bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of the domestic COVID-19 pandemic on the pediatric emergency department
Authors: Chen Ying-Ju , Chen Chun-Yu , Lee En-Pei , Huang Wun-Yan , Wu Han-Ping
Published: August 2022

Objectives

After the coronavirus disease 2019 (COVID-19) pandemic emerged, there has been a substantial decline in emergency department (ED) visits. However, the impact of the pandemic on pediatric ED (PED) visits has not been well discussed. This study aimed to compare the epidemiology and clinical characteristics of PED visits before and after the time of the COVID-19 outbreak.

Methods

Data of pediatric patients admitted to the PED between February 2019 and January 2021 were retrospectively collected. All patients were divided into two groups: 1 year before the COVID-19 pandemic (group 1) and 1 year after the COVID-19 outbreak (group 2). Basic demographics, clinical characteristics, triage levels, categories of diagnosis at PED, disposition, and hospitalization rates (wards and intensive care units) were further analyzed and compared between the two groups.

Results

During the study period, 48,146 pediatric patients were enrolled (30,823 in group 1, and 17,323 in group 2). PED visits represented a 43.8% annual decline. The most common diseases in the PED in group 1 were infectious diseases, whereas digestive system diseases were the most common diseases in group 2 (both P < 0.001). In group 2, shorter PED observational time, longer hospital stay, and higher admission rates were noted compared to those in group 1 (all P < 0.001).

Conclusion

During the COVID-19 pandemic, the proportion of respiratory system diseases and infectious diseases sharply decreased in the PED, whereas the proportion of digestive system diseases relatively increased. The COVID-19 pandemic has impacted the nature of PED visits and we should pay more attention on digestive system diseases and the rates of out-of-hospital cardiac arrest and overall mortality.
Feasibility of sentinel lymph node mapping in ovarian tumors: A systematic review and meta-analysis of the literature
Authors: Ataei Nakhaei Saeideh , Mostafavi Sayyed Mostafa , Farazestanian Marjaneh , Hassanzadeh Malihe , Sadeghi Ramin
Published: August 2022

Purpose of the report

Since the presence of lymph node metastases upstages the disease and to reduce the morbidity of total lymphadenectomy, sentinel lymph node (SLN) mapping in ovarian mass has been the focus of extensive research. This study aims to review all the literature associated with ovarian SLN mapping and assess the feasibility of ovarian SLN mapping.

Materials and methods

PubMed and Scopus were searched using the following keywords: (Sentinel lymph node) AND (Ovary OR Ovarian) AND (Tumor OR Neoplasm OR Cancer). All studies with information regarding sentinel node biopsy in ovaries were included. Different information including mapping material, injection sites, etc., was extracted from each study. In total, two indices were calculated for included studies: detection rate and false-negative rate. Meta-analysis was conducted using Meta-MUMS software. Pooled detection rate, sensitivity, heterogeneity, and publication bias were evaluated. Quality of the studies was evaluated using the Oxford center for evidence-based medicine checklist.

Results

Overall, the systematic review included 14 studies. Ovarian SLN detection rate can vary depending on the type of tracer, site of injection, etc., which signifies an overall pooled detection rate of 86% [95% CI: 75–93]. The forest plot of detection rate pooling is provided (Cochrane Q-value = 31.57, p = 0.003; I2 = 58.8%). Trim and fill method resulted in trimming of 7 studies, which decreased the pooled detection rate to 79.1% [95% CI: 67.1–87.5]. Overall, pooled sensitivity was 91% [59–100] (Cochrane Q-value = 3.93; p = 0.41; I2 = 0%). The proportion of lymph node positive patients was 0–25% in these studies with overall 14.28%.

Conclusion

Sentinel lymph node mapping in ovarian tumors is feasible and seems to have high sensitivity for detection of lymph node involvement in ovarian malignant tumors. Mapping material, injection site, and previous ovarian surgery were associated with successful mapping. Larger studies are needed to better evaluate the sensitivity of this procedure in ovarian malignancies.
Clonal serotype 1c multidrug-resistant Shigella flexneri detected in multiple institutions by sentinel-site sequencing
Authors: Ko Karrie K. K. , Chu Joash Jun Keat , Lim Kar Mun , Yingtaweesittikul Hatairat , Huang Wenjie , Tan Shireen Yan Ling , Goh Kenneth Choon Meng , Tan Si Huei , Ng Tong Yong , Maiwald Matthias , Chia Jonathan Wei Zhong , Cao Delphine Yanhong , Tan Yen Ee , Sim James Heng Chiak , Koh Tse Hsien , Nagarajan Niranjan , Suphavilai Chayaporn
Published: August 2022

Shigella flexneri is a major diarrhoeal pathogen, and the emergence of multidrug-resistant S. flexneri is of public health concern. We report the detection of a clonal cluster of multidrug-resistant serotype 1c (7a) S. flexneri in Singapore in April 2022. Long-read whole-genome sequence analysis found five S. flexneri isolates to be clonal and harboring the extended-spectrum β-lactamases blaCTX−M−15 and blaTEM−1. The isolates were phenotypically resistant to ceftriaxone and had intermediate susceptibility to ciprofloxacin. The S. flexneri clonal cluster was first detected in a tertiary hospital diagnostic laboratory (sentinel-site), to which the S. flexneri isolates were sent from other hospitals for routine serogrouping. Long-read whole-genome sequence analysis was performed in the sentinel-site near real-time in view of the unusually high number of S. flexneri isolates received within a short time frame. This study demonstrates that near real-time sentinel-site sequence-based surveillance of convenience samples can detect possible clonal outbreak clusters and may provide alerts useful for public health mitigations at the earliest possible opportunity.
Improving treatment for acute ischemic stroke—Clot busting innovation in the pipeline
Authors: Liu Joanna Shu Ting , Ding Yiran , Schoenwaelder Simone , Liu Xuyu
Published: August 2022

Acute ischemic stroke is a consequence of disrupted blood flow to the brain, caused by thrombosis—the pathological formation of occlusive clots within blood vessels, which can embolize distally to downstream tissues and microvasculature. The highest priority of stroke treatment is the rapid removal of occlusive clots and restoration of tissue perfusion. Intravenous thrombolysis is the pharmacological standard-of-care for the dissolution of blood clots, wherein thrombolytic drugs are administered to restore vessel patency. While the introduction of recombinant tissue-plasminogen activator (rtPA) in 1996 demonstrated the benefit of acute thrombolysis for clot removal, this was countered by severe limitations in terms of patient eligibility, lytic efficacy, rethrombosis and safety implications. Development of safer and efficacious treatment strategies to improve clot lysis has not significantly progressed over many decades, due to the challenge of maintaining the necessary efficacy-safety balance for these therapies. As such, rtPA has remained the sole approved acute therapeutic for ischemic stroke for over 25 years. Attempts to improve thrombolysis with coadministration of adjunct antithrombotics has demonstrated benefit in coronary vessels, but remain contraindicated for stroke, given all currently approved antithrombotics adversely impact hemostasis, causing bleeding. This Perspective provides a brief history of stroke drug development, as well as an overview of several groups of emerging drugs which have the potential to improve thrombolytic strategies in the future. These include inhibitors of the platelet receptor glycoprotein VI and the signaling enzyme PI3-Kinase, novel anticoagulants derived from hematophagous creatures, and proteolysis-targeting chimeras.
Hypoxia Increases the Tempo of Phage Resistance and Mutational Bottlenecking of Pseudomonas aeruginosa
Authors: Schumann Ashley R. , Sue Andrew D. , Roach Dwayne R.
Published: August 2022

Viruses that infect bacteria (i.e., phages) are abundant and widespread in the human body, and new anti-infective approaches such as phage therapy are essential for the future of effective medicine. Our understanding of microenvironmental factors such as tissue oxygen availability at the site of phage–bacteria interaction remains limited, and it is unknown whether evolved resistance is sculpted differentially under normoxia vs. hypoxia. We, therefore, analyzed the phage–bacteria interaction landscape via adsorption, one-step, time-kill dynamics, and genetic evolution under both normoxia and hypoxia. This revealed that adsorption of phages to Pseudomonas aeruginosa decreased under 14% environmental oxygen (i.e., hypoxia), but phage time-kill and one-step growth kinetics were not further influenced. Tracking the adaptation of P. aeruginosa to phages uncovered a higher frequency of phage resistance and constrained types of spontaneous mutation under hypoxia. Given the interest in developing phage therapies, developing our understanding of the phage–pathogen interaction under microenvironmental conditions resembling those in the body offers insight into possible strategies to overcome multidrug-resistant (MDR) bacteria.
Antimicrobial susceptibilities and mechanisms of resistance of commensal and invasive Mycoplasma salivarium isolates
Authors: Xiao Li , Totten Arthur H. , Crabb Donna M. , Atkinson Thomas Prescott , Waites Ken B.
Published: August 2022

Mycoplasma salivarium, an oral commensal organism, can cause severe invasive infections in immunocompromised individuals. Currently there is no treatment guidance for such infections. We performed antimicrobial susceptibility tests on 39 commensal and invasive M. salivarium isolates and investigated the mechanisms of antimicrobial resistance. Clindamycin was the most active agent [minimum inhibition concentration (MIC) range: 0.004–128 mg/L, MIC50 = 0.031 mg/L, MIC90 = 0.125 mg/ml], followed by tetracycline and levofloxacin. All isolates were resistant to erythromycin (MIC ≥4 mg/L) due to the presence of 2057A (Escherichia coli numbering) in 23S rRNA. Three isolates with elevated clindamycin MICs (≥8 mg/L) harbored A2058T/G mutations in 23S rRNA gene; four sequential isolates from one patient developed C2611T and A2059G mutations accompanying the increase of clindamycin MICs. Five isolates with elevated tetracycline MICs (≥4 mg/L) had mutations in 16S rRNA gene (A965G/T, G966T, or A967C/T) and one of them harbored TetM. Nine isolates with elevated levofloxacin MICs (≥4 mg/L) had one or more mutations in gyrA, gyrB, parC, or parE. Susceptibility breakpoints for clindamycin, tetracycline and levofloxacin were suggested to be ≤0.125, ≤2, and ≤2 mg/L, respectively. Antimicrobial resistance to any of the three agents (clindamycin, tetracycline, or levofloxacin) was documented in 12 (34.3%) non-duplicate isolates, of which 10 were invasive. Levofloxacin resistance was most frequent (25.7%). Multi-drug resistance was also observed (14.3%). This study demonstrates the frequent occurrence of antimicrobial resistance in M. salivarium, emphasizing the need for culture and susceptibility testing to guide antimicrobial therapy.
Supplementation of multi-enzymes alone or combined with inactivated Lactobacillus benefits growth performance and gut microbiota in broilers fed wheat diets
Authors: Gao Qingtao , Wang Yanchun , Li Jiaheng , Bai Guosong , Liu Lei , Zhong Ruqing , Ma Teng , Pan Hongbin , Zhang Hongfu
Published: August 2022

The effects of multi-enzymes mixture supplementation or combination with inactivated Lactobacillus on growth performance, intestinal barrier, and cecal microbiota were investigated in broilers at the age of 15–42 days fed a wheat-based diet. A total of 576 broilers (12 broilers/cage; n = 12) were used and divided into four groups and randomly allotted to four experimental diets throughout grower (15–28 days of age) and finisher (29–42 days of age) phases. Diets consisted of a corn-soybean meal-based diet (BD), a wheat-soybean meal-based diet (WD), and WD supplemented multi-enzymes (WED) or combined with inactivated Lactobacillus (WEPD). The results showed that the average daily gain (ADG) and body weight (BW) were reduced in broilers fed WD diet compared with those fed BD diet during the grower period (P < 0.05). Broilers in the WED or WEPD group had higher ADG and BW during the grower period (P < 0.05) and had a lower feed-to-gain ratio (F/G) compared to broilers in the WD group during the grower and overall periods (P < 0.05). Improved expression of intestinal barrier genes (claudin-1, ZO-1, and mucin-2) was observed in WEPD compared to the BD or WD group (P < 0.05). Compared to the BD group, the WD group decreased the abundance of Oscillospira, norank_f__Erysipelotrichaceae, and Peptococcus, which are related to anti-inflammatory function and BW gain. The WD also increased Bifidobacterium and some short-chain fatty acid (SCFA)-producing bacteria (Anaerotruncus, Blautia, and Oscillibacter), and Barnesiella, which were presumed as “harmful microbes” [false discovery rate (FDR) < 0.05]. WED and WEPD groups, respectively, improved Bilophila and Eubacterium_hallii_group compared with those in the WD group (FDR < 0.05). In addition, the Enterococcus abundance was reduced in the WEPD group compared to the WD group (FDR < 0.05). Higher acetate and total SCFA concentrations were observed (P < 0.05) among broilers who received a WD diet. Compared with the WD group, the WED or WEPD group further increased cecal propionate content (P < 0.05) and tended to improve butyrate concentration. These results suggested that supplemental multi-enzymes alone and combined with inactivated Lactobacillus could improve the growth performance based on the wheat-based diet and offer additional protective effects on the intestinal barrier function of broilers.
Endophytic fungus Serendipita indica accelerates ascorbate-glutathione cycle of white clover in response to water stress
Authors: Rong Zi-Yi , Jiang Dao-Ju , Cao Jin-Li , Hashem Abeer , Abd_Allah Elsayed Fathi , Alsayed Mashail Fahad , Harsonowati Wiwiek , Wu Qiang-Sheng
Published: August 2022

Ascorbate-glutathione cycle is an important pathway for plants to scavenge reactive oxygen species (ROS) under environmental stress conditions. The objective of this study was to investigate the effects of the endophytic fungus Serendipita indica on biomass, chlorophyll concent, ROS levels, antioxidant enzyme activities, and ascorbate-glutathione cycle in white clover under ample water and water stress conditions. The results showed that 46 days of soil water stress distinctly promoted root colonization by S. indica. Under water stress, S. indica inoculation significantly promoted shoot and root biomass, total chlorophyll content, and activities of superoxide dismutases (SOD; e.g., Fe-SOD and Cu/Zn-SOD) and peroxidase in roots, coupled with a decrease in malondialdehyde content in roots. In the ascorbate-glutathione cycle of roots, S. indica also significantly increased the activity of ascorbate peroxidase and glutathione reductase activities in water-stressed white clover, along with the increase in reduced ascorbic acid and reduced/oxidized glutathione contents, thus accelerating the ascorbate-glutathione cycle in inoculated plants to scavenge more ROS (e.g., hydrogen peroxide). As a result, S. indica enhanced the tolerance of white clover in response to water stress by enhancing antioxidant enzyme activities and accelerating the ascorbate-glutathione cycle.
Ramping activity in the striatum
Authors: Ponzi Adam , Wickens Jeff
Published: August 2022

Control of the timing of behavior is thought to require the basal ganglia (BG) and BG pathologies impair performance in timing tasks. Temporal interval discrimination depends on the ramping activity of medium spiny neurons (MSN) in the main BG input structure, the striatum, but the underlying mechanisms driving this activity are unclear. Here, we combine an MSN dynamical network model with an action selection system applied to an interval discrimination task. We find that when network parameters are appropriate for the striatum so that slowly fluctuating marginally stable dynamics are intrinsically generated, up and down ramping populations naturally emerge which enable significantly above chance task performance. We show that emergent population activity is in very good agreement with empirical studies and discuss how MSN network dysfunction in disease may alter temporal perception.
Efficacy and Safety of the Ketogenic Diet for Mitochondrial Disease With Epilepsy: A Prospective, Open-labeled, Controlled Study
Authors: Huang Lijuan , Li Hua , Zhong Jianmin , Yang Liming , Chen Guohong , Wang Dong , Zheng Guo , Han Hong , Han Xiong , Long Yiqin , Wang Xu , Liang Jianmin , Yu Mei , Shen Xiaoyun , Fan Mengke , Fang Fang , Liao Jianxiang , Sun Dan
Published: August 2022

Background

The ketogenic diet (KD) is increasingly used to treat drug-resistant epilepsy because of its favorable effect on seizure reduction. Patients with mitochondrial diseases tend to experience seizures. Therefore, this study aimed to test the efficacy of the KD on participants with mitochondrial diseases in a controlled trial.

Methods

Participants from fourteen clinical centers who were diagnosed with mitochondrial disease were semi-randomized to either the intervention (KD) or control group. The KD group followed a 3-month KD intervention, while the control group received a 1-month normal diet initially and then a 3-month KD intervention. The primary outcome measure was seizure reduction. Biomarker changes, cognitive impairments, and side effects were also recorded, if available.

Result

A total of 33 participants were assigned to the KD (n = 22) and control groups (n = 11). In the KD group, 31.8% (7/22) of participants achieved ≥50% seizure reduction after 1 month of diet intervention, which increased to 40.9% (9/22) at 3 months. In the control group, only 18.2% (2/11) of the participants had ≥50% seizure reduction during the normal diet period. After the control group was transferred to the KD, 63.6% (7/11) of participants had >50% seizure reduction, and this rate increased to 72.7% (8/11) at 3 months. The KD also showed high efficacy in participants with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) or pathogenic variants in mitochondrial DNA (mtDNA) (90% and 93.3% response rates, respectively). The most frequent side effects reported at the 3-month review were vomiting, cold, hyperlipidemia, and bloating.

Conclusion

The KD is a safe and effective therapy for seizure control in mitochondrial diseases, especially MELAS and pathogenic variants of mtDNA. KD intervention can be considered in the management of these patients.
Reliable and Valid Robotic Assessments of Hand Active and Passive Position Sense in Children With Unilateral Cerebral Palsy
Authors: Zbytniewska-Mégret Monika , Decraene Lisa , Mailleux Lisa , Kleeren Lize , Kanzler Christoph M. , Gassert Roger , Ortibus Els , Feys Hilde , Lambercy Olivier , Klingels Katrijn
Published: August 2022

Impaired hand proprioception can lead to difficulties in performing fine motor tasks, thereby affecting activities of daily living. The majority of children with unilateral cerebral palsy (uCP) experience proprioceptive deficits, but accurately quantifying these deficits is challenging due to the lack of sensitive measurement methods. Robot-assisted assessments provide a promising alternative, however, there is a need for solutions that specifically target children and their needs. We propose two novel robotics-based assessments to sensitively evaluate active and passive position sense of the index finger metacarpophalangeal joint in children. We then investigate test-retest reliability and discriminant validity of these assessments in uCP and typically developing children (TDC), and further use the robotic platform to gain first insights into fundamentals of hand proprioception. Both robotic assessments were performed in two sessions with 1-h break in between. In the passive position sense assessment, participant's finger is passively moved by the robot to a randomly selected position, and she/he needs to indicate the perceived finger position on a tablet screen located directly above the hand, so that the vision of the hand is blocked. Active position sense is assessed by asking participants to accurately move their finger to a target position shown on the tablet screen, without visual feedback of the finger position. Ten children with uCP and 10 age-matched TDC were recruited in this study. Test-retest reliability in both populations was good (intraclass correlation coefficients (ICC) >0.79). Proprioceptive error was larger for children with uCP than TDC (passive: 11.49° ± 5.57° vs. 7.46° ± 4.43°, p = 0.046; active: 10.17° ± 5.62° vs. 5.34° ± 2.03°, p < 0.001), indicating discriminant validity. The active position sense was more accurate than passive, and the scores were not correlated, underlining the need for targeted assessments to comprehensively evaluate proprioception. There was a significant effect of age on passive position sense in TDC but not uCP, possibly linked to disturbed development of proprioceptive acuity in uCP. Overall, the proposed robot-assisted assessments are reliable, valid and a promising alternative to commonly used clinical methods, which could help gain a better understanding of proprioceptive impairments in uCP, facilitating the design of novel therapies.
Assessment of instantaneous cognitive load imposed by educational multimedia using electroencephalography signals
Authors: Sarailoo Reza , Latifzadeh Kayhan , Amiri S. Hamid , Bosaghzadeh Alireza , Ebrahimpour Reza
Published: August 2022

The use of multimedia learning is increasing in modern education. On the other hand, it is crucial to design multimedia contents that impose an optimal amount of cognitive load, which leads to efficient learning. Objective assessment of instantaneous cognitive load plays a critical role in educational design quality evaluation. Electroencephalography (EEG) has been considered a potential candidate for cognitive load assessment among neurophysiological methods. In this study, we experiment to collect EEG signals during a multimedia learning task and then build a model for instantaneous cognitive load measurement. In the experiment, we designed four educational multimedia in two categories to impose different levels of cognitive load by intentionally applying/violating Mayer’s multimedia design principles. Thirty university students with homogenous English language proficiency participated in our experiment. We divided them randomly into two groups, and each watched a version of the multimedia followed by a recall test task and filling out a NASA-TLX questionnaire. EEG signals are collected during these tasks. To construct the load assessment model, at first, power spectral density (PSD) based features are extracted from EEG signals. Using the minimum redundancy - maximum relevance (MRMR) feature selection approach, the best features are selected. In this way, the selected features consist of only about 12% of the total number of features. In the next step, we propose a scoring model using a support vector machine (SVM) for instantaneous cognitive load assessment in 3s segments of multimedia. Our experiments indicate that the selected feature set can classify the instantaneous cognitive load with an accuracy of 84.5 ± 2.1%. The findings of this study indicate that EEG signals can be used as an appropriate tool for measuring the cognitive load introduced by educational videos. This can be help instructional designers to develop more effective content.
Tremor evaluation using smartphone accelerometry in standardized settings
Authors: Sahin Gürdal , Halje Pär , Uzun Sena , Jakobsson Andreas , Petersson Per
Published: August 2022

Tremor can be highly incapacitating in everyday life and typically fluctuates depending on motor state, medication status as well as external factors. For tremor patients being treated with deep-brain stimulation (DBS), adapting the intensity and pattern of stimulation according the current needs therefore has the potential to generate better symptomatic relief. We here describe a procedure for how patients independently could perform self-tests in their home to generate sensor data for on-line adjustments of DBS parameters. Importantly, the inertia sensor technology needed exists in any standard smartphone, making the procedure widely accessible. Applying this procedure, we have characterized detailed features of tremor patterns displayed by both Parkinson’s disease and essential tremor patients and directly compared measured data against both clinical ratings (Fahn-Tolosa-Marin) and finger-attached inertia sensors. Our results suggest that smartphone accelerometry, when used in a standardized testing procedure, can provide tremor descriptors that are sufficiently detailed and reliable to be used for closed-loop control of DBS.
Multimodal explainable AI predicts upcoming speech behavior in adults who stutter
Authors: Das Arun , Mock Jeffrey , Irani Farzan , Huang Yufei , Najafirad Peyman , Golob Edward
Published: August 2022

A key goal of cognitive neuroscience is to better understand how dynamic brain activity relates to behavior. Such dynamics, in terms of spatial and temporal patterns of brain activity, are directly measured with neurophysiological methods such as EEG, but can also be indirectly expressed by the body. Autonomic nervous system activity is the best-known example, but, muscles in the eyes and face can also index brain activity. Mostly parallel lines of artificial intelligence research show that EEG and facial muscles both encode information about emotion, pain, attention, and social interactions, among other topics. In this study, we examined adults who stutter (AWS) to understand the relations between dynamic brain and facial muscle activity and predictions about future behavior (fluent or stuttered speech). AWS can provide insight into brain-behavior dynamics because they naturally fluctuate between episodes of fluent and stuttered speech behavior. We focused on the period when speech preparation occurs, and used EEG and facial muscle activity measured from video to predict whether the upcoming speech would be fluent or stuttered. An explainable self-supervised multimodal architecture learned the temporal dynamics of both EEG and facial muscle movements during speech preparation in AWS, and predicted fluent or stuttered speech at 80.8% accuracy (chance=50%). Specific EEG and facial muscle signals distinguished fluent and stuttered trials, and systematically varied from early to late speech preparation time periods. The self-supervised architecture successfully identified multimodal activity that predicted upcoming behavior on a trial-by-trial basis. This approach could be applied to understanding the neural mechanisms driving variable behavior and symptoms in a wide range of neurological and psychiatric disorders. The combination of direct measures of neural activity and simple video data may be applied to developing technologies that estimate brain state from subtle bodily signals.
Case report: Combined therapy of bilateral subthalamic nucleus deep brain stimulation and spinal cord stimulation significantly improves motor function in a patient with multiple system atrophy with predominant parkinsonism
Authors: Li Jiping , Mei Shanshan , Zhang Xiaohua , Wang Yunpeng , Jia Xiaofei , Liu Jinlong , Xu Erhe , Mao Wei , Zhang Yuqing
Published: August 2022

Multiple system atrophy with predominant parkinsonism (MSA-P) is a highly incapacitating disease with a short life expectancy and symptomatic therapy is still limited. In this report, we presented the case of a 65-year-old woman with a 3-year history of severe rigidity, bradykinesia, and gait dysfunction alongside severe freezing of gait diagnosed with MSA-P. She underwent combined therapy of bilateral subthalamic nucleus deep brain stimulation (DBS) and low-thoracic spinal cord stimulation (SCS). The double-blind evaluation of the Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part III and 7-m Timed Up and Go at follow-ups showed her cardinal parkinsonian symptoms benefit significantly from DBS stimulation, while the improvement of SCS was mainly embodied in lower-limb symptoms. The combined stimulation achieved a better improvement of motor function than either DBS or SCS stimulation alone. Most notably, the improvement of lower-limb symptoms was significantly enhanced by the combined stimulation.
Hydroxy-γ-sanshool from Zanthoxylum bungeanum (prickly ash) induces apoptosis of human colorectal cancer cell by activating P53 and Caspase 8
Authors: Zhaojun Chen , Lulin Tan , Xin Feng , Abdel-nasser Singab , Zunguo Lei , Xiong Liu
Published: August 2022

Sanshools, long-chain polyunsaturated amides in Zanthoxylum bungeanum (prickly ash), have important bioactivity. The objective was to assess inhibitory effects and molecular mechanisms of sanshools isolated from supercritical fluid (SCF) extract on human colon adenocarcinoma cells (HCT-116) cultured in vitro. Cells were exposed to various concentrations (0, 50, 90, or 130 μM) of sanshools for 24 or 48 h, with assessment of apoptosis and cell cycle arrest as well as regulatory gene and protein expression associated with apoptosis and the cell cycle. Sanshools profoundly inhibited growth of HCT-116 cells, with hydroxy-γ-sanshool (HRS) being the optimal active component (IC50 = 88.01 μM) inhibiting cell proliferation and having no cytotoxic effect to normal cells (IC50 = 481.52 μM) by CCK-8 assay. In HCT-116 cells, HRS inhibited cell growth, induced morphological distortion, and arrested the cell cycle at G1 phase (50.31 ± 4.13% vs. 72.16 ± 8.14% in Control and 130 μM HRS, respectively), and also caused programmed cell death in a dose-dependent manner. The percentage of apoptotic cells were remarkably increased after treated with HRS (6.2, 11.9, 19.8, and 30.7% for 0, 50, 90, and 130 μM, respectively). Moreover, in HCT-116 cells, HRS significantly inhibited mRNA and protein levels of Cyclin D1, CDK4, PCNA, and increased mRNA and protein levels of P21, P53, Fas, and Caspase 8. Furthermore, inhibitors of P53 and Caspase 8 proteins significantly mitigated the HRS-induced cell cycle arrest and apoptosis. In conclusion, our study provides evidence that HRS induced human colorectal cancer cell apoptosis by up-regulating P53 and Caspase 8.
Matcha green tea targets the gut–liver axis to alleviate obesity and metabolic disorders induced by a high-fat diet
Authors: Wang Yuefei , Yu Yueer , Ding Lejia , Xu Ping , Zhou Jihong
Published: August 2022

Obesity induced by a high-fat diet (HFD) is an increasing global health problem, leading to many metabolic syndromes. As the emerging food additive rich in tea polyphenols, theanine, caffeine, and so on, matcha green tea has gained more and more popularity for its outstanding potential in ameliorating metabolic disorders. This study investigated the composition and antioxidant activity of matcha green tea and further explored its effects on gut–liver axis homeostasis in an HFD-induced obese mouse model. Male (7–8 weeks old) C57BL/6J mice were divided into four groups with the following dietary supplementation for 8 weeks: a normal chow diet (NCD), a normal chow diet+1.0% matcha (NCM), a high-fat diet (HFD), and a high-fat diet+1.0% matcha (HFM). The results demonstrated that matcha green tea ameliorated the development of obesity, lipid accumulation, and hepatic steatosis induced by HFD. Subsequently, dietary matcha supplementation restored the alterations in fecal bile acid profile and gut microbial composition. Meanwhile, the levels of mRNA expression in hepatocytes demonstrated that matcha intervention made significant regulatory on the multiple metabolic pathways of hosts involved in glucose, lipid, and bile acid metabolism. These findings present new evidence for matcha green tea as an effective nutritional strategy to mitigate obesity and relevant metabolic disorders through the gut–liver axis.
Structural characterization of polysaccharides recovered from extraction residue of ginseng root saponins and its fruit nutrition preservation performance
Authors: Sun Jing , Zhong Xinyu , Sun Dandan , Cao Xinxin , Yao Fan , Shi Lingling , Liu Yujun
Published: August 2022

Polysaccharides recovered from extraction residue of ginseng root saponins, i.e., ginsenosides-extracting residue polysaccharides (GRP), were separated into two fractions, GRP-1 and GRP-2. Fourier infrared and nuclear magnetic resonance spectra, as well as high-performance liquid chromatography and gel permeation chromatography measurements, showed GRP-1 was composed of mainly starch-like glucans and GRP-2, relatively a smaller portion, was a mixture of heteropolysaccharides composed of starch-like glucans, rhamnogalacturonan-I pectin, and arabinogalactans, and they had similar molecular weights. These results proved that the structure of GRP was not destroyed and GRP still maintained strong antioxidant activities. In addition, GRP coating on surfaces of fruit slowed their deterioration and maintained their nutritional effects. Correlation and PCA analyses on various quality and antioxidant parameters supported the above findings and a possible mechanism in fruit preservation was then proposed. Knowing the structural features and bioactivities of GRP gives insights into its application. Specifically, GRP served as an environmentally friendly coating that can be used to preserve the nutrients and other quality indicators of strawberries and fresh-cut apples, paving the way for future new approaches to food preservation using polysaccharides or other natural products.
Age-, sex-, and maturity-associated variation in the phase angle after adjusting for size in adolescents
Authors: de Moraes Anderson M. , Quinaud Ricardo T. , Ferreira Giovana O. C. , Lima Ahlan B. , Carvalho Humberto M. , Guerra-Júnior Gil
Published: August 2022

Background

Applied research using the phase angle (PhA) in children and adolescents has increased notably. Using multilevel modeling in a fully Bayesian framework, we examined the relationships between PhA, age, sex, biological maturity status, and body size in 10–16-year-old adolescents.

Methods

The sample comprised 519 adolescents (women, n = 241; men, n = 278) from Campinas, São Paulo, Brazil. Biological maturity status was assessed with self-examination of pubertal development for sexual maturity and maturity offset protocol to estimate age at peak height velocity (PHV) for somatic maturity status. Stature and body mass were measured by anthropometry. Phase angle was calculated based on raw resistance and reactance values (50 kHz frequency) obtained by bioelectrical impedance with the foot-to-hand technology.

Results

The multilevel regression analysis revealed that boys had significantly higher values of phase angle than girls, adjusting for age group and sexual maturity status. Overall, older and more mature adolescents had higher values of phase angle. When considering aligning variation in the phase angle by distance to estimated PHV (maturity offset), there was a higher association between the phase angle and time before and after predicted age at PHV for boys (r = 0.31, 90% CI: 0.23 to 0.39) than girls (r = 0.2, 90% CI: 0.11 to 0.28). When including body mass in the multilevel models, corresponding changes in the overall body mass mediate most of the influence of the maturity status and age group on the phase angle.

Conclusion

The present study demonstrated that the variability in phase angle is related to inter-individual variation in sex, age, and maturity status, as well as differences in body size. Research with adolescents considering phase angle should use multilevel modeling with standardized parameters as default to adjust for the concurrent influence of sex, age, maturity status, and body size.
Circulating choline pathway nutrients and risk of moyamoya disease
Authors: Ge Peicong , Zhao Yaobo , Zhai Yuanren , Zhang Qian , Ye Xun , Wang Jia , Wang Rong , Zhang Yan , Zhang Dong , Zhao Jizong
Published: August 2022

Background

Circulating choline pathway nutrients play a critical role in first stroke and recurrent stroke. However, there is limited information available on the effects of choline pathway nutrients on the risk of moyamoya disease (MMD) and its subtypes. We investigated the association between circulating choline and betaine and the incident risk of MMD and its subtypes.

Methods

The case-control study enrolled 385 patients with MMD [i.e., 110 transient ischemic attack (TIA)-type MMD, 157 infarction-type MMD, and 118 hemorrhagic-type MMD] and 89 matched healthy controls.

Results

Serum choline and betaine were inversely related to the risk of MMD and its subtypes. The risk of MMD was decreased with each increment in choline level [per 1 μmol increase: odds ratio (OR), 0.756; 95% CI, 0.678–0.843] and betaine level (per 1 μmol increase: OR, 0.952; 95% CI, 0.932–0.972), respectively. When choline and betaine were assessed as quartiles, compared with the lowest quartile of serum choline and betaine levels, those in the highest quartile had a significantly decreased risk of MMD (choline, Q4 vs. Q1: OR, 0.023; 95% CI, 0.005–0.118; betaine, Q4 vs. Q1: OR, 0.058; 95% CI, 0.018–0.184).

Conclusions

Serum choline and betaine were associated with the decreased risk of MMD and its subtypes.
Light flash and odor during proton beam therapy for pediatric patients: a prospective observational study
Authors: Mizumoto Masashi , Oshiro Yoshiko , Miyamoto Toshio , Sumiya Taisuke , Baba Keiichiro , Murakami Motohiro , Shimizu Shosei , Iizumi Takashi , Saito Takashi , Makishima Hirokazu , Numajiri Haruko , Nakai Kei , Okumura Toshiyuki , Maruo Kazushi , Sakae Takeji , Sakurai Hideyuki
Published: August 2022

Light flash and odor during radiation therapy are well-known phenomena, but the details are poorly understood, particularly in pediatric patients. Therefore, we conducted a prospective observational study of these events in pediatric patients (age ≤20 years old) who received radiotherapy at our center from January 2019 to November 2021. Light flash and odor were evaluated using a patient-reported checklist including the presence, strength, and duration of the phenomenon, and color of light or type of odor. 53 patients who received proton therapy (n=47) and photon radiotherapy (n=6) were enrolled in this study. The median age of the patients was 10, ranged from 5 to 20. The patients who was able to see the light flash was 4, and all of them received retina irradiation. This was equivalent to 57% of the patients who received radiotherapy to retina (n=7). The light was bright and colored mainly blue and purple, which seemed to be consistent with Cherenkov light. Odor was sensed by 9 (17%) patients, and seven patients of the 9 received nasal cavity irradiation. This was equivalent to 41% of the patients who received nasal cavity irradiation (n=17). Other 2 patients received proton therapy to brain tumor. The odors were mainly described as plastic, burnt and disinfectant, which may be caused by ozone generated during irradiation. These data suggest that pediatric patients with retinal and nasal cavity irradiation frequently sense light flashes or odor. So adequate care is necessary so that these patients are not worried about this phenomenon.
Case report: 125I seed implantation for rare malignant solitary fibrous tumor in the pelvic cavity: a case report
Authors: Gao Zhen , Yu Huimin , Di Xuemin , Zhao Jinxin , Liang Yansong , Liu Zezhou , Wang Juan , Zhang Hongtao
Published: August 2022

Solitary fibrous tumor (SFT) is a rare spindle cell tumor, benign or low-grade malignant, with an extremely low possibility of occurrence of malignant solitary fibrous tumor (MSFT). Surgery is an effective way for treating SFT, but it is often difficult to resect completely due to a large size, with a high recurrence rate and mortality rate after operation. Additionally, SFT is relatively resistant to chemotherapy, and there is a lack of effective systemic drug treatment. These lead to certain difficulties in the treatment of SFT. We report a case of a rare MSFT in the pelvic cavity. With a history of recurrence after two surgeries, this patient underwent surgical removal combined with 125I seed implantation at our hospital in the context that the tumor could not be completely removed because it was large and adhered to surrounding tissues; after up to 43 months of progression-free survival (PFS), the patient underwent 125I seed implantation alone, and achieved a complete remission, with a PFS up to 35 months. 125I seed implantation can be a safe and effective treatment option for unresectable MSFT as well as a potential solution to repeated local recurrence.
Cyclic adenosine monophosphate/phosphodiesterase 4 pathway associated with immune infiltration and PD-L1 expression in lung adenocarcinoma cells
Authors: Tong Ling , Shan Minjie , Zou Wen , Liu XianLing , Felsher Dean W. , Wang Jingjing
Published: August 2022

Background

The cyclic adenosine monophosphate/phosphodiesterase 4 (cAMP/PDE4) pathway is involved in inflammation and immune regulation; however, the effect of cAMP/PDE4 on immune infiltration and immune evasion in lung adenocarcinoma (LUAD) remains unclear.

Methods

CBioPortal, which is the The Cancer Genome Atlas (TCGA) online database, and the Kaplan Meier plotter were used to analyze the association between genes and the prognosis of TCGA-LUAD. Tumor Immune Estimation Resource (TIMER) was used to analyze the association between gene expression and immune infiltration. The Genecards database was used to identify the transcription factors of related genes. The lung adenocarcinoma cell line H1299 and A549 were treated with cAMP pathway drugs. Flow cytometry and qRT-PCR were used to detect the PD-L1 protein and gene expression, respectively. A one-way analysis of variance with Tukey’s post-hoc test or a Student’s t-test were used.

Results

It was found that PDE4B and CREB1, which are downstream genes of the cAMP/PDE4 axis, were differentially expressed in LUAD and adjacent tissues and are correlated with the prognosis and immune infiltration of LUAD. In the CBioPortal database, cAMP pathway genes are closely related to programmed cell death-ligand 1 (PD-L1) expression in TCGA-LUAD. The protein-protein interaction revealed that there was a direct interaction between CREB1/CREBBP, which are the downstream molecules of the cAMP/PDE4 axis, and MYC; additionally, MYC was predicted to bind to the PD-L1 transcription site and regulate PD-L1 expression. CREB1 was also predicted to transcriptionally bind to both MYC and PD-L1. These results predicted the interaction network of cAMP/PDE4/CREB1/CREBP/MYC/PD-L1, and the core factor may be related to MYC. In the cell experiment, forskolin (an adenylate cyclase activator) and zardaverine (a PDE4 inhibitor) enhance the cAMP pathway and decrease PD-L1 expression, while SQ2253 (an adenylate cyclase inhibitor) inhibits the cAMP pathway and increases PD-L1 expression of the LUAD cell lines H1299 and A549, and MYC regulation by these drugs was positively correlated with PD-L1 regulation, which verified the regulation of the cAMP/PDE4 pathway on MYC and PD-L1.

Conclusions

This study showed that the cAMP/PDE4 pathway may play an important role in PD-L1 regulation and immune infiltration in LUAD.
Receptor tyrosine kinase (RTK) targeting in pediatric high-grade glioma and diffuse midline glioma: Pre-clinical models and precision medicine
Authors: Schwark Kallen , Messinger Dana , Cummings Jessica R. , Bradin Joshua , Kawakibi Abed , Babila Clarissa M. , Lyons Samantha , Ji Sunjong , Cartaxo Rodrigo T. , Kong Seongbae , Cantor Evan , Koschmann Carl , Yadav Viveka Nand
Published: August 2022

Pediatric high-grade glioma (pHGG), including both diffuse midline glioma (DMG) and non-midline tumors, continues to be one of the deadliest oncologic diagnoses (both henceforth referred to as “pHGG”). Targeted therapy options aimed at key oncogenic receptor tyrosine kinase (RTK) drivers using small-molecule RTK inhibitors has been extensively studied, but the absence of proper in vivo modeling that recapitulate pHGG biology has historically been a research challenge. Thankfully, there have been many recent advances in animal modeling, including Cre-inducible transgenic models, as well as intra-uterine electroporation (IUE) models, which closely recapitulate the salient features of human pHGG tumors. Over 20% of pHGG have been found in sequencing studies to have alterations in platelet derived growth factor-alpha (PDGFRA), making growth factor modeling and inhibition via targeted tyrosine kinases a rich vein of interest. With commonly found alterations in other growth factors, including FGFR, EGFR, VEGFR as well as RET, MET, and ALK, it is necessary to model those receptors, as well. Here we review the recent advances in murine modeling and precision targeting of the most important RTKs in their clinical context. We additionally provide a review of current work in the field with several small molecule RTK inhibitors used in pre-clinical or clinical settings for treatment of pHGG.
Mortality due to respiratory system disease and lung cancer among female workers exposed to chrysotile in Eastern China: A cross-sectional study
Authors: Jiang Zhaoqiang , Chen Junqiang , Chen Junfei , Feng Lingfang , Jin Mingying , Zhong Huixian , Ju Li , Zhu Lijin , Xiao Yun , Jia Zhenyu , Xu Chengmin , Yu Difang , Zhang Xing , Lou Jianlin
Published: August 2022

Female workers in the asbestos processing industry of Eastern China are at high risk of developing multiple types of cancer, and more data are urgently needed to better understand and address this issue. Death certificate data were selected from an asbestos processing city in China from 2005 to 2006. Information was investigated using the relatives of those individuals who had died as sources of information. Individuals were classified into one of three asbestos exposure levels. Standardized mortality ratio and 95% confidence interval were calculated. A total of 2,964 individual deaths were identified from 2005 to 2006; of these, 21.4% were occupationally exposed to asbestos. The main cause of death was circulatory system diseases (21.2%). The proportion of individuals with respiratory system diseases increased by age among each exposure subgroup (Ptrend < 0.01). Among females, a significant trend was observed between increased asbestos exposure and mortality due to respiratory system diseases and lung cancer. Our study indicated that asbestos exposure was associated with excess mortality from lung cancer and respiratory diseases, particularly among female workers in an asbestos processing area in Eastern China.