bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative neuroprotective effects of Cerebrolysin, dexamethasone, and ascorbic acid on sciatic nerve injury model: Behavioral and histopathological study
Authors: Elhessy Heba M. , Habotta Ola A. , Eldesoqui Mamdouh , Elsaed Wael M. , Soliman Mona F. M. , Sewilam Haitham M. , Elhassan Y. H. , Lashine Nermeen H. 
Published: February 2023

BackgroundThe majority of the suggested experimental modalities for peripheral nerve injury (PNI) result in varying degrees of recovery in animal models; however, there are not many reliable clinical pharmacological treatment models available. To alleviate PNI complications, research on approaches to accelerate peripheral nerve regeneration is encouraged. Cerebrolysin, dexamethasone, and ascorbic acid (vitamin C) drug models were selected in our study because of their reported curative effects of different mechanisms of action.MethodologyA total of 40 adult male albino rats were used in this study. Sciatic nerve crush injury was induced in 32 rats, which were divided equally into four groups (model, Cerebrolysin, dexamethasone, and vitamin C groups) and compared to the sham group (n= 8). The sciatic nerve sensory and motor function regeneration after crushing together with gastrocnemius muscle histopathological changes were evaluated by the sciatic function index, the hot plate test, gastrocnemius muscle mass ratio, and immune expression of S100 and apoptosis cascade (BAX, BCL2, and BAX/BCL2 ratio).ResultsSignificant improvement of the behavioral status and histopathological assessment scores occurred after the use of Cerebrolysin (as a neurotrophic factor), dexamethasone (as an anti-inflammatory), and vitamin C (as an antioxidant). Despite these seemingly concomitant, robust behavioral and pathological changes, vitamin C appeared to have the best results among the three main outcome measures. There was a positive correlation between motor and sensory improvement and also between behavioral and histopathological changes, boosting the effectiveness, and implication of the sciatic function index as a mirror for changes occurring on the tissue level.ConclusionVitamin C is a promising therapeutic in the treatment of PNI. The sciatic function index (SFI) test is a reliable accurate method for assessing sciatic nerve integrity after both partial disruption and regrowth.
Efficacy of vamorolone in treatment of Duchene muscle dystrophy. A meta-analysis
Authors: Elhalag Rowan H. , Motawea Karam R. , Talat Nesreen Elsayed , Rouzan Samah S. , Shah Jaffer 
Published: February 2023

Background and aimRecent studies evaluated the role of vamorolone in treating Duchenne muscular dystrophy (DMD), so we aimed in our Meta-analysis to assess the efficacy of vamorolone in comparison with placebo and corticosteroids for treating DMD patients.MethodsWe searched PubMed, Web of Science, Scopus, and Cochrane library databases. We included any randomized control trials and controlled observational studies that investigated the role of vamorolone in treating DMD patients. We used RevMan software, version 5.4. to perform our meta-analysis.ResultsAfter a search of the literature, 4 studies were included in the meta-analysis; the total number of patients included in the study is 277 patients, 125 patients in the vamorolone group, 106 in the glucocorticoids group, and 46 in placebo (steroid naïve) group. The pooled analysis showed a statistically significant association between the vamorolone group and increased TTSTAND velocity, TTRW velocity and TTCLIMB velocity compared with the placebo group (MD = 0.04, 95% CI = 0.02–0.07, p = 0.002), (MD = 0.24, 95% CI = 0.11–0.37, p = 0.0003), and (MD = 0.06, 95% CI = 0.05–0.06, p &lt; 0.00001), respectively. Also, the analysis showed a statistically significant association between vamorolone and increased TTRW velocity and increased Height percentile for age compared with the glucocorticoid group (MD = −0.14, 95% CI = −0.26 to −0.01, p = 0.03) and (MD = 17.82, 95% CI = 3.89–31.75, p = 0.01), respectively.ConclusionOur study revealed a significant association between vamorolone and increased TTSTAND velocity, TTRW velocity, and TTCLIMB velocity compared with the placebo (steroid naïve), also showed a statistically significant association between increased TTRW velocity and increased Height percentile for age compared with the glucocorticoid that enhances the privilege of vamorolone over glucocorticoid in treating DMD patients. More multicenter randomized studies are needed to support our results.
Persistence and generalization of adaptive changes in auditory localization behavior following unilateral conductive hearing loss
Authors: Sanchez Jimenez Ana , Willard Katherine J. , Bajo Victoria M. , King Andrew J. , Nodal Fernando R. 
Published: February 2023

IntroductionSound localization relies on the neural processing of binaural and monaural spatial cues generated by the physical properties of the head and body. Hearing loss in one ear compromises binaural computations, impairing the ability to localize sounds in the horizontal plane. With appropriate training, adult individuals can adapt to this binaural imbalance and largely recover their localization accuracy. However, it remains unclear how long this learning is retained or whether it generalizes to other stimuli.MethodsWe trained ferrets to localize broadband noise bursts in quiet conditions and measured their initial head orienting responses and approach-to-target behavior. To evaluate the persistence of auditory spatial learning, we tested the sound localization performance of the animals over repeated periods of monaural earplugging that were interleaved with short or long periods of normal binaural hearing. To explore learning generalization to other stimulus types, we measured the localization accuracy before and after adaptation using different bandwidth stimuli presented against constant or amplitude-modulated background noise.ResultsRetention of learning resulted in a smaller initial deficit when the same ear was occluded on subsequent occasions. Each time, the animals’ performance recovered with training to near pre-plug levels of localization accuracy. By contrast, switching the earplug to the contralateral ear resulted in less adaptation, indicating that the capacity to learn a new strategy for localizing sound is more limited if the animals have previously adapted to conductive hearing loss in the opposite ear. Moreover, the degree of adaptation to the training stimulus for individual animals was significantly correlated with the extent to which learning extended to untrained octave band target sounds presented in silence and to broadband targets presented in background noise, suggesting that adaptation and generalization go hand in hand.ConclusionsTogether, these findings provide further evidence for plasticity in the weighting of monaural and binaural cues during adaptation to unilateral conductive hearing loss, and show that the training-dependent recovery in spatial hearing can generalize to more naturalistic listening conditions, so long as the target sounds provide sufficient spatial information.
Comparison of Praat and Computerized Speech Lab for formant analysis of five Japanese vowels in maxillectomy patients
Authors: Ali Islam E. , Sumita Yuka , Wakabayashi Noriyuki 
Published: February 2023

IntroductionSpeech impairment is a common complication after surgical resection of maxillary tumors. Maxillofacial prosthodontists play a critical role in restoring this function so that affected patients can enjoy better lives. For that purpose, several acoustic software packages have been used for speech evaluation, among which Computerized Speech Lab (CSL) and Praat are widely used in clinical and research contexts. Although CSL is a commercial product, Praat is freely available on the internet and can be used by patients and clinicians to practice several therapy goals. Therefore, this study aimed to determine if both software produced comparable results for the first two formant frequencies (F1 and F2) and their respective formant ranges obtained from the same voice samples from Japanese participants with maxillectomy defects.MethodsCSL was used as a reference to evaluate the accuracy of Praat with both the default and newly proposed adjusted settings. Thirty-seven participants were enrolled in this study for formant analysis of the five Japanese vowels (a/i/u/e/o) using CSL and Praat. Spearman’s rank correlation coefficient was used to judge the correlation between the analysis results of both programs regarding F1 and F2 and their respective formant ranges.ResultsAs the findings pointed out, highly positive correlations between both software were found for all acoustic features and all Praat settings.DiscussionThe strong correlations between the results of both CSL and Praat suggest that both programs may have similar decision strategies for atypical speech and for both sexes. This study highlights that the default settings in Praat can be used for formant analysis in maxillectomy patients with predictable accuracy. The proposed adjusted settings in Praat can yield more accurate results for formant analysis of atypical speech in maxillectomy cases when the examiner cannot precisely locate the formant frequencies using the default settings or confirm analysis results obtained using CSL.
A nutritional assessment tool, GNRI, predicts sarcopenia and its components in type 2 diabetes mellitus: A Japanese cross-sectional study
Authors: Shiroma Kaori , Tanabe Hayato , Takiguchi Yoshinori , Yamaguchi Mizuki , Sato Masahiro , Saito Haruka , Tanaka Kenichi , Masuzaki Hiroaki , Kazama Junichiro J. , Shimabukuro Michio 
Published: February 2023

BackgroundThere are few reports evaluating the relationship between undernutrition and the risk of sarcopenia in type 2 diabetes mellitus (T2DM) patients.ObjectiveWe investigated whether undernutritional status assessed by the geriatric nutritional risk index (GNRI) and controlling nutritional status (CONUT) were associated with the diagnosis of sarcopenia.MethodsThis was a cross-sectional study of Japanese individuals with T2DM. Univariate or multivariate logistic regression analysis was performed to assess the association of albumin, GNRI, and CONUT with the diagnosis of sarcopenia. The optimal cut-off values were determined by the receiver operating characteristic (ROC) curve to diagnose sarcopenia.ResultsIn 479 individuals with T2DM, the median age was 71 years [IQR 62, 77], including 264 (55.1%) men. The median duration of diabetes was 17 [11, 23] years. The prevalence of sarcopenia was 41 (8.6%) in all, 21/264 (8.0%) in men, and 20/215 (9.3%) in women. AUCs were ordered from largest to smallest as follows: GNRI &gt; albumin &gt; CONUT. The cut-off values of GNRI were associated with a diagnosis of sarcopenia in multiple logistic regression analysis (odds ratio 9.91, 95% confidential interval 5.72–17.2), P &lt; 0.001. The superiority of GNRI as compared to albumin and CONUT for detecting sarcopenia was also observed in the subclasses of men, women, body mass index (BMI) &lt; 22, and BMI ≥ 22.ConclusionsResults showed that GNRI shows a superior diagnostic power in the diagnosis of sarcopenia. Additionally, its optimal cut-off points were useful overall or in the subclasses. Future large and prospective studies will be required to confirm the utility of the GNRI cut-off for undernutrition individuals at risk for sarcopenia.
Characterization of volatile organic compounds with anti-atherosclerosis effects in Allium macrostemon Bge. and Allium chinense G. Don by head space solid phase microextraction coupled with gas chromatography tandem mass spectrometry
Authors: Qin Zifei , Duan Shuyi , Li Yuan , Li Xinqiang , Xing Han , Yao Zhihong , Zhang Xiaojian , Yao Xinsheng , Yang Jing 
Published: February 2023

IntroductionAllium macrostemon Bge. (AMB) and Allium chinense G. Don (ACGD) are both edible Allium vegetables and named officinal Xiebai (or Allii Macrostemonis Bulbus) in East Asia. Their medicinal qualities involve in lipid lowering and anti-atherosclerosis effects. And steroidal saponins, nitrogenous compounds and sulfur compounds are like the beneficial components responsible for medicinal functions. Sulfur compounds are the recognized main components both in the volatile oils of AMB and ACGD. Besides, few researches were reported about their holistic chemical profiles of volatile organic compounds (VOCs) and pharmacodynamic effects.MethodsIn this study, we first investigated the lipid-lowering and anti-atherosclerotic effects of volatile oils derived from AMB and ACGD in ApoE–/– mice with high fat and high cholesterol diets.ResultsThe results showed the volatile oils of AMB and ACGD both could markedly reduce serum levels of TG, TC, and LDL-C (p &lt; 0.05), and had no alterations of HDL-C, ALT, and AST levels (p &gt; 0.05). Pathological results displayed they both could obviously improve the morphology of cardiomyocytes and the degree of myocardial fibrosis in model mice. Meanwhile, oil red O staining results also proved they could apparently decrease the lesion areas of plaques in the aortic intima (p &lt; 0.05). Furthermore, head space solid phase microextraction coupled with gas chromatography tandem mass spectrometry combined with metabolomics analysis was performed to characterize the VOCs profiles of AMB and ACGD, and screen their differential VOCs. A total of 121 and 115 VOCs were identified or tentatively characterized in the volatile oils of AMB and ACGD, respectively. Relative-quantification results also confirmed sulfur compounds, aldehydes, and heterocyclic compounds accounted for about 85.6% in AMB bulbs, while approximately 86.6% in ACGD bulbs were attributed to sulfur compounds, ketones, and heterocyclic compounds. Multivariate statistical analysis showed 62 differentially expressed VOCs were observed between AMB and ACGD, of which 17 sulfur compounds were found to be closely associated with the garlic flavor and efficacy.DiscussionTaken together, this study was the first analysis of holistic chemical profiles and anti-atherosclerosis effects of AMB and ACGD volatile oils, and would benefit the understanding of effective components in AMB and ACGD.
Autolysosomal activation combined with lysosomal destabilization efficiently targets myeloid leukemia cells for cell death
Authors: Shah Harshit , Stankov Metodi , Panayotova-Dimitrova Diana , Yazdi Amir , Budida Ramachandramouli , Klusmann Jan-Henning , Behrens Georg M. N. 
Published: February 2023

IntroductionCurrent cancer research has led to a renewed interest in exploring lysosomal membrane permeabilization and lysosomal cell death as a targeted therapeutic approach for cancer treatment. Evidence suggests that differences in lysosomal biogenesis between cancer and normal cells might open a therapeutic window. Lysosomal membrane stability may be affected by the so-called ‘busy lysosomal behaviour’ characterized by higher lysosomal abundance and activity and more intensive fusion or interaction with other vacuole compartments.MethodsWe used a panel of multiple myeloid leukemia (ML) cell lines as well as leukemic patient samples and updated methodology to study auto-lysosomal compartment, lysosomal membrane permeabilization and lysosomal cell death.ResultsOur analyses demonstrated several-fold higher constitutive autolysosomal activity in ML cells as compared to human CD34+ hematopoietic cells. Importantly, we identified mefloquine as a selective activator of ML cells' lysosomal biogenesis, which induced a sizeable increase in ML lysosomal mass, acidity as well as cathepsin B and L activity. Concomitant mTOR inhibition synergistically increased lysosomal activity and autolysosomal fusion and simultaneously decreased the levels of key lysosomal stabilizing proteins, such as LAMP-1 and 2.DiscussionIn conclusion, mefloquine treatment combined with mTOR inhibition synergistically induced targeted ML cell death without additional toxicity. Taken together, these data provide a molecular mechanism and thus a rationale for a therapeutic approach for specific targeting of ML lysosomes.
Association between the types of bystander cardiopulmonary resuscitation and the survival with good neurologic outcome of preschool pediatric out-of-hospital cardiac arrest cases in Japan: A propensity score matching analysis using an extended nationwide database
Authors: Murasaka Kenshi , Yamashita Akira , Owada Hitoshi , Wato Yukihiro , Inaba Hideo 
Published: February 2023

BackgroundPediatric out-of-hospital cardiac arrests (OHCAs) are frequently associated with a respiratory etiology. Despite the high proportion of preschool children with OHCAs, very few studies on this special population exist. This study characterizes the epidemiologic features of preschool pediatric OHCAs and analyzes the advantage of conventional (ventilations with chest compressions) bystander cardiopulmonary resuscitation (CPR) over compression-only bystander CPR (BCPR) on the one-month post-event neurological status of the patient.MethodsJapanese nationwide databases for all ambulance transport events and OHCAs occurring during a 4-year period between 2016 and 2019 were combined, totalling 3,608 patient events. Children ≤6-years-old were included; physician- and EMS-witnessed events, no prehospital resuscitation effort events, and neonatal patient events were excluded. Neurologically favorable 1-month survival rates were compared among groups using univariate and multivariate analyses before and after propensity score matching.ResultsFrom the combined database, 2,882 pediatric OHCAs meeting selection criteria were categorized as no BCPR (984), compression-only BCPR (1,428), and conventional BCPR (470). The proportion of bystander-witnessed cases was low (22.3%). Most OHCA witnesses were family members (88.5%), and most OHCAs occurred at home (88.0%). The neurologically favorable 1-month survival rates were: no BCPR 2.4%, compression only, 3.2%, and conventional 6.6% (P &lt; 0.01). Multivariate logistic regression analysis before and after matching showed that conventional BCPR was associated with higher neurologically favorable 1-month survival than compression-only BCPR. Subgroup analyses after matching demonstrated that conventional BCPR was associated with better outcomes in nonmedical (adjusted odds ratio; 95% confidence interval, 2.83; 1.09–7.32) and unwitnessed OHCA cases (3.42; 1.09–10.8).ConclusionsConventional CPR is rarely performed by bystanders in preschool pediatric OHCA. However, conventional BCPR results in neurologically favorable outcomes in nonmedical and unwitnessed cases.
IgM deposition is a risk factor for delayed remission and early relapse of the pediatric minimal change disease
Authors: Ju Tao , Peng Yingchao , Wei Yaqin , Li Xiaojie , Wang Meiqiu , Wang Ren , Yang Xiao , Zhang Zhiqiang , Gao Chunlin , Xia Zhengkun 
Published: February 2023

BackgroundMinimal change disease (MCD) is the most common pathological subtype of pediatric idiopathic nephrotic syndrome (INS). It has been suggested that IgM deposition might predict kidney function deterioration in the course of MCD. However, the specific role of IgM deposition in the prognosis of MCD is still controversial. This study aims to investigate the clinical significance of IgM deposition on delayed remission and early relapse in a pediatric population.MethodsThis study enrolled 283 children diagnosed with MCD by renal biopsy in a single center from 2010 to 2022. These cases were divided into two groups according to the histopathological deposition of IgM. Patients' demographics, clinical parameters, and follow-up data were collected and analyzed. The primary and secondary outcomes were defined as the time to the first remission and the first relapse.ResultsThe IgM-positive group had a weaker response to steroids (steroid-sensitive: 23.5% vs. 40.8%; steroid-dependent: 74.0% vs. 51.0%; steroid-resistant: 18.4% vs. 8.2%, P = 0.001), and showed more recurrent cases (47.2% vs. 34.4%, P = 0.047) compared with the IgM-negative group. The Kaplan-Meier analysis showed that the IgM-positive group had a lower cumulative rate of the first remission (Log-rank, P &lt; 0.001) and a higher rate of the first relapse (Log-rank, P = 0.034) than the IgM-negative group. Multivariate Cox analysis showed that IgM deposition was independently associated with the delayed first remission (hazard ratio [HR] = 0.604, 95% confidence interval [CI] = 0.465–0.785, P &lt; 0.001) and the early first relapse (HR = 1.593, 95% CI = 1.033–2.456, P = 0.035).ConclusionIgM deposition was associated with a weaker steroid response. MCD children with IgM deposition were prone to delayed first remission and early first relapse.
Prenatal methadone exposure selectively alters protein expression in primary motor cortex: Implications for synaptic function
Authors: Haggerty David L. , Grecco Gregory G. , Huang Jui-Yen , Doud Emma H. , Mosley Amber L. , Lu Hui-Chen , Atwood Brady K. 
Published: February 2023

As problematic opioid use has reached epidemic levels over the past 2 decades, the annual prevalence of opioid use disorder (OUD) in pregnant women has also increased 333%. Yet, how opioids affect the developing brain of offspring from mothers experiencing OUD remains understudied and not fully understood. Animal models of prenatal opioid exposure have discovered many deficits in the offspring of prenatal opioid exposed mothers, such as delays in the development of sensorimotor function and long-term locomotive hyperactivity. In attempt to further understand these deficits and link them with protein changes driven by prenatal opioid exposure, we used a mouse model of prenatal methadone exposure (PME) and preformed an unbiased multi-omic analysis across many sensoriomotor brain regions known to interact with opioid exposure. The effects of PME exposure on the primary motor cortex (M1), primary somatosensory cortex (S1), the dorsomedial striatum (DMS), and dorsolateral striatum (DLS) were assessed using quantitative proteomics and phosphoproteomics. PME drove many changes in protein and phosphopeptide abundance across all brain regions sampled. Gene and gene ontology enrichments were used to assess how protein and phosphopeptide changes in each brain region were altered. Our findings showed that M1 was uniquely affected by PME in comparison to other brain regions. PME uniquely drove changes in M1 glutamatergic synapses and synaptic function. Immunohistochemical analysis also identified anatomical differences in M1 for upregulating the density of glutamatergic and downregulating the density of GABAergic synapses due to PME. Lastly, comparisons between M1 and non-M1 multi-omics revealed conserved brain wide changes in phosphopeptides associated with synaptic activity and assembly, but only specific protein changes in synapse activity and assembly were represented in M1. Together, our studies show that lasting changes in synaptic function driven by PME are largely represented by protein and anatomical changes in M1, which may serve as a starting point for future experimental and translational interventions that aim to reverse the adverse effects of PME on offspring.