation of results.MethodsThis study is a cross-sectional analysis based on ADNI cohort. Renal function was determined by the estimated glomerular filtration rate (eGFR). Plasma Aβ42/40 was measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Plasma p-tau181 and NfL were analyzed by Single Molecule array (Simoa) technique. [18F] florbetapir-PET (Aβ-PET) was used as a reference standard to estimate the brain amyloid load. The cutoff of Aβ-PET positivity was defined as ≥1.11. Linear regression models were used to investigate the associations of continuous eGFR with each plasma biomarker separately. The diagnostic accuracies of plasma biomarkers for positive brain amyloid across different renal function groups were analyzed by Receiver operating characteristic (ROC) curve. Youden-Index was used to determine the cutoff levels.ResultsA total of 645 participants were included in this study. The levels and diagnostic performance of Aβ42/40 were not affected by renal function. eGFR was only found negatively associated with p-tau181 levels in Aβ-PET negetive sample (β = −0.09, p = 0.039). eGFR was found negatively associated with NfL levels both in whole sample and Aβ-PET stratified groups (β = −0.27, p &lt; 0.001 in whole sample; β = −0.28, p = 0.004 in A−; β = −0.27, p &lt; 0.001 in A+). The diagnostic accuracies of p-tau181 and NfL were not affected by renal function. But the cutoff values of p-tau181 and NfL changed in participants with mild to moderate eGFR decline compared to participants with normal eGFR.ConclusionPlasma Aβ42/40 was a robust biomarker for AD which was not affected by renal function. Plasma p-tau181 and NfL levels were affected by renal function, specific reference values of them should be considered in populations with different renal function stages.
Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization
Authors: Assis-Mendonça Guilherme Rossi , Athié Maria Carolina Pedro , Tamanini João Vitor Gerdulli , Souza Arethusa de , Zanetti Gabriel Gerardini , Araújo Patrícia Aline Oliveira Ribeiro de Aguiar , Ghizoni Enrico , Tedeschi Helder , Alvim Marina Koutsodontis Machado , Almeida Vanessa Simão de , de Souza Welliton , Coras Roland , Yasuda Clarissa Lin , Blümcke Ingmar , Vieira André Schwambach , Cendes Fernando , Lopes-Cendes Iscia , Rogerio Fabio 
Published: March 2023

IntroductionFocal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy. According to the 2022 International League Against Epilepsy classification, FCD type II is characterized by dysmorphic neurons (IIa and IIb) and may be associated with balloon cells (IIb). We present a multicentric study to evaluate the transcriptomes of the gray and white matters of surgical FCD type II specimens. We aimed to contribute to pathophysiology and tissue characterization.MethodsWe investigated FCD II (a and b) and control samples by performing RNA-sequencing followed by immunohistochemical validation employing digital analyses.ResultsWe found 342 and 399 transcripts differentially expressed in the gray matter of IIa and IIb lesions compared to controls, respectively. Cholesterol biosynthesis was among the main enriched cellular pathways in both IIa and IIb gray matter. Particularly, the genes HMGCS1, HMGCR, and SQLE were upregulated in both type II groups. We also found 12 differentially expressed genes when comparing transcriptomes of IIa and IIb lesions. Only 1 transcript (MTRNR2L12) was significantly upregulated in FCD IIa. The white matter in IIa and IIb lesions showed 2 and 24 transcripts differentially expressed, respectively, compared to controls. No enriched cellular pathways were detected. GPNMB, not previously described in FCD samples, was upregulated in IIb compared to IIa and control groups. Upregulations of cholesterol biosynthesis enzymes and GPNMB genes in FCD groups were immunohistochemically validated. Such enzymes were mainly detected in both dysmorphic and normal neurons, whereas GPNMB was observed only in balloon cells.DiscussionOverall, our study contributed to identifying cortical enrichment of cholesterol biosynthesis in FCD type II, which may correspond to a neuroprotective response to seizures. Moreover, specific analyses in either the gray or the white matter revealed upregulations of MTRNR2L12 and GPNMB, which might be potential neuropathological biomarkers of a cortex chronically exposed to seizures and of balloon cells, respectively.
Implications of quantitative susceptibility mapping at 7 Tesla MRI for microbleeds detection in cerebral small vessel disease
Authors: Perosa Valentina , Rotta Johanna , Yakupov Renat , Kuijf Hugo J. , Schreiber Frank , Oltmer Jan T. , Mattern Hendrik , Heinze Hans-Jochen , Düzel Emrah , Schreiber Stefanie 
Published: March 2023

BackgroundCerebral microbleeds (MBs) are a hallmark of cerebral small vessel disease (CSVD) and can be found on T2*-weighted sequences on MRI. Quantitative susceptibility mapping (QSM) is a postprocessing method that also enables MBs identification and furthermore allows to differentiate them from calcifications.AimsWe explored the implications of using QSM at submillimeter resolution for MBs detection in CSVD.MethodsBoth 3 and 7 Tesla (T) MRI were performed in elderly participants without MBs and patients with CSVD. MBs were quantified on T2*-weighted imaging and QSM. Differences in the number of MBs were assessed, and subjects were classified in CSVD subgroups or controls both on 3T T2*-weighted imaging and 7T QSM.Results48 participants [mean age (SD) 70.9 (8.8) years, 48% females] were included: 31 were healthy controls, 6 probable cerebral amyloid angiopathy (CAA), 9 mixed CSVD, and 2 were hypertensive arteriopathy [HA] patients. After accounting for the higher number of MBs detected at 7T QSM (Median = Mdn; Mdn7T−QSM = 2.5; Mdn3T−T2 = 0; z = 4.90; p &lt; 0.001) and false positive MBs (6.1% calcifications), most healthy controls (80.6%) demonstrated at least one MB and more MBs were discovered in the CSVD group.ConclusionsOur observations suggest that QSM at submillimeter resolution improves the detection of MBs in the elderly human brain. A higher prevalence of MBs than so far known in healthy elderly was revealed.
Altered cerebral neurovascular coupling in medication-overuse headache: A study combining multi-modal resting-state fMRI with 3D PCASL
Authors: Li Xin , Liu Mengqi , Fan Wenping , Xu Huan , Chen Zhiye 
Published: March 2023

AimStructural and functional changes in the brain have been identified in individuals with medication-overuse headache (MOH) using MRI. However, it has not been clearly established whether neurovascular dysfunction occurs in MOH, which could be elucidated by examining neurovascular coupling (NVC) from the viewpoints of neuronal activity and cerebral blood flow. The aim of this study was to investigate potential alterations in NVC function of the brain in individuals with MOH using resting-state functional MRI (rs-fMRI) and 3D pseudo-continuous arterial spin labeling (3D PCASL) imaging techniques.MethodsA total of 40 patients with MOH and 32 normal controls (NCs) were recruited, and rs-fMRI and 3D PCASL data were obtained using a 3.0 T MR scanner. Standard preprocessing of the rs-fMRI data was performed to generate images representing regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuation (fALFF), and degree centrality (DC); cerebral blood flow (CBF) images were generated using 3D PCASL sequence data. These functional maps were all normalized into Montreal Neurological Institute (MNI) space, and NVC was subsequently determined on the basis of Pearson correlation coefficients between the rs-fMRI maps (ReHo, fALFF, and DC) and CBF maps. The statistical significance of differences between the MOH and NC groups in terms of NVC in different brain regions was established via Z-test. Further analysis was performed to examine correlations between NVC in the brain regions with NVC dysfunction and clinical variables among patients with MOH.ResultsNVC mainly presented a negative correlation in patients with MOH and NCs. No significant difference between the two groups was detected in terms of average NVC over the entire gray matter area. However, several brain regions with significantly decreased NVC in patients with MOH compared to NCs were identified: the left orbital region of the superior frontal gyrus, the bilateral gyrus rectus, and the olfactory cortex (P &lt; 0.05). A correlation analysis revealed that the DC of the brain regions with NVC dysfunction was significantly positively correlated with disease duration (r = 0.323, P = 0.042), and DC–CBF connectivity was negatively correlated with VAS score (r = −0.424, P = 0.035).ConclusionThe current study demonstrated that cerebral NVC dysfunction occurs in patients with MOH, and the NVC technique could function as a new imaging biomarker in headache research.
Chronic diseases attributable to a diet rich in processed meat in Brazil: Burden and financial impact on the healthcare system
Authors: Rocha Carla Eduarda Faustino , Parajára Magda do Carmo , Machado Ísis Eloah , Vegi Aline Siqueira Fogal , Menezes Mariana Carvalho de , Meireles Adriana Lúcia 
Published: March 2023

BackgroundThe consumption of processed meat causes negative impacts on health; however, this burden for the population living in developing countries is less explored. This study aimed to describe the burden of chronic noncommunicable diseases (NCDs) attributed to a diet rich in processed meat between 1990 and 2019 in Brazil and its federative units and the financial burden on the Unified Health System (SUS) in 2019.MethodsSecondary data from the Global Burden of Disease (GBD) and SUS Information Systems were used in this ecological study. The metrics to assess the burden of NCDs attributable to processed meat consumption were disability-adjusted life years (DALYs) and deaths. The age-standardized rates were presented per 100,000 inhabitants with 95% uncertainty intervals (95% UI). The cost of hospitalizations and outpatient procedures covered by SUS for the treatment of NCDs attributable to processed meat consumption was estimated using the population-attributable fraction. Both burdens were estimated for both sex and stratified by sex, specific cause, and federative units.ResultsThe age-standardized DALY rates attributable to a diet rich in processed meat increased between 1990 (75.31/100,000 [95% UI: 34.92–139.65]) and 2019 (79.35/100,000 [95% UI: 42.84–126.25]); while mortality rates remained stable between 1990 (2.64/100,000 [95% UI: 1.17–5.21) and 2019 (2.36/100,000 [95% UI: 1.22–4.09]). The cost of hospitalization and outpatient procedures in Brazil for NCDs attributable to the consumption of processed meat was approximately US$ 9,4 million, of which US$ 6,1 million was spent on ischemic heart disease, US$ 3,1 million on colorectal cancer, and US$ 200 thousand on type 2 diabetes mellitus.ConclusionThe NCD burden did not decrease during the years evaluated, while the financial burden was high in 2019, with higher treatment costs for ischemic heart disease. These results can guide political, economic, and health education interventions to advance the fight against NCDs.
Pathophysiology of gas exchange impairment in extreme prematurity: Insights from combining volumetric capnography and measurements of ventilation/perfusion ratio
Authors: Dassios Theodore , Williams Emma E. , Jones J. Gareth , Greenough Anne 
Published: March 2023

BackgroundInfants born extremely preterm often suffer from respiratory disease and are invasively ventilated. We aimed to test the hypothesis that gas exchange in ventilated extremely preterm infants occurs both at the level of the alveoli and via mixing of fresh deadspace gas in the airways.MethodsWe measured the normalised slopes of phase II and phase III of volumetric capnography and related them with non-invasive measurements of ventilation to perfusion ratio (VA/Q) and right-to-left shunt in ventilated extremely preterm infants studied at one week of life. Cardiac right-to-left shunt was excluded by concurrent echocardiography.ResultsWe studied 25 infants (15 male) with a median (range) gestational age of 26.0 (22.9–27.9) weeks and birth weight of 795 (515–1,165) grams. The median (IQR) VA/Q was 0.52 (0.46–0.56) and shunt was 8 (2–13) %. The median (IQR) normalised slope of phase II was 99.6 (82.7–116.1) mmHg and of phase III was 24.6 (16.9–35.0) mmHg. The VA/Q was significantly related to the normalised slope of phase III (ρ = −0.573, p = 0.016) but not to the slope of phase II (ρ = 0.045, p = 0.770). The right-to-left shunt was not independently associated with either the slope of phase II or the slope of phase III after adjusting for confounding parameters.ConclusionsAbnormal gas exchange in ventilated extremely preterm infants was associated with lung disease at the alveolar level. Abnormal gas exchange at the level of the airways was not associated with quantified indices of gas exchange impairment.
Distribution of CMV envelope glycoprotein B, H and N genotypes in infants with congenital cytomegalovirus symptomatic infection
Authors: Dong Niuniu , Cao Lingfeng , Zheng Danni , Su Liyun , Lu Lijuan , Dong Zuoquan , Xu Menghua , Xu Jin 
Published: March 2023

BackgroundCytomegalovirus (CMV) is the leading cause of congenital infections worldwide and contributes to long-term sequelae in neonates and children. CMV envelope glycoproteins play a vital role in virus entry and cell fusion. The association between CMV polymorphisms and clinical outcomes remains controversial. The present study aims to demonstrate the distribution of glycoprotein B (gB), H (gH) and N (gN) genotypes in congenitally CMV (cCMV) infected symptomatic infants and attempts to figure out the association between viral glycoprotein genotypes and clinical outcomes.MethodsGenotyping of gB, gH and gN was performed in 42 cCMV symptomatic infants and 149 infants with postnatal CMV (pCMV) infection in Children's hospital of Fudan university. Nested PCR, gene sequencing and phylogenetic analyses were used to identify the genotypes.ResultsOur study demonstrated that: 1. The CMV gB1, gH1 and gN1 were the predominant genotypes among symptomatic cCMV infected infants, while gB1, gH1 and gN3a were more prevalent in pCMV group. gH1 genotype has a significant association with symptomatic cCMV infection (p = 0.006). 2. No significant correlation was found between CMV genotypes and hearing impairment. However, gH1 was more prevalent among cCMV infected infants with moderate/severe hearing loss although without statistical difference (p = 0.130). 3. gB3 was more prevalent among infants with skin petechiae (p = 0.049) and found to be associated with an increased risk of skin petechiae (OR = 6.563). The gN4a subtype was significantly associated with chorioretinitis due to cCMV infection (p = 0.007). 4. Urine viral loads were not significantly associated with different genotypes or hearing impairment among symptomatic cCMV infected infants.ConclusionsOur findings demonstrated the overall distribution of gB, gH and gN genotypes in infants with symptomatic cCMV infection in Shanghai for the first time. The findings in our study may suggest a possible association between gH1 genotype and early infancy hearing loss. gB3 genotype was associated with a 6.5-fold increased risk of petechiae while gN4a strongly correlated with chorioretinitis due to cCMV infection. No significant correlation was found between urine viral loads and CMV genotypes or hearing impairment in cCMV infected infants.
Multidimensional evaluation of teaching strategies for pharmacology based on a comprehensive analysis involving 21,269 students
Authors: Xiao Chen-Lin , Ren Huan , Chen Hui-Qing , Liu Wen-Hui , Luo Zhi-Ying , Li Wen-Ru , Luo Jian-Quan 
Published: March 2023

Background: Given the limitations of traditional pharmacology pedagogical method, diverse novel teaching methods have been widely explored. In this study, we performed a network meta-analysis (NMA) to evaluate the effects of different strategies in pharmacology education.Methods: Literature databases were searched from their inception to November 2022, and the studies were screened according to predefined inclusion and exclusion criteria to extract important information. Outcomes, including theoretical test scores, experimental test scores, subjective test scores, satisfaction scores, and the proportion of satisfaction, were analyzed using R software (version 3.6.1) and STATA (version 15). The NMA was conducted with a random-effects model under the Bayesian framework to calculate odds ratios (ORs) or mean differences (MDs) with associated 95% credible intervals (95% CIs). Surface under the cumulative ranking curve (SUCRA) probability values were calculated to rank the teaching methods examined.Results: A total of 150 studies involving 21,269 students were included. This NMA systematically evaluated 24 teaching strategies, such as problem-based learning (PBL), team-based learning (TBL), case-based learning (CBL) and flipped classrooms (FC), etc., The results of the NMA showed that, PBL combined with CBL was most likely to improve students’ theoretical and subjective test scores (SUCRA = 75.49 and 98.19%, respectively), TBL was most likely to improve the experimental test score (SUCRA = 92.38%) and the satisfaction score (SUCRA = 88.37%), while FC had the highest probability of being the best option for improving the proportion of satisfaction (SUCRA = 84.45%).Conclusion: The current evidence indicates that TBL, PBL combined with CBL, and FC might be optimal strategies for pharmacology education since they have a more beneficial effect on students.
Effects of lower-extremity explosive strength on youth judo athletes adopting different types of power-based resistance training
Authors: Huang Ruiyin , Zhang Mingyang , Huang Linjie , Chen Zilong , Mo Yong , Gao Yuhua 
Published: March 2023

Objective: The present study compared the effects of two different resistance types (pneumatic resistance and free weight) of 6-week squat training on the performance for young female judo athletes in linear speed and vertical jump by utilizing the maximum power of each set of squats in each training session as the monitoring vehicle. Monitoring data were used to assess the effects and trends of the two resistance types on 70% 1RM weight-bearing during the 6-week intervention training.Methods: In a 6 weeks squat training (2 reps/week with a constant load), 23 adolescent female judo athletes (Age span: 13–16 years, 14.58 ± 0.96) were randomly selected and then divided into the traditional barbell (FW) group (n = 12) and the pneumatic resistance (PN) (n = 11) group according to different resistance types (free weight and pneumatic resistance), with 10 in FW group and 9 in PN group actually completed the study. Before and after training, the 30-m Sprint time (T-30M), vertical jump height and relative power (countermovement jump, static-squat jump, and drop jump), reactive strength index (DJ-RSI), and maximal strength were assessed. One-Way ANOVA was used to examine the pre-test differences of groups (FW and PN). A 2-factor mixed-model analysis of variance was used to examine the independent effects of group (FW and PN) and time (pre and post) on each dependent measure. Scheffe post hoc comparisons were used to examine the differences. Pre- and post-experimental differences between the two groups were analyzed using independent samples t-tests and magnitude-based inferences (MBI) derived from their p values, and effect statistics were applied to compare the pre- and post-changes exhibited by each group to identify the potential beneficiary groups.Results: The PN group outperformed the FW group in terms of maximal power output per training session (822.5 ± 55.22 vs. 927.42 ± 48.15, conventional vs. pneumatic, p &lt; 0.001, effect size = −2.02). After 6 weeks of training, the FW group showed significant increases in vertical jump height and relative strength (CMJ, SJ, DJ), with no significant gains observed in T-30 and maximal strength. The PN group showed significant improvements in maximal strength; however, no significant improvements were observed in the other tests. In addition, there was no significant difference in DJ-RSI between the two groups before and after training.Discussion: At 70% weight bearing, free weight resistance appears to be more conducive to vertical jump growth, while pneumatic resistance appears to be more conducive to maximal strength gains; however, the maximal strength gains from pneumatic resistance may not be well applied to athletic performance. In addition, the body adapts more quickly to pneumatic resistance than to free weight resistance.
Recombinant irisin prevents cell death and mineralization defects induced by random positioning machine exposure in primary cultures of human osteoblasts: A promising strategy for the osteoporosis treatment
Authors: Cariati Ida , Bonanni Roberto , Rinaldi Anna Maria , Marini Mario , Iundusi Riccardo , Gasbarra Elena , Tancredi Virginia , Tarantino Umberto 
Published: March 2023

Spaceflight exposure, like prolonged skeletal unloading, is known to result in significant bone loss, but the molecular mechanisms responsible are still partly unknown. This impairment, characterizing both conditions, suggests the possibility of identifying common signalling pathways and developing innovative treatment strategies to counteract the bone loss typical of astronauts and osteoporotic patients. In this context, primary cell cultures of human osteoblasts derived from healthy subjects and osteoporotic patients were exposed to random positioning machine (RPM) to reproduce the absence of gravity and to exacerbate the pathological condition, respectively. The duration of exposure to RPM was 3 or 6 days, with the aim of determining whether a single administration of recombinant irisin (r-irisin) could prevent cell death and mineralizing capacity loss. In detail, cellular responses were assessed both in terms of death/survival, by MTS assay, analysis of oxidative stress and caspase activity, as well as the expression of survival and cell death proteins, and in terms of mineralizing capacity, by investigating the pentraxin 3 (PTX3) expression. Our results suggest that the effects of a single dose of r-irisin are maintained for a limited time, as demonstrated by complete protection after 3 days of RPM exposure and only partial protection when RPM exposure was for a longer time. Therefore, the use of r-irisin could be a valid strategy to counteract the bone mass loss induced by weightlessness and osteoporosis. Further studies are needed to determine an optimal treatment strategy based on the use of r-irisin that is fully protective even over very long periods of exposure and/or to identify further approaches to be used in a complementary manner.