bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac magnetic resonance findings in neuronal ceroid lipofuscinosis: A case report
Authors: Todiere Giancarlo , Della Vecchia Stefania , Morales Maria Aurora , Barison Andrea , Ricca Ivana , Tessa Alessandra , Colombi Elisa , Santorelli Filippo Maria
Published: August 2022

Cardiac magnetic resonance imaging (MRI) is an essential tool for the study of hypertrophic cardiomyopathies (HCM) and for differentiating HCM from conditions with increased ventricular wall thickness, such as cardiac storage diseases. Although cardiac MRI is already used for the diagnosis and characterization of some forms of storage diseases involving the myocardium, it has not yet been used to study myocardial involvement in neuronal ceroid lipofuscinosis (NCL). Here, we describe comprehensive cardiac MRI findings in a patient with the CLN3 form of NCL showing basal inferior interventricular septal hypertrophy with maintained indexed LV mass within reference values and low T1-native values. MRI findings support a finding of abnormal storage material within the myocardium in CLN3 disease. We recommend the possible routine use of cardiac MRI for early diagnosis of cardiac involvement in CLN3 disease (also termed juvenile NCL) and to monitor the effects of emerging CLN3 therapies on the myocardium as well.
A surrogate gradient spiking baseline for speech command recognition
Authors: Bittar Alexandre , Garner Philip N.
Published: August 2022

Artificial neural networks (ANNs) are the basis of recent advances in artificial intelligence (AI); they typically use real valued neuron responses. By contrast, biological neurons are known to operate using spike trains. In principle, spiking neural networks (SNNs) may have a greater representational capability than ANNs, especially for time series such as speech; however their adoption has been held back by both a lack of stable training algorithms and a lack of compatible baselines. We begin with a fairly thorough review of literature around the conjunction of ANNs and SNNs. Focusing on surrogate gradient approaches, we proceed to define a simple but relevant evaluation based on recent speech command tasks. After evaluating a representative selection of architectures, we show that a combination of adaptation, recurrence and surrogate gradients can yield light spiking architectures that are not only able to compete with ANN solutions, but also retain a high degree of compatibility with them in modern deep learning frameworks. We conclude tangibly that SNNs are appropriate for future research in AI, in particular for speech processing applications, and more speculatively that they may also assist in inference about biological function.
Lateralized brain activities in subcortical vascular mild cognitive impairment with differential Chinese medicine patterns: A resting-state functional magnetic resonance imaging study
Authors: Wang Jianjun , Kong Fanxin , Zheng Haotao , Cai Dongbin , Liu Lijin , Lian Jie , Lyu Hanqing , Lin Songjun , Chen Jianxiang , Qin Xiude
Published: August 2022

Background

Subcortical vascular mild cognitive impairment (svMCI) is one of the most treatable cognitive impairments, but could be hampered by the high clinical heterogeneities. Further classification by Chinese Medicine (CM) patterns has been proved to stratify its clinical heterogeneities. It remains largely unknown of the spontaneous brain activities regarding deficiency patterns (DPs) and excess patterns (EPs) of svMCI patients based on fMRI data.

Objective

We aim to provide neuroimaging evidence of altered resting-state brain activities associated with DPs and EPs in svMCI patients.

Methods

Thirty-seven svMCI patients (PAs) and 23 healthy controls (CNs) were consecutively enrolled. All patients were categorized into either the EP group (n = 16) and the DP group (n = 21) based on a quantitative CM scale. The fractional amplitude of low-frequency fluctuation (fALFF) value was used to make comparisons between different subgroups.

Results

The DP group showed significant differences of fALFF values in the right middle frontal gyrus and the right cerebellum, while the EP group showed significant differences in the left orbitofrontal gyrus and the left cerebellum, when compared with the CN group. When compared with the EP group, the DP group had markedly increased fALFF values in the left superior temporal gyrus, right middle temporal gyrus and brainstem. The decreased fALFF values was shown in the right anterior cingulate and paracingulate gyri. Among the extensive areas of frontotemporal lobe, the Montreal Cognitive Assessment (MoCA) scores were significantly correlated with the reduced fALFF value of the right middle frontal gyrus and the left orbitofrontal gyrus.

Conclusion

Our results indicated that the DPs and EPs presented the lateralization pattern in the bilateral frontal gyrus, which will probably benefit the future investigation of the pathogenesis of svMCI patients.
Enhancing spiking neural networks with hybrid top-down attention
Authors: Liu Faqiang , Zhao Rong
Published: August 2022

As the representatives of brain-inspired models at the neuronal level, spiking neural networks (SNNs) have shown great promise in processing spatiotemporal information with intrinsic temporal dynamics. SNNs are expected to further improve their robustness and computing efficiency by introducing top-down attention at the architectural level, which is crucial for the human brain to support advanced intelligence. However, this attempt encounters difficulties in optimizing the attention in SNNs largely due to the lack of annotations. Here, we develop a hybrid network model with a top-down attention mechanism (HTDA) by incorporating an artificial neural network (ANN) to generate attention maps based on the features extracted by a feedforward SNN. The attention map is then used to modulate the encoding layer of the SNN so that it focuses on the most informative sensory input. To facilitate direct learning of attention maps and avoid labor-intensive annotations, we propose a general principle and a corresponding weakly-supervised objective, which promotes the HTDA model to utilize an integral and small subset of the input to give accurate predictions. On this basis, the ANN and the SNN can be jointly optimized by surrogate gradient descent in an end-to-end manner. We comprehensively evaluated the HTDA model on object recognition tasks, which demonstrates strong robustness to adversarial noise, high computing efficiency, and good interpretability. On the widely-adopted CIFAR-10, CIFAR-100, and MNIST benchmarks, the HTDA model reduces firing rates by up to 50% and improves adversarial robustness by up to 10% with comparable or better accuracy compared with the state-of-the-art SNNs. The HTDA model is also verified on dynamic neuromorphic datasets and achieves consistent improvements. This study provides a new way to boost the performance of SNNs by employing a hybrid top-down attention mechanism.
China is implementing the national nutrition plan of action
Authors: Cai Li , Hu Xinyi , Liu Shuang , Wang Lei , Wang Xuehong , Tu Hua , Tong Yeqing
Published: August 2022

With the transformation of Chinese economic and social structure, the social determinants of nutrition have undergone significant changes, which have a great influence on the dietary patterns and nutrition status of its population. The transition in the structure of nutrition intake in China can be characterized by a rapid trend in food accessibility, affordability, and diversity. However, challenges, such as the triple burden of malnutrition (undernourishment, micronutrient deficiencies, and obesity), still seriously threaten the population's health. To approach the targets for the “Healthy China 2030,” the General Office of the State Council of the People's Republic of China issued the National Nutrition Plan of Action (2017–2030), which specifies multi-sectoral transdisciplinary measures to improve population nutrition status. In our study, we recognized the role of the National Nutrition Plan of China in responding to the call for the Sustainable Development Goals (SDGs). Under the global- and country-level targets, this paper presented six primary intervention measures specified in the National Nutrition Plan of Action in China, highlighting the importance of collaborative actions for participants in all sectors.
Tracking fibrosis in myeloproliferative neoplasms by CCR2 expression on CD34+ cells
Authors: Pozzi Giulia , Carubbi Cecilia , Gobbi Giuliana , Tagliaferri Sara , Mirandola Prisco , Vitale Marco , Masselli Elena
Published: August 2022

In myeloproliferative neoplasm (MPNs), bone marrow fibrosis - mainly driven by the neoplastic megakaryocytic clone - dictates a more severe disease stage with dismal prognosis and higher risk of leukemic evolution. Therefore, accurate patient allocation into different disease categories and timely identification of fibrotic transformation are mandatory for adequate treatment planning. Diagnostic strategy still mainly relies on clinical/laboratory assessment and bone marrow histopathology, which, however, requires an invasive procedure and frequently poses challenges also to expert hemopathologists. Here we tested the diagnostic accuracy of the detection, by flow cytometry, of CCR2+CD34+ cells to discriminate among MPN subtypes with different degrees of bone marrow fibrosis. We found that the detection of CCR2 on MPN CD34+ cells has a very good diagnostic accuracy for the differential diagnosis between “true” ET and prePMF (AUC 0.892, P<0.0001), and a good diagnostic accuracy for the differential diagnosis between prePMF and overtPMF (AUC 0.817, P=0.0089). Remarkably, in MPN population, the percentage of CCR2-expressing cells parallels the degree of bone marrow fibrosis. In ET/PV patients with a clinical picture suggestive for transition into spent phase, we demonstrated that only patients with confirmed secondary MF showed significantly higher levels of CCR2+CD34+ cells. Overall, flow cytometric CCR2+CD34+ cell detection can be envisioned in support of conventional bone marrow histopathology in compelling clinical scenarios, with the great advantage of being extremely rapid. For patients in follow-up, its role can be conceived as an initial patient screening for subsequent bone marrow biopsy when disease evolution is suspected.
Case report: Heterogeneous mutations of SOX10 gene in a Chinese infant with Waardenburg syndrome type 4C
Authors: Zhang Suli , Lin Shuangzhu , Liu Zhenxian , Wang Wanqi , Li Jiayi , Chen Qiandui , Yang Li , Wang Cui , Pang Qiming
Published: August 2022

A 5-month-old patient presented with grayish-blue iris bilaterally, skin and mucosal pigmentation loss, Hirschsprung's disease, full-blown growth retardation, and sensorineural deafness. The patient's whole exon gene sequencing revealed a spontaneous heterozygous code-shifting mutation in the SOX10 gene: c.803del:p.K268Sfs*18. The parents of the child were wild-type, and the site of the mutation is novel.
Short- and long-term outcome of allogeneic stem cell transplantation in infants: A single-center experience over 20 years
Authors: Miśkiewicz-Bujna Justyna , Miśkiewicz-Migoń Izabella , Szmit Zofia , Przystupski Dawid , Rosa Monika , Król Anna , Kałwak Krzysztof , Ussowicz Marek , Gorczyńska Ewa
Published: August 2022

Introduction

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a treatment method for a wide range of malignant and non-malignant diseases. Infants constitute a distinct patient group, especially due to their organ immaturity and differences in drug metabolism. The present paper aims to analyse the short- and long-term outcomes after allo-HSCT in infants.

Material and methods

In the study period, 67 patients under 12 months of age underwent allo-HSCT. This study is a retrospective analysis of patient medical records, in the form of paper and electronic documentation.

Results

The probability of 5-year OS was 69% and 72% in patients with malignant and non-malignant diseases, respectively. The allo-HSCT from a matched donor was associated with improved OS in comparison to haploidentical donor (0.8 vs. 0.58%, p = 0.0425). The overall incidence of acute graft-vs.-host disease (aGVHD) was 59.3%, and grade III–IV aGVHD was diagnosed in 23% of patients. The 100-day non-relapse mortality (NRM) in the study cohort was 17.9%, while the 5-year NRM was 26.9%. Among the causes of NRM, infections occurred in 83.3% of patients, and aGVHD in 16.3% of individuals. Twenty-two children (32.8%) required hospitalization in the pediatric intensive care unit (PICU). The median length of PICU hospitalization was 6 days (range 1 to 12 days). Late sequelae diagnosed during post-transplant surveillance included ocular disorders in 26.8% of patients, cardiac complications in 4.4%, as well as endocrinopathy with short stature (<3rd percentile) in 37.2% and overt hypothyroidism in 35.4%. In the long-term perspective, 83.3% of survivors were able to attend a regular school.

Conclusions

Improvements in unrelated donor availability, and better supportive care resulted in better outcomes. Management of infant allo-HSCT recipients requires the formation of multi-disciplinary specialist teams. In addition, the role of parental empowerment must be acknowledged; for example, in speech therapy and rehabilitation.
Physicians’ Knowledge, Altitudes, and Perceived Barriers of Inappropriate Prescribing for Older Patients in Shanghai, China
Authors: Yuan Jing , Yin Guizhi , Gu Meng , Lu Kevin Z. , Jiang Bin , Li Minghui
Published: August 2022

Background: Inappropriate medication use is common around the world, particularly among older patients, and, despite potentially being preventable, often leads to adverse clinical and economic outcomes. However, there is a dearth of information regarding this prominent issue in China.

Objectives: To evaluate the extent to which the physician can correctly identify potentially inappropriate medication (PIM) in older patients and to understand physicians’ attitudes towards improving PIM knowledge.

Methods: An online, cross-sectional survey was conducted anonymously among practicing physicians in China from November through December 2020. Knowledge of PIM was accessed using seven clinical vignettes covering a wide variety of therapeutic areas. Source of information and perceived barriers regarding PIM were also evaluated. We performed the ordinary least square regression analysis to understand the potential factors related to physicians’ knowledge of PIM.

Results: A total of 597 study participants were included in the analysis. More than half of them had never heard of any screening tool for PIMs (n = 328, 54.9%) and the most frequently acknowledged tool was the China PIM Criteria (n = 259, 43.4%). For the seven clinical vignettes testing physicians’ knowledge on the medications that should be generally avoided in older patients, the mean score was 2.91 points out of 7 (SD: 1.32), with the median score of three points (IQR: 2–4). Only one-third of the respondents were feeling confident when prescribing for older patients (n = 255, 35.08%). Package inserts have been used as the major source of PIM information (always, n = 177, 29.65%; frequently, n = 286, 47.91%). Perceived barriers to appropriate prescribing include polypharmacy (n = 460, 77.05%), lack of formal education on prescribing for the older patients (n = 428, 71.69%).

Conclusion: In this online survey evaluating physicians’ ability to detect PIM for older patients, approximately 40% of PIM were recognized, suggesting an insufficient level of knowledge about appropriate prescribing.
Current situation and future development of the biopharmaceutical industry in China: A mixed-method study
Authors: Yang Ruomeng , Kabba John Alimamy , Yao Xuelin , Yang Caijun , Chang Jie , Ji Wenjing , Jiang Minghuan , Zhao Mingyue , Wen Jun , Fang Yu
Published: August 2022

Introduction: The biomedical industry has grown significantly both globally and in China; however, there are still challenges. This study aimed at evaluating the biopharmaceutical sector of China, in terms of ability to innovate, current sales volume, investment, and R&D expenditure, as well as providing a case study detailing the progress and challenges of the industry in Shaanxi province.

Method: A cross-sectional mixed-method study design was used to generate a comprehensive profile of the nature of biopharmaceutical innovation capacity and development in China by triangulating country-wide survey and interview data from Shaanxi province. Only biopharmaceutical companies that are currently marketing or conducting research and development were eligible for inclusion, and Shaanxi province was selected for conducting the interviews. Categorical and continuous variables were analyzed descriptively. Interviews were thematically analyzed by using NVivo version 12.

Results: The analysis includes responses from 77 biopharmaceutical enterprises; the majority (36, 46.8%) are in Eastern China, followed by 26 (33.8%) in Central China. In 2018, the total sales of biological products amounted to 26.28 billion yuan, and in 2019, a slight increase was observed (30.34 billion); the amount doubled in 2020 to about 67.91 billion yuan. The top three biopharmaceutical products on sale in 2020 were Camrelizumab (5.14 billion yuan), human albumin (4.56 billion yuan), and human immunoglobulin for injection (3.78 billion yuan). Expenditure on R&D has also increased; it amounted to 1657.7 million yuan in 2018, which more than doubled in 2019 to 3572.1 million yuan and further increased to 5857.7 million yuan in 2020. Nonetheless, the progress is not uniform across all provinces, as shown from the results from Shaanxi province, because of lack of local government policies that will impact on the funding, incentives, and market share that motivate the producers.

Conclusion: China’s biopharmaceutical industry has expand significantly. The increase in sales indicates that there is an increase in demand for biologicals; moreover, R&D funding is increasing. These are key indicators that influence innovation and development. However, the sector’s capacity to innovate and develop needs to be improved, particularly in the western region, where research and production are relatively weak.
Efficacy of immune checkpoint inhibitors in EGFR-Mutant NSCLC patients with EGFR-TKI resistance: A systematic review and meta-analysis
Authors: Qian Xiaoyu , Guo Xiaodan , Li Ting , Hu Wei , Zhang Lin , Wu Caisheng , Ye Feng
Published: August 2022

Background: Epidermal growth factor receptor (EGFR) mutations are common in patients with non-small-cell lung cancer (NSCLC), particularly in Asian populations. Tyrosine kinase inhibitors (TKIs) are a first-line treatment in patients with mutant EGFR, but their use is often accompanied by drug resistance, which leads to disease progression. Chemotherapy and immunotherapy are the main treatment options after progression. The efficacy of immune checkpoint inhibitors (ICIs) and their combination therapy in patients with EGFR-TKI resistant is not clear. It is thus necessary to evaluate the efficacy of ICIs and ICI-based combination therapies in patients with EGFR-TKI-resistant NSCLC.

Methods: We searched for randomized controlled trials (RCTs) comparing ICI therapy alone or in combination versus other therapies using PubMed, the Cochrane Library, Web of Science, EMBASE, MEDLINE, ClinicalTrials.gov, and several international conference databases, from database inception to 10 March 2022. The hazard ratio (HR) and 95% confidence interval (95% CI) for median overall survival (OS) and median progression-free survival (PFS) were evaluated. Odds ratio (OR), risk ratio (RR), and 95% CI were used as effect indicators for objective response rate (ORR) and safety data.

Results: Seven eligible RCTs were included in the present meta-analysis. The results showed that neither ICIs nor combination therapy prolonged median OS in EGFR-TKI resistant NSCLC patients (HR = 1.04, 95% CI: 0.84–1.29, p = 0.73). However, compared with the control group, the patients treated with ICI-based combination therapy had better PFS (HR = 0.62, 95% CI: 0.45–0.86, p = 0.004) and ORR (OR = 1.84, 95% CI: 1.28–2.66, p = 0.001).

Conclusion: ICI monotherapy did not improve the OS or PFS of NSCLC patients previously treated with EGFR-TKIs, whereas patients treated with ICI-based combination therapy had better PFS compared with those receiving conventional chemotherapy, indicating that this therapy could be offered to patients with EGFR-mutant NSCLC after progression following TKI treatment. There was no significant difference in all-grade treatment-related adverse events (TRAEs) between the combination therapy group and the control group. However, a higher incidence of discontinuation due to TRAEs was observed; this requires attention in future studies. The results of this meta-analysis provide a reference for clinical practice and future trial design.

PROSPERO registration number: CRD42021282207
Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation
Authors: Yi Xiaojiao , Wang Fugen , Feng Yan , Zhu Junfeng , Wu Yongjiang
Published: August 2022

Doxorubicin (DOX) is a potent chemotherapeutic agent that is used against various types of human malignancies. However, the associated risk of cardiotoxicity has limited its clinical application. Danhong injection (DHI) is a Chinese medicine with multiple pharmacological activities and is widely used for treating cardiovascular diseases. The aim of the present study was to evaluate the potential protective effect of DHI on DOX-induced cardiotoxicity in vivo and to investigate the possible underlying mechanisms. First, a sensitive and reliable HPLC−ESI-Q-TOF-MS/MS method was developed to comprehensively analyze the chemical compositions of DHI. A total of 56 compounds were identified, including phenolic acids, tanshinones, and flavonoids. Then, a DOX-induced chronic cardiotoxicity rat model was established to assess the therapeutic effect of DHI. As a result, DHI administration prevented the reduction in body weight and heart weight, and improved electrocardiogram performance. Additionally, the elevated levels of serum biochemical indicators were reduced, and the activities of oxidative enzymes were restored in the DOX-DHI group. Network pharmacology analysis further revealed that these effects might be attributed to 14 active compounds (e.g., danshensu, salvianolic acid A, salvianolic acid B, rosmarinic acid, and tanshinone IIA) and 15 potential targets (e.g., CASP3, SOD1, NOS3, TNF, and TOP2A). The apoptosis pathway was highly enriched according to the KEGG analysis. Molecular docking verified the good binding affinities between the active compounds and the corresponding apoptosis targets. Finally, experimental validation demonstrated that DHI treatment significantly increased the Bcl-2 level and suppressed DOX-induced Bax and caspase-3 expression in rat heart tissue. Furthermore, DHI treatment obviously decreased the apoptosis rate of DOX-treated H9c2 cells. These results indicate that DHI attenuated DOX-induced cardiotoxicity via regulating the apoptosis pathway. The present study suggested that DHI is a promising agent for the prevention of DOX-induced cardiotoxicity.
Dose-dependent reduction of lymphocyte count and heart rate after multiple administration of LC51-0255, a novel sphingosine-1-phosphate receptor 1 modulator, in healthy subjects
Authors: Hwang Inyoung , Lee Sang Won , Oh Jaeseong , Lee SeungHwan , Jang In-Jin , Yu Kyung-Sang
Published: August 2022

Aim: Sphingosine-1-phosphate receptor mediates the egress of lymphocytes from lymphoid organs, and its inhibition results in a decreased number of circulating lymphocytes. The aim of the current study was to investigate the safety and pharmacodynamic and pharmacokinetic characteristics of a novel sphingosine-1-phosphate receptor modulator, LC51-0255.

Methods: A phase 1 randomized, double-blind, placebo-controlled, multiple dosing, dose-escalation study was conducted on healthy Korean male subjects.

Results: After single and daily administration of LC51-0255 for 21 days, a dose-dependent decrease in lymphocyte count and heart rate was observed through 0.25–2 mg dose range of LC51-0255. The mean elimination half-life of LC51-0255 was 76–95 h. LC51-0255 was accumulated with a mean accumulation ratio of 5.17–6.64. During the study, LC51-0255 was generally well tolerated. The most common treatment-emergent adverse event was bradycardia. No clinically significant event of arrhythmia, including AV block, was observed. No clinically significant difference in blood pressure was observed between the dose groups. In other safety assessments, no clinically significant abnormalities were observed, except for bradycardia.

Conclusion: Daily administration of LC51-0255 in the range of 0.25–2 mg resulted in a dose-dependent reduction of lymphocyte counts and heart rate. LC51-0255 is generally safe and well tolerated in healthy volunteers.
Huangkui lianchang decoction attenuates experimental colitis by inhibiting the NF-κB pathway and autophagy
Authors: Cheng Xudong , Du Jun , Zhou Qing , Wu Bensheng , Wang Haodong , Xu Zhizhong , Zhen Shuguang , Jiang Jieyu , Wang Xiaopeng , He Zongqi
Published: August 2022

Ulcerative colitis (UC) is a chronic inflammatory colorectal disease characterized by excessive mucosal immune response activation and dysfunction of autophagy in intestinal epithelial cells. Traditional herbal preparations, including the Huangkui lianchang decoction (HLD), are effective in UC clinical treatment in East Asia, but the underlying mechanism is unclear. This study evaluated the therapeutic effects and associated molecular mechanisms of HLD in UC in vivo and in vitro. A C57BL/6 UC mouse model was established using 2.5% dextran sulfate sodium. The effects of HLD on the colonic structure and inflammation in mice were evaluated using mesalazine as the control. The anti-inflammatory effects of HLD were assessed using disease activity index (DAI) scores, histological scores, enzyme-linked immunosorbent assay, immunohistochemistry, immunofluorescence, and western blotting. HLD displayed a protective effect in UC mice by reducing the DAI and colonic histological scores, as well as levels of inflammatory cytokines and NF-κB p65 in colonic tissues. NCM460 lipopolysaccharide-induced cells were administered drug serum-containing HLD (HLD-DS) to evaluate the protective effect against UC and the effect on autophagy. HLD-DS exhibited anti-inflammatory effects in NCM460 cells by reducing the levels of inflammatory cytokines and increasing interleukin 10 levels. HLD-DS reduced p-NF-κB p65, LC3II/I, and Beclin 1 expression, which suggested that HLD alleviated colitis by inhibiting the NF-κB pathway and autophagy. However, there was no crosstalk between the NF-κB pathway and autophagy. These findings confirmed that HLD was an effective herbal preparation for the treatment of UC.
Pharmacokinetics of baicalin and oroxyloside in plasma and different tissues of rats after transnasal aerosol inhalation and intravenous injection of Tanreqing
Authors: Chen Teng-Fei , Song Ling , Gao Yun-Hang , Li Han , Li Jian-Liang , Hou Hong-Ping , Peng Bo , Wang Hui-Ying , Cheng Wen-Hao , Ye Zu-Guang , Li Ying-Fei , Zhang Guang-Ping
Published: August 2022

To avoid adverse drug reactions associated with injection, off-label nebulization of Tanreqing (TRQ) injection is often used in China to treat respiratory diseases. However, the aerodynamic properties and lung availability of TRQ aerosols remain largely uninvestigated. This study aimed to investigate the size distribution of TRQ aerosols and to compare the pharmacokinetics and tissue distribution of two compounds from TRQ (baicalin and oroxyloside) after transnasal aerosol inhalation and intravenous administration. Furthermore, this study aimed to evaluate the efficacy of TRQ against lipopolysaccharide-induced lung inflammation. The Dv(50) and transmission of TRQ aerosols were 2.512 μm and 74.867%, respectively. The Cmax of baicalin and oroxyloside in rat plasma after inhalation was lower than that after intravenous injection. After inhalation, the area under the curve (AUC) of baicalin and oroxyloside in tissues (lung, bronchoalveolar lavage fluid, and trachea) was 7.9–115.3 and 9.5–16.0 times that observed after intravenous administration, respectively. Baicalin and oroxyloside maintained high concentrations 4 h after inhalation, but only 1 h after intravenous injection. The mean lung-to-plasma concentration ratios of baicalin and oroxyloside were 287.6 and 49.9 times higher than with intravenous administration. Inhaled TRQ achieved the same effect against lipopolysaccharide-induced lung inflammation in mice at doses of only 1/16–1/8 of those administered intravenously. The results indicate that TRQ inhalation is a promising alternative to intravenous injections for the treatment of respiratory infection.
Ganoderma lucidum: Unutilized natural medicine and promising future solution to emerging diseases in Africa
Authors: Oke M. A. , Afolabi F. J. , Oyeleke O. O. , Kilani T. A. , Adeosun A. R. , Olanbiwoninu A. A. , Adebayo E. A.
Published: August 2022

Ganoderma lucidum is a well-known medicinal mushroom that has been used for the prevention and treatment of different ailments to enhance longevity and health specifically in China, Japan, and Korea. It was known as “God’s herb” in ancient China as it was believed to prolong life, enhance the youthful spirit and sustain/preserve vitality. G. lucidum is seldom collected from nature and is substantially cultivated on wood logs and sawdust in plastic bags or bottles to meet the international market demand. Both in vitro and in vivo studies on the copious metabolic activities of G. lucidum have been carried out. Varied groups of chemical compounds including triterpenoids, polysaccharides, proteins, amino acids, nucleosides, alkaloids, steroids, lactones, lectins, fatty acids, and enzymes with potent pharmacological activities have been isolated from the mycelia and fruiting bodies of G. lucidum. Several researchers have reported the abundance and diversification of its biological actions triggered by these chemical compounds. Triterpenoids and polysaccharides of G. lucidum have been reported to possess cytotoxic, hepatoprotective, antihypertensive, hypocholesterolemic, antihistaminic effects, antioxidant, antimicrobial, anti-inflammatory, hypoglycemic antiallergic, neuroprotective, antitumor, immunomodulatory and antiangiogenic activities. Various formulations have been developed, patented, and utilized as nutraceuticals, cosmeceuticals, and pharmaceuticals from G. lucidum extracts and active compounds. Thus, this review presents current updates on emerging infectious diseases and highlights the scope, dynamics, and advances in infectious disease management with a particular focus on Ganoderma lucidum, an unutilized natural medicine as a promising future solution to emerging diseases in Africa. However, details such as the chemical compound and mode of action of each bioactive against different emerging diseases were not discussed in this study.
Link of sorafenib resistance with the tumor microenvironment in hepatocellular carcinoma: Mechanistic insights
Authors: Tian Xinchen , Yan Tinghao , Liu Fen , Liu Qingbin , Zhao Jing , Xiong Huabao , Jiang Shulong
Published: August 2022

Sorafenib, a multi-kinase inhibitor with antiangiogenic, antiproliferative, and proapoptotic properties, is the first-line treatment for patients with late-stage hepatocellular carcinoma (HCC). However, the therapeutic effect remains limited due to sorafenib resistance. Only about 30% of HCC patients respond well to the treatment, and the resistance almost inevitably happens within 6 months. Thus, it is critical to elucidate the underlying mechanisms and identify effective approaches to improve the therapeutic outcome. According to recent studies, tumor microenvironment (TME) and immune escape play critical roles in tumor occurrence, metastasis and anti-cancer drug resistance. The relevant mechanisms were focusing on hypoxia, tumor-associated immune-suppressive cells, and immunosuppressive molecules. In this review, we focus on sorafenib resistance and its relationship with liver cancer immune microenvironment, highlighting the importance of breaking sorafenib resistance in HCC.
Analyzing rotational bands in odd-mass nuclei using effective field theory and Bayesian methods
Authors: Alnamlah I. K. , Coello Pérez E. A. , Phillips D. R.
Published: August 2022

We recently developed an Effective Field Theory (EFT) for rotational bands in odd-mass nuclei. Here we use EFT expressions to perform a Bayesian analysis of data on the rotational energy levels of 99Tc, 155,157Gd, 159Dy, 167,169Er, 167,169Tm, 183W, 235U and 239Pu. The error model in our Bayesian analysis includes both experimental and EFT truncation uncertainties. It also accounts for the fact that low-energy constants (LECs) at even and odd orders are expected to have different sizes. We use Markov Chain Monte Carlo (MCMC) sampling to explore the joint posterior of the EFT and error-model parameters and show both the LECs and the breakdown scale can be reliably determined. We extract the LECs up to fourth order in the EFT and find that, provided we correctly account for EFT truncation errors in our likelihood, results for lower-order LECs are stable as we go to higher orders. LEC results are also stable with respect to the addition of higher-energy data. We extract the expansion parameter for all the nuclei listed above and find a clear correlation between the extracted and the expected value of the inverse breakdown scale, W, based on the single-particle and vibrational energy scales. However, the W that actually determines the convergence of the EFT expansion is markedly smaller than would be naively expected based on those scales.
Performance analysis of repeater spoofing suppression based on GNSS multi-beam receiver
Authors: Ren Binbin , Chen Feiqiang , Ni Shaojie , Han Chunyang , Lu Zukun , Han Shujian
Published: August 2022

In order to analyze the anti-spoofing performance of the Global Navigation Satellite System (GNSS) multi-beam anti-jamming receiver in the presence of direct repeater spoofing, this paper deduces the theoretical formulas of the output real signal and the direct repeater spoofing signal power of the multi-beam anti-jamming receiver using the minimum variance distortionless response (MVDR) algorithm, when the number of snapshots is limited. The influence of the power of the spoofing signal reaching the surface of the antenna array on the output power of the real signal and the spoofing signal is analyzed in detail. The analysis shows that no matter how the power of the direct repeater spoofing signal is set, the multi-beam anti-jamming receiver using the MVDR algorithm can always suppress the spoofing below the real signal power level, and the suppression effect is more significant when the spoofing signal-to-noise ratio is high. Finally, the correctness of the conclusion is verified by simulation.
Psychophysiological Responses of Exercise Distribution During High Intensity Interval Training Using Whole Body Exercise
Authors: Machado Alexandre F. , Zovico Paulo Vinicios Camuzi , Evangelista Alexandre L. , Rica Roberta L. , Miranda João Marcelo de Q. , Alberton Cristine Lima , Bullo Valentina , Gobbo Stefano , Bergamin Marco , Baker Julien S. , Bocalini Danilo S.
Published: August 2022

The time-efficient nature of HIIT using bodyweight exercises can facilitate the application of exercise programs at home by encouraging more people to perform regular physical exercise. However, there are no studies investigating the influence of the distribution/order of exercises during HIIT training sessions using this method. The aim of the present study was to evaluate the effects of different exercise orders on training load indicators during HIIT sessions using body weight. Twenty male participants performed three 20-min sessions of HIIT using whole body exercise, consisting of 20 sets with 30 s of activity performed at maximal intensity, followed by 30 s of passive recovery. Three designs of exercise protocols were randomly performed according to the following exercise distribution: A: jumping jack, burpee, mountain climb and squat jump); B: jumping jack, mountain climb, burpee, and squat jump) and C: burpee, squat jump, jumping jack and mountain climb. No differences were found between protocols for relative heart rate, perceived exertion, and lactate concentrations. Significant differences (p < 0.001) were found for the number of movements (A:712 ± 59, B:524 ± 49, C:452 ± 65). No differences were observed for the area under curve when examining perceived exertion between protocols. However, the values for perceived recovery significantly differed (p < 0.001) between protocols (A:64 ± 19; B:52 ± 11; C:17 ± 13). Interestingly, protocol B and C induced a displeasure perception compared to protocol A. Our findings suggest that exercise distribution/order using HIIT whole body exercise promotes alterations in psychophysiological responses in HIIT using whole body exercises.
Expression and functional analysis of CsA-IPT5 splice variants during shoot branching in Camellia sinensis
Authors: Zhang Liping , Wang Donghui , Zhang Lan , Fu Jianyu , Yan Peng , Ge Shibei , Li Zhengzhen , Ahammed Golam Jalal , Han Wenyan , Li Xin
Published: August 2022

Alternative splicing (AS) is a process by which several functional splice variants are generated from the same precursor mRNA. In our recent study, five CsA-IPT5 splice variants with various numbers of ATTTA motifs in the untranslated regions (UTRs) were cloned. Meanwhile, their transient expression, as well as the expression and functional analysis in the two shoot branching processes were studied. Here, we examined how these splice variants regulate the other three important shoot branching processes, including the spring tea development, the distal branching of new shoots, and the shoot branching induced by 2,3,5-triiodobenzoic acid (TIBA) spraying, and thus unraveling the key CsA-IPT5 transcripts which play the most important roles in the shoot branching of tea plants. The results showed that the increased expression of 5′ UTR AS3, 3′ UTR AS1 and 3′ UTR AS2 could contribute to the increased synthesis of tZ/iP-type cytokinins (CKs), thus promoting the spring tea development. Meanwhile, in the TIBA-induced shoot branching or in the distal branching of the new shoots, CsA-IPT5 transcripts regulated the synthesis of CsA-IPT5 protein and CKs through transcriptional regulation of the ratios of its splice variants. Moreover, 3′ UTR AS1 and 3′ UTR AS2 both play key roles in these two processes. In summary, it is revealed that 3′ UTR AS1 and 3′ UTR AS2 of CsA-IPT5 might act as the predominant splice variants in shoot branching of the tea plant, and they both can serve as gene resources for tea plant breeding.
Barriers general education teachers face regarding the inclusion of students with autism
Authors: Al Jaffal Mohammed
Published: August 2022

As the number of students diagnosed with autism spectrum disorder (ASD) present in general education (GE) classrooms has increased in the past few decades, GE teachers must adapt to meet the needs of these students. Laws and regulations require students with ASD to be educated in the least restrictive environment, as well as that they be instructed by the teachers who were qualified to teach them. Unfortunately, GE teachers face the challenges supporting students with ASD in GE settings. This qualitative research investigates the barriers that prevent teachers from successfully implementing an inclusive environment in the GE classroom. In total, four elementary school teachers at a school in the northeast of the United States were interviewed and observed. The data were analyzed to identify emerging themes. The findings showed that GE teachers lack training in how to work with students with ASD in their GE classrooms, lack collaboration opportunities with their special education colleagues to better support their students with ASD, and are not provided sufficient resources by their schools and programs to create an appropriate inclusive environment in their GE classrooms. Based on these findings, certain improvements in professional development offerings for in-service general educators on how to teach students with ASD are recommended, such as providing broader training programs that give teachers the opportunity to practice interventions and teaching plans for inclusive classrooms and receive feedback from the training instructor(s). Furthermore, certain additions to the curriculum of pre-service university education programs for GE teachers are suggested. In addition, the research found that schools must make certain resources, including technology, available to GE teachers to meet the requirements of United States law regarding educating students with disabilities, including ASD, in the least restrictive environment, which is the GE classroom.
Small number enumeration processes of deaf or hard-of-hearing students: A study using eye tracking and artificial intelligence
Authors: Schindler Maike , Doderer Jan H. , Simon Anna L. , Schaffernicht Erik , Lilienthal Achim J. , Schäfer Karolin
Published: August 2022

Students who are deaf or hard-of-hearing (DHH) often show significant difficulties in learning mathematics. Previous studies have reported that students who are DHH lag several years behind in their mathematical development compared to hearing students. As possible reasons, limited learning opportunities due to a lesser incidental exposure to numerical ideas, delays in language and speech development, and further idiosyncratic difficulties of students who are DHH are discussed; however, early mathematical skills and their role in mathematical difficulties of students who are DHH are not explored sufficiently. In this study, we investigate whether students who are DHH differ from hearing students in their ability to enumerate small sets (1–9)—an ability that is associated with mathematical difficulties and their emergence. Based on a study with N = 63 who are DHH and N = 164 hearing students from third to fifth grade attempting 36 tasks, we used eye tracking, the recording of students' eye movements, to qualitatively investigate student enumeration processes. To reduce the effort of qualitative analysis of around 8,000 student enumeration processes (227 students x 36 tasks), we used Artificial Intelligence, in particular, a clustering algorithm, to identify student enumeration processes from the heatmaps of student gaze distributions. Based on the clustering, we found that gaze distributions of students who are DHH and students with normal hearing differed significantly on a group level, indicating differences in enumeration processes, with students who are DHH using advantageous processes (e.g., enumeration “at a glance”) more often than hearing students. The results indicate that students who are DHH do not lag behind in small number enumeration as compared to hearing students but, rather, appear to perform better than their hearing peers in small number enumeration processes, as well as when conceptual knowledge about the part-whole relationship is involved. Our study suggests that the mathematical difficulties of students who are DHH are not related to difficulties in the small number enumeration, which offers interesting perspectives for further research.
Impact of abusive leader behavior on employee job insecurity: A mediating roles of emotional exhaustion and abusive peer behavior
Authors: Li Miao , Ahmed Ammar , Syed Obed Rashdi , Khalid Nadeem , Muñoz José E.
Published: August 2022

Based on the social exchange theory, the present study aimed to investigate the association between abusive leader behavior and job insecurity while considering the serial intervention of abusive peer behavior and emotional exhaustion. Abusive leader behavior triggers abusive peer behaviors, emotional exhaustion, and job insecurity. Results from the data of 323 final responses indicated support for all the hypothesized relationships. Moreover, the findings also reported sequential mediation of abusive peer behavior and emotional exhaustion in the association between abusive leader behavior and job insecurity. The results indicate that mistreatment by an immediate boss can encourage peers to engage in similar unethical behaviors, leading to employees feeling emotionally exhausted, which ultimately results in job insecurity concerns. The study hopes that the findings will help practitioners dedicate more efforts to curtailing abusive behaviors that lead to several unintended consequences at work.
Perspectives of transformative learning and professional agency: A native Chinese language teacher’s story of teacher identity transformation in Australia
Authors: Yang Suling , Han Jinghe
Published: August 2022

The notion of teacher identity has gained momentum in second language (L2) teacher education in the past decade. However, the research into Chinese as a Foreign Language (CFL) teacher identity has yet to receive more attention. The study employed a narrative inquiry to explore a native Chinese CFL in-service teacher’s identity negotiation and transformation within an international teacher education program. Self-reported narrative accounts, including multiple in-depth interviews and once-a-term reflective journals, were complemented by field notes and program documents. This data captured how the participant teacher negotiated internally with self and externally with the new environment to pursue professional growth. Mezirow’s transformative learning theory was used to reveal the cognitive trajectory of the participant’s teacher identity transformation with critical reflection as the central stage. Further, guided by Eteläpelto et al.’s framework of professional agency, the study also unraveled multiple external and internal influences on the transformational trajectory. The findings confirmed the value of integrating these two theoretical perspectives to explore language teacher identity development and offer insights into L2 teacher education practices focusing on teacher identity development.
Time estimation and passage of time judgment predict eating behaviors during COVID-19 lockdown
Authors: Isham Eve A. , Lomayesva Sara , Teng Jiaxuan
Published: August 2022

Poor eating habits often lead to health concerns. While mental health conditions such as stress and anxiety have been linked as predictors for eating behaviors, cognitive factors may also contribute to eating practices during the early stages of the mandatory COVID-19 lockdown. In the current study, participants responded to a survey that asked them to judge the passing of time (PoTJ) and to produce short intervals (via a time production task) as an index of the internal clock speed. Additionally, they responded to questions about snacking frequency and the tendency to overeat during lockdown. We observed that those who judged time to pass slowly also reported a greater tendency to snack and overeat during the pandemic. Additional analysis also revealed that the effect of PoTJ on snacking is moderated by the internal clock speed such that those who felt time was passing by slowly, and in combination with a faster internal clock (as indexed by shorter duration production), had a greater tendency to snack. The results suggest that different aspects of temporal cognition play potential roles in influencing different types of eating behaviors. Our findings therefore have implications for eating disorders, along with the potential of time-based intervention or behavioral modification approaches.