bluuebunny/crossref_metadata_2025 huggingface dataset:
Robot-Assisted Bimanual Training Improves Hand Function in Patients With Subacute Stroke: A Randomized Controlled Pilot Study
Authors: Ma Di , Li Xin , Xu Quan , Yang Fei , Feng Yutong , Wang Wenxu , Huang Jian-Jia , Pei Yu-Cheng , Pan Yu
Published: July 2022

Study Design

A randomized controlled pilot study.

Background

Bimanual therapy (BMT) is an effective neurorehabilitation therapy for the upper limb, but its application to the distal upper limb is limited due to methodological difficulties. Therefore, we applied an exoskeleton hand to perform robot-assisted task-oriented bimanual training (RBMT) in patients with stroke.

Objective

To characterize the effectiveness of RBMT in patients with hemiplegic stroke with upper limb motor impairment.

Interventions

A total of 19 patients with subacute stroke (1–6 months from onset) were randomized and allocated to RBMT and conventional therapy (CT) groups. The RBMT and CT groups received 90 min of training/day (RBMT: 60 min RBMT + 30 min CT; CT: 60 min CT for hand functional training + 30 min regular CT), 5 days/week, for 4 weeks (20 sessions during the experimental period).

Assessments

Clinical assessments, including the Fugl–Meyer assessment of the upper extremity (FMA-UE), action research arm test (ARAT), and wolf motor arm function test (WMFT), were conducted before and after the intervention.

Results

Within-group analysis showed a significant improvement in the FMA-UE and WMFT in both the CT and RBMT groups. A significant improvement in the Fugl–Meyer assessment (FMA) of the wrist and hand for the distal part in the RBMT group occurred earlier than that in the CT group. A significant improvement in WMFT time was found in both groups, but the WMFT functional ability assessment was only found in the RBMT group. No significant improvements in ARAT assessment were observed in either the CT or RBMT groups. Compared with CT, significant improvements were found in terms of the proportion of minimally clinically important differences after RBMT in FMA-UE (χ2 = 4.34, p = 0.037). No adverse events were reported by any of the participants across all sessions.

Conclusions

This study is the first to apply RBMT to the distal part of the upper limb. Both RBMT and CT are effective in improving the upper limb function in patients with subacute stroke. RBMT shows superior potential efficacy in facilitating recovery of the distal part of upper extremity (UE) motor function in the early stage. Future randomized control studies with a large sample size and follow-up assessments are needed to validate the present conclusions.
Derkash's Classification and Vas Visual Analog Scale to Access the Long-Term Outcome of Neurothoracic Outlet Syndrome: A Meta-Analysis and Systematic Review
Authors: Lingyun Wei , Ke Sha , Jinmin Zhao , Yu Qiao , Jun Qin
Published: July 2022

Objective

Many publications report outcomes of surgical treatment for neurothoracic outlet syndrome (NTOS); however, high-quality meta-analyses regarding objective evaluation system accessing the long-term outcome of NTOS are lacking. This meta-analysis summarizes and compares the outcomes of Derkosh's classification and vas visual analog scale of the supraclavicular neuroplastic of brachial plexus (SNBP) and trams auxiliary first rib resection (TFRR).

Methods

The Cochrane Library, PubMed, EMBASE, Allied and Complementary Medicine (AMED) were searched for papers published between January 1980 and February 2021, using the keywords “thoracic outlet syndrome,” “treatment, surgical.” Articles were eligible for inclusion if the following criteria were met studies describing outcomes of surgery for NTOS, published in English, human studies, and available in full text. The exclusion criteria were case reports (n < 10), reviews, abstracts, and studies lacking a control group or without evaluation for two types of surgery.

Results

We included 10 studies with 1,255 cases, out of which 622 were in the SNBP group; and 633 were in the TFRR group. After surgery (≥12 months), Derkash's classification was improved in 425 cases with SNBP and 364 cases with TFRR. OR = 1.34 (95% CI: 0.94, 1.92), P = 0.03; vas visual analog scale was improved in 282 cases in the SNBP group and 214 cases in the TFRR group. OR = 1.08 (95% CI: 0.63, 1.85), P = 0.78.

Conclusion

This meta-analysis shows that both SNBP and TFRR are effective for NTOS, but that SNBP is better than TFRR in improving Derkash's classification in the long term. Although patients treated with SNBP are more satisfactory, there is no significant difference in vas visual analog scale from TFRR.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42021254203, PROSPERO CRD42021254203.
BCI-FES With Multimodal Feedback for Motor Recovery Poststroke
Authors: Remsik Alexander B. , van Kan Peter L. E. , Gloe Shawna , Gjini Klevest , Williams Leroy , Nair Veena , Caldera Kristin , Williams Justin C. , Prabhakaran Vivek
Published: July 2022

An increasing number of research teams are investigating the efficacy of brain-computer interface (BCI)-mediated interventions for promoting motor recovery following stroke. A growing body of evidence suggests that of the various BCI designs, most effective are those that deliver functional electrical stimulation (FES) of upper extremity (UE) muscles contingent on movement intent. More specifically, BCI-FES interventions utilize algorithms that isolate motor signals—user-generated intent-to-move neural activity recorded from cerebral cortical motor areas—to drive electrical stimulation of individual muscles or muscle synergies. BCI-FES interventions aim to recover sensorimotor function of an impaired extremity by facilitating and/or inducing long-term motor learning-related neuroplastic changes in appropriate control circuitry. We developed a non-invasive, electroencephalogram (EEG)-based BCI-FES system that delivers closed-loop neural activity-triggered electrical stimulation of targeted distal muscles while providing the user with multimodal sensory feedback. This BCI-FES system consists of three components: (1) EEG acquisition and signal processing to extract real-time volitional and task-dependent neural command signals from cerebral cortical motor areas, (2) FES of muscles of the impaired hand contingent on the motor cortical neural command signals, and (3) multimodal sensory feedback associated with performance of the behavioral task, including visual information, linked activation of somatosensory afferents through intact sensorimotor circuits, and electro-tactile stimulation of the tongue. In this report, we describe device parameters and intervention protocols of our BCI-FES system which, combined with standard physical rehabilitation approaches, has proven efficacious in treating UE motor impairment in stroke survivors, regardless of level of impairment and chronicity.
Development and Validation of a Daily Habit Scale
Authors: Georgiev Dejan , Christie Rosie , Torkamani Mariam , Song Ruifeng , Limousin Patricia , Jahanshahi Marjan
Published: July 2022

Habits are defined as automatic behaviours triggered by cues and performed without awareness. They are difficult to control and mentally efficient, which contrasts with goal-directed behaviour, which is characterised by active thought, high computational effort, and the ability to modify this behaviour in response to a changing environment and contextual demands. Habits are not only defined by the frequency with which a behaviour is performed but represent a complex construct that also includes the strength and automaticity of the habitual behaviour. We report here the development and validation of a Daily Habit Scale (DHS) to assess the frequency, automaticity, and strength of daily habits in healthy individuals. Item reduction based on factor analysis resulted in a scale with 38 items grouped into eight factors explaining 52.91% of the variance. The DHS showed very good internal consistency (Cronbach alpha = 0.738) and test-retest reliability (Intraclass correlation coefficient = 0.892, p<0.001) as well as convergent and divergent reliability compared to other scales measuring habits. We found a significant effect of age, gender, anxiety, and depression on the DHS. Considering certain limitations of the DHS, such as not considering the context of performance of habits, and the absence of certain items, such as transportation use, the results of this study suggest that DHS is a reliable and valid measure of daily habits that can be used by both clinicians and researchers as a measure of daily habits.
Awake Mouse fMRI and Pupillary Recordings in the Ultra-High Magnetic Field
Authors: Zeng Hang , Jiang Yuanyuan , Beer-Hammer Sandra , Yu Xin
Published: July 2022

Awake rodent fMRI is becoming a promising non-invasive brain imaging module when investigating large-scale brain function given behavioral tasks. Previous studies have either applied sedatives during scanning or pre-treatment of anesthetics, e.g., isoflurane, to reduce the motion of animals, which could confound the brain function of “awake” states in rodents. Here, we have established a long training awake mouse fMRI-pupillometry paradigm/setup without the initial use of anesthesia. To validate the awake mouse fMRI platform, evoked BOLD-fMRI was performed to identify brain activation in the visual cortex, dorsal lateral geniculate nuclei, and superior colliculus. Furthermore, pupil signal fluctuation was investigated during scanning, showing a less dilated pupil after 5–8 weeks of intermittent training. Thus, using the awake mouse fMRI with real-time pupillometry provides a longitudinal functional mapping tool to study fully conscious mice.
Convolutional Recurrent Neural Network for Dynamic Functional MRI Analysis and Brain Disease Identification
Authors: Lin Kai , Jie Biao , Dong Peng , Ding Xintao , Bian Weixin , Liu Mingxia
Published: July 2022

Dynamic functional connectivity (dFC) networks derived from resting-state functional magnetic resonance imaging (rs-fMRI) help us understand fundamental dynamic characteristics of human brains, thereby providing an efficient solution for automated identification of brain diseases, such as Alzheimer's disease (AD) and its prodromal stage. Existing studies have applied deep learning methods to dFC network analysis and achieved good performance compared with traditional machine learning methods. However, they seldom take advantage of sequential information conveyed in dFC networks that could be informative to improve the diagnosis performance. In this paper, we propose a convolutional recurrent neural network (CRNN) for automated brain disease classification with rs-fMRI data. Specifically, we first construct dFC networks from rs-fMRI data using a sliding window strategy. Then, we employ three convolutional layers and long short-term memory (LSTM) layer to extract high-level features of dFC networks and also preserve the sequential information of extracted features, followed by three fully connected layers for brain disease classification. Experimental results on 174 subjects with 563 rs-fMRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) demonstrate the effectiveness of our proposed method in binary and multi-category classification tasks.
Chondroitin Sulphate Proteoglycan Axonal Coats in the Human Mediodorsal Thalamic Nucleus
Authors: Pantazopoulos Harry , Hossain Nayeem Mubarak , Chelini Gabriele , Durning Peter , Barbas Helen , Zikopoulos Basilis , Berretta Sabina
Published: July 2022

Mounting evidence supports a key involvement of the chondroitin sulfate proteoglycans (CSPGs) NG2 and brevican (BCAN) in the regulation of axonal functions, including axon guidance, fasciculation, conductance, and myelination. Prior work suggested the possibility that these functions may, at least in part, be carried out by specialized CSPG structures surrounding axons, termed axonal coats. However, their existence remains controversial. We tested the hypothesis that NG2 and BCAN, known to be associated with oligodendrocyte precursor cells, form axonal coats enveloping myelinated axons in the human brain. In tissue blocks containing the mediodorsal thalamic nucleus (MD) from healthy donors (n = 5), we used dual immunofluorescence, confocal microscopy, and unbiased stereology to characterize BCAN and NG2 immunoreactive (IR) axonal coats and measure the percentage of myelinated axons associated with them. In a subset of donors (n = 3), we used electron microscopy to analyze the spatial relationship between axons and NG2- and BCAN-IR axonal coats within the human MD. Our results show that a substantial percentage (∼64%) of large and medium myelinated axons in the human MD are surrounded by NG2- and BCAN-IR axonal coats. Electron microscopy studies show NG2- and BCAN-IR axonal coats are interleaved with myelin sheets, with larger axons displaying greater association with axonal coats. These findings represent the first characterization of NG2 and BCAN axonal coats in the human brain. The large percentage of axons surrounded by CSPG coats, and the role of CSPGs in axonal guidance, fasciculation, conductance, and myelination suggest that these structures may contribute to several key axonal properties.
Identification of a Novel Small RNA Encoded in the Mouse Urokinase Receptor uPAR Gene (Plaur) and Its Molecular Target Mef2d
Authors: Rysenkova Karina D. , Troyanovskiy Konstantin E. , Klimovich Polina S. , Bulyakova Taisiya R. , Shelomentseva Ekaterina M. , Shmakova Anna A. , Tanygina Daria Yu. , Ivashkina Olga I. , Anokhin Konstantin V. , Karagyaur Maxim N. , Zvereva Maria I. , Rubina Kseniya A. , Tkachuk Vsevolod A. , Semina Ekaterina V.
Published: July 2022

Urokinase receptor (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored receptor of urokinase (uPA), which is involved in brain development, nerve regeneration, wound healing and tissue remodeling. We have recently shown that Plaur, which encodes uPAR, is an early response gene in murine brain. Assumingly, diverse functions of Plaur might be attributed to hypothetical, unidentified microRNAs encoded within introns of the Plaur gene. Using a bioinformatic approach we identified novel small RNAs within the Plaur gene and named them Plaur-miR1-3p and Plaur-miR1-5p. We confirmed Plaur-dependent expression of Plaur-miR1-3p and Plaur-miR1-5p in the mouse brain and mouse neuroblastoma Neuro2a cells. Utilizing an in silico MR-microT algorithm in DianaTools we selected two target genes – Mef2d and Emx2 with the highest binding scores to small RNAs selected from identified Plaur-Pre-miR1. Furthermore, sequencing of mouse brain samples for Plaur-miR1-5p target genes revealed two more genes—Nrip3 and Snrnp200. The expression of Emx2, Mef2d, and Snrnp200 in the mouse brain and Mef2d and Snrnp200 in Neuro2a cells correlated with expression of Plaur and small RNAs—Plaur-miR1-3p and Plaur-miR1-5p. Finally, we demonstrated elevated MEF2D protein expression in the mouse brain after Plaur induction and displayed activating effects of Plaur-miR1-5p on Mef2d expression in Neuro2a cells using Luciferase reporter assay. In conclusion, we have identified Plaur-miR1-3p and Plaur-miR1-5p as novel small RNAs encoded in the Plaur gene. This finding expands the current understanding of Plaur function in brain development and functioning.
Mitophagy: An Emergence of New Player in Alzheimer’s Disease
Authors: Sharma Bunty , Pal Deeksha , Sharma Ujjawal , Kumar Aman
Published: July 2022

Mitochondria provide neurons not only energy as ATP to keep them growing, proliferating and developing, but they also control apoptosis. Due to their high bioenergetic demand, neurons which are highly specific terminally differentiated cells, essentially depend on mitochondria. Defective mitochondrial function is thus related to numerous age-linked neurodegenerative ailments like Alzheimer’s disease (AD), in which the build-up of impaired and malfunctioning mitochondria has been identified as a primary sign, paying to disease development. Mitophagy, selective autophagy, is a key mitochondrial quality control system that helps neurons to stay healthy and functional by removing undesired and damaged mitochondria. Dysfunctional mitochondria and dysregulated mitophagy have been closely associated with the onset of ADs. Various proteins associated with mitophagy were found to be altered in AD. Therapeutic strategies focusing on the restoration of mitophagy capabilities could be utilized to strike the development of AD pathogenesis. We summarize the mechanism and role of mitophagy in the onset and advancement of AD, in the quality control mechanism of mitochondria, the consequences of dysfunctional mitophagy in AD, and potential therapeutic approaches involving mitophagy modulation in AD. To develop new therapeutic methods, a better knowledge of the function of mitophagy in the pathophysiology of AD is required.
Zebrafish Is a Powerful Tool for Precision Medicine Approaches to Neurological Disorders
Authors: Ochenkowska Katarzyna , Herold Aveeva , Samarut Éric
Published: July 2022

Personalized medicine is currently one of the most promising tools which give hope to patients with no suitable or no available treatment. Patient-specific approaches are particularly needed for common diseases with a broad phenotypic spectrum as well as for rare and yet-undiagnosed disorders. In both cases, there is a need to understand the underlying mechanisms and how to counteract them. Even though, during recent years, we have been observing the blossom of novel therapeutic techniques, there is still a gap to fill between bench and bedside in a patient-specific fashion. In particular, the complexity of genotype-to-phenotype correlations in the context of neurological disorders has dampened the development of successful disease-modifying therapeutics. Animal modeling of human diseases is instrumental in the development of therapies. Currently, zebrafish has emerged as a powerful and convenient model organism for modeling and investigating various neurological disorders. This model has been broadly described as a valuable tool for understanding developmental processes and disease mechanisms, behavioral studies, toxicity, and drug screening. The translatability of findings obtained from zebrafish studies and the broad prospect of human disease modeling paves the way for developing tailored therapeutic strategies. In this review, we will discuss the predictive power of zebrafish in the discovery of novel, precise therapeutic approaches in neurosciences. We will shed light on the advantages and abilities of this in vivo model to develop tailored medicinal strategies. We will also investigate the newest accomplishments and current challenges in the field and future perspectives.
Case Report: Mature Plasmacytoid Dendritic Cell Proliferation Associated With a Lymphoid Neoplasm
Authors: Fei Fei , Liedtke Michaela , Silva Oscar
Published: July 2022

Mature plasmacytoid dendritic cell proliferations (MPDCPs) are clonal, non-malignant pDC proliferations that have been reported to occur in association with myeloid neoplasms such as CMML, AML (pDC-AML), and, rarely, MDS or MPNs. Here we report the first case of a MPDCP associated with T-lymphoblastic leukemia (T-ALL), a lymphoid neoplasm. The MPDCP in this case involved ~50% of the bone marrow, was found in nodular aggregates, expressed CD123, CD4, and CD303, and lacked CD56 and TCL1 expression. In addition, the MPDCP lacked CD34 and TdT but showed aberrant expression of CD7, CD5, CD10, and CD13, markers expressed by the abnormal T-lymphoblastic cells. Mutational analysis demonstrated mutations in JAK3, NOTCH1, NRAS, KRAS, DNMT3A, and SH2B3 but no mutations in TET2, ASLX1 or ZRSR2. Analysis of the pDC frequency in a separate cohort of T-ALL and control patients demonstrated that bone marrow pDCs are often decreased in patients with T-ALL compared to controls. This is the first report of a MPDCP associated with a lymphoid neoplasm and provides further support that MPDCP can arise from a multipotent hematopoietic progenitor with lymphoid and dendritic cell potential.
Can CT Radiomics Detect Acquired T790M Mutation and Predict Prognosis in Advanced Lung Adenocarcinoma With Progression After First- or Second-Generation EGFR TKIs?
Authors: Yang Xiaohuang , Fang Chao , Li Congrui , Gong Min , Yi Xiaochun , Lin Huashan , Li Kunyan , Yu Xiaoping
Published: July 2022

Objective

To explore the potential of CT radiomics in detecting acquired T790M mutation and predicting prognosis in patients with advanced lung adenocarcinoma with progression after first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy.

Materials and Methods

Contrast-enhanced thoracic CT was collected from 250 lung adenocarcinoma patients (with acquired T790M mutation, n = 146, without mutation, n = 104) after progression on first- or second-generation TKIs. Radiomic features were extracted from each volume of interest. The maximum relevance minimum redundancy and the least absolute shrinkage and selection operator (LASSO) regression method were used to select the optimized features in detecting acquired T790M mutation. Univariate Cox regression and LASSO Cox regression were used to establish the radiomics model to predict the progression-free survival of osimertinib treatment. Finally, nomograms (which) combined clinical factors with radscore to predict the acquired T790M mutation and prognosis were built separately. In addition, the two nomograms were validated by the concordance index (C-index), decision curve analysis (DCA), and calibration curve analysis where appropriate.

Results

Clinical factors including the progression-free survival of first-line EGFR TKIs, EGFR mutation, and N stage and 12 radiomic features were useful in predicting the acquired T790M mutation. The area under the receiver operating characteristic curves (AUC) of clinical, radiomics, and nomogram models were 0.70, 0.74, and 0.78 in the training set and 0.71, 0.71, and 0.76 in the validation set, respectively. The DCA and calibration curve analysis demonstrated a good performance of the nomogram model. Clinical factors including age and first-generation EGFR TKIs and 12 radiomic features were useful in patients’ outcome prediction. The C-index of the combined nomogram was 0.686 in the training set and 0.630 in the validation set, respectively. Calibration curves demonstrated a relatively poor performance of the nomogram model.

Conclusion

Nomogram combined clinical factors with radiomic features might be helpful to detect whether patients developed acquired T790M mutation or not after progression on first- or second-generation EGFR TKIs. Nomogram prognostic model combined clinical factors with radiomic features might have a limited value in predicting the survival of patients harboring acquired T790M mutation treated with osimertinib.
Methods of a New Chronic Pancreatitis and Spontaneous Pancreatic Cancer Mouse Model Using Retrograde Pancreatic Duct Injection of Dibutyltin Dichloride
Authors: Zhang Deyu , Li Wanshun , Wang Meiqi , Yin Hua , Xia Chuanchao , Li Keliang , Huang Haojie
Published: July 2022

The current study aimed to develop a new chronic pancreatitis and spontaneous pancreatic cancer model on C57/BL6 mouse through retrograde pancreatic duct injection of dibutyltin dichloride (DBTC) and explore its basic pathological changes as compared to the previous published chronic pancreatitis model through tail vein injection of DBTC with alcohol drinking. C57/BL6 mice were randomly divided into 3 groups: CG (control group; n = 15), VG (tail vein injection of DBTC (8 mg/kg) with 10% alcohol drinking group; n = 20), and PG (retrograde pancreatic duct injection of DBTC group (1 mg/kg); n = 30). Five mice in each group were sacrificed at a specific time point after the first treatment. The pathological section was observed. The activities of amylase, bilirubin, and hyaluronic acid in serum were determined. The expression of fibronectin, COL1A1, α-SMA, MMP-1, and TIMP-1 in the pancreas was assayed. Severe fibrosis of the pancreas with inflammatory cell infiltration could be observed on day 21 in the PG. In the VG, slight fibrosis of the pancreas with inflammatory cell infiltration was observed on day 28. There were significant differences in serum amylase, bilirubin, and hyaluronic acid levels between the PG and VG. The protein level of COL1A1 and α-SMA significantly increased in the PG. The mRNA expression of TIMP-1 is upregulated and the MMP-1 mRNA level is downregulated in the PG. Finally, typical neoplastic pathological change is significantly obvious in the PG. In conclusion, we established and validated a new chronic pancreatitis (CP) and spontaneous pancreatic cancer mouse model through retrograde injection of DBTC into the pancreatic duct. Previously reported mouse model through tail vein injection of DBTC with alcohol drinking could not cause obvious CP and neoplastic pathological change in mice.
Nuclear Imaging in Pediatric Cardiology: Principles and Applications
Authors: Venet Maelys , Friedberg Mark K. , Mertens Luc , Baranger Jerome , Jalal Zakaria , Tlili Ghoufrane , Villemain Olivier
Published: July 2022

Nuclear imaging plays a unique role within diagnostic imaging since it focuses on cellular and molecular processes. Using different radiotracers and detection techniques such as the single photon emission scintigraphy or the positron emission tomography, specific parameters can be assessed: myocardial perfusion and viability, pulmonary perfusion, ventricular function, flow and shunt quantification, and detection of inflammatory processes. In pediatric and congenital cardiology, nuclear imaging can add complementary information compared to other imaging modalities such as echocardiography or magnetic resonance imaging. In this state-of-the-art paper, we appraise the different techniques in pediatric nuclear imaging, evaluate their advantages and disadvantages, and discuss the current clinical applications.
Differences in Cardiopulmonary Fitness Between Boy and Girls With Repaired Tetralogy of Fallot
Authors: Chang Yung-Liang , Kuan Tzu-Hsuan , Chen Chia-Hsin , Tsai Yi-Ju , Chen Guan-Bo , Lin Ko-Long , Tuan Sheng-Hui
Published: July 2022

Objective

Many studies have demonstrated that patients with repaired tetralogy of Fallot (rTOF) have generally poorer cardiopulmonary fitness (CPF). However, little is known about how the disease results in different CPF in each sex. Therefore, this study aimed to investigate whether sex (and gender) differences affect CPF in children and adolescents with rTOF.

Methods

This retrospective study recruited adolescents and children (aged 10–18) with rTOF following an acute stage of tetralogy of Fallot (TOF) who received cardiopulmonary exercise testing (CPET) in the past 10 years. CPF was determined by symptom-limited CPET with a treadmill under ramped Bruce protocol. Boys and girls were categorized into groups based on body mass index (BMI) and fat mass index (FMI). The BMI was grouped by Taiwanese obesity cutoff points. The FMI was categorized by the body fat percentage. Excess adiposity was defined as (1) “overweight” and “obese” by BMI and (2) greater than the sex- and age-specific 75th percentile of whole subjects by FMI.

Results

A total of 185 participants (104 boys and 81 girls) with rTOF were recruited for the final analysis. Within the BMI category, 76 boys and 63 girls were in the normal group, whereas 28 boys and 18 girls were in the excessive adiposity group. Within the FMI category, 77 boys and 60 girls were in the normal group, whereas 27 boys and 21 girls were in the excessive adiposity group. The analysis of the body composition of rTOF subjects showed that there was no statistically significant difference between the subgroups of the two sexes, but both showed a smaller body size than normal Taiwanese children. When comparing the CPF within different BMI and FMI groups, the children in the excessive adiposity group had significantly lower values in metabolic equivalents (MET) at anaerobic threshold, peak MET, and measured peak oxygen consumption (VO2) to predicted peak VO2, regardless of sex. Moreover, boys (60.90%) presented poorer CPF than girls (74.22%, p < 0.001).

Conclusion

In Taiwan, patients with rTOF had poorer CPF than healthy peers. This study found that girls with rTOF had better CPF than boys with rTOF. The effect of gender stereotypes on sports participation and self-efficacy might be one of the contributing factors; however, further investigations are warranted to determine the causal effect.
Gastric Point-of-Care Ultrasound in Acutely and Critically Ill Children (POCUS-ped): A Scoping Review
Authors: Valla Frederic V. , Tume Lyvonne N. , Jotterand Chaparro Corinne , Arnold Philip , Alrayashi Walid , Morice Claire , Nabialek Tomasz , Rouchaud Aymeric , Cercueil Eloise , Bouvet Lionel
Published: July 2022

Introduction

Point-of-care ultrasound (POCUS) use is increasing in pediatric clinical settings. However, gastric POCUS is rarely used, despite its potential value in optimizing the diagnosis and management in several clinical scenarios (i.e., assessing gastric emptying and gastric volume/content, gastric foreign bodies, confirming nasogastric tube placement, and hypertrophic pyloric stenosis). This review aimed to assess how gastric POCUS may be used in acute and critically ill children.

Materials and Methods

An international expert group was established, composed of pediatricians, pediatric intensivists, anesthesiologists, radiologists, nurses, and a methodologist. A scoping review was conducted with an aim to describe the use of gastric POCUS in pediatrics in acute and critical care settings. A literature search was conducted in three databases, to identify studies published between 1998 and 2022. Abstracts and relevant full texts were screened for eligibility, and data were extracted, according to the JBI methodology (Johanna Briggs Institute).

Results

A total of 70 studies were included. Most studies (n = 47; 67%) were conducted to assess gastric emptying and gastric volume/contents. The studies assessed gastric volume, the impact of different feed types (breast milk, fortifiers, and thickeners) and feed administration modes on gastric emptying, and gastric volume/content prior to sedation or anesthesia or during surgery. Other studies described the use of gastric POCUS in foreign body ingestion (n = 6), nasogastric tube placement (n = 5), hypertrophic pyloric stenosis (n = 8), and gastric insufflation during mechanical ventilatory support (n = 4). POCUS was performed by neonatologists, anesthesiologists, emergency department physicians, and surgeons. Their learning curve was rapid, and the accuracy was high when compared to that of the ultrasound performed by radiologists (RADUS) or other gold standards (e.g., endoscopy, radiography, and MRI). No study conducted in critically ill children was found apart from that in neonatal intensive care in preterms.

Discussion

Gastric POCUS appears useful and reliable in a variety of pediatric clinical settings. It may help optimize induction in emergency sedation/anesthesia, diagnose foreign bodies and hypertrophic pyloric stenosis, and assist in confirming nasogastric tube placement, avoiding delays in obtaining confirmatory examinations (RADUS, x-rays, etc.) and reducing radiation exposure. It may be useful in pediatric intensive care but requires further investigation.
Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice
Authors: Chun Jaemoo , Park Sang-Min , Yi Jin-Mu , Ha In Jin , Kang Han Na , Jeong Mi-Kyung
Published: July 2022

Immune checkpoint blockage targeting PD-L1 has led to breakthroughs in cancer treatment. Although anti-PD-L1-based immunotherapy has been approved as standard therapy in various cancer types, its therapeutic efficacy in most colorectal cancers (CRC) is still limited due to the low response to immunotherapy. Therefore, combining treatment with herbal medicines could be an alternative approach for treating CRC to overcome this limitation. Bojungikki-Tang (BJIKT), a herbal formula used in traditional Chinese medicine, clinically improves the quality of life for cancer patients and has been associated with antitumor and immune-modulating activities. However, the regulatory effect of BJIKT on the immune response in the tumor microenvironment remains largely uninvestigated. In this study, we verified the inhibitory effect of BJIKT on tumor growth and investigated the regulatory effect of combination therapy with BJIKT and anti-PD-L1 on antitumor immune responses in an MC38 CRC-bearing C57BL/6 mouse model. Immune profiling analysis by flow cytometry was used to characterize the exact cell types contributing to anticancer activities. Combination treatment with BJIKT and anti-PD-L1 therapy significantly suppressed tumor growth in MC38-bearing mice and increased the proportion of cytotoxic T lymphocytes and natural killer cells in tumor tissues. Furthermore, BJIKT suppressed the population of myeloid-derived suppressor cells, suggesting that this combination treatment effectively regulates the immunological function of T-cells by improving the tumor microenvironment. The herbal formula BJIKT can be a novel therapeutic option for improving anti-PD-L1-based immunotherapy in patients with CRC.
Detection of Synergistic Interaction on an Additive Scale Between Two Drugs on Abnormal Elevation of Serum Alanine Aminotransferase Using Machine-Learning Algorithms
Authors: Akimoto Hayato , Nagashima Takuya , Minagawa Kimino , Hayakawa Takashi , Takahashi Yasuo , Asai Satoshi
Published: July 2022

Drug-induced liver injury (DILI) is a common adverse drug reaction, with abnormal elevation of serum alanine aminotransferase (ALT). Several clinical studies have investigated whether a combination of two drugs alters the reporting frequency of DILI using traditional statistical methods such as multiple logistic regression (MLR), but this model may over-fit the data. This study aimed to detect a synergistic interaction between two drugs on the risk of abnormal elevation of serum ALT in Japanese adult patients using three machine-learning algorithms: MLR, logistic least absolute shrinkage and selection operator (LASSO) regression, and extreme gradient boosting (XGBoost) algorithms. A total of 58,413 patients were extracted from Nihon University School of Medicine’s Clinical Data Warehouse and assigned to case (N = 4,152) and control (N = 54,261) groups. The MLR model over-fitted a training set. In the logistic LASSO regression model, three combinations showed relative excess risk due to interaction (RERI) for abnormal elevation of serum ALT: diclofenac and famotidine (RERI 2.427, 95% bootstrap confidence interval 1.226–11.003), acetaminophen and ambroxol (0.540, 0.087–4.625), and aspirin and cilostazol (0.188, 0.135–3.010). Moreover, diclofenac (adjusted odds ratio 1.319, 95% bootstrap confidence interval 1.189–2.821) and famotidine (1.643, 1.332–2.071) individually affected the risk of abnormal elevation of serum ALT. In the XGBoost model, not only the individual effects of diclofenac (feature importance 0.004) and famotidine (0.016), but also the interaction term (0.004) was included in important predictors. Although further study is needed, the combination of diclofenac and famotidine appears to increase the risk of abnormal elevation of serum ALT in the real world.
Impairment of Ceramide-Mediated Endothelial Instant Membrane Resealing During Diabetes Mellitus
Authors: Chen Yang , Li Guangbi , Bhat Owais M. , Li Xiang , Zhang Yang , Li Pin-Lan
Published: July 2022

Recent studies have indicated that instant cell membrane resealing (ICMR) controls the activation of NOD-like receptor pyrin domain containing 3 (Nlrp3) inflammasomes in endothelial cells, thereby initiating and promoting vascular inflammation. It remains unknown whether this impaired ICMR occurs under diabetic condition or hyperglycemia contributing to endothelial dysfunction leading to vascular inflammation, a hallmark of diabetic vascular injury. The present study aims to examine whether ICMR occurs during in control and diabetic mice and to explore related molecular mechanisms associated with acid sphingomyelinase (ASM)-mediated ceramide production. Using confocal microscopy, we demonstrated that mouse aortic endothelial cells (MAECs) exposed to high glucose levels exhibited much more retarded ICMR after laser-induced membrane injury, compared to that in control cells. The high glucose-induced impairment of membrane resealing in MAECs was prevented when these cells were pretreated with sphingomyelin or C24-ceramide. Mechanistically, high glucose treatment decreased association of membrane ceramide with annexin A5, an essential element of membrane repair machinery. Consistently, the association of ceramide with annexin A5 was significantly reduced in the coronary arterial endothelium of mice with streptozotocin-induced diabetes mellitus compared to that in non-diabetic control mice. Moreover, a marked reduction of the association of ceramide with annexin A5 was observed in coronary arterial endothelium of ASM knockout mice regardless of their diabetic status. Lastly, high glucose treatment or ASM gene deletion substantially impaired ICMR in coronary arterial endothelium of mice receiving membrane puncturing agents. Collectively, our data suggest that ceramide-mediated ICMR in vascular endothelial cells is impaired during diabetes mellitus due to dissociation of ceramide with annexin A5 and ASM play a critical role in this ICMR.
Multifunctional Contribution of the Inflated Fruiting Calyx: Implication for Cuticular Barrier Profiles of the Solanaceous Genera Physalis, Alkekengi, and Nicandra
Authors: de Souza Aline Xavier , Riederer Markus , Leide Jana
Published: July 2022

Pivotal barrier properties of the hydrophobic plant cuticle covering aerial plant surfaces depend on its physicochemical composition. Among plant species and organs, compounds of this boundary layer between the plant interior and the environment vary considerably but cuticle-related studies comparing different organs from the same plant species are still scarce. Thus, this study focused on the cuticle profiles of Physalis peruviana, Physalis ixocarpa, Alkekengi officinarum, and Nicandra physalodes species. Inflated fruiting calyces enveloping fruits make Physalis, Alkekengi, and Nicandra highly recognizable genera among the Solanoideae subfamily. Although the inflation of fruiting calyces is well discussed in the literature still little is known about their post-floral functionalities. Cuticular composition, surface structure, and barrier function were examined and compared in fully expanded amphistomatous leaves, ripe astomatous fruits, and fully inflated hypostomatous fruiting calyces. Species- and organ-specific abundances of non-glandular and glandular trichomes revealed high structural diversity, covering not only abaxial and adaxial leaf surfaces but also fruiting calyx surfaces, whereas fruits were glabrous. Cuticular waxes, which limit non-stomatal transpiration, ranged from <1 μg cm−2 on P. peruviana fruiting calyces and N. physalodes fruits to 22 μg cm−2 on P. peruviana fruits. Very-long-chain aliphatic compounds, notably n-alkanes, iso-, and anteiso-branched alkanes, alkanols, alkanoic acids, and alkyl esters, dominated the cuticular wax coverages (≥86%). Diversity of cuticular wax patterns rose from leaves to fruiting calyces and peaked in fruits. The polymeric cutin matrix providing the structural framework for cuticular waxes was determined to range from 81 μg cm−2 for N. physalodes to 571 μg cm−2 for A. officinarum fruits. Cuticular transpiration barriers were highly efficient, with water permeabilities being ≤5 × 10−5 m s−1. Only the cuticular water permeability of N. physalodes fruits was 10 × 10−5 m s−1 leading to their early desiccation and fruits that easily split, whereas P. peruviana, P. ixocarpa, and A. officinarum bore fleshy fruits for extended periods after maturation. Regarding the functional significance, fruiting calyces establish a physicochemical shield that reduces water loss and enables fruit maturation within a protective microclimate, and promotes different seed dispersal strategies among plant species investigated.
The Critical Role of Arbuscular Mycorrhizal Fungi to Improve Drought Tolerance and Nitrogen Use Efficiency in Crops
Authors: Tang Haiying , Hassan Muhammad Umair , Feng Liang , Nawaz Muhammad , Shah Adnan Noor , Qari Sameer H. , Liu Ying , Miao Jianqun
Published: July 2022

Drought stress (DS) is a serious abiotic stress and a major concern across the globe as its intensity is continuously climbing. Therefore, it is direly needed to develop new management strategies to mitigate the adverse effects of DS to ensure better crop productivity and food security. The use of arbuscular mycorrhizal fungi (AMF) has emerged as an important approach in recent years to improve crop productivity under DS conditions. AMF establishes a relationship with 80% of land plants and it induces pronounced impacts on plant growth and provides protection to plants from abiotic stress. Drought stress significantly reduces plant growth and development by inducing oxidative stress, disturbing membrane integrity, plant water relations, nutrient uptake, photosynthetic activity, photosynthetic apparatus, and anti-oxidant activities. However, AMF can significantly improve the plant tolerance against DS. AMF maintains membrane integrity, improves plant water contents, nutrient and water uptake, and water use efficiency (WUE) therefore, improve the plant growth under DS. Moreover, AMF also protects the photosynthetic apparatus from drought-induced oxidative stress and improves photosynthetic efficiency, osmolytes, phenols and hormone accumulation, and reduces the accumulation of reactive oxygen species (ROS) by increasing anti-oxidant activities and gene expression which provide the tolerance to plants against DS. Therefore, it is imperative to understand the role of AMF in plants grown under DS. This review presented the different functions of AMF in different responses of plants under DS. We have provided a detailed picture of the different mechanisms mediated by AMF to induce drought tolerance in plants. Moreover, we also identified the potential research gaps that must be fulfilled for a promising future for AMF. Lastly, nitrogen (N) is an important nutrient needed for plant growth and development, however, the efficiency of applied N fertilizers is quite low. Therefore, we also present the information on how AMF improves N uptake and nitrogen use efficiency (NUE) in plants.
Dissecting the Genetic Architecture of Phenology Affecting Adaptation of Spring Bread Wheat Genotypes to the Major Wheat-Producing Zones in India
Authors: Bhati Pradeep Kumar , Juliana Philomin , Singh Ravi Prakash , Joshi Arun Kumar , Vishwakarma Manish Kumar , Poland Jesse , Govindan Velu , Shrestha Sandesh , Crespo-Herrera Leonardo , Mondal Suchismita , Huerta-Espino Julio , Kumar Uttam
Published: July 2022

Spring bread wheat adaptation to diverse environments is supported by various traits such as phenology and plant architecture. A large-scale genome-wide association study (GWAS) was designed to investigate and dissect the genetic architecture of phenology affecting adaptation. It used 48 datasets from 4,680 spring wheat lines. For 8 years (2014–2021), these lines were evaluated for days to heading (DH) and maturity (DM) at three sites: Jabalpur, Ludhiana, and Samastipur (Pusa), which represent the three major Indian wheat-producing zones: the Central Zone (CZ), North-Western Plain Zone (NWPZ), and North-Eastern Plain Zone (NEPZ), respectively. Ludhiana had the highest mean DH of 103.8 days and DM of 148.6 days, whereas Jabalpur had the lowest mean DH of 77.7 days and DM of 121.6 days. We identified 119 markers significantly associated with DH and DM on chromosomes 5B (76), 2B (18), 7D (10), 4D (8), 5A (1), 6B (4), 7B (1), and 3D (1). Our results clearly indicated the importance of the photoperiod-associated gene (Ppd-B1) for adaptation to the NWPZ and the Vrn-B1 gene for adaptation to the NEPZ and CZ. A maximum variation of 21.1 and 14% was explained by markers 2B_56134146 and 5B_574145576 linked to the Ppd-B1 and Vrn-B1 genes, respectively, indicating their significant role in regulating DH and DM. The results provide important insights into the genomic regions associated with the two phenological traits that influence adaptation to the major wheat-producing zones in India.
Why Do We Pursue Ed.D.?: A Qualitative Analysis on the Motivation of Chinese Candidates
Authors: Gong Wenting , Wang Weihua , Xu Chuang
Published: July 2022

This study aims to explore what motivates Chinese mid-career educational practitioners to pursue Ed. D. A university in South China was selected as a case university, and 18 Ed.D. candidates were recruited to participate in semi-structured interviews. Grounded theory analysis was conducted on the transcripts of the interviewees' information. The findings uncovered four motivational patterns (pre-intrinsic, pre-extrinsic, post-intrinsic, and post-extrinsic) of Ed.D. candidates in China that mutually influence and reinforce one another. A theoretical model was thus constructed in which extrinsic factors moderate intrinsic factors, prepositional factors stimulate post-positional factors, with pre-intrinsic factors act as incentives, pre-extrinsic factors act as preconditions, and post-intrinsic factors and post-extrinsic factors act as internal and external reinforcers, respectively. This study broadens critical understanding of Ed.D. students' motivation and offers several implications that should be of interest to Chinese Ed.D. candidates, educational researchers, universities, and government officials.
A Stage 1 Pilot Cohort Exploring the Use of EMDR Therapy as a Videoconference Psychotherapy During COVID-19 With Frontline Mental Health Workers: A Proof of Concept Study Utilising a Virtual Blind 2 Therapist Protocol
Authors: Farrell Derek , Fadeeva Anastasia , Zat Zeynep , Knibbs Lorraine , Miller Paul , Barron Ian , Matthess Helga , Matthess Cordula , Gazit Neta , Kiernan Matthew D.
Published: July 2022

Objective

The COVID-19 pandemic has had a major impact on the delivery of psychological treatment. Due to social distancing requirements, the provision moved to videoconferencing psychotherapy (VCP). There is a paucity of empirical data supporting the efficacy of EMDR therapy as a VCP. This stage 1 pilot study tested an EMDR therapy scripted protocol, such as Virtual Blind 2 Therapist (VB2Tr), on frontline mental health workers as a VCP regarding fitness for purpose, distinctiveness, relevance, and efficiency.

Methods

A total of 24 participants were recruited for the study. The design included a one-session treatment intervention with pre, post, 1-month, and 6-month follow-up (FU) measurements. This treatment session used a “Blind 2 Therapist” EMDR therapy scripted protocol as videoconference psychotherapy that involves non-disclosure of traumatic memory. The research explored the treatment effect on the core characteristics of trauma memory, including subjective disturbance, belief systems, memory intensity (MI), vividness, and levels of emotionality. Additionally, the research explored participants’ experiences of adverse and benevolent childhood experiences (ACEs/BCEs) during their childhood.

Results

Regarding the four tests, namely, fitness for purpose, distinctiveness, relevance, and efficiency, results are favourably suggesting potential clinical benefits of using EMDR as videoconference psychotherapy. Although this is a proof-of-concept study showing positive results, no clinical population or control group was used. The purpose of the study is to explore the potential for scalability toward a larger clinical trial. The treatment intervention was achieved irrespective of either ACEs/BCEs during childhood.

Conclusion

The research tentatively supports the case for EMDR therapy as a credible treatment when used as video conference psychotherapy and in using the Blind 2 Therapist protocol. However, more research is needed to scale toward a clinical trial.

Clinical Trial Registration

Clinical Trial Registration:https://www.isrctn.com/ISRCTN12099530, identifier ISRCTN12099530.