bluuebunny/crossref_metadata_2025 huggingface dataset:
External Validation of the Early Prediction of Functional Outcome After Stroke Prediction Model for Independent Gait at 3 Months After Stroke
Authors: Veerbeek Janne M. , Pohl Johannes , Held Jeremia P. O. , Luft Andreas R.
Published: May 2022

Introduction

The Early Prediction of Functional Outcome after Stroke (EPOS) model for independent gait is a tool to predict between days 2 and 9 poststroke whether patients will regain independent gait 6 months after stroke. External validation of the model is important to determine its clinical applicability and generalizability by testing its performance in an independent cohort. Therefore, this study aimed to perform a temporal and geographical external validation of the EPOS prediction model for independent gait after stroke but with the endpoint being 3 months instead of the original 6 months poststroke.

Methods

Two prospective longitudinal cohort studies consisting of patients with first-ever stroke admitted to a Swiss hospital stroke unit. Sitting balance and strength of the paretic leg were tested at days 1 and 8 post-stroke in Cohort I and at days 3 and 9 in Cohort II. Independent gait was assessed 3 months after symptom onset. The performance of the model in terms of discrimination (area under the receiver operator characteristic (ROC) curve; AUC), classification, and calibration was assessed.

Results

In Cohort I [N= 39, median age: 74 years, 33% women, median National Institutes of Health Stroke Scale (NIHSS) 9], the AUC (95% confidence interval (CI)] was 0.675 (0.510, 0.841) on day 1 and 0.921 (0.811, 1.000) on day 8. For Cohort II (N= 78, median age: 69 years, 37% women, median NIHSS 8), this was 0.801 (0.684, 0.918) on day 3 and 0.846 (0.741, 0.951) on day 9.

Discussion and Conclusion

External validation of the EPOS prediction model for independent gait 3 months after stroke resulted in an acceptable performance from day 3 onward in mild-to-moderately affected patients with first-ever stroke without severe prestroke disability. The impact of applying this model in clinical practice should be investigated within this subgroup of patients with stroke. To improve the generalizability of patients with recurrent stroke and those with more severe, neurological comorbidities, the performance of the EPOS model within these patients should be determined across different geographical areas.
Locomotor Adaptation Deficits in Older Individuals With Cognitive Impairments: A Pilot Study
Authors: Pottorf Tana S. , Nocera Joe R. , Eicholtz Steven P. , Kesar Trisha M.
Published: May 2022

Gait dysfunction and fall risk have been well documented in people with Alzheimer's Disease (AD) and individuals with mild cognitive impairment (MCI). Normal locomotor adaptation may be an important prerequisite for normal and safe community walking function, especially in older adults with age-related neural, musculoskeletal, or cardiovascular changes and cognitive impairments. The split-belt walking task is a well-studied and robust method to evaluate locomotor adaptation (e.g., the ability to adjust stepping movements to changing environmental demands). Here, we capitalized on the split-belt adaptation task to test our hypothesis that a decreased capacity for locomotor adaptation may be an important contributing factor and indicator of increased fall risk and cognitive decline in older individuals with MCI and AD. The objectives of this study were to (1) compare locomotor adaptation capacity in MCI and AD compared to healthy older adults (HOA) during split-belt treadmill walking, and (2) evaluate associations between locomotor adaptation and cognitive impairments. Our results demonstrated a significant decrease in split-belt locomotor adaptation magnitude in older individuals with MCI and AD compared to HOA. In addition, we found significant correlations between the magnitude of early adaptation and de-adaptation vs. cognitive test scores, demonstrating that individuals with greater cognitive impairment also display a reduced capacity to adapt their walking in response to the split-belt perturbation. Our study takes an important step toward understanding mechanisms underlying locomotor dysfunction in older individuals with cognitive impairment.
Through-Plane Super-Resolution With Autoencoders in Diffusion Magnetic Resonance Imaging of the Developing Human Brain
Authors: Kebiri Hamza , Canales-Rodríguez Erick J. , Lajous Hélène , de Dumast Priscille , Girard Gabriel , Alemán-Gómez Yasser , Koob Mériam , Jakab András , Bach Cuadra Meritxell
Published: May 2022

Fetal brain diffusion magnetic resonance images (MRI) are often acquired with a lower through-plane than in-plane resolution. This anisotropy is often overcome by classical upsampling methods such as linear or cubic interpolation. In this work, we employ an unsupervised learning algorithm using an autoencoder neural network for single-image through-plane super-resolution by leveraging a large amount of data. Our framework, which can also be used for slice outliers replacement, overperformed conventional interpolations quantitatively and qualitatively on pre-term newborns of the developing Human Connectome Project. The evaluation was performed on both the original diffusion-weighted signal and the estimated diffusion tensor maps. A byproduct of our autoencoder was its ability to act as a denoiser. The network was able to generalize fetal data with different levels of motions and we qualitatively showed its consistency, hence supporting the relevance of pre-term datasets to improve the processing of fetal brain images.
Effects of Sublethal Organophosphate Toxicity and Anti-cholinergics on Electroencephalogram and Respiratory Mechanics in Mice
Authors: Bugay Vladislav , Gregory Summer Rain , Belanger-Coast Matthieu Gibson , Zhao Raymond , Brenner Robert
Published: May 2022

Organophosphates are used in agriculture as insecticides but are potentially toxic to humans when exposed at high concentrations. The mechanism of toxicity is through antagonism of acetylcholinesterase, which secondarily causes excess activation of cholinergic receptors leading to seizures, tremors, respiratory depression, and other physiological consequences. Here we investigated two of the major pathophysiological effects, seizures and respiratory depression, using subcutaneous injection into mice of the organophosphate diisopropylfluorophosphate (DFP) at sublethal concentrations (2.1 mg/Kg) alone and co-injected with current therapeutics atropine (50 mg/Kg) or acetylcholinesterase reactivator HI6 (3 mg/Kg). We also tested a non-specific cholinergic antagonist dequalinium chloride (2 mg/Kg) as a novel treatment for organophosphate toxicity. Electroencephalogram (EEG) recordings revealed that DFP causes focal delta frequency (average 1.4 Hz) tonic spikes in the parietal region that occur transiently (lasting an average of 171 ± 33 min) and a more sustained generalized theta frequency depression in both parietal and frontal electrode that did not recover the following 24 h. DFP also caused behavioral tremors that partially recovered the following 24 h. Using whole body plethysmography, DFP revealed acute respiratory depression, including reduced breathing rates and tidal volumes, that partially recover the following day. Among therapeutic treatments, dequalinium chloride had the most potent effect on all physiological parameters by reducing acute EEG abnormalities and promoting a full recovery after 24 h from tremors and respiratory depression. Atropine and HI6 had distinct effects on EEGs. Co-treatment with atropine converted the acute 1.4 Hz tonic spikes to 3 Hz tonic spikes in the parietal electrode and promoted a partial recovery after 24 h from theta frequency and respiratory depression. HI6 fully removed the parietal delta spike increase and promoted a full recovery in theta frequency and respiratory depression. In summary, while all anticholinergic treatments promoted survival and moderated symptoms of DFP toxicity, the non-selective anti-cholinergic dequalinium chloride had the most potent therapeutic effects in reducing EEG abnormalities, moderating tremors and reducing respiratory depression.
Translational Magnetic Resonance Imaging in Autism Spectrum Disorder From the Mouse Model to Human
Authors: Tsurugizawa Tomokazu
Published: May 2022

Autism spectrum disorder (ASD) is a heterogeneous syndrome characterized by behavioral features such as impaired social communication, repetitive behavior patterns, and a lack of interest in novel objects. A multimodal neuroimaging using magnetic resonance imaging (MRI) in patients with ASD shows highly heterogeneous abnormalities in function and structure in the brain associated with specific behavioral features. To elucidate the mechanism of ASD, several ASD mouse models have been generated, by focusing on some of the ASD risk genes. A specific behavioral feature of an ASD mouse model is caused by an altered gene expression or a modification of a gene product. Using these mouse models, a high field preclinical MRI enables us to non-invasively investigate the neuronal mechanism of the altered brain function associated with the behavior and ASD risk genes. Thus, MRI is a promising translational approach to bridge the gap between mice and humans. This review presents the evidence for multimodal MRI, including functional MRI (fMRI), diffusion tensor imaging (DTI), and volumetric analysis, in ASD mouse models and in patients with ASD and discusses the future directions for the translational study of ASD.
Enhancing Emotion Recognition Using Region-Specific Electroencephalogram Data and Dynamic Functional Connectivity
Authors: Liu Jun , Sun Lechan , Liu Jun , Huang Min , Xu Yichen , Li Rihui
Published: May 2022

Recognizing the emotional states of humans through EEG signals are of great significance to the progress of human-computer interaction. The present study aimed to perform automatic recognition of music-evoked emotions through region-specific information and dynamic functional connectivity of EEG signals and a deep learning neural network. EEG signals of 15 healthy volunteers were collected when different emotions (high-valence-arousal vs. low-valence-arousal) were induced by a musical experimental paradigm. Then a sequential backward selection algorithm combining with deep neural network called Xception was proposed to evaluate the effect of different channel combinations on emotion recognition. In addition, we also assessed whether dynamic functional network of frontal cortex, constructed through different trial number, may affect the performance of emotion cognition. Results showed that the binary classification accuracy based on all 30 channels was 70.19%, the accuracy based on all channels located in the frontal region was 71.05%, and the accuracy based on the best channel combination in the frontal region was 76.84%. In addition, we found that the classification performance increased as longer temporal functional network of frontal cortex was constructed as input features. In sum, emotions induced by different musical stimuli can be recognized by our proposed approach though region-specific EEG signals and time-varying functional network of frontal cortex. Our findings could provide a new perspective for the development of EEG-based emotional recognition systems and advance our understanding of the neural mechanism underlying emotion processing.
A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report
Authors: Lobbes Hervé , Reynaud Quitterie , Mainbourg Sabine , Savy-Stortz Claire , Ropert Martine , Bardou-Jacquet Edouard , Durupt Stéphane
Published: May 2022

Aceruloplasminemia is a rare autosomal recessive inherited disorder. Mutations in the ceruloplasmin gene cause depressed ferroxidase activity leading to iron accumulation. The clinical phenotype is highly variable: anemia, retinopathy, diabetes mellitus, psychiatric disorders, and neurological symptoms including parkinsonian disorders and dementia are the main features of this disease. Characterized by high serum ferritin with low transferrin saturation, aceruloplasminemia uniquely combines brain, liver and systemic iron overload. We report here four new cases of aceruloplasminemia in a consanguineous North-African family. Genetic sequencing revealed a homozygous missense variant c.656T>A in exon 4 of the ceruloplasmin gene, which had been described previously as of “unknown significance” in the dbSNP database and never associated with ACP in the HGMD database. Ferroxidase activity was strongly depressed. Clinical manifestations varied among cases. The proband exhibited mild microcytic anemia, diabetes mellitus, psychosis and parkinsonism, whereas the other cases were asymptomatic or mildly anemic, although high serum ferritin and brain iron deposition were documented in all of them. Therapeutic management was complex. The proband started deferoxamine treatment when already symptomatic and he rapidly declined. In the asymptomatic cases, the treatment was associated with poor tolerance and was discontinued due to anemia requiring red blood cell transfusion. Our series illustrates the need for new therapeutic approaches to aceruloplasminemia.
Aerobic Exercise Improves Methamphetamine-Induced Olfactory Dysfunction Through α-Synuclein Intervention in Male Mice
Authors: Wang Zhuo , Zheng Rui , Wang Xiaohan , Huang Xuekun , Huang Jian , Gu Cihang , He Yitong , Wu Shuo , Chen Jingyuan , Yang Qintai , Qiu Pingming
Published: May 2022

Methamphetamine (Meth) is a predominantly abused neurostimulant, and its abuse is often associated with multiple neurological symptoms. Olfaction, the sense of smell, is a highly neurotransmission-dependent physiological process; however, the effect of Meth on olfactory function and its underlying mechanisms remain largely unknown. This study aimed to explore the impact of Meth abuse on the olfactory system and the potential mechanisms. Chronic Meth abuse was induced by daily administration of Meth in male mice for 4 weeks, and we then systematically examined olfactory performance. Behavioral tests found that Meth-treated animals showed increased olfactory threshold, decreased olfactory sensitivity, reduced olfactory-dependent discrimination, and difficulty in seeking buried food. Notably, the increased deposition of α-synuclein (α-syn) in the olfactory bulb was detected. Adeno-associated virus (AAV)-mediated α-syn intervention therapy in the olfactory bulb significantly alleviated Meth-induced olfactory function impairment, and 8 weeks of aerobic exercise showed similar effects through the same principle of α-syn intervention. Notably, exercise-mediated reduction of α-syn inhibited abnormal firing activity and restored the inhibitory synaptic regulation of mitral cells in the olfactory bulb. These findings suggest the involvement of α-syn in the pathogenic mechanisms of Meth-induced olfactory dysfunction and shed light on the possible therapeutic applications of aerobic exercise in Meth-induced olfactory dysfunction.
Higher Consumption of Fruit and Vegetables Is Associated With Lower Worries, Tension and Lack of Joy Across the Lifespan
Authors: Radavelli-Bagatini Simone , Sim Marc , Blekkenhorst Lauren C. , Bondonno Nicola P. , Bondonno Catherine P. , Woodman Richard , Dickson Joanne M. , Harms Craig , Magliano Dianna J. , Shaw Jonathan E. , Daly Robin M. , Hodgson Jonathan M. , Lewis Joshua R.
Published: May 2022

Background and Aims

Higher total fruit and vegetable (FV) intakes have been associated with lower perceived stress. However, the relationship of FV intake with domains of perceived stress is unclear. The aim of this cross-sectional study was to explore the relationship between consumption of FV and four perceived stress domains (worries, tension, lack of joy and demands) in a population-based cohort of Australian adults.

Methods

Participants (n = 8,640) were men and women aged ≥25 years from the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. Dietary intake was assessed using a 74-item validated Food Frequency Questionnaire. Perceived stress domains were determined using a validated 20-item version of the Perceived Stress Questionnaire, with higher scores representing higher perceived stress. Cut-offs for high perceived stress domains were obtained from the highest quartiles of each domain for each sex. Multivariable-adjusted logistic regression was performed to investigate cross-sectional associations.

Results

The mean age of participants (50.1% females) was 47.8 (SD 15) years. Those with higher intakes of FV, combined and separately, had a significantly lower odds (16–36%) for higher worries, tension and lack of joy, independent of other lifestyle factors.

Conclusion

In Australian adults, higher consumption of FV was associated with lower odds of worries, tension and lack of joy. Following the dietary guidelines for the recommended intake of FV may help improve feelings of worries, tension and lack of joy, which are linked to mental health problems.
Multiple Metrics of Carbohydrate Quality Place Starchy Vegetables Alongside Non-starchy Vegetables, Legumes, and Whole Fruit
Authors: Drewnowski Adam , Maillot Matthieu , Vieux Florent
Published: May 2022

Background

Starchy vegetables, including white potatoes, are often categorized as “lower-quality” carbohydrate foods, along with refined grains, 100% fruit juices, sweetened beverages, and sugars, snacks and sweets. Among “higher-quality” carbohydrates are whole grains, non-starchy vegetables, legumes, and whole fruits.

Objective

To apply multiple nutrient profiling (NP) models of carbohydrate quality to foods containing >40% carbohydrate by dry weight in the USDA Food and Nutrient Database for Dietary Studies (FNDDS 2017-18).

Methods

Carbohydrate foods in the FNDDS (n = 2423) were screened using four recent Carbohydrate Quality Indices (CQI) and a new Carbohydrate Food Quality Score (CFQS-4). Cereal products containing >25% whole grains by dry weight were classified as whole grain foods.

Results

Based on percent items meeting the criteria for 4 CQI scores, legumes, non-starchy and starchy vegetables, whole fruit, and whole grain foods qualified as “high quality” carbohydrate foods. Distribution of mean CFQS-4 values showed that starchy vegetables, including white potatoes placed closer to non-starchy vegetables and fruit than to candy and soda.

Conclusion

Published a priori determinations of carbohydrate quality do not always correspond to published carbohydrate quality metrics. Based on CQI metrics, specifically designed to assess carbohydrate quality, starchy vegetables, including white potatoes, merit a category reassignment and a more prominent place in dietary guidance.
Effects of Intermittent Fasting in Human Compared to a Non-intervention Diet and Caloric Restriction: A Meta-Analysis of Randomized Controlled Trials
Authors: Gu Lihu , Fu Rongrong , Hong Jiaze , Ni Haixiang , Yu Kepin , Lou Haiying
Published: May 2022

Background

The popularity of applying intermittent fasting (IF) has increased as more and more people are trying to avoid or alleviate obesity and metabolic disease. This study aimed to systematically explore the effects of various IF in humans.

Methods

The randomized controlled trials (RCTs) related to IF vs. non-intervention diet or caloric restriction (CR) were retrieved in PubMed, Web of Science, Cochrane Library database, and Embase. Extraction outcomes included, but were not limited to, weight, body mass index (BMI), waist circumference (WC), fasting glucose, and triglyceride (TG).

Results

This study includes 43 RCTs with 2,483 participants. The intervention time was at least 1 month, and the median intervention time was 3 months. Contrasting results between IF and non-intervention diet showed that participants had lower weight (weighted mean difference (WMD) = 1.10, 95% CI: 0.09–2.12, p = 0.03) and BMI after IF (WMD = 0.38, 95% CI: 0.08–0.68, p = 0.01). The WC of participants after IF decreased significantly compared with the non-intervention diet (WMD = 1.02, 95% CI: 0.06–1.99, p = 0.04). IF regulated fat mass (FM) more effectively than non-intervention diet (WMD = 0.74, 95% CI: 0.17–1.31, p = 0.01). The fat-free mass of people after IF was higher (WMD = −0.73, 95% CI: (−1.45)–(−0.02), p = 0.05). There was no difference in fasting blood glucose concentrations between participants in the after IF and non-intervention diet groups. The results of insulin concentrations and HOMA-IR, though, indicated that IF was significantly more beneficial than non-intervention diet (standard mean difference (SMD) = −0.21, 95% CI: 0.02–0.40, p = 0.03, and WMD = 0.35, 95% CI: 0.04–0.65, p = 0.03, respectively). Cholesterol and TG concentrations in participants after IF were also lower than that after a nonintervention diet (SMD = 0.22, 95% CI: 0.09–0.35, p = 0.001 and SMD = 0.13, 95% CI: 0.00–0.26, p = 0.05, respectively). IF outcomes did not differ from CR except for reduced WC.

Conclusion

Intermittent fasting was more beneficial in reducing body weight, WC, and FM without affecting lean mass compared to the non-intervention diet. IF also effectively improved insulin resistance and blood lipid conditions compared with non-intervention diets. However, IF showed less benefit over CR.
Asporin Interacts With HER2 to Promote Thyroid Cancer Metastasis via the MAPK/EMT Signaling Pathway
Authors: Zhan Shaohua , Wang Tianxiao , Li Jingying , Zhu Hanyang , Ge Wei , Li Jinming
Published: May 2022

Approximately 85% of histological subtypes of thyroid cancer are papillary thyroid cancer (PTC), and the morbidity and mortality of PTC patients rapidly increased due to lymph node metastases or distant metastasis. Therefore, it needs to distill an enhanced understanding of the pathogenesis of PTC patients with lymph node metastases or distant metastasis. We employed the TMT-based quantitative proteomics approach to identify and analyze differentially expressed proteins in PTC with different degrees of lymph node metastases. Compared with paired normal tissues, asporin is overexpressed in PTC-N0, PTC-N1a, and PTC-N1b tumorous tissues via proteomics, western blotting, and immunohistochemistry assays. Functionally, asporin is mainly expressed in the extracellular matrix, cell membrane, and cytoplasm of PTC tumorous tissues, and promotes thyroid cancer cell proliferation, migration, and invasion. Mechanistically, asporin, interacting with HER2, co-localizes HER2 on the cell membrane and cytoplasm, and the asporin/HER2/SRC/EGFR axis upregulate the expression of EMT-activating transcription factors through the MAPK signaling pathway. Clinically, asporin can be regarded as a serological biomarker to identify PTC patients with or without lymph node metastasis, and high expression of asporin in PTC tumorous tissues is a risk factor for poor prognosis.
Acute, Subchronic, and Chronic Complications of Radical Prostatectomy Versus Radiotherapy With Hormone Therapy in Older Adults With High-Risk Prostate Adenocarcinoma
Authors: Wu Szu-Yuan , Huy Le Duc , Liao Chih Jung , Huang Chung-Chien
Published: May 2022

Purpose

To compare acute, subchronic, and chronic complications between older patients with high-risk localized prostate cancer (HR-LPC) receiving radical prostatectomy (RP) and high-dose intensity-modulated radiotherapy (IMRT) combined with long-term hormone therapy (HT).

Patients and Methods

We recruited older patients (≥80 years) with HR-LPC from the Taiwan Cancer Registry database. After propensity score matching, logistic regression analysis was used to compare the acute, subchronic, and chronic complication rates between patients who underwent RP (the RP group) and high-dose IMRT combined with long-term HT (the IMRT+HT group).

Results

Benign prostatic hyperplasia (BPH) symptoms and urinary incontinence (UI) were the most common complications over 5 years (BPH symptoms: RP, 17.69%; IMRT+HT, 29.58%; UI: RP, 10.47%; IMRT+HT, 5.50%). Compared with the RP group, the IMRT+HT group had higher odds of BPH symptoms and lower odds of UI and hernia after the 5-year follow-up period. The impotence rates were significantly higher in the IMRT+HT group than in the RP group at 3 months and 1 year after treatment and became nonsignificant after 2 years. At 5 years after treatment, the IMRT+HT group had lower risks of UI (adjusted odds ratio [aOR], 0.50; 95% confidence interval [CI], 0.28–0.88) and hernia (aOR, 0.21; 95% CI, 0.11–0.82) and a higher risk of BPH symptoms (aOR, 4.15; 95% CI, 2.82–7.37) than the RP group.

Conclusion

IMRT+HT was associated with lower UI and hernia risks than RP. By contrast, RP was associated with fewer complications of BPH over the follow-up period and less impotence during the first year after treatment. Our findings provide important and valuable references for shared decision-making for optimal therapy selection among older men with HR-LPC.
A Primary Extraskeletal Osteosarcoma of the Spleen: Rare Case Report
Authors: Pan Xian , Wang Han-Lu , Lin Shi-Ming , Lin Jia-Li , Ruan Dan-Dan , Zhang Jian-Hui , Chen Ting , Luo Jie-Wei , Fang Zhu-Ting
Published: May 2022

Extraskeletal osteosarcoma is a rare malignant soft-tissue sarcoma that is difficult to diagnose. Surgery is a common treatment, although chemotherapy and radiotherapy are also used. Patients at risk of bleeding can undergo embolization combined with resection. The occurrence of primary splenic extraskeletal osteosarcoma in humans does not seem to have been reported in the literature. A 50-year-old woman who complained of pain in the left upper abdomen for 1 day was initially diagnosed with “splenic hemangioma with a high possibility of rupture and bleeding” and urgently underwent digital subtraction angiography, combined with splenic arteriography and embolization. Abdominal pain worsened 2 days postoperatively, with a hemoglobin level of 106.0 g/L. Consequently, emergency laparotomy combined with splenectomy was performed. The clinical and imaging features, pathological diagnosis, and embolization treatment of this case were analyzed retrospectively. CT of the upper abdomen revealed splenomegaly, an irregular low-density shadow in the spleen, and a flake-like calcification in the lateral margin of the left kidney. Nuclear MRI of the upper abdomen showed splenomegaly and a mass (approximately 8.4 cm × 5.7 cm × 6.3 cm) below the spleen with clear boundaries—this exhibited an uneven signal, which was slightly low in T1-weighted imaging (T1WI) and slightly high in T2-weighted imaging (T2WI). Several small cystic lesions or cystic cavities were observed in the mass, which exhibited a longer T2 signal. During the enhanced scan, the signal of the lesion showed progressive enhancement, and the enhancement range increased in the delayed phase scan, as well as a hematoma below the spleen capsule and calcification below the lesion (nodular T1WI/T2WI hypointense, approximately 3.3 cm × 3.6 cm). Postoperative biopsy pathology showed splenic soft tissue tumor: at low magnification, the multinucleated giant cells were scattered; at medium magnification, osteoclast-like multinucleated giant cells were observed; and at high magnification, lace- or grid-like tumor osteogenesis was detected. Immunohistochemistry showed that the expression of CD31, CD34, F8, s-100, desmin, SMA, and CD99 was negative, whereas the expression of β-catenin, BCL-2, SATB-2, and P16 was positive. CD68 and MDM-2 showed low expression, while 50% of the cells were positive for Ki-67 expression. No abnormal concentration of radioactivity was found on the bone scan with 99mTc-MDP after the operation, further ruling out the occurrence of other bone tumors. The patient was diagnosed with primary extraskeletal osteosarcoma. It is necessary for multidisciplinary teams to diagnose malignant extraskeletal osteosarcomas.
Delayed Neuropsychiatric Sequel Following Pediatric Carbon Monoxide Poisoning: A Case Report and Literature Review
Authors: Gavrieli Hila , Noyman Iris , Hershkovitz Eli , Taragin Benjamin , Hazan Guy
Published: May 2022

Carbon monoxide (CO) poisoning is a serious health problem. The main pathophysiological mechanism of acute CO poisoning is hypoxia due to the formation of carboxyhemoglobin (COHb). Delayed neuropsychiatric sequel (DNPS) occurs following an interval of several days to several weeks post-CO exposure and can present in many different manifestations, ranging from behavioral and mood disorders to encephalopathy and seizures and cause long-term neuropsychiatric sequel. The pathogenesis of DNPS following CO poisoning is a complex one that encompasses hypoxia-induced encephalopathy as well as inflammation, direct cellular changes and damage. The incidence varies and treatment is debated. We display a case of a previously healthy 13-year-old boy suffering from DNPS, presenting with seizures and encephalopathy and later developing optic nerve damage. Increased awareness to this condition might help diagnose future patients and aid in the understanding of the pathogenesis and treatment options for this poorly understood condition.
Modified ABCDEF-Bundles for Critically Ill Pediatric Patients - What Could They Look Like?
Authors: Engel Juliane , von Borell Florian , Baumgartner Isabella , Kumpf Matthias , Hofbeck Michael , Michel Jörg , Neunhoeffer Felix
Published: May 2022

Background and Significance

Advances in pediatric intensive care have led to markedly improved survival rates in critically ill children. Approximately 70% of those children survive with varying forms of complex chronic diseases or impairment/disabilities. Length of stay, length of mechanical ventilation and number of interventions per patient are increasing with rising complexity of underlying diseases, leading to increasing pain, agitation, withdrawal symptoms, delirium, immobility, and sleep disruption. The ICU-Liberation Collaborative of the Society of Critical Care Medicine has developed a number of preventative measures for prevention, early detection, or treatment of physical and psychiatric/psychological sequelae of oftentimes traumatic intensive care medicine. These so called ABCDEF-Bundles consist of elements for (A) assessment, prevention and management of pain, (B) spontaneous awakening and breathing trials (SAT/SBT), (C) choice of analgesia and sedation, (D) assessment, prevention and management of delirium, (E) early mobility and exercise and (F) family engagement and empowerment. For adult patients in critical care medicine, research shows significant effects of bundle-implementation on survival, mechanical ventilation, coma, delirium and post-ICU discharge disposition. Research regarding PICS in children and possible preventative or therapeutic intervention is insufficient as yet. This narrative review provides available information for modification and further research on the ABCDEF-Bundles for use in critically ill children.

Material and Methods

A narrative review of existing literature was used.

Results

One obvious distinction to adult patients is the wide range of different developmental stages of children and the even closer relationship between patient and family. Evidence for pediatric ABCDEF-Bundles is insufficient and input can only be collected from literature regarding different subsections and topics.

Conclusion

In addition to efforts to improve analgesia, sedation and weaning protocols with the aim of prevention, early detection and effective treatment of withdrawal symptoms or delirium, efforts are focused on adjusting ABCDEF bundle for the entire pediatric age group and on strengthening families' decision-making power, understanding parents as a resource for their child and involving them early in the care of their children.
The Bradycardic Agent Ivabradine Acts as an Atypical Inhibitor of Voltage-Gated Sodium Channels
Authors: Hackl Benjamin , Lukacs Peter , Ebner Janine , Pesti Krisztina , Haechl Nicholas , Földi Mátyás C , Lilliu Elena , Schicker Klaus , Kubista Helmut , Stary-Weinzinger Anna , Hilber Karlheinz , Mike Arpad , Todt Hannes , Koenig Xaver
Published: May 2022

Background and purpose: Ivabradine is clinically administered to lower the heart rate, proposedly by inhibiting hyperpolarization-activated cyclic nucleotide-gated cation channels in the sinoatrial node. Recent evidence suggests that voltage-gated sodium channels (VGSC) are inhibited within the same concentration range. VGSCs are expressed within the sinoatrial node and throughout the conduction system of the heart. A block of these channels thus likely contributes to the established and newly raised clinical indications of ivabradine. We, therefore, investigated the pharmacological action of ivabradine on VGSCs in sufficient detail in order to gain a better understanding of the pro- and anti-arrhythmic effects associated with the administration of this drug.

Experimental Approach: Ivabradine was tested on VGSCs in native cardiomyocytes isolated from mouse ventricles and the His-Purkinje system and on human Nav1.5 in a heterologous expression system. We investigated the mechanism of channel inhibition by determining its voltage-, frequency-, state-, and temperature-dependence, complemented by a molecular drug docking to the recent Nav1.5 cryoEM structure. Automated patch-clamp experiments were used to investigate ivabradine-mediated changes in Nav1.5 inactivation parameters and inhibition of different VGSC isoforms.

Key results: Ivabradine inhibited VGSCs in a voltage- and frequency-dependent manner, but did not alter voltage-dependence of activation and fast inactivation, nor recovery from fast inactivation. Cardiac (Nav1.5), neuronal (Nav1.2), and skeletal muscle (Nav1.4) VGSC isoforms were inhibited by ivabradine within the same concentration range, as were sodium currents in native cardiomyocytes isolated from the ventricles and the His-Purkinje system. Molecular drug docking suggested an interaction of ivabradine with the classical local anesthetic binding site.

Conclusion and Implications: Ivabradine acts as an atypical inhibitor of VGSCs. Inhibition of VGSCs likely contributes to the heart rate lowering effect of ivabradine, in particular at higher stimulation frequencies and depolarized membrane potentials, and to the observed slowing of intra-cardiac conduction. Inhibition of VGSCs in native cardiomyocytes and across channel isoforms may provide a potential basis for the anti-arrhythmic potential as observed upon administration of ivabradine.
An in silico Model of T Cell Infiltration Dynamics Based on an Advanced in vitro System to Enhance Preclinical Decision Making in Cancer Immunotherapy
Authors: Lewin Thomas D. , Avignon Blandine , Tovaglieri Alessio , Cabon Lauriane , Gjorevski Nikolche , Hutchinson Lucy G.
Published: May 2022

Cancer immunotherapy often involves the use of engineered molecules to selectively bind and activate T cells located within tumour tissue. Fundamental to the success of such treatments is the presence or recruitment of T cells localised within the tumour microenvironment. Advanced organ-on-a-chip systems provide an in vitro setting in which to investigate how novel molecules influence the spatiotemporal dynamics of T cell infiltration into tissue, both in the context of anti-tumour efficacy and off-tumour toxicity. While highly promising, the complexity of these systems is such that mathematical modelling plays a crucial role in the quantitative evaluation of experimental results and maximising the mechanistic insight derived. We develop a mechanistic, mathematical model of a novel microphysiological in vitro platform that recapitulates T cell infiltration into epithelial tissue, which may be normal or transformed. The mathematical model describes the spatiotemporal dynamics of infiltrating T cells in response to chemotactic cytokine signalling. We integrate the model with dynamic imaging data to optimise key model parameters. The mathematical model demonstrates a good fit to the observed experimental data and accurately describes the distribution of infiltrating T cells. This model is designed to complement the in vitro system; with the potential to elucidate complex biological mechanisms, including the mode of action of novel therapies and the drivers of safety events, and, ultimately, improve the efficacy-safety profile of T cell-targeted cancer immunotherapies.
Targeting HMGB1-NFκb Axis and miR-21 by Glycyrrhizin: Role in Amelioration of Corneal Injury in a Mouse Model of Alkali Burn
Authors: Wang Peihong , Hao Peng , Chen Xi , Li Linghan , Zhou Yongying , Zhang Xiaohan , Zhu Lin , Ying Ming , Han Ruifang , Wang Liming , Li Xuan
Published: May 2022

Corneal neovascularization (CNV) is a sight-threatening condition usually associated with various inflammatory settings including chemical injury. High mobility group box 1 (HMGB1) is identified as an inflammatory alarmin in diverse tissue damage. Here, we evaluate the expression of HMGB1 and the consequences of its inhibition through its selective inhibitor glycyrrhizin (GLY) in alkali burn-induced corneal inflammation and neovascularization. GLY effectively attenuated alkali burn-induced HMGB1 expression at both mRNA and protein levels. Furthermore, slit-lamp analysis, ink perfusion, H&E staining, and CD31 histochemical staining showed that GLY relieved corneal neovascularization, while GLY attenuated VEGF expression via inhibiting HMGB1/NF-κB/HIF-1α signal pathway. In addition, GLY treatment decreased the cytokine expression of CCL2 and CXCL5, accompanied by the reduction of their receptors of CCR2 and CXCR2. GLY diminished the inflammatory cell infiltration of the cornea, as well as reduced the expression of IL-1β, IL-6, and TNF-α. Moreover, treatment with GLY reduced the degree of cornea opacity through inactivating extracellular HMGB1 function, which otherwise induces TGF-β1 release and myofibroblast differentiation. Furthermore, we found that GLY treatment attenuated the upregulation of miR-21 levels in alkali burned cornea; while inhibition of miR-21in keratocytes in vitro, significantly inhibited TGF-β1-induced myofibroblast differentiation. Collectively, our results suggested that targeting HMGB1-NFκb axis and miR-21 by GLY could introduce a therapeutic approach to counter CNV.
LINC00586 Represses ASXL1 Expression Thus Inducing Epithelial-To-Mesenchymal Transition of Colorectal Cancer Cells Through LSD1-Mediated H3K4me2 Demethylation
Authors: Liu Fengting , Ma Xiaofang , Bian Xiyun , Zhang Chunyan , Liu Xiaozhi , Liu Qiang
Published: May 2022

Colorectal cancer (CRC) is a major public health problem on a global scale by virtue of its relatively high incidence. The transition of tumor cells from an epithelial to a mesenchymal-like phenotype, so-called epithelial-to-mesenchymal transition (EMT), is a key hallmark of human cancer metastasis, including CRC. Understanding the signaling events that initiate this phenotypic switch may provide opportunities to limit the metastasis of CRC. In this study, we aim to identify long non-coding RNA (lncRNA) mediated epigenetic regulation under the context of CRC. 54 paired samples of tumor tissues and surrounding non-tumor tissues were collected from CRC patients. Cultured human CRC cells HCT116 and LoVo were assayed for their viability and migration using CCK-8 tests and transwell migration assays. The expression of EMT-specific markers (E-cadherin, N-cadherin and vimentin) was analyzed biochemically by RT-qPCR and immunoblot analyses. Interaction among LINC00586, LSD1, and ASXL1 was determined by RNA immunoprecipitation and chromatin immunoprecipitation. In vivo analysis of LINC00586 was performed in nude mice xenografted with HCT116 cells. LINC00586 was overexpressed in CRC tissues and associated with patient survival. LINC00586 knockdown repressed HCT116 and LoVo cell viability, migration, their phenotypic switch from epithelial to a mesenchymal, and tumorigenesis in vivo. We demonstrated LINC00586 recruited the LSD1 into the ASXL1 promoter region and epigenetically silenced the ASXL1 expression. An ASXL1 gene resisting to LINC00586 attack was demonstrated in cultured HCT116 and LoVo cells and mouse xenograft models of human CRC. Overall, discovery of the LINC00586/LSD1/ASXL1 axis partially explains epigenetic mechanism regulating EMT in CRC, providing a therapeutic target to limit CRC metastasis.
Antiviral Activity of Selected Lamiaceae Essential Oils and Their Monoterpenes Against SARS-Cov-2
Authors: Ćavar Zeljković Sanja , Schadich Ermin , Džubák Petr , Hajdúch Marián , Tarkowski Petr
Published: May 2022

This study presents the very first report on the in vitro antiviral activity of selected essential oils of Lamiaceae plant species and their monoterpenes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nineteen essential oils were obtained by hydrodistillation of dried plant material, and their monoterpene profiles were determined. In addition, the exact concentrations of each monoterpene that were found at a significant level were defined. Both essential oils and their monoterpene components were tested for cytotoxic and antiviral activity against SARS-CoV-2 in infected Vero 76 cells. The results showed that the essential oils of four Mentha species, i.e., M. aquatica L. cv. Veronica, M. pulegium L., M. microphylla K.Koch, and M. x villosa Huds., but also Micromeria thymifolia (Scop.) Fritsch and Ziziphora clinopodioides Lam., and five different monoterpenes, i.e., carvacrol, carvone, 1,8-cineol, menthofuran, and pulegone, inhibited the SARS-CoV-2 replication in the infected cells. However, the antiviral activity varied both among essential oils and monoterpenes. Carvone and carvacrol exhibited moderate antiviral activity with IC50 concentrations of 80.23 ± 6.07 μM and 86.55 ± 12.73 μM, respectively, while the other monoterpenes were less active (IC50 > 100.00 μM). Structure-activity relations of related monoterpenes showed that the presence of keto and hydroxyl groups is associated with the activity of carvone and carvacrol, respectively. Furthermore, the carvone-rich essential oil of M. x villosa had the greatest activity among all active essential oils (IC50 127.00 ± 4.63 ppm) while the other active oils exhibited mild (140 ppm < IC50 < 200 ppm) to weak antiviral activity (IC50 > 200 ppm). Both essential oils and monoterpenes showed limited or no cytotoxicity against Vero 76 cells. Hierarchical cluster analysis showed that the differences in the antiviral activity of essential oils were directly attributed to the antiviral efficacies of their particular single monoterpenes. The findings presented here on the novel antiviral property of plant essential oils and monoterpenes might be used in the development of different measures against SARS-CoV-2.
Glycosylation of Zein Hydrolysate as a Nanocarrier for Lutein Delivery: Preparation and Stability
Authors: Han He , Jiao Yan , Chang Ying , Cheng Yue , Shi Lei
Published: May 2022

Lutein is a functional carotenoid that has a wide range of physiological benefits in humans. However, it easily degrades and becomes inactivated during storage and processing, resulting in low bioavailability. The development of new nanocarriers can effectively improve the stability and biological activity of lutein. In this study, zein hydrolysate (ZH) carriers were glycosylated with glucosamine (GLU) under the action of transglutaminase, and lutein-loaded glycosylated ZH nanoparticles (GZH-LUT) were constructed by liquid–liquid dispersion. The results showed that the GZH-LUT particles had a narrow size distribution in the range of 200–300 nm and a decreased zeta potential and polydispersity index. In particular, GZH trapped lutein more efficiently than ZH. In addition, GZH-LUT had better physical and chemical properties, including better water solubility, oxidative stability, and environmental stability than free lutein and ZH-LUT. These results indicate that glycosylated zein hydrolysate has the potential to be used as a novel protein-based nanocarrier to enhance the solubility and stability of lutein, which can further improve its bioavailability.
Thoracic Computed Tomography to Assess ARDS and COVID-19 Lungs
Authors: Barbas Carmen Silvia Valente
Published: May 2022

This review was designed to discuss the role of thoracic-computed tomography (CT) in the evaluation and treatment of patients with ARDS and COVID-19 lung disease. Non-aerated lungs characterize the ARDS lungs, compared to normal lungs in the lowermost lung regions, compressive atelectasis. Heterogenous ARDS lungs have a tomographic vertical gradient characterized by progressively more aerated lung tissues from the gravity-dependent to gravity-independent lungs levels. The application of positive pressure ventilation to these heterogeneous ARDS lungs provides some areas of high shear stress, others of tidal hyperdistension or tidal recruitment that increases the chances of appearance and perpetuation of ventilator-induced lung injury. Other than helping to the correct diagnosis of ARDS, thoracic-computed tomography can help to the adjustments of PEEP, ideal tidal volume, and a better choice of patient position during invasive mechanical ventilation. Thoracic tomography can also help detect possible intra-thoracic complications and in the follow-up of the ARDS patients’ evolution during their hospital stay. In COVID-19 patients, thoracic-computed tomography was the most sensitive imaging technique for diagnosing pulmonary involvement. The most common finding is diffuse pulmonary infiltrates, ranging from ground-glass opacities to parenchymal consolidations, especially in the lower portions of the lungs’ periphery. Tomographic lung volume loss was associated with an increased risk for oxygenation support and patient intubation and the use of invasive mechanical ventilation. Pulmonary dual-energy angio-tomography in COVID-19 patients showed a significant number of pulmonary ischemic areas even in the absence of visible pulmonary arterial thrombosis, which may reflect micro-thrombosis associated with COVID-19 pneumonia. A greater thoracic tomography severity score in ARDS was independently related to poor outcomes.
Strength and Power-Related Measures in Assessing Core Muscle Performance in Sport and Rehabilitation
Authors: Zemková Erika
Published: May 2022

While force-velocity-power characteristics of resistance exercises, such as bench presses and squats, have been well documented, little attention has been paid to load, force, and power-velocity relationships in exercises engaging core muscles. Given that power produced during lifting tasks or trunk rotations plays an important role in most sport-specific and daily life activities, its measurement should represent an important part of the test battery in both athletes and the general population. The aim of this scoping review was 1) to map the literature related to testing methods assessing core muscle strength and stability in sport and rehabilitation, chiefly studies with particular focus on force-velocity-power characteristics of exercises involving the use of core muscles, 2) and to identify gaps in existing studies and suggest further research in this field. The literature search was conducted on Cochrane Library databases, Scopus, Web of Science, PubMed and MEDLINE, which was completed by SpringerLink, Google Scholar and Elsevier. The inclusion criteria were met in 37 articles. Results revealed that among a variety of studies investigating the core stability and core strength in sport and rehabilitation, only few of them analyzed force–velocity–power characteristics of exercises involving the use of core muscles. Most of them evaluated maximal isometric strength of the core and its endurance. However, there are some studies that assessed muscle power during lifting tasks at different loads performed either with free weights or using the Smith machine. Similarly, power and velocity were assessed during trunk rotations performed with different weights when standing or sitting. Nevertheless, there is still scant research investigating the power-velocity and force-velocity relationship during exercises engaging core muscles in able-bodied and para athletes with different demands on stability and strength of the core. Therefore, more research is needed to address this gap in the literature and aim research at assessing strength and power-related measures within cross-sectional and intervention studies. A better understanding of the power-force-velocity profiles during exercises with high demands on the core musculature has implications for designing sport training and rehabilitation programs for enhancement of athletes’ performance and/or decrease their risk of back pain.