bluuebunny/crossref_metadata_2025 huggingface dataset:
A new classification network for diagnosing Alzheimer's disease in class-imbalance MRI datasets
Authors: Chen Ziyang , Wang Zhuowei , Zhao Meng , Zhao Qin , Liang Xuehu , Li Jiajian , Song Xiaoyu
Published: August 2022

Automatic identification of Alzheimer's Disease (AD) through magnetic resonance imaging (MRI) data can effectively assist to doctors diagnose and treat Alzheimer's. Current methods improve the accuracy of AD recognition, but they are insufficient to address the challenge of small interclass and large intraclass differences. Some studies attempt to embed patch-level structure in neural networks which enhance pathologic details, but the enormous size and time complexity render these methods unfavorable. Furthermore, several self-attention mechanisms fail to provide contextual information to represent discriminative regions, which limits the performance of these classifiers. In addition, the current loss function is adversely affected by outliers of class imbalance and may fall into local optimal values. Therefore, we propose a 3D Residual RepVGG Attention network (ResRepANet) stacked with several lightweight blocks to identify the MRI of brain disease, which can also trade off accuracy and flexibility. Specifically, we propose a Non-local Context Spatial Attention block (NCSA) and embed it in our proposed ResRepANet, which aggregates global contextual information in spatial features to improve semantic relevance in discriminative regions. In addition, in order to reduce the influence of outliers, we propose a Gradient Density Multiple-weighting Mechanism (GDMM) to automatically adjust the weights of each MRI image via a normalizing gradient norm. Experiments are conducted on datasets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Australian Imaging, Biomarker and Lifestyle Flagship Study of Aging (AIBL). Experiments on both datasets show that the accuracy, sensitivity, specificity, and Area Under the Curve are consistently better than for state-of-the-art methods.
Neuronal cell death mechanisms in Alzheimer’s disease: An insight
Authors: Goel Parul , Chakrabarti Sasanka , Goel Kapil , Bhutani Karanpreet , Chopra Tanya , Bali Sharadendu
Published: August 2022

Regulated cell death (RCD) is an ordered and tightly orchestrated set of changes/signaling events in both gene expression and protein activity and is responsible for normal development as well as maintenance of tissue homeostasis. Aberrant activation of this pathway results in cell death by various mechanisms including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death. Such pathological changes in neurons alone or in combination have been observed in the pathogenesis of various neurodegenerative diseases including Alzheimer’s disease (AD). Pathological hallmarks of AD focus primarily on the accumulation of two main protein markers: amyloid β peptides and abnormally phosphorylated tau proteins. These protein aggregates result in the formation of A-β plaques and neuro-fibrillary tangles (NFTs) and induce neuroinflammation and neurodegeneration over years to decades leading to a multitude of cognitive and behavioral deficits. Autopsy findings of AD reveal massive neuronal death manifested in the form of cortical volume shrinkage, reduction in sizes of gyri to up to 50% and an increase in the sizes of sulci. Multiple forms of cell death have been recorded in neurons from different studies conducted so far. However, understanding the mechanism/s of neuronal cell death in AD patients remains a mystery as the trigger that results in aberrant activation of RCD is unknown and because of the limited availability of dying neurons. This review attempts to elucidate the process of Regulated cell death, how it gets unregulated in response to different intra and extracellular stressors, various forms of unregulated cell death, their interplay and their role in pathogenesis of Alzheimer’s Disease in both human and experimental models of AD. Further we plan to explore the correlation of both amyloid-beta and Tau with neuronal loss as seen in AD.
Emerging evidence of genotype–phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405G
Authors: Wang Sumei , Yu Yejing , Wang Xu , Deng Xiaolong , Ma Jiehui , Liu Zhisheng , Gu Weiyue , Sun Dan
Published: August 2022

Developmental and epileptic encephalopathies (DEEs) have high genetic heterogeneity, and DEE due to the potassium voltage-gated channel subfamily C member 2 (KCNC2) variant remains poorly understood, given the scarcity of related case studies. We report on two unrelated Chinese patients, an 11-year-old boy and a 5-year-old girl, diagnosed with global developmental delay (GDD), intellectual disability (ID), and focal impaired awareness seizure characterized by generalized spike and wave complexes on electroencephalogram (EEG) in the absence of significant brain lesions. Whole-exome sequencing (WES) and electrophysiological analysis were performed to detect genetic variants and evaluate functional changes of the mutant KCNC2, respectively. Importantly, we identified a novel gain-of-function KCNC2 variant, R405G, in both patients. Previously reported variants, V471L, R351K, T437A, and T437N, and novel R405G were found in multiple unrelated patients with DEE, showing consistent genotype–phenotype associations. These findings emphasize that the KCNC2 gene is causative for DEE and facilitates treatment and prognosis in patients with DEE due to KCNC2 mutations.
Assessment of the bifidogenic and antibacterial activities of xylooligosaccharide
Authors: Sun Zhongke , Yue Zonghao , Liu Erting , Li Xianfeng , Li Chengwei
Published: August 2022

Xylooligosaccharide (XOS) is an attractive prebiotic mainly due to its bifidogenic effect. However, commercial XOS with different compositions is often applied in the food industry at different doses without specifications. In this study, we evaluated the bifidogenic activity of XOS at different doses with either mixtures or pure fractions with different degrees of polymerization (DP), using three strains of Bifidobacterium spp., including B. breve ATCC 15700, B. bifidum ATCC 29521, and B. animalis subsp. lactis HN019. Three growth indicators showed strain-specific bifidogenic activity of XOS, and the activity was both dose- and fraction-dependent as only certain fractions stimulated significant growth. Adding 0.25% XOS (w/v) also promoted increase in total bifidobacterial population of rat fecal samples fermented in vitro. Albeit the antibacterial activity of XOS fractions can be demonstrated, significant growth inhibition can only be achieved when 4.0% XOS mixture was added in Staphylococcus aureus ATCC 6538 pure culture. In contrast, in the presence of B. lactis HN019, 1.0% XOS showed significant antibacterial activity against S. aureus ATCC 6538 in milk. In addition, RNA sequencing suggested downregulation of genes involved in S. aureus ATCC 6538 infection, pathogenesis, and quorum sensing, by XOS. In conclusion, the report urges scientific specifications on XOS chemistry for its effective application as a novel food ingredient or functional food and provides novel insights into its bifidogenic and antibacterial activities.
The Body Adiposity Index is not applicable to the Brazilian adult population
Authors: Ribeiro da Costa José Ronaldo , Costa Roberto Fernandes da , Goncalves Ciro Alexandre Mercês , de Oliveira Borges Michelle Vasconcelos , Almeida-Neto Paulo Francisco De , De Assis Gilmara Gomes , Cabral Breno Guilherme De Araujo Tinoco , Dantas Paulo Moreira Silva
Published: August 2022

Background

Obesity is a serious disease that burdens public health systems around the world. It is a risk factor for the development of several non-communicable chronic diseases that are related to the amount and distribution of body fat. Body composition assessment using simple and low-cost techniques can help in the early detection of excess fat, allowing for the prevention and treatment of both obesity and associated diseases. Thus, identifying and proposing valid anthropometric indices for this purpose can be a great ally of health programs.

Objective

To verify the validity of the Body Adiposity Index (BAI) in relation to Dual Energy X-Ray Absorptiometry (DXA) for estimating body fat percentage in Brazilian adults, as well as to propose a new mathematical model to estimate the fat-free mass of this population.

Methods

In a cross-sectional study, 424 subjects (of which 220 were women), aged between 20 and 59 years, were evaluated by BAI and DXA, then randomly divided into two groups stratified by sex: the development group (n = 283) and the cross-validation group (n = 141). Statistical analyses to test the validity of BAI as a predictor of fat mass, in addition to proposing a new mathematical model for estimating fat-free mass, using DXA as a reference method. The analysis included paired t-test, stepwise multiple regression, coefficient of concordance correlation, and Bland-Altman plots.

Results

The BAI validity analysis showed a low correlation coefficient of agreement [CCC = 0.626; ρ (precision) = 0.795; Cb(accuracy) = 0.787]; in addition, the mean difference in the Bland-Altman plot was different from zero in the cross-validation group (p < 0.01) and limits of agreement (LOA) ranged between−8.0 and 14.4 kg, indicating a poor agreement between the BAI and the reference method. The new mathematical model for estimating FFM showed a high correlation coefficient of agreement (CCC = 0.952; ρ = 0.953; Cb = 0.999), in addition to acceptable LOA in the Bland-Altman plot (-6.7 and 6.7).

Conclusion

In the studied sample, the BAI showed low validity for estimating body fat, while the new proposed model was found to be a good option to assess the body composition of Brazilian adults.
Advances in endoscopic resection techniques of small gastric tumors originating from the muscularis propria
Authors: Khan Suliman , Cui Xiaona , Nasir Safyan , Rafiq Shoaib Mohammad , Qin Bo , Bai Qian
Published: August 2022

Gastrointestinal stromal tumors are common gastrointestinal tumors typically originating from the muscularis propria layer of the stomach. Small gastric stromal tumors are usually detected incidentally during routine endoscopic examination. Although they may have malignant potentially, controversies remain regarding the need for endoscopic resection of small gastric stromal tumors originating from the muscularis propria. According to the guidelines of the European Society of Medical Oncology, all gastrointestinal stromal tumors >2 cm in size should be resected with endoscopic surveillance recommended for tumors <2 cm. Endoscopic resection including endoscopic mucosal dissection (EMD), endoscopic submucosal dissection (ESD), submucosal tunneling endoscopic resection and snare assisted endoscopic resection. However, EMD and ESD procedures may be accompanied with serious complications including perforation, bleeding, and abdominal infection. Snare-assisted endoscopic resection is an alternative approach and has the advantages of a shorter procedure time and a low rate of perforation or bleeding. This study summarizes the safety and feasibility of a novel snare-assisted endoscopic resection technique and highlights the pros and cons of the different endoscopic approaches currently used for subepithelia small gastric tumors.
Based on clinical Ki-67 expression and serum infiltrating lymphocytes related nomogram for predicting the diagnosis of glioma-grading
Authors: Zhang Zhi , Gu Weiguo , Hu Mingbin , Zhang Guohua , Yu Feng , Xu Jinbiao , Deng Jianxiong , Xu Linlin , Mei Jinhong , Wang Chunliang , Qiu Feng
Published: August 2022

Background

Compelling evidence indicates that elevated peripheral serum lymphocytes are associated with a favorable prognosis in various cancers. However, the association between serum lymphocytes and glioma is contradictory. In this study, a nomogram was established to predict the diagnosis of glioma-grading through Ki-67 expression and serum lymphocytes.

Methods

We performed a retrospective analysis of 239 patients diagnosed with LGG and 178 patients with HGG. Immunohistochemistry was used to determine the Ki-67 expression. Following multivariate logistic regression analysis, a nomogram was established and used to identify the most related factors associated with HGG. The consistency index (C-index), decision curve analysis (DCA), and a calibration curve were used to validate the model.

Results

The number of LGG patients with more IDH1/2 mutations and 1p19q co-deletion was greater than that of HGG patients. The multivariate logistic analysis identified Ki-67 expression, serum lymphocyte count, and serum albumin (ALU) as independent risk factors associated with HGG, and these factors were included in a nomogram in the training cohort. In the validation cohort, the nomogram demonstrated good calibration and high consistency (C-index = 0.794). The Spearman correlation analysis revealed a significant association between HGG and serum lymphocyte count (r = −0.238, P <0.001), ALU (r = −0.232, P <0.001), and Ki-67 expression (r = 0.457, P <0.001). Furthermore, the Ki-67 expression was negatively correlated with the serum lymphocyte count (r = −0.244, P <0.05). LGG patients had lower Ki-67 expression and higher serum lymphocytes compared with HGG patients, and a combination of these two variables was significantly higher in HGG patients.

Conclusion

The constructed nomogram is capable of predicting the diagnosis of glioma-grade. A decrease in the level of serum lymphocyte count and increased Ki-67 expression in HGG patients indicate that their immunological function is diminished and the tumor is more aggressive.
Adjuvant chemotherapy is not a decisive factor in improving the overall survival of pulmonary sarcoma: A population-based study
Authors: Liang Long , Liu Zixuan , Wang Changhui , Xie Shuanshuan
Published: August 2022

Objective

This study aimed to investigate the impact of adjuvant chemotherapy on overall survival (OS) for pulmonary sarcomatoid carcinoma (PSC) and non-small-cell lung cancer (NSCLC) cohorts and to identify its potential risk factors.

Methods

A retrospective analysis was performed by querying the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed as having PSC (n=460) and NSCLC (n=140,467) from 2004 to 2015. The demographics, tumor characteristics, treatment modes, and survival were included in the scope of statistical analysis. Confounding factors were controlled by propensity score matching (PSM) analysis. Kaplan–Meier survival curves were performed to compare the effects of adjuvant chemotherapy on OS of the patients in the two cohorts (PSC vs. NSCLC). A multivariable Cox regression model was constructed, and Kaplan–Meier analysis on each variate was applied to predict risk factors associated with OS.

Results

When adjuvant chemotherapy approach was applied in the treatment of patients with PSC or adjusted NSCLC, respectively, an improved OS could be observed in the NSCLC cohort (p=0.017). For the entire PSC cohort, 1-, 3-, and 5-year OS were 25.43%, 13.04%, and 6.96%, respectively, compared with 41.96%, 17.39%, and 10.00%, respectively, for the new adjusted NSCLC cohort after PSM, which were statistically significant difference (p<0.001). Multivariable Cox regression analysis was performed on OS covering prognostic factors such as primary site (p=0.036), first malignant indicator (p<0.001), age at diagnosis (p<0.001), marital status at diagnosis (p=0.039), and high school education (p=0.045). Additionally, patients with the following parameters had the worse impact on OS: a poorly differentiated pathology (Grade III/IV, p=0.023), older age (p<0.001), liver or lung metastasis (p=0.004, p=0.029), and the number of lymph nodes removed <4 (p<0.001).

Conclusions

Adjuvant chemotherapy did not play a decisive role in improving the OS of PSC, while it was associated with improved OS of NSCLC.
SimRFlow: An R-based workflow for automated high-throughput PBPK simulation with the Simcyp® simulator
Authors: Khalidi Hiba , Onasanwo Anthonia , Islam Barira , Jo Heeseung , Fisher Ciarán , Aidley Rich , Gardner Iain , Bois Frederic Y.
Published: August 2022

SimRFlow is a high-throughput physiologically based pharmacokinetic (PBPK) modelling tool which uses Certara’s Simcyp® simulator. The workflow is comprised of three main modules: 1) a Data Collection module for automated curation of physicochemical (from ChEMBL and the Norman Suspect List databases) and experimental data (i.e.: clearance, plasma-protein binding, and blood-to-plasma ratio, from httk-R package databases), 2) a Simulation module which activates the Simcyp® simulator and runs Monte Carlo simulations on virtual subjects using the curated data, and 3) a Data Visualisation module for understanding the simulated compound-specific profiles and predictions. SimRFlow has three administration routes (oral, intravenous, dermal) and allows users to change some simulation parameters including the number of subjects, simulation duration, and dosing. Users are only expected to provide a file of the compounds they wish to simulate, and in return the workflow provides summary statistics, concentration-time profiles of various tissue types, and a database file (containing in-depth results) for each simulated compound. This is presented within a guided and easy-to-use R Shiny interface which provides many plotting options for the visualisation of concentration-time profiles, parameter distributions, trends between the different parameters, as well as comparison of predicted parameters across all batch-simulated compounds. The in-built R functions can be assembled in user-customised scripts which allows for the modification of the workflow for different purposes. SimRFlow proves to be a time-efficient tool for simulating a large number of compounds without any manual curation of physicochemical or experimental data necessary to run Simcyp® simulations.
Emerging role of different DNA methyltransferases in the pathogenesis of cancer
Authors: Liu Pengcheng , Yang Fan , Zhang Lizhi , Hu Ying , Chen Bangjie , Wang Jianpeng , Su Lei , Wu Mingyue , Chen Wenjian
Published: August 2022

DNA methylation is one of the most essential epigenetic mechanisms to regulate gene expression. DNA methyltransferases (DNMTs) play a vital role in DNA methylation in the genome. In mammals, DNMTs act with some elements to regulate the dynamic DNA methylation patterns of embryonic and adult cells. Conversely, the aberrant function of DNMTs is frequently the hallmark in judging cancer, including total hypomethylation and partial hypermethylation of tumor suppressor genes (TSGs), which improve the malignancy of tumors, aggravate the ailment for patients, and significantly exacerbate the difficulty of cancer therapy. Since DNA methylation is reversible, currently, DNMTs are viewed as an important epigenetic target for drug development. However, the impression of DNMTs on cancers is still controversial, and therapeutic methods targeting DNMTs remain under exploration. This review mainly summarizes the relationship between the main DNMTs and cancers as well as regulatory mechanisms and clinical applications of DNMTs in cancer and highlights several forthcoming strategies for targeting DNMTs.
How zoledronic acid improves osteoporosis by acting on osteoclasts
Authors: Wang Biao , Zhan Yi , Yan Liang , Hao Dingjun
Published: August 2022

Osteoporosis is called a silent disease, because it is difficult to detect until comprehensive examinations for osteoporosis are performed or osteoporotic fractures occur. Zoledronic acid is currently the first-line anti-osteoporotic drug, with good efficacy and treatment compliance. A major advantage of zoledronic acid is that intravenous zoledronic acid often guarantees a therapeutic effect for up to 1 year after infusion. The reasons why zoledronic acid is effective in improving osteoporosis are that it can inhibit osteoclast differentiation and induce osteoclast apoptosis, thus suppressing bone resorption and increasing bone density. The story between zoledronic acid and osteoclasts has been written long time ago. Both the canonical receptor activator of the receptor activator of nuclear factor-κB ligand (RANKL) pathway and the non-canonical Wnt pathway are the main pathways by which zoledronic acid inhibits osteoclast differentiation. Farnesyl pyrophosphate synthase (FPPS), reactive oxygen species (ROS), and ferroptosis that was first proposed in 2012, are all considered to be closely associated with zoledronic acid-induced osteoclast apoptosis. Here, we provide a brief review of the recent progress on the study of zoledronic acid and osteoclasts, and hope to elaborate how zoledronic acid improves osteoporosis by acting on osteoclasts.
Honokiol improves depression-like behaviors in rats by HIF-1α- VEGF signaling pathway activation
Authors: Fan Xiao-Xu , Sun Wen-Yan , Li Yu , Tang Qin , Li Li-Na , Yu Xue , Wang Shu-Yan , Fan Ang-Ran , Xu Xiang-Qing , Chang Hong-Sheng
Published: August 2022

Increasing evidence indicates that the pathogenesis of depression is closely linked to impairments in neuronal synaptic plasticity. Honokiol, a biologically active substance extracted from Magnolia Officinalis, has been proven to exert significant antidepressant effects. However, the specific mechanism of action remains unclear. In this study, PC12 cells and chronic unpredictable mild stress (CUMS) model rats were used to explore the antidepressant effects and potential mechanisms of honokiol in vitro and in rats. In vitro experiment, a cell viability detection kit was used to screen the concentration and time of honokiol administration. PC12 cells were administered with hypoxia-inducible factor-1α (HIF-1α) blocker, 2-methoxyestradiol (2-ME), and vascular endothelial growth factor receptor 2 (VEGFR-2) blocker, SU5416, to detect the expression of HIF-1α, VEGF, synaptic protein 1 (SYN 1), and postsynaptic density protein 95 (PSD 95) by western blotting. In effect, we investigated whether the synaptic plasticity action of honokiol was dependent on the HIF-1α-VEGF pathway. In vivo, behavioral tests were used to evaluate the reproducibility of the CUMS depression model and depression-like behaviors. Molecular biology techniques were used to examine mRNA and protein expression of the HIF-1α-VEGF signaling pathway and synaptic plasticity-related regulators. Additionally, molecular docking techniques were used to study the interaction between honokiol and target proteins, and predict their binding patterns and affinities. Experimental results showed that honokiol significantly reversed CUMS-induced depression-like behaviors. Mechanically, honokiol exerted a significant antidepressant effect by enhancing synaptic plasticity. At the molecular level, honokiol can activate the HIF-1α-VEGF signaling pathway in vitro and in vivo, as well as promote the protein expression levels of SYN 1 and PSD 95. Taken together, the results do not only provide an experimental basis for honokiol in the clinical treatment of depression but also suggest that the HIF-1α-VEGF pathway may be a potential target for the treatment of depression.
Effects of Piper sarmentosum Roxb. on hypertension and diabetes mellitus: A systematic review and meta-analysis
Authors: Othman Nur Syakirah , Che Roos Nur Aishah , Aminuddin Amilia , Murthy Jaya Kumar , A. Hamid Adila , Ugusman Azizah
Published: August 2022

Hypertension and diabetes mellitus are among the most prevalent diseases affecting people from all walks of life. Medicinal herbs have garnered interest as potential agents for the prevention and treatment of diabetes mellitus and hypertension due to their multiple beneficial effects.Piper sarmentosumRoxb. (PS) is an edible medicinal plant that has been traditionally used in Asia for treating hypertension and diabetes mellitus. This review is aimed to provide comprehensive information from the literature on the effects of PS on hypertension and diabetes mellitus. A computerized database search was performed on Scopus, PubMed and Web of Science databases with the following set of keywords: Piper sarmentosum AND diabetes mellitus OR diabetic OR diabetes OR hyperglyc*emia OR blood glucose OR HbA1c OR glycated h*emoglobin OR h*emoglobin A1c OR hyperten* OR blood pressure. A total of 47 articles were screened and 14 articles published between the years 1998 until 2021 were included for data extraction, comprising of six articles on antihypertensive and eight articles on antidiabetic effects of PS. These studies consist of twoin vitrostudies and elevenin vivoanimal studies. Meta-analysis of three studies on hypertension showed that PS versus no treatment significantly lowered the systolic blood pressure with mean difference (MD) −39.84 mmHg (95% confidence interval (CI) −45.05, −34.62; p < 0.01), diastolic blood pressure with MD −26.68 mmHg (95% CI −31.48, −21.88; p < 0.01), and mean arterial pressure with MD −30.56 mmHg (95% CI −34.49, −26.63; p < 0.01). Most of the studies revealed positive effects of PS against hypertension and diabetes mellitus, suggesting the potential of PS as a natural source of antidiabetic and antihypertensive agents.
Toxicological safety evaluation of Qin-Zhi-Zhu-Dan formula in rats during the treatment and recovery periods
Authors: Xu Wenxiu , Chen Dan , Zhang Zehan , Liu Shuling , Chen Congai , Sun Chunyan , Ni Wenchao , Kang Xiangdong , Shang Guojiao , Wang Xueqian , Cheng Fafeng , Wang Qingguo
Published: August 2022

Background: Qinzhi Zhudan Formula (QZZD), optimized from Angong Niuhuang Wan, consists of Radix Scutellariae, Fructus Gardeniae and Pulvis Fellis Suis. We had investigated the neuroprotective effects of QZZD and its active components, and demonstrated that it could treat cerebral ischemia and dementia through multiple pathways and mechanisms. Nevertheless, toxicological data on this formula still remains limited. In the study, we sought to examine the toxicological effects of QZZD during the treatment and recovery periods.

Methods: We investigated potential toxicities of QZZD in Sprague-Dawley (SD) rats via 28-day gavage administration. SD rats were randomly divided into control group and treatment groups of A (0.5 g/kg/d QZZD), B (1.5 g/kg/d QZZD), and C (5.0 g/kg/d QZZD). The 56-day course includes treatment period (administration with water or QZZD once a day for 28 consecutive days) and recovery period (28 days). The rats received daily monitoring of general signs of toxicity and mortality, as well as weekly determination of body weight and food consumption. Moreover, the complete blood cell count, biochemistry, coagulation, and urine indicators, organ weights, and histopathological report were analyzed respectively at the end of the treatment and recovery periods.

Results: There was no death related to the active pharmaceutical ingredients of QZZD during the treatment period. The maximum no observed adverse effect level (NOAEL) was 0.5 g/kg/d, which is approximately 16.7 times of the equivalent dose of clinical dose in rats. In group TB (1.5 g/kg/d QZZD) and TC (5.0 g/kg/d QZZD), there were adverse effects of blue coloring of tail skin, weight loss, a significant increase of total bilirubin (TBIL), blackening of liver and kidney in gross examination, hyperplasia of bile duct and karyomegaly of hepatocytes in histopathological examination. Besides, in females rats, the food consumption was reduced, while in male rats, there was decrease in triglycerides (TG) and slight increase in white blood cell (WBC) count and neutrophils. In group TC (5.0 g/kg/d QZZD), the indicators of red blood cell (RBC) count, hemoglobin (HGB) and hematocrit (HCT) were decreased slightly, while the platelet count (PLT) was increased. However, these changes were not considered to be toxicologically significant because they resolved during the recovery period.

Conclusion: Overall, QZZD exhibited a good safety profile. The maximum no observed adverse effect level was 0.5 g/kg/d, and no target organs toxicity were identified. The present findings might confirm the safety of QZZD in clinical practices.
Nonequilibrium thermal transport in the two-mode qubit-resonator system
Authors: Wang Fei-Yu , Lu Jin-Cheng , Wang Zi , Duan Li-Wei , Wang Chen , Ren Jie
Published: August 2022

Nonequilibrium thermal transport in circuit quantum electrodynamics emerges as one interdisciplinary field, due to the tremendous advance of quantum technology. Here, we study steady-state heat flow in a two-mode qubit-resonator model under the influence of both the qubit-resonator and resonator-resonator interactions. The heat current is suppressed and enhanced by tuning up resonator-resonator interaction strength with given weak and strong qubit-resonator couplings respectively, which is cooperative contributed by the eigen-mode of coupled resonators and qubit-photon scattering. Negative differential thermal conductance and significant thermal rectification are exhibited at weak qubit-resonator coupling, which are dominated by cycle transition processes. Moreover, the heat flow through the resonator decoupled from the qubit can be dramatically enhanced via the resonator-resonator interaction, which is attributed by the generation of eigen-mode channels of resonators.
Evaluation of therapeutic efficacy, safety and economy of ERCP and LTCBDE in the treatment of common bile duct stones
Authors: Zhang Renjie , Liu Jialin , Li Huizhen , Zeng Qingteng , Wu Shenfeng , Tian Hengyu
Published: August 2022

Objectives: This study further compared the endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic transcystic common bile duct exploration (LTCBDE) approaches in the treatment of common bile duct stones (CBDS) from the perspective of efficacy, safety and economy.

Methods: The therapeutic efficacy and safety of ERCP and LTCBDE approaches were retrospectively compared. Cost-effectiveness analysis of clinical economics was performed to analyze and evaluate the two approaches.

Results: There was no significant difference in the success rate of surgery and bile stone residue between ERCP and LTCBDE group. The incidence of postoperative complications in ERCP group was significantly higher than that in the LTCBDE group; while the incidence of pancreatitis in the ERCP group was significantly higher than that in the LTCBDE group. There was no significant difference in biliary infection, bile leakage and sepsis between ERCP and LTCBDE groups. In terms of cost, the costs of surgery and nursing were significantly lower, the costs of treatment and sanitary materials were significantly higher in the ERCP group than that in the LTCBDE group. There was no significant difference in the costs of medical examination, laboratory test, medicine cost and total cost between ERCP group and LTCBDE group. The total length of hospital stay, length of hospital stay before surgery and duration of surgery in the ERCP group were significantly lower than that in the LTCBDE group; there was no significant difference in length of hospital stay after surgery between the ERCP and LTCBDE group. The cost-effectiveness ratio of ERCP group was 34171.25, and the cost-effectiveness of LTCBDE group was 34524.25. The incremental cost-effectiveness ratio (ICER) of the two groups was 51415.

Conclusion: ERCP and LTCBDE approaches had similar therapeutic efficacy in the treatment of CBDS. The safety of LTCBDE approach is superior to that of ERCP approach for the treatment of CBDS. ERCP approach is more economical in the treatment of CBDS than LTCBDE approach.
Transcriptome response of proliferating muscle satellite cells to thermal challenge in commercial turkey
Authors: Reed Kent M. , Mendoza Kristelle M. , Strasburg Gale M. , Velleman Sandra G.
Published: August 2022

Thermal stress poses a threat to agricultural systems through increased risk to animal growth, health, and production. Exposure of poultry, especially hatchlings, to extreme temperatures can seriously affect muscle development and thus compromise subsequent meat quality. This study was designed to characterize transcriptional changes induced in turkey muscle satellite cells (SCs) cultured from commercial birds under thermal challenge to determine the applicability of previous results obtained for select research lines. Satellite cells isolated from the pectoralis major muscle of 1-week old commercial fast-growing birds (Nicholas turkey, NCT) and from a slower-growing research line (RBC2) were proliferated in culture at 38°C or 43°C for 72 h. RNAseq analysis found statistically significant differences in gene expression among treatments and between turkey lines with a greater number of genes altered in the NCT SCs suggesting early myogenesis. Pathway analysis identified cell signaling and regulation of Ca2+ as important responses. Expression of the intercellular signaling Wnt genes, particularly Wnt5a and 7a was significantly altered by temperature with differential response between lines. The peripheral calcium channel RYR3 gene was among the genes most highly upregulated by heat stress. Increased expression of RYR3 would likely result in higher resting cytosolic calcium levels and increased overall gene transcription. Although responses in the calcium signaling pathway were similar among the RBC2 and NCT lines, the magnitude of expression changes was greater in the commercially selected birds. These results provide evidence into how SC activity, cellular fate, and ultimately muscle development are altered by heat stress and commercial selection.
Effects of an experimental short-time high-intensity warm-up on explosive muscle strength performance in soccer players: A pilot study
Authors: Patti Antonino , Giustino Valerio , Hirose Norikazu , Messina Giuseppe , Cataldi Stefania , Grigoli Giuseppe , Marchese Alida , Mulè Giuseppe , Drid Patrik , Palma Antonio , Bianco Antonino
Published: August 2022

Objective: This study aimed to evaluate the effects of an experimental short-time warm-up consisting of a small number of intermittent high-intensity sprints on explosive muscle strength performance in soccer players and to identify recovery times after performing the sprints. Furthermore, we evaluated the reliability of a smartphone app in jumping performance.

Methods: Twenty male soccer players were given the following tests: 1) the counter-movement jump (CMJ) test with the Microgate system, 2) the counter-movement jump (CMJ) test with the MyJump smartphone app, and 3) the handgrip strength test. The experimental short-time high-intensity warm-up was carried out 1 week after test administration. The warm-up consisted of three maximum sprints over 60 m with 120 s of recovery between sprints. Then, the tests were administered again: the vertical jump height (VJH) performances (five trials) were measured 90 s after the last sprint; the handgrip strength performances (three trials) were measured 120 s after the last vertical jump test.

Results: The maximum VJH was found in the third trial of the CMJ test, 330 s after the last sprint (p < 0.01), the result closest to the baseline. The lowest VJH was found in the first trial of the CMJ test, 90 s after the last sprint (p < 0.05). Pearson’s analysis between the CMJ test with the Microgate system and the CMJ test with MyJump showed a strong correlation (R = 0.96). Lin’s concordance correlation coefficient showed a substantial concordance (ρc = 0.959) between measures.

Conclusion: This experimental short-time warm-up of high-intensity intermittent sprints appears to be a simple, quick, and efficient activity to accelerate soccer players’ optimal performance.
Impact of foliar application of syringic acid on tomato (Solanum lycopersicum L.) under heavy metal stress-insights into nutrient uptake, redox homeostasis, oxidative stress, and antioxidant defense
Authors: Ma Jing , Saleem Muhammad Hamzah , Ali Baber , Rasheed Rizwan , Ashraf Muhammad Arslan , Aziz Humera , Ercisli Sezai , Riaz Sana , Elsharkawy Mohsen Mohamed , Hussain Iqbal , Alhag Sadeq K. , Ahmed Ahmed Ezzat , Vodnar Dan C. , Mumtaz Sahar , Marc Romina Alina
Published: August 2022

Soil contamination with toxic heavy metals [such as lead (Pb)] is becoming a serious global problem due to the rapid development of the social economy. However, accumulation of Pb in plant parts is very toxic for plant growth and decreases crop yield and productivity. In the present study, we have investigated the different concentrations of Pb in the soil i.e., [0 (no Pb), 50, and 100 mg kg–1] to study plant growth and biomass, photosynthetic pigments and gas exchange characteristics, oxidative stress indicators and the response of various antioxidants (enzymatic and non-enzymatic), nutritional status of the plant, organic acid exudation pattern and also Pb accumulation in the roots and shoots of the plants of two varieties of tomato (Solanum lycopersicumL.) i.e., Roma and Cchuas, grown under different levels of synergic acid [no spray (NS), water spray (WS), 0.3-0.5°μM]. Results from the present study showed that the increasing levels of Pb in the soil decreased non-significantly (P< 0.05) shoot length, root length, shoot fresh weight, root fresh weight, shoot dry weight, root dry weight, chlorophyll-a, chlorophyll-b, total chlorophyll, carotenoid content, net photosynthesis, stomatal conductance, transpiration rate, soluble sugar, reducing sugar, non-reducing sugar contents, calcium (Ca2+), magnesium (Mg2+), iron (Fe2+), and phosphorus (P) contents in the roots and shoots of the plants. However, Pb toxicity also induced oxidative stress in the roots and shoots of the plants by increasing malondialdehyde (MDA), hydrogen peroxide (H2O2), and electrolyte leakage (EL) which also induced increased the compounds of various enzymatic and non-enzymatic antioxidants and also organic acids exudation pattern in the roots such as fumaric acid, acetic acid, citric acid, formic acid, malic acid, oxalic acid contents and increased the concentration of Pb in different parts of the plants. Results also show that the Cchuas showed better growth and development compared to Roma, under the same levels of Pb in the soil. The alleviation of Pb toxicity was induced by the application of synergic acid, and results showed that the application of synergic acid increased plant growth and biomass and also increased the gas exchange characteristics and antioxidant capacity in the roots and shoots of the plants. Research findings, therefore, suggested that synergic acid application can ameliorate Pb toxicity inS. lycopersicumvarieties and result in improved plant growth and composition under metal stress as depicted by balanced exudation of organic acids.
Tartary buckwheat FtF3′H1 as a metabolic branch switch to increase anthocyanin content in transgenic plant
Authors: Li Chenglei , Yang Jingjing , Yang Kai , Wu Huala , Chen Hui , Wu Qi , Zhao Haixia
Published: August 2022

Tartary buckwheat (TB) is a pseudocereal rich in flavonoids, mainly including flavonols and anthocyanins. The flavonoid 3′-hydroxylase (F3′H) is a key enzyme in flavonoid biosynthesis and is encoded by two copies in TB genome. However, its biological function and effects on flavonol and anthocyanin synthesis in TB have not been well validated yet. In this study, we cloned the full-length FtF3′H1 gene highly expressed in all tissues (compared with FtF3′H2) according to TB flowering transcriptome data. The corresponding FtF3′H1 protein contains 534 amino acids with the molecular properties of the typical plant F3′H and belongs to the CYP75B family. During the flowering stage, the FtF3′H1 expression was highest in flowers, and its expression pattern showed a significant and positive correlation with the total flavonoids (R2 > 0.95). The overexpression of FtF3′H1 in Arabidopsis thaliana, Nicotiana tabacum and TB hairy roots resulted in a significant increase in anthocyanin contents (p < 0.05) but a decrease in rutin (p < 0.05). The average anthocyanin contents were 2.94 mg/g (fresh weight, FW) in A. thaliana (about 135% increase), 1.18 mg/g (FW) in tobacco (about 17% increase), and 1.56 mg/g (FW) TB hairy roots (about 44% increase), and the rutin contents were dropped to about 53.85, 14.99, 46.31%, respectively. However, the expression of genes involved in anthocyanin (DFRs and ANSs) and flavonol (FLSs) synthesis pathways were significantly upregulated (p < 0.05). In particular, the expression level of DFR, a key enzyme that enters the anthocyanin branch, was upregulated thousand-fold in A. thaliana and in N. tabacum. These results might be attributed to FtF3′H1 protein with a higher substrate preference for anthocyanin synthesis substrates. Altogether, we identified the basic biochemical activity of FtF3′H1 in vivo and investigated its involvement in anthocyanin and flavonol metabolism in plant.
A novel approach for estimating the flowering rate of litchi based on deep learning and UAV images
Authors: Lin Peiyi , Li Denghui , Jia Yuhang , Chen Yingyi , Huang Guangwen , Elkhouchlaa Hamza , Yao Zhongwei , Zhou Zhengqi , Zhou Haobo , Li Jun , Lu Huazhong
Published: August 2022

Litchi flowering management is an important link in litchi orchard management. Statistical litchi flowering rate data can provide an important reference for regulating the number of litchi flowers and directly determining the quality and yield of litchi fruit. At present, the statistical work regarding litchi flowering rates requires considerable labour costs. Therefore, this study aims at the statistical litchi flowering rate task, and a combination of unmanned aerial vehicle (UAV) images and computer vision technology is proposed to count the numbers of litchi flower clusters and flushes in a complex natural environment to improve the efficiency of litchi flowering rate estimation. First, RGB images of litchi canopies at the flowering stage are collected by a UAV. After performing image preprocessing, a dataset is established, and two types of objects in the images, namely, flower clusters and flushes, are manually labelled. Second, by comparing the pretraining and testing results obtained when setting different training parameters for the YOLOv4 model, the optimal parameter combination is determined. The YOLOv4 model trained with the optimal combination of parameters tests best on the test set, at which time the mean average precision (mAP) is 87.87%. The detection time required for a single image is 0.043 s. Finally, aiming at the two kinds of targets (flower clusters and flushes) on 8 litchi trees in a real orchard, a model for estimating the numbers of flower clusters and flushes on a single litchi tree is constructed by matching the identified number of targets with the actual number of targets via equation fitting. Then, the data obtained from the manual counting process and the estimation model for the other five litchi trees in the real orchard are statistically analysed. The average error rate for the number of flower clusters is 4.20%, the average error rate for the number of flushes is 2.85%, and the average error for the flowering rate is 1.135%. The experimental results show that the proposed method is effective for estimating the litchi flowering rate and can provide guidance regarding the management of the flowering periods of litchi orchards.
Whitefly-tolerant transgenic common bean (Phaseolus vulgaris) line
Authors: Ferreira Amanda Lopes , Faria Josias Correa de , da Costa Moura Matheus , de Mendonça Zaidem Antônia Lopes , Pizetta Carolina Senhorinho Ramalho , de Oliveira Freitas Elínea , Coelho Gesimária Ribeiro Costa , Silva Jose Francisco Arruda e , Barrigossi José Alexandre Freitas , Hoffmann Lucia Vieira , de Souza Thiago Lívio Pessoa Oliveira , Aragão Francisco José Lima , Pinheiro Patricia Valle
Published: August 2022

Common bean (Phaseolus vulgaris L.) is a staple food in Brazil with both nutritional and socioeconomic importance. As an orphan crop, it has not received as much research attention as the commodity crops. Crop losses are strongly related to virus diseases transmitted by the whitefly Bemisia tabaci, one of the most important agricultural pests in the world. The main method of managing whitefly-transmitted viruses has been the application of insecticides to reduce vector populations. Compared to chemical vector control, a more sustainable strategy for managing insect-borne viruses is the development of resistant/tolerant cultivars. RNA interference has been applied to develop plant lines resistant to the whitefly in other species, such as tomato, lettuce and tobacco. Still, no whitefly-resistant plant has been made commercially available to date. Common bean is a recalcitrant species to in vitro regeneration; therefore, stable genetic transformation of this plant has been achieved only at low frequencies (<1%) using particle bombardment. In the present work, two transgenic common bean lines were obtained with an intron-hairpin construct to induce post-transcriptional gene silencing against the B. tabaci vATPase (Bt-vATPase) gene, with stable expression of siRNA. Northern blot analysis revealed the presence of bands of expected size for siRNA in leaf samples of the line Bt-22.5, while in the other line (11.5), the amount of siRNA produced was significantly smaller. Bioassays were conducted with both lines, but only the line Bt-22.5 was associated with significant mortality of adult insects (97% when insects were fed on detached leaves and 59% on the whole plant). The expression of the Bt-vATPase gene was 50% lower (p < 0.05) in insects that fed on the transgenic line Bt-22.5, when compared to non-transgenic controls. The transgenic line did not affect the virus transmission ability of the insects. Moreover, no effect was observed on the reproduction of non-target organisms, such as the black aphid Aphis craccivora, the leafminer Liriomyza sp. and the whitefly parasitoid Encarsia formosa. The results presented here serve as a basis for the development of whitefly-tolerant transgenic elite common bean cultivars, with potential to contribute to the management of the whitefly and virus diseases.
From ivory tower to inclusion: Stakeholders’ experiences of community engagement in Australian autism research
Authors: den Houting Jacquiline , Higgins Julianne , Isaacs Kathy , Mahony Joanne , Pellicano Elizabeth
Published: August 2022

Autistic people, and other community stakeholders, are gaining increasing recognition as valuable contributors to autism research, resulting in a growing corpus of participatory autism research. Yet, we know little about the ways in which stakeholders practice and experience community engagement in autism research. In this study, we interviewed 20 stakeholders (academics, autistic people, family members/careers, research students, and service providers) regarding their experiences of community engagement in Australian autism research. Through reflexive thematic analysis of interview data, we generated four themes. First, our participants perceived academia as an “ivory tower,” disconnected from community members’ lives and priorities. Second, our participants identified that different stakeholders tended to hold different roles within their research projects: academics typically retained power and control, while community members’ roles tended toward tokenism. Third, our participants spoke of the need to “bridge the gap” between academia and the community, highlighting communication, accessibility, and planning as key to conducting effective participatory research. Lastly, participants emphasized the changing nature of autism research, describing participatory research as “the way of the future.” Our findings reflect both the progress achieved to date, and the challenges that lie ahead, as the field advances toward genuine co-production of autism research.