bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Brain Activity and Functional Connectivity by Acupuncture Combined With Donepezil on Mild-to-Moderate Alzheimer's Disease: A Neuroimaging Pilot Study
Authors: Zhan Yijun , Fu Qinhui , Pei Jian , Fan Mingxia , Yu Qiurong , Guo Miao , Zhou Houguang , Wang Tao , Wang Liaoyao , Chen Yaoxin
Published: July 2022

Background

Functional brain imaging changes have been proven as potential pathophysiological targets in early-stage AD. Current longitudinal neuroimaging studies of AD treated by acupuncture, which is one of the growingly acknowledged non-pharmacological interventions, have neither adopted comprehensive acupuncture protocols, nor explored the changes after a complete treatment duration. Thus, the mechanisms of acupuncture effects remain not fully investigated.

Objective

This study aimed to investigate the changes in spontaneous brain activity and functional connectivity and provide evidence for central mechanism of a 12-week acupuncture program on mild-to-moderate AD.

Methods

A total of forty-four patients with mild-to-moderate AD and twenty-two age- and education-level-matched healthy subjects were enrolled in this study. The forty-four patients with AD received a 12-week intervention of either acupuncture combined with Donepezil (the treatment group) or Donepezil alone (the control group). The two groups received two functional magnetic resonance imaging (fMRI) scans before and after treatment. The healthy subject group underwent no intervention, and only one fMRI scan was performed after enrollment. The fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) were applied to analyze the imaging data. The correlations between the imaging indicators and the changed score of Alzheimer's Disease Assessment Scale-Cognitive Section (ADAS-cog) were also explored.

Results

After the 12-week intervention, compared to those in the control group, patients with AD in the treatment group scored significantly lower on ADAS-cog value. Moreover, compared to healthy subjects, the areas where the fALFF value decreased in patients with AD were mainly located in the right inferior temporal gyrus, middle/inferior frontal gyrus, middle occipital gyrus, left precuneus, and bilateral superior temporal gyrus. Compared with the control group, the right precuneus demonstrated the greatest changed value of fALFF after the intervention in the treatment group. The difference in ADAS-cog after interventions was positively correlated with the difference in fALFF value in the left temporal lobe. Right precuneus-based FC analysis showed that the altered FC by the treatment group compared to the control group was mainly located in the bilateral middle temporal gyrus.

Conclusion

The study revealed the key role of precuneus in the effect of the combination of acupuncture and Donepezil on mild-to-moderate AD for cognitive function, as well as its connection with middle temporal gyrus, which provided a potential treating target for AD.

Trial Registration Number:

NCT03810794 (http://www.clinicaltrials.gov).
An Activation Likelihood Estimation Meta-Analysis of Specific Functional Alterations in Dorsal Attention Network in Mild Cognitive Impairment
Authors: Wu Huimin , Song Yu , Chen Shanshan , Ge Honglin , Yan Zheng , Qi Wenzhang , Yuan Qianqian , Liang Xuhong , Lin Xingjian , Chen Jiu
Published: July 2022

Background

Mild cognitive impairment (MCI) is known as the prodromal stage of the Alzheimer’s disease (AD) spectrum. The recent studies have advised that functional alterations in the dorsal attention network (DAN) could be used as a sensitive marker to forecast the progression from MCI to AD. Therefore, our aim was to investigate specific functional alterations in the DAN in MCI.

Methods

We systematically searched PubMed, EMBASE, and Web of Science and chose relevant articles based on the three functional indicators, the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in the DAN in MCI. Based on the activation likelihood estimation, we accomplished the aggregation of specific coordinates and the analysis of functional alterations.

Results

A total of 38 studies were involved in our meta-analysis. By summing up included articles, we acquired specific brain region alterations in the DAN mainly in the superior temporal gyrus (STG), middle temporal gyrus (MTG), superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), precentral gyrus (preCG), inferior parietal lobule (IPL), superior parietal lobule (SPL). At the same time, the key area that shows anti-interaction with default mode network included the IPL in the DAN. The one showing interactions with executive control network was mainly in the MFG. Finally, the frontoparietal network showed a close connection with DAN especially in the IPL and IFG.

Conclusion

This study demonstrated abnormal functional markers in the DAN and its interactions with other networks in MCI group, respectively. It provided the foundation for future targeted interventions in preventing the progression of AD.

Systematic Review Registration

[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021287958].
Complex Interactions Between Circulating Fatty Acid Levels, Desaturase Activities, and the Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study
Authors: Liu Yue , Xia Yin-Yin , Zhang Ting , Yang Yang , Cannon Richard D. , Mansell Toby , Novakovic Boris , Saffery Richard , Han Ting-Li , Zhang Hua , Baker Philip N.
Published: July 2022

Objective

Maternal abnormal fatty acid desaturation has previously been linked to gestational diabetes mellitus (GDM). However, few studies have investigated this relationship longitudinally throughout pregnancy. In this study, we investigated the relationship between GDM and desaturase activities across the pregnancy trimesters.

Methods

A total of 661 women (GDM = 189, non-GDM = 472) were selected from the Complex Lipids in Mothers and Babies (CLIMB) cohort study. Clinical information and maternal serum were collected at 11–14, 22–28, and 32–34 weeks of gestation. Totally, 20 serum fatty acids were quantified using gas chromatography–mass spectrometry (GC-MS) analysis at each timepoint. Polyunsaturated fatty acid (PUFA) product-to-precursor ratios were used to estimate desaturase and elongase activities including delta-5 desaturase, delta-6 desaturase, stearoyl-CoA desaturase, and elongase.

Results

After adjusting for major potential confounders including maternal age, BMI, primiparity, smoking, and alcohol consumption, we observed a significant increase in the levels of γ-linolenic acid (GLA) and eicosatrienoic acid (DGLA) in the first trimester of women with GDM, whereas GLA and DGLA were reduced in the third trimester, when compared to the non-GDM group. Arachidonic acid (AA) showed an upward trend in the GDM group throughout pregnancy. Estimated delta-6 desaturase and delta-5 desaturase activity were elevated in the first trimester (OR = 1.40, 95% CI 1.03–1.91; OR = 0.56, 95% CI 0.32–0.96) but attenuated in the third trimester (OR = 0.78, 95% CI 0.58–1.07; OR = 2.64, 95% CI 1.46–4.78) in GDM pregnancies, respective to controls. Estimated delta-9–18 desaturase activity (OR = 3.70, 95% CI 1.49–9.19) was increased in women with GDM in later pregnancy.

Conclusions

Our study highlights the potential importance of fatty acid desaturase activities, particularly estimated delta-5 desaturase and delta-9–18 desaturase in the pathophysiology of GDM. These findings may have applications for the early diagnosis and management of GDM.
Mitigation of Acrylamide in Potato Chips by Pre-drying and Pulsed Electric Field Treatment
Authors: Liu Caiyun , Zhang Rui , Vorobiev Eugene , Grimi Nabil
Published: July 2022

The object of this work was to study the effects of preliminary vacuum drying (VD), pulsed electric field (PEF) treatment, frying temperature on color, oil uptake, and acrylamide (AA) content in fried potato chips. The results of this study indicated that an increase of frying temperature from 120 to 180°C led to a decrease of frying time of around 70% for untreated and PEF pre-treated samples. The color value of L* and a* decreased with the increase of frying temperature, and those values of the sample pre-treated by PEF were significantly higher compared to those obtained from untreated samples. The PEF pre-treatment promoted the reduction of oil content of fried samples by up to 17.6, 14.2, and 16% compared with untreated samples at the frying temperatures of 120, 150, and 180°C, respectively. Higher efficiency was observed by applying the preliminary VD in the case of the frying temperature of 150°C. Furthermore, it was revealed that PEF pre-treatment and preliminary VD application lead to a synergetic effect on the reduction of AA content in potato chips. For example, with the initial moisture ratio of 0.5, pre-dried by VD and pre-treated by PEF, the AA content was noticeably decreased from 2,220 to 311 μg/kg compared to untreated and undehydrated samples at the frying temperature of 150°C. Our findings provide reference for a new pre-treatment to mitigate AA formation and to improve the quality of potato chips.
From Function to Metabolome: Metabolomic Analysis Reveals the Effect of Probiotic Fermentation on the Chemical Compositions and Biological Activities of Perilla frutescens Leaves
Authors: Wang Zhenxing , Jin Ximeng , Zhang Xuechun , Xie Xing , Tu Zongcai , He Xiahong
Published: July 2022

This study aimed to investigate the impact of probiotic fermentation on the active components and functions of Perilla frutescens leaves (PFL). PFL was fermented for 7 days using six probiotics (Lacticaseibacillus Paracasei SWFU D16, Lactobacillus Plantarum ATCC 8014, Lactobacillus Rhamnosus ATCC 53013, Streptococcus Thermophilus CICC 6038, Lactobacillus Casei ATCC 334, and Lactobacillus Bulgaricus CICC 6045). The total phenol and flavonoid contents, antioxidant abilities, as well as α-glucosidase and acetylcholinesterase inhibition abilities of PFL during the fermentation process were evaluated, and its bioactive compounds were further quantified by high-performance liquid chromatography (HPLC). Finally, non-targeted ultra-HPLC–tandem mass spectroscopy was used to identify the metabolites affected by fermentation and explore the possible mechanisms of the action of fermentation. The results showed that most of the active component contents and functional activities of PFL exhibited that it first increased and then decreased, and different probiotics had clearly distinguishable effects from each other, of which fermentation with ATCC 53013 for 1 day showed the highest enhancement effect. The same trend was also confirmed by the result of the changes in the contents of 12 phenolic acids and flavonoids by HPLC analysis. Further metabolomic analysis revealed significant metabolite changes under the best fermentation condition, which involved primarily the generation of fatty acids and their conjugates, flavonoids. A total of 574 and 387 metabolites were identified in positive ion and negative ion modes, respectively. Results of Spearman’s analysis indicated that some primary metabolites and secondary metabolites such as flavonoids, phenols, and fatty acids might play an important role in the functional activity of PFL. Differential metabolites were subjected to the KEGG database and 97 metabolites pathways were obtained, of which biosyntheses of unsaturated fatty acids, flavonoid, and isoflavonoid were the most enriched pathways. The above results revealed the potential reason for the differences in metabolic and functional levels of PFL after fermentation. This study could provide a scientific basis for the further study of PFL, as well as novel insights into the action mechanism of probiotic fermentation on the chemical composition and biological activity of food/drug.
A Novel Polysaccharide From Heimioporus retisporus Displays Hypoglycemic Activity in a Diabetic Mouse Model
Authors: Feng Xiaobin , Wang Peng , Lu Yuxiao , Zhang Zejun , Yao Chunxin , Tian Guoting , Liu Qinghong
Published: July 2022

A novel polysaccharide, Heimioporus retisporus Polysaccharide (HRP) was extracted from the edible mushroom Heimioporus retisporus. HRP had weight-average molecular weight 1,949 kDa and number-average molecular weight 873 kDa, and its major components were arabinose (0.71%), galactose (12.93%), glucose (49.00%), xylose (8.59%), mannose (17.78%), and glucuronic acid (10.99%). Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy revealed that HRP was composed of 1,3-linked β-D-glucose, 1,6-linked β-D-mannose, 1,6-linked β-D-galactose, 1,4-linked β-D-galactose, 1,4-linked β-D-xylose, and 1,5-linked α-L-arabinose. Thermogravimetric analysis indicated that degradation temperature (T0) of HRP was 200°C. In an STZ-induced diabetic mouse model, oral administration of HRP (40 mg/kg/d) for 28 days significantly reduced blood glucose levels, and reduced heart organ index by decreasing expression of IL-6 and TNF-α. Our findings indicate hypoglycemic effect of HRP, and its potential application as a hypoglycemic agent.
Comprehensive Analysis of the Transcriptome-wide m6A Methylome in Lung Adenocarcinoma by MeRIP Sequencing
Authors: Mao Wenli , Yu Qingzhen , Wang Kefeng , Ma Qiang , Zheng Yuxin , Zhang Guojun , Luo Wei , Wang Nianwu , Wang Yukun
Published: July 2022

N6-methyladenosine (m6A) is the most abundant internal modification on eukaryotic mRNAs. There is increasing evidence that m6A plays a key role in tumor progression, so it is important to analyze m6A modifications within the transcriptome-wide in lung adenocarcinoma (LUAD). Three pairs of LUAD samples and tumor-adjacent normal tissues were obtained from the South University of Science and Technology Hospital. And then methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were used to identify differential m6A modifications between tumor and tumor-adjacent normal tissues. We identified 4041 aberrant m6A peaks, of which 1192 m6A peaks were upregulated and 2849 m6A peaks downregulated. It was found that genes with the dysregulated m6A peaks were enriched in the pathways in cancer, Rap1 signaling pathway, and insulin resistance. Additionally, 612 genes with abnormal regulation of m6A peaks and RNA expression were identified by combining MeRIP-seq and RNA-seq data. Through KEGG analysis, the 612 genes were enriched in cancer-related signaling pathways, such as the cGMP-PKG signaling pathway, and the Rap1 signaling pathway. What’s more, GSEA enrichment analysis showed these genes were enriched in cell cycle phase transition, cell division, cellular response to DNA damage stimulus, and chromosome organization. To further explore the relationship between differential m6A modified genes and clinical parameters of LUAD patients, we searched The Cancer Genome Atlas (TCGA) and identified 2 genes (FCRL5 and GPRIN1) that were associated with the prognosis and diagnosis of LUAD patients. Furthermore, we found a positive correlation between GPRIN1 and m6A reader YTHDF1 in the GEPIA2 database. It was verified that YTHDF1 binds to GPRIN1 mRNA and regulates its expression. Our study results suggest that m6A modification plays important role in the progression and prognosis of LUAD and maybe a potential new therapeutic target for LUAD patients in the future.
Novel Diagnostic and Prognostic Tools for Lung Cancer Cachexia: Based on Nutritional and Inflammatory Status
Authors: Liu Chen-An , Zhang Qi , Ruan Guo-Tian , Shen Liu-Yi , Xie Hai-Lun , Liu Tong , Tang Meng , Zhang Xi , Yang Ming , Hu Chun-Lei , Zhang Kang-Ping , Liu Xiao-Yue , Shi Han-Ping
Published: July 2022

Background

Cachexia is one of the most common complications affecting lung cancer patients that seriously affects their quality-of-life and survival time. This study aimed to analyze the predictors and prognostic factors of lung cancer cachexia as well as to develop a convenient and accurate clinical prediction tool for oncologists.

Methods

In this multicenter cohort study, 4022 patients with lung cancer were retrospectively analyzed. The patients were randomly categorized into training and verification sets (7:3 ratio). Univariate and multivariate logistic regression analyses were performed to determine the risk factors of cachexia in patients with lung cancer. Cox regression analysis was applied to determine independent prognostic factors in the patients with lung cancer cachexia. Meanwhile, two nomograms were established and evaluated by time-dependent receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA).

Results

Stage, serum albumin, ALI, anemia, and surgery were independent risk factors for cachexia in patients with lung cancer. Patients with lung cancer cachexia have a shorter survival time. Sex, stage, serum albumin, ALI, KPS score, and surgery served as independent prognostic factors for patients with lung cancer cachexia. The area under the curves (AUCs) of diagnostic nomogram in the training and validation sets were 0.702 and 0.688, respectively, the AUCs of prognostic nomogram in the training set for 1-, 3-, and 5-year were 0.70, 0.72, and 0.75, respectively, while in the validation set the AUCs were 0.71, 0.75, and 0.79, respectively. The calibration curves and DCA of the two nomograms were consistent and the clinical benefit rate was high.

Conclusion

Cachexia brings an additional economic burden and worsens the prognosis of lung cancer patients. The two nomograms can accurately screen and predict the probability of occurrence of cachexia in lung cancer and the prognosis of patients with lung cancer cachexia, and guide clinical work.
The Role of SETBP1 in Gastric Cancer: Friend or Foe
Authors: Fang Fujin , Liu Chengyou , Li Qiong , Xu Rui , Zhang Tiantian , Shen Xiaobing
Published: July 2022

Background

Gastric cancer (GC) remains a common disease with a poor prognosis worldwide. The SET binding protein 1 (SETBP1) has been implicated in the pathogenesis of several cancers and plays a dual role as an oncogene and a tumor suppressor gene. However, the role and underlying mechanism of SETBP1 in GC remain unclear.

Materials and Methods

We used next-generation RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) to explore the correlation between SETBP1 expression and tumor progression. We then quantified SETBP1 expression in GC cells with real-time quantitative polymerase chain reactions (RT-qPCR). The chi-square test and logistic regression were used to assess the correlation between SETBP1 expression and clinicopathological features. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to assess the relationship between SETBP1 expression and survival. Finally, gene set enrichment analyses (GSEA) were used to examine GC-related signaling pathways in low and high SETBP1 expressing samples.

Results

We found SETBP1 expression levels in GC tissues to be significantly lower than in adjacent non-tumor tissues in the TCGA database. In addition, SETBP1 expression differed significantly between groups classified by tumor differentiation. Furthermore, SETBP1 expression in diffuse-type GC was significantly higher than in intestinal-type GC. However, it did not differ significantly across pathological- or T-stage groups. RT-qPCR and comprehensive meta-analysis showed that SETBP1 expression is downregulated in GC cells and tissues. Interestingly, SETBP1 expression in poorly- or un-differentiated GC cells was higher than in well-differentiated GC cells. Moreover, the chi-square test and logistic regression analyses showed that SETBP1 expression correlates significantly with tumor differentiation. Kaplan–Meier curves indicated that patients with relatively high SETBP1 expression had a poor prognosis. Multivariate analyses indicated that SETBP1 expression might be an important predictor of poor overall survival in GC patients. GSEA indicated that 20 signaling pathways were significantly enriched in samples with high and low SETBP1 expression.

Conclusion

SETBP1 may play a dual role in GC progression.
A Dramatic Response to Toripalimab With Chemotherapy and Antiangiogenic Agent Followed by Surgery in a Stage IIIB Lung Adenocarcinoma Patient With an Uncommon EGFR Mutation: A Case Report
Authors: Zhai Pengda , Niu Xueliang , Zheng Kai
Published: July 2022

Lung cancer patients with high programmed cell death-ligand 1 (PD-L1) expression in tumor cells and epidermal growth factor receptor (EGFR) mutations are rare, but there is no clinical standard for which treatment such patients should receive. Here, we report a 52-year-old male smoker who was diagnosed with stage IIIB lung adenocarcinoma. A rare EGFR G719A mutation was detected in the lymph node samples by next-generation sequencing (NGS), and a high PD-L1 expression was found by immunohistochemistry (IHC). After 10 cycles of induction therapy (toripalimab plus pemetrexed plus nedaplatin plus apatinib), surgery was successfully performed, followed by 2 cycles of consolidation therapy (toripalimab plus pemetrexed) and 4 cycles of maintenance therapy (toripalimab). A progression-free survival (PFS) of 7 months was achieved. In this case, we showed that the programmed cell death protein 1 (PD-1) inhibitor toripalimab plus chemotherapy and apatinib was effective and tolerable in a locally advanced EGFR-mutant non-small cell lung cancer (NSCLC) patient with a positive PD-L1 expression.
Rapid Recovery of Postoperative Pulmonary Function in Patients With Lung Cancer and Influencing Factors
Authors: Fuzhi Yang , Dongfang Tang , Wentao Fu , Jing Wang , Yingting Wu , Nianping Mo , Wen Gao , Xiaoyong Shen
Published: July 2022

Among malignant tumors, lung cancer has the highest morbidity and mortality worldwide. Surgery is the first-line treatment for early-stage lung cancers, and has gradually advanced from conventional open-chest surgery to video-assisted thoracic surgery (VATS). Additionally, increasingly smaller surgical incisions and less surgical trauma have resulted in reduced pulmonary function damage. Previous studies have found that the level of pulmonary function loss and recovery is significantly correlated with postoperative complications and the quality of life. Thus, an accurate assessment of the preoperative pulmonary function and effective rehabilitation of postoperative pulmonary function are highly important for patients undergoing lung surgery. In addition, pulmonary function assessment after pulmonary rehabilitation serves as an objective indicator of the postoperative pulmonary rehabilitation status and is crucial to facilitating pulmonary function recovery. Furthermore, a complete preoperative assessment and effective rehabilitation are especially critical in elderly patients with pulmonary tumors, poor basic physiological functions, comorbid lung diseases, and other underlying diseases. In this review, we summarize the clinical significance of pulmonary function assessment in patients undergoing lung cancer surgery, postoperative changes in pulmonary function, effective pulmonary function rehabilitation, and the influencing factors of pulmonary function rehabilitation.
Learning Curve of Robotic-Assisted Total Mesorectal Excision for Rectal Cancer
Authors: Tang Bo , Li Tao , Gao Gengmei , Shi Jun , Li Taiyuan
Published: July 2022

Background

Although some studies have assessed the learning curve of robotic-assisted total mesorectal excision for rectal cancer, most studies included limited sample sizes, no study used postoperative complications as an independent variable to analyze the learning curve of robotic rectal surgery, and no study evaluated the influence of the learning curve on long-term oncologic outcomes.

Methods

Clinical data on consecutive patients who underwent robotic-assisted total mesorectal excision for rectal cancer by a single surgeon between January 2015 and December 2018 at the First Affiliated Hospital of Nanchang University were retrospectively collected. The cumulative sum (CUSUM) and risk-adjusted cumulative sum (RA-CUSUM) were used to visualize the learning curve of operation time and postoperative complications (CD ≥ grade II). Comparisons of clinical outcomes at different learning phases analyzed by RA-CUSUM were performed after propensity score matching.

Results

A total of 389 consecutive patients were included in the analysis. The numbers of patients needed to overcome the learning curves of operation time and postoperative complications of robotic-assisted laparoscopic surgery for rectal cancer were 34 and 36, respectively. The learning process was divided into two phases based on RA-CUSUM: the learning phase (1st-36th cases) and the mastery phase (37th-389th cases). Before matching, the mastery phase had more patients with older age, lower tumor location, and neoadjuvant therapy. After matching, the two phases exhibited similar characteristics. The operation time, intraoperative blood loss, postoperative hospital stay, and postoperative complications in the mastery phase were reduced compared with the learning phase, with a median follow-up of 35 months, and the long-term oncologic outcomes were not significantly different between the two phases.

Conclusions

An experienced laparoscopic surgeon initially implements robotic-assisted total mesorectal excision for rectal cancer, surgical outcomes improved after 36 cases, and the learning curve seemingly did not have an obvious impact on long-term oncologic outcomes.
Targeted Arginine Metabolism Therapy: A Dilemma in Glioma Treatment
Authors: Hou Xiaoshuang , Chen Sui , Zhang Po , Guo Dongsheng , Wang Baofeng
Published: July 2022

Efforts in the treatment of glioma which is the most common primary malignant tumor of the central nervous system, have not shown satisfactory results despite a comprehensive treatment model that combines various treatment methods, including immunotherapy. Cellular metabolism is a determinant of the viability and function of cancer cells as well as immune cells, and the interplay of immune regulation and metabolic reprogramming in tumors has become an active area of research in recent years. From the perspective of metabolism and immunity in the glioma microenvironment, we elaborated on arginine metabolic reprogramming in glioma cells, which leads to a decrease in arginine levels in the tumor microenvironment. Reduced arginine availability significantly inhibits the proliferation, activation, and function of T cells, thereby promoting the establishment of an immunosuppressive microenvironment. Therefore, replenishment of arginine levels to enhance the anti-tumor activity of T cells is a promising strategy for the treatment of glioma. However, due to the lack of expression of argininosuccinate synthase, gliomas are unable to synthesize arginine; thus, they are highly dependent on the availability of arginine in the extracellular environment. This metabolic weakness of glioma has been utilized by researchers to develop arginine deprivation therapy, which ‘starves’ tumor cells by consuming large amounts of arginine in circulation. Although it has shown good results, this treatment modality that targets arginine metabolism in glioma is controversial. Exploiting a suitable strategy that can not only enhance the antitumor immune response, but also “starve” tumor cells by regulating arginine metabolism to cure glioma will be promising.
Prognostic Value of Thrombocytopenia in Myelodysplastic Syndromes After Hematopoietic Stem Cell Transplantation
Authors: Wang Hong , Qi Jiaqian , Li Xueqian , Chu Tiantian , Qiu Huiying , Fu Chengcheng , Tang Xiaowen , Ruan Changgeng , Wu Depei , Han Yue
Published: July 2022

Prolonged isolated thrombocytopenia (PT) is a common complication affecting the outcome of stem cell transplantation. In this study, we undertook a real-world study of 303 myelodysplastic syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (HSCT) between December 2007 and June 2018. 28.4% of MDS patients suffered from PT after HSCT. Survival analysis indicated that PT was associated with worse overall survival (OS) in MDS patients. The 2-year and 5-year OS in MDS patients with PT after HSCT were 49% and 47%, significantly worse than that of 68% and 60% in patients without PT (P=0.005). For RFS, patients with PT did not have an increased risk of disease relapse (P=0.964). After multivariate adjustment, PT was proved to be the independent risk factor associated with the worse OS (HR 1.49, 95% CI 1.00-2.21, P =0.048). We further analyzed risk factors associated with the occurrence of PT in MDS patients. Multiple logistic regression identified grade II-IV aGVHD, extensive chronic GVHD, hemorrhagic cystitis, and CMV activation as significant risk factors for developing PT. Among these variables, the Odds Ratio (OR) of grade II-IV aGVHD was the highest (P =0.001, OR: 2.65, 95% CI: 1.51-4.64). These data indicated the prognostic value of PT in MDS after HSCT. The identification of risk factors for PT may help improve patient management and lead to the design of effective treatment strategies.
Cost-Effectiveness of BRCA 1/2 Genetic Test and Preventive Strategies: Using Real-World Data From an Upper-Middle Income Country
Authors: Lourenção Marina , Simões Correa Galendi Julia , Galvão Henrique de Campos Reis , Antoniazzi Augusto Perazzolo , Grasel Rebeca Silveira , Carvalho André Lopes , Mauad Edmundo Carvalho , Oliveira Jorge Henrique Caldeira de , Reis Rui Manuel , Mandrik Olena , Palmero Edenir Inêz
Published: July 2022

Although BRCA1/2 genetic testing in developed countries is part of the reality for high-risk patients for hereditary breast and ovarian cancer (HBOC), the same is not true for upper-middle-income countries. For that reason, this study aimed to evaluate whether the BRCA1/2 genetic test and preventive strategies for women at high risk for HBOC are cost-effective compared to not performing these strategies in an upper-middle-income country. Adopting a payer perspective, a Markov model with a time horizon of 70 years was built to delineate the health states for a cohort of healthy women aged 30 years that fulfilled the BRCA1/2 testing criteria according to the guidelines. Transition probabilities were calculated based on real-world data of women tested for BRCA1/2 germline mutations in a cancer reference hospital from 2011 to 2020. We analyzed 275 BRCA mutated index cases and 356 BRCA mutation carriers that were first- or second-degree relatives of the patients. Costs were based on the Brazilian public health system reimbursement values. Health state utilities were retrieved from literature. The BRCA1/2 genetic test and preventive strategies result in more quality-adjusted life years (QALYs) and costs with an incremental cost-effectiveness ratio of R$ 11,900.31 (U$ 5,504.31)/QALY. This result can represent a strong argument in favor of implementing genetic testing strategies for high-risk women even in countries with upper-middle income, considering not only the cancer prevention possibilities associated with the genetic testing but also its cost-effectiveness to the health system. These strategies are cost-effective, considering a willingness-to-pay threshold of R$ 25,000 (U$ 11,563.37)/QALY, indicating that the government should consider offering them for women at high risk for HBOC. The results were robust in deterministic and probabilistic sensitivity analyses.
The Spectrum of Parenchymal Changes in Kidneys Affected by Intrarenal Reflux, Diagnosed by Contrast-Enhanced Voiding Urosonography and DMSA Scan
Authors: Simičić Majce Ana , Arapović Adela , Čapkun Vesna , Brdar Dubravka , Brekalo Marko , Zebić Ileana , Barić Ana , Punda Ante , Saraga-Babić Mirna , Vukojević Katarina , Saraga Marijan
Published: July 2022

Purpose

To describe the parenchymal defects in kidneys with intrarenal reflux (IRR) diagnosed using contrast-enhanced voiding urosonography (ceVUS) and 99mTc-DMSA scintigraphy (DMSA scan).

Materials and Methods

A group of 186 uretero-renal units (URUs) was analyzed using ceVUS and DMSA scans: 47 without vesicoureteral reflux (VUR) (group A) and 139 with VURs, comprising 73 VURs without (group B), and 66 with IRR (group C). VURs included non-dilating (grades I–II), mildly non-dilating (grade III), and non-dilating (grades IV–V) grades. The parenchymal changes were analyzed using a DMSA scan.

Results

The median age for VUR diagnosis was 16.5 months in girls, and 8.5 months in boys (Z = 3.9; p = 0.001). IRR occurred in 51.4% of boys and in 25.9% of girls (χ2 = 12.4; p < 0.001). The non-dilating VUR occurred in 44% of boys and 24.1% of girls (χ2 = 7.7; p = 0.005). IRRs characterized upper and lower renal segments (81.8 and 63.6%) and middle segments (33.3%). Both incidence and increase in IRR correlated with the grade of VUR (p < 0.001). The incidence of reduced DMSA signal was statistically different among groups A + B and C, but not between groups A and B (χ2 = 32.2; p < 0.001). No statistically significant relationship existed between the reduced DMSA signal and the grade of VUR in group C. The reduced DMSA signal appeared in 9.9% positions in kidneys from group A, 14% from group B, and 32% from group C. Out of all 118 IRRs, 38.1% had reduced and 61.9% had normal DMSA signal. Among 11 parenchymal scars found in all three groups, 2 belonged to group B, 9 to group C, while group A had no scars.

Conclusion

The parenchymal changes are the most prominent in the group with IRR, but they do not significantly differ among kidneys with different grades of VUR. VURs of higher grades are associated with a higher incidence of IRR and early clinical presentation. Scars can also appear in lower-grade VURs accompanied by IRR. Boys with VUR have earlier clinical presentation than girls, as they have significantly higher grades of VUR with a higher proportion of IRRs. Therefore, we suggest a subdivision of VURs into those with IRR and abundant parenchymal damage, and those without IRR and less parenchymal damage.
The Associations Among Physical Activity, Quality of Life, and Self-Concept in Children and Adolescents With Disabilities: A Moderated Mediation Model
Authors: Yang Wen , Yu Jane Jie , Wong Stephen Heung-Sang , Sum Raymond Kim-Wai , Li Ming Hui , Sit Cindy Hui-Ping
Published: July 2022

Objectives

This study aimed to examine a moderated mediation model of the associations among physical activity (PA), quality of life (QoL), and self-concept (SC) in children and adolescents with physical disabilities (PDs) and intellectual disabilities (IDs).

Materials and Methods

A total of 288 children and adolescents with PDs and IDs, aged between 6 and 17 years, were recruited from 16 special schools in Hong Kong. PA, QoL, and SC were measured using the Physical Activity Questionnaire for Older Children (PAQ-C), Paediatric Quality of Life Inventory (PedsQL), and Physical Self-Description Questionnaire Short Form, respectively. Mediation (i.e., PA, QoL, and SC) and moderation analyses (i.e., age, sex, and parental education level) were conducted by structural equation modelling (SEM) using the M plus and PROCESS macro for SPSS.

Results

Physical activity (PA) was positively associated with SC (PDs: β = 0.373; IDs: β = 0.343), and SC significantly mediated the associations between PA and QoL in children and adolescents with PDs (parent proxy-report QoL: β = 0.114; self-report QoL: β = 0.141) and IDs (self-report QoL: β = 0.204). The mediating effects of SC accounted for 16 and 15% of the total effects of PA on QoL (parent proxy-report and self-report) respectively, in participants with PDs, and 8 and 4%, respectively, in those with IDs. Males and participants with higher parental education levels reported stronger associations among PA, QoL, and SC than their counterparts.

Conclusion

This study supports mediating and moderating effects on the associations among PA, QoL, and SC in children and adolescents with PDs and IDs. Future researchers should consider PA intervention in mental health services and provide tailor-made PA programmes based on personal and environmental factors for children and adolescents with disabilities.
Successful Application of Argatroban During VV-ECMO in a Pregnant Patient Complicated With ARDS due to Severe Tuberculosis: A Case Report and Literature Review
Authors: Wu Hongxia , Tang Yongjiang , Xiong Xiaofeng , Zhu Min , Yu He , Cheng Deyun
Published: July 2022

Severe tuberculosis during pregnancy may progress to acute respiratory distress syndrome (ARDS), and venovenous (VV) extracorporeal membrane oxygenation (ECMO) should be considered if conventional lung-protective mechanical ventilation fails. However, thrombocytopenia often occurs with ECMO, and there are limited reports of alternative anticoagulant therapies for pregnant patients with thrombocytopenia during ECMO. This report describes the first case of a pregnant patient who received argatroban during ECMO and recovered. Furthermore, we summarized the existing literature on VV-ECMO and argatroban in pregnant patients. A 31-year-old woman at 17 weeks of gestation was transferred to our hospital with ARDS secondary to severe tuberculosis. We initiated VV-ECMO after implementing a protective ventilation strategy and other conventional therapies. Initially, we selected unfractionated heparin anticoagulant therapy. However, on ECMO day 3, the patient’s platelet count and antithrombin III (AT-III) level declined to 27 × 103 cells/μL and 26.9%, respectively. Thus, we started the patient on a 0.06 μg/kg/min argatroban infusion. The argatroban infusion maintenance dose ranged between 0.9 and 1.2 μg/kg/min. The actual activated partial thromboplastin clotting time and activated clotting time ranged from 43 to 58 s and 220–260 s, respectively, without clinically significant bleeding and thrombosis. On day 27, the patient was weaned off VV-ECMO and eventually discharged. VV-ECMO may benefit pregnant women with refractory ARDS, and argatroban may be an alternative anticoagulant for pregnant patients with thrombocytopenia and AT-III deficiency during ECMO.
Frequency Conversion of Optical Vortex Arrays Through Four-Wave Mixing in Hot Atomic Gases
Authors: Mendoza-López L. A. , Acosta-Montes J. G. , Bernal-Orozco J. A. , Torres Y. M. , Arias-Téllez N. , Jáuregui R. , Sánchez D. Sahagún
Published: July 2022

Arrays of multiple vortices were transferred from infrared to the blue region of the optical spectrum. This demonstration was achieved by inducing four-wave mixing in an atomic gas with a Gaussian beam and a quasi-invariant propagation beam of the Mathieu type. The latter structure was analyzed in the Fourier space for the pump and the generated light. In both cases, the phase structure can be written with a compact mathematical expression by using the same parameters within experimental error bars. A Michelson–Morley interferometer was used to confirm that a phase singularity was present at each site as predicted by the theory. These studies add to the available control over orbital angular momentum in photons generated by atoms, which has a broad span of applications in quantum and classical information management.
Dynamic Transcriptomic Profiling During Liver Development in Schizothorax Prenanti
Authors: Ni Jiahui , Zhu Peng , Mo Qilang , Luo Wei , Du Zongjun , Jiang Jun , Yang Song , Zhao Liulan , Gong Quan , Wang Yan
Published: July 2022

Liver is an important organ for glucose and lipid metabolism, immunity, and detoxification in fish. However, the gene regulatory network of postnatal liver development still remains unknown in teleost fish. In this study, we performed transcriptome analysis on the liver of S. prenanti at three stages. A total of 1692 differentially expressed genes (DGEs) were identified across three liver developmental stages. The oil red O staining and PAS staining revealed that the lipid content of liver was increased and the glycogen content of liver was decreased during liver development. The fatty acids biosynthesis related genes were upregulated in adult and young stages compared with juvenile stage, while lipid degradation related genes were downregulated. The genes related to glycolysis, gluconeogenesis and glycogenolysis were upregulated in juvenile or young stages compared with adult stage. Further pathway analysis indicated that the CYP450 pathway, cell cycle and amino acid metabolic pathway were induced in the process of liver maturation. Our study presents the gene expression pattern in different liver development stages of S. prenanti and may guide future studies on metabolism of S. prenanti liver.
Automatic and Accurate Acquisition of Stem-Related Phenotypes of Mature Soybean Based on Deep Learning and Directed Search Algorithms
Authors: Guo Yixin , Gao Zhiqiang , Zhang Zhanguo , Li Yang , Hu Zhenbang , Xin Dawei , Chen Qingshan , Zhu Rongsheng
Published: July 2022

The stem-related phenotype of mature stage soybean is important in soybean material selection. How to improve on traditional manual methods and obtain the stem-related phenotype of soybean more quickly and accurately is a problem faced by producers. With the development of smart agriculture, many scientists have explored soybean phenotypes and proposed new acquisition methods, but soybean mature stem-related phenotype studies are relatively scarce. In this study, we used a deep learning method within the convolutional neural network to detect mature soybean stem nodes and identified soybean structural features through a novel directed search algorithm. We subsequently obtained the pitch number, internodal length, branch number, branching angle, plant type spatial conformation, plant height, main stem length, and new phenotype-stem curvature. After 300 epochs, we compared the recognition results of various detection algorithms to select the best. Among them, YOLOX had a maximum average accuracy (mAP) of 94.36% for soybean stem nodes and scale markers. Through comparison of the phenotypic information extracted by the directed search algorithm with the manual measurement results, we obtained the Pearson correlation coefficients, R, of plant height, pitch number, internodal length, main stem length, stem curvature, and branching angle, which were 0.9904, 0.9853, 0.9861, 0.9925, 0.9084, and 0.9391, respectively. These results show that our algorithm can be used for robust measurements and counting of soybean phenotype information, which can reduce labor intensity, improve efficiency, and accelerate soybean breeding.
Source Apportionment and Health Risk Assessment of Heavy Metals in Endemic Tree Species in Southern China: A Case Study of Cinnamomum camphora (L.) Presl
Authors: Li Ning , Li Yan , Zhou Shenglu , Zhang Huanchao , Wang Genmei
Published: July 2022

As a developed economic region in China, the problem of heavy metals (HMs) pollution in the Yangtze River Delta has become increasingly prominent. As an important evergreen broad-leaved tree species in southern China, the camphor tree cannot only be used as a street tree but also its various tissues and organs can be used as raw materials for Chinese herbal medicine. In order to explore whether heavy metal contamination in the region threatens the safety of camphor trees as pharmaceutical raw materials, we collected the bark and leaves of the tree most commonly used for pharmaceuticals in Yixing City. Based on the determination of HMs content, the health risks after human intake are evaluated, the sources and contributions of HMs are analyzed, and then the health risks of pollution sources are spatially visualized. The results showed that under the influence of human activities, the camphor trees in the study area had obvious enrichment of HMs, and the over-standard rate of Pb in the bark was as high as 90%. The non-carcinogenic risks of bark and leaves are acceptable, but the carcinogenic risks are not acceptable. The bark had the highest average carcinogenic risk, approaching six times the threshold. The results of Pb isotope ratio analysis showed that the average contribution rate of industrial activities to HMs in camphor trees in the study area was the highest, reaching 49.70%, followed by fossil fuel burning (37.14%) and the contribution of natural sources was the smallest, only 13.16%. The locations of the high-risk areas caused by the three pollution sources in the study area are basically similar, mainly concentrated in the northwest, northeast, and southeast, which are consistent with the distribution of industries and resources in the study area. This study can provide a reference for the precise prevention of HMs pollution of camphor and the safe selection of its pharmaceutical materials.
In-Depth Characterization of greenflesh Tomato Mutants Obtained by CRISPR/Cas9 Editing: A Case Study With Implications for Breeding and Regulation
Authors: Gianoglio Silvia , Comino Cinzia , Moglia Andrea , Acquadro Alberto , García-Carpintero Víctor , Diretto Gianfranco , Sevi Filippo , Rambla José Luis , Dono Gabriella , Valentino Danila , Moreno-Giménez Elena , Fullana-Pericàs Mateu , Conesa Miguel A. , Galmés Jeroni , Lanteri Sergio , Mazzucato Andrea , Orzáez Diego , Granell Antonio
Published: July 2022

Gene editing has already proved itself as an invaluable tool for the generation of mutants for crop breeding, yet its ultimate impact on agriculture will depend on how crops generated by gene editing technologies are regulated, and on our ability to characterize the impact of mutations on plant phenotype. A starting operational strategy for evaluating gene editing-based approaches to plant breeding might consist of assessing the effect of the induced mutations in a crop- and locus-specific manner: this involves the analysis of editing efficiency in different cultivars of a crop, the assessment of potential off-target mutations, and a phenotypic evaluation of edited lines carrying different mutated alleles. Here, we targeted the GREENFLESH (GF) locus in two tomato cultivars (‘MoneyMaker’ and ‘San Marzano’) and evaluated the efficiency, specificity and mutation patterns associated with CRISPR/Cas9 activity for this gene. The GF locus encodes a Mg-dechelatase responsible for initiating chlorophyll degradation; in gf mutants, ripe fruits accumulate both carotenoids and chlorophylls. Phenotypic evaluations were conducted on two transgene-free T2 ‘MoneyMaker’ gf lines with different mutant alleles (a small insertion of 1 nucleotide and a larger deletion of 123 bp). Both lines, in addition to reduced chlorophyll degradation, showed a notable increase in carotenoid and tocopherol levels during fruit ripening. Infection of gf leaves and fruits with Botrytis cinerea resulted in a significant reduction of infected area and pathogen proliferation compared to the wild type (WT). Our data indicates that the CRISPR/Cas9-mediated mutation of the GF locus in tomato is efficient, specific and reproducible and that the resulting phenotype is robust and consistent with previously characterized greenflesh mutants obtained with different breeding techniques, while also shedding light on novel traits such as vitamin E overaccumulation and pathogen resistance. This makes GF an appealing target for breeding tomato cultivars with improved features for cultivation, as well as consumer appreciation and health.