bluuebunny/crossref_metadata_2025 huggingface dataset:
Desflurane is risk factor for postoperative delirium in older patients’ independent from intraoperative burst suppression duration
Authors: Koch Susanne , Blankertz Benjamin , Windmann Victoria , Spies Claudia , Radtke Finn M. , Röhr Vera
Published: February 2023

Background

Postoperative Delirium (POD) is the most frequent neurocognitive complication after general anesthesia in older patients. The development of POD is associated with prolonged periods of burst suppression activity in the intraoperative electroencephalogram (EEG). The risk to present burst suppression activity depends not only on the age of the patient but is also more frequent during propofol anesthesia as compared to inhalative anesthesia. The aim of our study is to determine, if the risk to develop POD differs depending on the anesthetic agent given and if this correlates with a longer duration of intraoperative burst suppression.

Methods

In this secondary analysis of the SuDoCo trail [ISRCTN 36437985] 1277 patients, older than 60 years undergoing general anesthesia were included. We preprocessed and analyzed the raw EEG files from each patient and evaluated the intraoperative burst suppression duration. In a logistic regression analysis, we assessed the impact of burst suppression duration and anesthetic agent used for maintenance on the risk to develop POD.

Results

18.7% of patients developed POD. Burst suppression duration was prolonged in POD patients (POD 27.5 min ± 21.3 min vs. NoPOD 21.4 ± 16.2 min, p < 0.001), for each minute of prolonged intraoperative burst suppression activity the risk to develop POD increased by 1.1% (OR 1.011, CI 95% 1.000–1.022, p =  0.046). Burst suppression duration was prolonged under propofol anesthesia as compared to sevoflurane and desflurane anesthesia (propofol 32.5 ± 20.3 min, sevoflurane 17.1 ± 12.6 min and desflurane 20.1 ± 16.0 min, p < 0.001). However, patients receiving desflurane anesthesia had a 1.8fold higher risk to develop POD, as compared to propofol anesthesia (OR 1.766, CI 95% 1.049–2.974, p =  0.032).

Conclusion

We found a significantly increased risk to develop POD after desflurane anesthesia in older patients, even though burst suppression duration was shorter under desflurane anesthesia as compared to propofol anesthesia. Our finding might help to explain some discrepancies in studies analyzing the impact of burst suppression duration and EEG-guided anesthesia on the risk to develop POD.
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

Background

The 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.

Methodology

A 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).

Results

Significant 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.

Conclusion

Vitamin 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.
National stroke management plan in Uruguay: Challenges and opportunities
Authors: Amorín Ignacio , Savia Adolfo , Gaye Andres , Camejo Claudia , Triviño Brayan , Muñoz Matías , Yancev Sebastian , Menendez Tamara , Decima Rodrigo
Published: February 2023

Stroke accounts for 5.5% of the national Global Burden of Disease (GBD) and ~2,000 deaths per year in Uruguay. To respond to this medical emergency, the Ministry of Public Health (MPH) of Uruguay devised the National Stroke Plan (NSP). Scientific associations, universities, scholars, and patient organizations, both at the national and international levels, took part in the process, which ended with the generation of the national stroke management guidelines, including measures based on the best evidence available. This was accompanied by presidential regulatory decrees and several ordinances that set the foundations of the legal framework for their implementation as of 2020. Forty-two Stroke Ready Centers (SRC) and seven Comprehensive Stroke Centers (CSC) were strategically established and interlinked to ensure compliance with international accessibility recommendations, offering, in turn, the required training for their healthcare teams. A pre-hospital care protocol was also created for all countrywide mobile units. For NSP assessment, stroke was included as a “Care Goal (objective)” for the whole health system, providing the involved healthcare organizations with a financial incentive for compliance with the basic objectives related to the treatment of hyper acute stroke. The NSP came into force during the COVID-19 pandemic and, considering the special circumstances imposed, it made it possible to maintain hyper acute medical care and increase population access to recanalization treatment, particularly mechanical thrombectomy. The purpose of this article is to share our experience in the development of the NSP by describing some preliminary outcomes.
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 aim

Recent 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.

Methods

We 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.

Results

After 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 < 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.

Conclusion

Our 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.
Motor imagery training to improve language processing: What are the arguments?
Authors: Bayram Mariam , Palluel-Germain Richard , Lebon Florent , Durand Edith , Harquel Sylvain , Perrone-Bertolotti Marcela
Published: February 2023

Studies showed that motor expertise was found to induce improvement in language processing. Grounded and situated approaches attributed this effect to an underlying automatic simulation of the motor experience elicited by action words, similar to motor imagery (MI), and suggest shared representations of action conceptualization. Interestingly, recent results also suggest that the mental simulation of action by MI training induces motor-system modifications and improves motor performance. Consequently, we hypothesize that, since MI training can induce motor-system modifications, it could be used to reinforce the functional connections between motor and language system, and could thus lead to improved language performance. Here, we explore these potential interactions by reviewing recent fundamental and clinical literature in the action-language and MI domains. We suggested that exploiting the link between action language and MI could open new avenues for complementary language improvement programs. We summarize the current literature to evaluate the rationale behind this novel training and to explore the mechanisms underlying MI and its impact on language performance.
A deep residual model for characterization of 5D spatiotemporal network dynamics reveals widespread spatiodynamic changes in schizophrenia
Authors: Kazemivash Behnam , van Erp Theo G. M. , Kochunov Peter , Calhoun Vince D.
Published: February 2023

Schizophrenia is a severe brain disorder with serious symptoms including delusions, disorganized speech, and hallucinations that can have a long-term detrimental impact on different aspects of a patient's life. It is still unclear what the main cause of schizophrenia is, but a combination of altered brain connectivity and structure may play a role. Neuroimaging data has been useful in characterizing schizophrenia, but there has been very little work focused on voxel-wise changes in multiple brain networks over time, despite evidence that functional networks exhibit complex spatiotemporal changes over time within individual subjects. Recent studies have primarily focused on static (average) features of functional data or on temporal variations between fixed networks; however, such approaches are not able to capture multiple overlapping networks which change at the voxel level. In this work, we employ a deep residual convolutional neural network (CNN) model to extract 53 different spatiotemporal networks each of which captures dynamism within various domains including subcortical, cerebellar, visual, sensori-motor, auditory, cognitive control, and default mode. We apply this approach to study spatiotemporal brain dynamism at the voxel level within multiple functional networks extracted from a large functional magnetic resonance imaging (fMRI) dataset of individuals with schizophrenia (N = 708) and controls (N = 510). Our analysis reveals widespread group level differences across multiple networks and spatiotemporal features including voxel-wise variability, magnitude, and temporal functional network connectivity in widespread regions expected to be impacted by the disorder. We compare with typical average spatial amplitude and show highly structured and neuroanatomically relevant results are missed if one does not consider the voxel-wise spatial dynamics. Importantly, our approach can summarize static, temporal dynamic, spatial dynamic, and spatiotemporal dynamics features, thus proving a powerful approach to unify and compare these various perspectives. In sum, we show the proposed approach highlights the importance of accounting for both temporal and spatial dynamism in whole brain neuroimaging data generally, shows a high-level of sensitivity to schizophrenia highlighting global but spatially unique dynamics showing group differences, and may be especially important in studies focused on the development of brain-based biomarkers.
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

Introduction

Sound 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.

Methods

We 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.

Results

Retention 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.

Conclusions

Together, 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.
Sirtuins and redox signaling interplay in neurogenesis, neurodegenerative diseases, and neural cell reprogramming
Authors: Mormone Elisabetta , Iorio Eugenio Luigi , Abate Lucrezia , Rodolfo Carlo
Published: February 2023

Since the discovery of Neural Stem Cells (NSCs) there are still mechanism to be clarified, such as the role of mitochondrial metabolism in the regulation of endogenous adult neurogenesis and its implication in neurodegeneration. Although stem cells require glycolysis to maintain their stemness, they can perform oxidative phosphorylation and it is becoming more and more evident that mitochondria are central players, not only for ATP production but also for neuronal differentiation’s steps regulation, through their ability to handle cellular redox state, intracellular signaling, epigenetic state of the cell, as well as the gut microbiota-brain axis, upon dietary influences. In this scenario, the 8-oxoguanine DNA glycosylase (OGG1) repair system would link mitochondrial DNA integrity to the modulation of neural differentiation. On the other side, there is an increasing interest in NSCs generation, from induced pluripotent stem cells, as a clinical model for neurodegenerative diseases (NDs), although this methodology still presents several drawbacks, mainly related to the reprogramming process. Indeed, high levels of reactive oxygen species (ROS), associated with telomere shortening, genomic instability, and defective mitochondrial dynamics, lead to pluripotency limitation and reprogramming efficiency’s reduction. Moreover, while a physiological or moderate ROS increase serves as a signaling mechanism, to activate differentiation and suppress self-renewal, excessive oxidative stress is a common feature of NDs and aging. This ROS-dependent regulatory effect might be modulated by newly identified ROS suppressors, including the NAD+-dependent deacetylase enzymes family called Sirtuins (SIRTs). Recently, the importance of subcellular localization of NAD synthesis has been coupled to different roles for NAD in chromatin stability, DNA repair, circadian rhythms, and longevity. SIRTs have been described as involved in the control of both telomere’s chromatin state and expression of nuclear gene involved in the regulation of mitochondrial gene expression, as well as in several NDs and aging. SIRTs are ubiquitously expressed in the mammalian brain, where they play important roles. In this review we summarize the current knowledge on how SIRTs-dependent modulation of mitochondrial metabolism could impact on neurogenesis and neurodegeneration, focusing mainly on ROS function and their role in SIRTs-mediated cell reprogramming and telomere protection.
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

Introduction

Speech 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.

Methods

CSL 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.

Results

As the findings pointed out, highly positive correlations between both software were found for all acoustic features and all Praat settings.

Discussion

The 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

Background

There are few reports evaluating the relationship between undernutrition and the risk of sarcopenia in type 2 diabetes mellitus (T2DM) patients.

Objective

We investigated whether undernutritional status assessed by the geriatric nutritional risk index (GNRI) and controlling nutritional status (CONUT) were associated with the diagnosis of sarcopenia.

Methods

This 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.

Results

In 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 > albumin > 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 < 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) < 22, and BMI ≥ 22.

Conclusions

Results 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.
Emerging role of hypothalamus in the metabolic regulation in the offspring of maternal obesity
Authors: Zhang Jingyi , Li Sujuan , Luo Xiaoping , Zhang Cai
Published: February 2023

Maternal obesity has a significant impact on the metabolism of offspring both in childhood and adulthood. The metabolic regulation of offspring is influenced by the intrauterine metabolic programming induced by maternal obesity. Nevertheless, the precise mechanisms remain unclear. The hypothalamus is the primary target of metabolic programming and the principal regulatory center of energy metabolism. Accumulating evidence has indicated the crucial role of hypothalamic regulation in the metabolism of offspring exposed to maternal obesity. This article reviews the development of hypothalamus, the role of the hypothalamic regulations in energy homeostasis, possible mechanisms underlying the developmental programming of energy metabolism in offspring, and the potential therapeutic approaches for preventing metabolic diseases later in life. Lastly, we discuss the challenges and future directions of hypothalamic regulation in the metabolism of children born to obese mothers.
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

Introduction

Allium 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.

Methods

In 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.

Results

The results showed the volatile oils of AMB and ACGD both could markedly reduce serum levels of TG, TC, and LDL-C (p < 0.05), and had no alterations of HDL-C, ALT, and AST levels (p > 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 < 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.

Discussion

Taken 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.
Identification of NLE1/CDK1 axis as key regulator in the development and progression of non-small cell lung cancer
Authors: Xu Pei , Wang Lei , Mo Bin , Xie Xiao , Hu Rui , Jiang Lianyong , Hu Fengqing , Ding Fangbao , Xiao Haibo
Published: February 2023

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, which is a severer threaten to human health because of its extremely high morbidity and mortality. In this study, the role of Notchless homolog 1 (NLE1) in the development of NSCLC was investigated and the underlying mechanism was explored. The outcomes showed that NLE1 expression is significantly higher in tumor tissues than normal tissues, and is correlated with the pathological stage. The regulation of NSCLC development by NLE1 was also visualized by the in vitro and in vivo loss-of-function studies, which indicated the inhibition of cell growth and migration, as well as enhancement of cell apoptosis on condition of NLE1 knockdown. As for the mechanism, it was demonstrated that NLE1 may execute its tumor-regulating function through activating E2F1-mediated transcription of CDK1, and PI3K/Akt signaling pathway was also supposed as a downstream of NLE1 in the regulation of NSCLC. Both CDK1 overexpression and treatment of Akt pathway activator could reverse the NLE1 knockdown induced NSCLC inhibition to some extent. In conclusion, this study identified NLE1 as a novel tumor promotor in the development and progression of NSCLC, which may be a potential therapeutic target in the treatment of NSCLC.
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

Introduction

Current 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.

Methods

We 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.

Results

Our 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.

Discussion

In 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

Background

Pediatric 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.

Methods

Japanese 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.

Results

From 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 < 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).

Conclusions

Conventional 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

Background

Minimal 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.

Methods

This 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.

Results

The 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 < 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 < 0.001) and the early first relapse (HR = 1.593, 95% CI = 1.033–2.456, P = 0.035).

Conclusion

IgM 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.
Localized activity attenuates the combined impact of a high fat meal and prolonged sitting on arterial stiffness: A randomized, controlled cross-over trial
Authors: Fryer Simon , Paterson Craig , Turner Louise , Moinuddin Arsalan , Faulkner James , Stoner Lee , Daykin Anne , Stone Keeron
Published: February 2023

Exposure to acute prolonged sitting and consumption of a high fat (HF) meal have been shown to independently and additively impair central and peripheral cardiovascular function. This study sought to determine whether localized activity, namely leg fidgeting, offers a protective effect to these deleterious effects. Using a randomized crossover design with three trials, 18 healthy males sat uninterrupted for 180 min following the consumption of a low fat (LF, trial 1) or HF meal (trial 2). The third trial consisted of a HF meal but sitting was interrupted with 1 min of leg fidgeting (isolated bilateral plantar flexion) consisting of −250 taps per min every 5 min for the 180 min duration. Carotid-femoral pulse wave velocity (cfPWV), aortic-femoral stiffness gradient (af-SG), superficial femoral blood flow, shear-rate and PWVβ, triglyceride concentrations and lower-limb venous pooling (HHb) were assessed pre and post sitting in all trials. General linear mixed model found that following the uninterrupted HF trial, there was a significant worsening of cfPWV (mean difference (MD) = 0.57 mˑs−1; d = 1.04) and the af-SG (MD = 0.14, d = 0.50), and femoral artery blood flow (MD = 18 mlˑmin−1; d = 0.48) and shear rate (MD = 15 S1; d = 0.67) decreased. However, leg fidgeting was enough to prevent the combined deleterious effects of prolonged sitting following a HF meal. As there were no significant changes in the LF trial, the HF meal maybe the predominant driver when uninterrupted sitting is combined with a HF meal.
Computational models for prediction of protein–protein interaction in rice and Magnaporthe grisea
Authors: Karan Biswajit , Mahapatra Satyajit , Sahu Sitanshu Sekhar , Pandey Dev Mani , Chakravarty Sumit
Published: February 2023

Introduction

Plant–microbe interactions play a vital role in the development of strategies to manage pathogen-induced destructive diseases that cause enormous crop losses every year. Rice blast is one of the severe diseases to rice Oryza sativa (O. sativa) due to Magnaporthe grisea (M. grisea) fungus. Protein–protein interaction (PPI) between rice and fungus plays a key role in causing rice blast disease.

Methods

In this paper, four genomic information-based models such as (i) the interolog, (ii) the domain, (iii) the gene ontology, and (iv) the phylogenetic-based model are developed for predicting the interaction between O. sativa and M. grisea in a whole-genome scale.

Results and Discussion

A total of 59,430 interacting pairs between 1,801 rice proteins and 135 blast fungus proteins are obtained from the four models. Furthermore, a machine learning model is developed to assess the predicted interactions. Using composition-based amino acid composition (AAC) and conjoint triad (CT) features, an accuracy of 88% and 89% is achieved, respectively. When tested on the experimental dataset, the CT feature provides the highest accuracy of 95%. Furthermore, the specificity of the model is verified with other pathogen–host datasets where less accuracy is obtained, which confirmed that the model is specific to O. sativa and M. grisea. Understanding the molecular processes behind rice resistance to blast fungus begins with the identification of PPIs, and these predicted PPIs will be useful for drug design in the plant science community.
Genomic prediction for grain yield and micro-environmental sensitivity in winter wheat
Authors: Raffo Miguel A. , Cuyabano Beatriz C. D. , Rincent Renaud , Sarup Pernille , Moreau Laurence , Mary-Huard Tristan , Jensen Just
Published: February 2023

Individuals within a common environment experience variations due to unique and non-identifiable micro-environmental factors. Genetic sensitivity to micro-environmental variation (i.e. micro-environmental sensitivity) can be identified in residuals, and genotypes with lower micro-environmental sensitivity can show greater resilience towards environmental perturbations. Micro-environmental sensitivity has been studied in animals; however, research on this topic is limited in plants and lacking in wheat. In this article, we aimed to (i) quantify the influence of genetic variation on residual dispersion and the genetic correlation between genetic effects on (expressed) phenotypes and residual dispersion for wheat grain yield using a double hierarchical generalized linear model (DHGLM); and (ii) evaluate the predictive performance of the proposed DHGLM for prediction of additive genetic effects on (expressed) phenotypes and its residual dispersion. Analyses were based on 2,456 advanced breeding lines tested in replicated trials within and across different environments in Denmark and genotyped with a 15K SNP-Illumina-BeadChip. We found that micro-environmental sensitivity for grain yield is heritable, and there is potential for its reduction. The genetic correlation between additive effects on (expressed) phenotypes and dispersion was investigated, and we observed an intermediate correlation. From these results, we concluded that breeding for reduced micro-environmental sensitivity is possible and can be included within breeding objectives without compromising selection for increased yield. The predictive ability and variance inflation for predictions of the DHGLM and a linear mixed model allowing heteroscedasticity of residual variance in different environments (LMM-HET) were evaluated using leave-one-line-out cross-validation. The LMM-HET and DHGLM showed good and similar performance for predicting additive effects on (expressed) phenotypes. In addition, the accuracy of predicting genetic effects on residual dispersion was sufficient to allow genetic selection for resilience. Such findings suggests that DHGLM may be a good choice to increase grain yield and reduce its micro-environmental sensitivity.
Diverse environmental bacteria displaying activity against Phakopsora pachyrhizi, the cause of soybean rust
Authors: Twizeyimana Mathias , Hammer Philip E. , Gachango Esther , Craig Kelly , Espejo Billie , Biggs Matthew B. , Kremer James , Ingham David J.
Published: February 2023

The management of soybean rust (SBR) caused by the obligate fungus Phakopsora pachyrhizi mostly relies on the use of synthetic fungicides, especially in areas where the disease inflicts serious yield losses. The reliance on synthetic fungicides to manage this disease has resulted in resistance of P. pachyrhizi populations to most fungicides. In this study, bacteria isolated from diverse environments were evaluated for their biocontrol potential against P. pachyrhizi using soybean detached-leaf method and on-plant in the growth chamber, greenhouse, and field. Among 998 bacterial isolates evaluated using the detached-leaf method; 58% were isolated from plant-related materials, 27% from soil, 10% from insects, and 5% from other environments. Of the isolates screened, 73 were active (they had ⪖ 75% rust reduction) with an active rate of 7.3%. From the active isolates, 65 isolates were re-tested on-plant in the growth chamber for activity confirmation. In the confirmation test, 49 bacteria isolated from plant-related materials maintained their activity with a confirmation rate of 75%. The majority of bacteria with confirmed activity belonged to the taxonomic classes Bacilli and Gammaproteobacteria (70%). Active isolates were prioritized for greenhouse and field testing based on activity in the initial screen and confirmation test. Six bacterial isolates AFS000009 (Pseudomonas_E chlororaphis), AFS032321 (Bacillus subtilis), AFS042929 (Bacillus_C megaterium), AFS065981 (Bacillus_X simplex_A), AFS090698 (Bacillus_A thuringiensis_S), and AFS097295 (Bacillus_A toyonensis) were selected from those bacteria that maintained activity in the confirmation test and were evaluated in the greenhouse, and five among them were evaluated in the field. From the Alabama field evaluation, all bacterial isolates reduced rust infection as well as azoxystrobin (Quadris® at 0.3 L/ha) used as the fungicide control (P > 0.05). Moreover, the scanning electron micrographs demonstrated evidence of antagonistic activity of AFS000009 and AFS032321 against P. pachyrhizi urediniospores. Bacterial isolates that consistently showed activity comparable to that of azoxystrobin can be improved through fermentation and formulation optimization, developed, and deployed. These bacteria strains would provide a valuable alternative to the synthetic fungicides and could play a useful role in integrated disease management programs for this disease.
Priority planting area planning for cash crops under heavy metal pollution and climate change: A case study of Ligusticum chuanxiong Hort
Authors: He Ping , Li Yunfeng , Huo Tongtong , Meng Fanyun , Peng Cheng , Bai Ming
Published: February 2023

Introduction

Soil pollution by heavy metals and climate change pose substantial threats to the habitat suitability of cash crops. Discussing the suitability of cash crops in this context is necessary for the conservation and management of species. We developed a comprehensive evaluation system that is universally applicable to all plants stressed by heavy metal pollution.

Methods

The MaxEnt model was used to simulate the spatial distribution ofLigusticum chuanxiongHort within the study area (Sichuan, Shaanxi, and Chongqing) based on current and future climate conditions (RCP2.6, RCP4.5, RCP6.0, and RCP8.5 scenarios). We established the current Cd pollution status in the study area using kriging interpolation and kernel density. Additionally, the three scenarios were used in prediction models to simulate future Cd pollution conditions based on current Cd pollution data. The current and future priority planting areas forL. chuanxiongwere determined by overlay analysis, and two levels of results were obtained.

Results

The results revealed that the current first- and secondary-priority planting areas forL. chuanxiongwere 2.06 ×103km2and 1.64 ×104km2, respectively. Of these areas, the seven primary and twelve secondary counties for currentL. chuanxiongcultivation should be given higher priority; these areas include Meishan, Qionglai, Pujiang, and other regions. Furthermore, all the priority zones based on the current and future scenarios were mainly concentrated on the Chengdu Plain, southeastern Sichuan and northern Chongqing. Future planning results indicated that Renshou, Pingwu, Meishan, Qionglai, Pengshan, and other regions are very important forL. chuanxiongplanting, and a pessimistic scenario will negatively impact this potential planting. The spatial dynamics of priority areas in 2050 and 2070 clearly fluctuated under different prediction scenarios and were mainly distributed in northern Sichuan and western Chongqing.

Discussion

Given these results, taking reasonable measures to replan and manage these areas is necessary. This study provides. not only a useful reference for the protection and cultivation ofL. chuanxiong, but also a framework for analyzing other cash crops.