bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Risk Model for Predicting Microalbuminuria in the Chinese Population Using Machine Learning Algorithms
Authors: Lin Wei , Shi Songchang , Huang Huibin , Wang Nengying , Wen Junping , Chen Gang
Published: February 2022

Objective

Microalbuminuria (MAU) occurs due to universal endothelial damage, which is strongly associated with kidney disease, stroke, myocardial infarction, and coronary artery disease. Screening patients at high risk for MAU may aid in the early identification of individuals with an increased risk of cardiovascular events and mortality. Hence, the present study aimed to establish a risk model for MAU by applying machine learning algorithms.

Methods

This cross-sectional study included 3,294 participants ranging in age from 16 to 93 years. R software was used to analyze missing values and to perform multiple imputation. The observed population was divided into a training set and a validation set according to a ratio of 7:3. The first risk model was constructed using the prepared data, following which variables with P <0.1 were extracted to build the second risk model. The second-stage model was then analyzed using a chi-square test, in which a P ≥ 0.05 was considered to indicate no difference in the fit of the models. Variables with P <0.05 in the second-stage model were considered important features related to the prevalence of MAU. A confusion matrix and calibration curve were used to evaluate the validity and reliability of the model. A series of risk prediction scores were established based on machine learning algorithms.

Results

Systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG) levels, sex, age, and smoking were identified as predictors of MAU prevalence. Verification using a chi-square test, confusion matrix, and calibration curve indicated that the risk of MAU could be predicted based on the risk score.

Conclusion

Based on the ability of our machine learning algorithm to establish an effective risk score, we propose that comprehensive assessments of SBP, DBP, FBG, TG, gender, age, and smoking should be included in the screening process for MAU.
Xanthine Oxidoreductase Inhibitor Use Associated With Reduced Risk of Sarcopenia and Severe Sarcopenia in Patients Undergoing Hemodialysis
Authors: Kurajoh Masafumi , Mori Katsuhito , Miyabe Mizuki , Matsufuji Shota , Kizu Akane , Tsujimoto Yoshihiro , Emoto Masanori
Published: February 2022

Background

Xanthine oxidoreductase (XOR) inhibition reduces reactive oxygen species (ROS) production and enhances adenosine triphosphate (ATP) synthesis. We investigated the protective effects of XOR inhibitor treatment on sarcopenia, frequently observed in patients undergoing hemodialysis (HD), in which increased ROS and ATP shortage are known to be involved.

Methods

This retrospective cross-sectional study included 296 HD patient (203 males, 93 females). Muscle mass, physical performance, and muscle strength were assessed using dual-energy X-ray absorptiometry, five-time chair stand testing, and handgrip strength, respectively. The Asian Working Group for Sarcopenia 2019 criteria were used to define low muscle mass, low physical performance, and low muscle strength, as well as sarcopenia and severe sarcopenia.

Results

Sarcopenia and severe sarcopenia prevalence rates were 42.2 and 20.9%, respectively. XOR inhibitor users (n = 119) showed a significantly (p < 0.05) lower prevalence of sarcopenia and severe sarcopenia, as well as reduced muscle mass, physical performance, and muscle strength than non-users (n = 177). Multivariate logistic regression analyses also revealed XOR inhibitor use to be significantly associated with low muscle mass [odds ratio (OR), 0.384; 95% confidence interval (CI), 0.183–0.806; p = 0.011] and low physical performance (OR, 0.286; 95% CI, 0.142–0.578; p < 0.001), while significance with low muscle strength was borderline. Furthermore, XOR inhibitor use was significantly associated with sarcopenia (OR, 0.462; 95% CI, 0.226–0.947; p = 0.035) and severe sarcopenia (OR, 0.236; 95% CI, 0.091–0.614; p = 0.003).

Conclusions

XOR inhibitor use was significantly associated with reduced risk of sarcopenia/severe sarcopenia in HD patients, suggesting that XOR inhibitor treatment has protective effects on sarcopenia in HD patients.
Myxococcus xanthus R31 Suppresses Tomato Bacterial Wilt by Inhibiting the Pathogen Ralstonia solanacearum With Secreted Proteins
Authors: Dong Honghong , Xu Xin , Gao Ruixiang , Li Yueqiu , Li Anzhang , Yao Qing , Zhu Honghui
Published: February 2022

The pathogenic bacterium Ralstonia solanacearum caused tomato bacterial wilt (TBW), a destructive soil-borne disease worldwide. There is an urgent need to develop effective control methods. Myxobacteria are microbial predators and are widely distributed in the soil. Compared with other biocontrol bacteria that produce antibacterial substances, the myxobacteria have great potential for biocontrol. This study reports a strain of Myxococcus xanthus R31 that exhibits high antagonistic activity to R. solanacearum. Plate test indicated that the strain R31 efficiently predated R. solanacearum. Pot experiments showed that the biocontrol efficacy of strain R31 against TBW was 81.9%. Further study found that the secreted protein precipitated by ammonium sulfate had significant lytic activity against R. solanacearum cells, whereas the ethyl acetate extract of strain R31 had no inhibitory activity against R. solanacearum. Substrate spectroscopy assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of secreted proteins showed that some peptidases, lipases, and glycoside hydrolases might play important roles and could be potential biocontrol factors involved in predation. The present study reveals for the first time that the use of strain M. xanthus R31 as a potential biocontrol agent could efficiently control TBW by predation and secreting extracellular lyase proteins.
Efficacy of Dimethyl Trisulfide on the Suppression of Ring Rot Disease Caused by Botryosphaeria dothidea and Induction of Defense-Related Genes on Apple Fruits
Authors: Sun Meng , Duan Yanxin , Liu Jun Ping , Fu Jing , Huang Yonghong
Published: February 2022

Apple ring rot caused by Botryosphaeria dothidea is prevalent in main apple-producing areas in China, bringing substantial economic losses to the growers. In the present study, we demonstrated the inhibitory effect of dimethyl trisulfide (DT), one of the main activity components identified in Chinese leek (Allium tuberosum) volatile, on the apple ring rot on postharvest fruits. In in vitro experiment, 250 μL/L DT completely suppressed the mycelia growth of B. dothidea. In in vivo experiment, 15.63 μL/L DT showed 97% inhibition against the apple ring rot on postharvest fruit. In addition, the soluble sugar content, vitamin C content, and the soluble sugar/titratable acidity ratio of the DT-treated fruit were significantly higher than those of the control fruit. On this basis, we further explored the preliminary underlying mechanism. Microscopic observation revealed that DT seriously disrupted the normal morphology of B. dothidea. qRT-PCR determination showed the defense-related genes in DT-treated fruit were higher than those in the control fruit by 4.13–296.50 times, which showed that DT inhibited apple ring rot on postharvest fruit by suppressing the growth of B. dothidea, and inducing the defense-related genes in apple fruit. The findings of this study provided an efficient, safe, and environment-friendly alternative to control the apple ring rot on apple fruit.
Lichenysin Production by Bacillus licheniformis Food Isolates and Toxicity to Human Cells
Authors: Yeak Kah Yen Claire , Perko Manca , Staring Guido , Fernandez-Ciruelos Blanca M. , Wells Jerry M. , Abee Tjakko , Wells-Bennik Marjon H. J.
Published: February 2022

Bacillus licheniformis can cause foodborne intoxication due to the production of the surfactant lichenysin. The aim of this study was to measure the production of lichenysin by food isolates of B. licheniformis in LB medium and skimmed milk and its cytotoxicity for intestinal cells. Out of 11 B. licheniformis isolates tested, most showed robust growth in high salt (1M NaCl), 4% ethanol, at 37 or 55°C, and aerobic and anaerobic conditions. All strains produced lichenysin (in varying amounts), but not all strains were hemolytic. Production of this stable compound by selected strains (high producers B4094 and B4123, and type strain DSM13T) was subsequently determined using LB medium and milk, at 37 and 55°C. Lichenysin production in LB broth and milk was not detected at cell densities < 5 log10 CFU/ml. The highest concentrations were found in the stationary phase of growth. Total production of lichenysin was 4–20 times lower in milk than in LB broth (maximum 36 μg/ml), and ∼10 times lower in the biomass obtained from milk agar than LB agar. Under all conditions tested, strain B4094 consistently yielded the highest amounts. Besides strain variation and medium composition, temperature also had an effect on lichenysin production, with twofold lower amounts of lichenysin produced at 55°C than at 37°C. All three strains produced lichenysin A with varying acyl chain lengths (C11–C18). The relative abundance of the C14 variant was highest in milk and the C15 variant highest in LB. The concentration of lichenysin needed to reduce cell viability by 50% (IC50) was 16.6 μg/ml for Caco-2 human intestinal epithelial cells and 16.8 μg/ml for pig ileum organoids. Taken together, the presence of low levels (<5 log10 CFU/ml) of B. licheniformis in foods is unlikely to pose a foodborne hazard related to lichenysin production. However, depending on the strain present, the composition, and storage condition of the food, a risk of foodborne intoxication may arise if growth to high levels is supported and such product is ingested.
Integrated Transcriptomics and Metabolomics Analyses of Stress-Induced Murine Hair Follicle Growth Inhibition
Authors: Wang Xuewen , Cai Changqing , Liang Qichang , Xia Meng , Lai Lihua , Wu Xia , Jiang Xiaoyun , Cheng Hao , Song Yinjing , Zhou Qiang
Published: February 2022

Psychological stress plays an important role in hair loss, but the underlying mechanisms are not well-understood, and the effective therapies available to regrow hair are rare. In this study, we established a chronic restraint stress (CRS)-induced hair growth inhibition mouse model and performed a comprehensive analysis of metabolomics and transcriptomics. Metabolomics data analysis showed that the primary and secondary metabolic pathways, such as carbohydrate metabolism, amino acid metabolism, and lipid metabolism were significantly altered in skin tissue of CRS group. Transcriptomics analysis also showed significant changes of genes expression profiles involved in regulation of metabolic processes including arachidonic acid metabolism, glutathione metabolism, glycolysis gluconeogenesis, nicotinate and nicotinamide metabolism, purine metabolism, retinol metabolism and cholesterol metabolism. Furthermore, RNA-Seq analyses also found that numerous genes associated with metabolism were significantly changed, such as Hk-1, in CRS-induced hair growth inhibition. Overall, our study supplied new insights into the hair growth inhibition induced by CRS from the perspective of integrated metabolomics and transcriptomics analyses.
Microglia and Microglia-Like Cells: Similar but Different
Authors: Cuadros Miguel A. , Sepulveda M. Rosario , Martin-Oliva David , Marín-Teva José L. , Neubrand Veronika E.
Published: February 2022

Microglia are the tissue-resident macrophages of the central nervous parenchyma. In mammals, microglia are thought to originate from yolk sac precursors and posteriorly maintained through the entire life of the organism. However, the contribution of microglial cells from other sources should also be considered. In addition to “true” or “bona-fide” microglia, which are of embryonic origin, the so-called “microglia-like cells” are hematopoietic cells of bone marrow origin that can engraft the mature brain mainly under pathological conditions. These cells implement great parts of the microglial immune phenotype, but they do not completely adopt the “true microglia” features. Because of their pronounced similarity, true microglia and microglia-like cells are usually considered together as one population. In this review, we discuss the origin and development of these two distinct cell types and their differences. We will also review the factors determining the appearance and presence of microglia-like cells, which can vary among species. This knowledge might contribute to the development of therapeutic strategies aiming at microglial cells for the treatment of diseases in which they are involved, for example neurodegenerative disorders like Alzheimer’s and Parkinson’s diseases.
Comparative Efficacy of Acupuncture-Related Techniques for Urinary Retention After a Spinal Cord Injury: A Bayesian Network Meta-Analysis
Authors: He Kelin , Li Xinyun , Qiu Bei , Jin Linzhen , Ma Ruijie
Published: February 2022

Background

Urinary retention is one of the most frequent complications of spinal cord injuries (SCI) and negatively impacts patient satisfaction and quality of life. Acupuncture as an integral part of traditional Chinese medicine (TCM) has recently drawn widespread attention for its potential in the management of urinary retention. However, there are many different styles of acupuncture-related techniques, and the optimal choice of acupuncture for urinary retention after SCI is still unclear. Hence, this study uses a Bayesian network meta-analysis (NMA) to compare the efficacy of different types of acupuncture therapies using both direct and indirect evidence.

Methods

Randomized controlled trials of acupuncture-related techniques for treating urinary retention after SCI were retrieved from the following electronic databases: Pubmed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Service System (SinoMed), the Wan-Fang database, and the Chinese Scientific Journals Database (VIP). The retrieval time was from inception to November 2020. Clinical effective rate (CER) was the primary outcome indicator and residual urine volume (RUV) was the secondary outcome indicator. A Bayesian NMA was performed using the Markov chain Monte Carlo method in R software (version 3.6.1) interfacing with JAGS software (version 4.3.0). The node-splitting method was used to identify inconsistencies. In addition, a comparative adjusted funnel plot was used to assess publication bias.

Results

A total of 26 randomized controlled trials involving 1,652 patients were included. Bayesian NMA showed that electroacupuncture combined with moxibustion ranks first in both CER and RUV. In addition, in terms of cumulative probability, electro-acupuncture combined with moxibustion ranked first in CER. The results of the node splitting method revealed that direct and indirect evidence were consistent (P > 0.05). In addition, publication bias was detected.

Conclusion

A Bayesian NMA that combined direct and indirect comparisons showed that electro-acupuncture combined with moxibustion had a better effect on urinary retention due to SCI. However, it still needs a large sample size and high-quality randomized controlled trials to verify this finding.

Systematic Review Registration:https://inplasy.com/, identifier: INPLASY2021110005.
The Neuroimmunology of Multiple Sclerosis: Fictions and Facts
Authors: Pachner Andrew R.
Published: February 2022

There have been tremendous advances in the neuroimmunology of multiple sclerosis over the past five decades, which have led to improved diagnosis and therapy in the clinic. However, further advances must take into account an understanding of some of the complex issues in the field, particularly an appreciation of “facts” and “fiction.” Not surprisingly given the incredible complexity of both the nervous and immune systems, our understanding of the basic biology of the disease is very incomplete. This lack of understanding has led to many controversies in the field. This review identifies some of these controversies and facts/fictions with relation to the basic neuroimmunology of the disease (cells and molecules), and important clinical issues. Fortunately, the field is in a healthy transition from excessive reliance on animal models to a broader understanding of the disease in humans, which will likely lead to many improved treatments especially of the neurodegeneration in multiple sclerosis (MS).
Efficacy of Acupuncture Treatment of Migraine Delivered by Senior or Junior Acupuncturists: Study Protocol for a Randomized Controlled Trial
Authors: Zhou Jun , Jiang Nan-nan , Fang Yu , Zhang Xin-yue , Cheng Shi-rui , Li Xin-ling , Hu Sheng-jie , Sun Rui-rui , Zheng Hua-bin , Huang Xiao-peng , Zeng Fang , Liang Fan-rong , Li Zheng-jie
Published: February 2022

Introduction

Acupuncture is an efficacious and safe treatment choice for migraine prevention. Results from clinical trials have shown that non-specific effects play an important role in acupuncture's efficacy. To date, however, there is no evidence available quantitatively evaluating the effect of non-specific effects, such as patients' expectations and beliefs for acupuncturists, on acupuncture efficacy, necessitating further exploration.

Methods

A total of 156 patients with migraine without aura (MwoA) will be randomized to either junior or senior acupuncturist group, at a ratio of 1:1. The study will last 24 weeks, for each patient, comprising baseline, treatment, and follow-up phases lasting 4, 8, and 12 weeks, respectively. All patients will undergo 12 sections of acupuncture treatment delivered by either a junior or senior acupuncturist following the same acupuncture prescription and manipulation. The primary outcomes will be changes in the number of migraine days and frequency of attacks per 4 weeks cycle, relative to the baseline. Secondary outcomes will include severity of headache pain, quality of life, anxiety/depression levels, and use of non-steroidal anti-inflammatory drugs (NSAIDs) per 4 weeks cycle, compared to the baseline, as well as adverse events and rate of positive response to treatment. Prior to randomization of patients into junior or senior acupuncturist groups, the Acupuncture Expectations Evaluation Scale (AES) will be used to evaluate their expectations and belief with regards to acupuncture efficacy delivered by senior or junior acupuncturists.

Discussion

Results from this clinical randomized controlled trial will help to quantitatively evaluate the extent of the effect of acupuncture treatment delivered by a senior or junior acupuncturist (high relative to low expectations) in migraine patients.

Ethics and Dissemination

This trial has been approved by the Institutional Review Boards and Ethics Committees of Hospital of Chengdu University of Traditional Chinese Medicine (Approval No. 2020KL-058).
The Effect of Abnormal Regional Homogeneity and Spontaneous Low-Frequency Brain Activity on Lower Cognitive Ability: A Cross-Sectional Study on Postoperative Children With Tetralogy of Fallot
Authors: Ma Siyu , Hu Yuanli , Liu Yuting , Pu Yiwei , Zuo Pengcheng , Hu Qinghui , Yang Zhaocong , Chen Feng , Xie Zongyun , Cun Yueshuang , Liu Xiaoxu , Yang Ming , Mo Xuming
Published: February 2022

Despite intracardiac malformation correction, children with Tetralogy of Fallot (TOF) may still suffer from brain injury. This cross-sectional study was primarily designed to determine the relationship between blood oxygenation level-dependent (BOLD) signal changes after surgery and cognition in school-aged children with TOF. To evaluate the differences between TOF children (n = 9) and healthy children (n = 9), resting-state functional magnetic resonance imaging (rs-fMRI) and the Wechsler Intelligence Scale for Children–Chinese revised edition (WISC-CR) were conducted in this study. The results showed that TOF children had a lower full-scale intelligence quotient (FSIQ, 95.444 ± 5.354, p = 0.022) and verbal intelligence quotient (VIQ, 92.444 ± 4.708, p = 0.003) than healthy children (FSIQ = 118.500 ± 4.330;VIQ = 124.250 ± 4.404), and that significant differences in regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) existed between the two groups. Besides, VIQ had significantly positive correlations with the decreased ALFF value of the middle inferior occipital gyrus (MIOG, beta = 0.908, p = 0.012) after fully adjusting for all covariates. In addition, elevated ReHo values of the left and right precuneus were positively related to ALFF in the MIOG. This study revealed that brain injury substantially influences neural activity and cognition in postoperative TOF children, providing direct evidence of an association between BOLD signal changes and the VIQ and prompting further attention to language development in TOF children.
An Exploratory Study of Physiological Linkage Among Strangers
Authors: Boyd Savannah M. , Kuelz Ashley , Page-Gould Elizabeth , Butler Emily A. , Danyluck Chad
Published: February 2022

The present study explores physiological linkage (i.e., any form of statistical interdependence between the physiological signals of interacting partners; PL) using data from 65 same-sex, same ethnicity stranger dyads. Participants completed a knot-tying task with either a cooperative or competitive framing while either talking or remaining silent. Autonomic nervous system activity was measured continuously by electrocardiograph for both individuals during the interaction. Using a recently developed R statistical package (i.e., rties), we modeled different oscillatory patterns of coordination between partner's interbeat interval (i.e., the time between consecutive heart beats) over the course of the task. Three patterns of PL emerged, characterized by differences in frequency of oscillation, phase, and damping or amplification. To address gaps in the literature, we explored (a) PL patterns as predictors of affiliation and (b) the interaction between individual differences and experimental condition as predictors of PL patterns. In contrast to prior analyses using this dataset for PL operationalized as covariation, the present analyses showed that oscillatory PL patterns did not predict affiliation, but the interaction of individual differences and condition differentially predicted PL patterns. This study represents a next step toward understanding the roles of individual differences, context, and PL among strangers.
Association Between Systemic Inflammation and Malnutrition With Survival in Patients With Cancer Sarcopenia—A Prospective Multicenter Study
Authors: Ruan Guo-Tian , Ge Yi-Zhong , Xie Hai-Lun , Hu Chun-Lei , Zhang Qi , Zhang Xi , Tang Meng , Song Meng-Meng , Zhang Xiao-Wei , Liu Tong , Li Xiang-Rui , Zhang Kang-Ping , Yang Ming , Li Qin-Qin , Chen Yong-Bing , Yu Kai-Ying , Braga Marco , Cong Ming-Hua , Wang Kun-Hua , Barazzoni Rocco , Shi Han-Ping
Published: February 2022

Objective

Systemic inflammation and malnutrition are correlated with cancer sarcopenia and have deleterious effects on oncological outcomes. However, the combined effect of inflammation and malnutrition in patients with cancer sarcopenia remains unclear.

Methods

We prospectively collected information on 1,204 patients diagnosed with cancer sarcopenia. the mean (SD) age was 64.5 (11.4%) years, and 705 (58.60%) of the patients were male. The patients were categorized into the high advanced lung cancer inflammation index (ALI) group (≥18.39) and the low ALI group (<18.39) according to the optimal survival cut-off curve. We selected the optimal inflammation marker using the C-index, decision curve analysis (DCA), and a prognostic receiver operating characteristic curve. Univariate and multivariate survival analyses were performed to determine the prognostic value of the optimal inflammation indicator. We also analyzed the association between inflammation and malnutrition in patients with cancer.

Results

The C-index, DCA, and prognostic area under the curve of ALI in patients with cancer sarcopenia were higher or better than those of neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). The prognosis for patients in the low ALI group was worse than that of patients in the high ALI group [HR (95%CI) = 1.584 (1.280–1.959), P < 0.001]. When the ALI was divided into quartiles, we observed that decreased ALI scores strongly correlated with decreased overall survival (OS). Patients with both a low ALI and severe malnutrition (vs. patients with high ALI and well-nourished) had a 2.262-fold death risk (P < 0.001). Subgroup analysis showed a significant interactive association between the ALI and death risk in terms of TNM stage (P for interaction = 0.030).

Conclusions

The inflammation indicator of the ALI was better than those of the NLR, PNI, SII, and PLR in patients with cancer sarcopenia. Inflammation combined with severe malnutrition has a nearly 3-fold death risk in patients with cancer sarcopenia, suggesting that reducing systemic inflammation, strengthening nutritional intervention, and improving skeletal muscle mass are necessary.
Association of Yogurt and Dietary Supplements Containing Probiotic Consumption With All-Cause and Cause-Specific Mortality in US Adults: A Population-Based Cohort Study
Authors: Lin Ping , Gui Xuezhen , Liang Zongan , Wang Ting
Published: February 2022

Background

Although probiotic intake had beneficial effects on several specific disorders, limited evidence was available about the benefits of probiotic intake in the general population. This study aimed to evaluate the relationship between yogurt (as a natural probiotic source) and dietary supplements containing probiotic consumption and mortality in US adults.

Methods

We conducted an observational cohort study comprised of a nationally representative sample of adults who were enrolled in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2014. Individuals were linked to the US National Death Index.

Results

We included 32,625 adults in our study. Of the study cohort, 3,539 participants had yogurt consumption, 213 had dietary supplements containing probiotic consumption, and the remaining participants (28,873) did not have yogurt and/or dietary supplements containing probiotic consumption. During 266,432 person-years of follow-up, 3,881 deaths from any cause were ascertained, of which 651 were due to cardiovascular disorders and 863 were due to cancer. Weighted Cox proportional hazards models suggested that yogurt consumption was inversely associated with all-cause mortality (adjusted hazard ratio (HR), 0.83 [95% confidence interval (CI), 0.71–0.98]) but not cardiovascular mortality (adjusted HR, 0.68 [95%CI, 0.43–1.08]) and cancer mortality (adjusted HR, 1.00 [95%CI, 0.72–1.38]). However, dietary supplements containing probiotic were not associated with decreased all-cause and cause-specific mortality.

Conclusions

The present study suggested that yogurt consumption was associated with a lower risk of all-cause mortality among U.S. adults. Yogurt consumption in diet might be a sensible strategy for reducing the risk of death.
Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer: A Controversial Area
Authors: Xue Shuyu , Zeng Hanqiao , Yan Shu , Wang Qianmeng , Jia Xiaojing
Published: February 2022

Small-cell lung cancer (SCLC) is a highly aggressive malignant tumor that is prone to lead to the development of brain metastases (BM). The application of prophylactic cranial irradiation (PCI) has been regarded as an important technological advance made in cancer therapy to reduce the occurrence of BM and improve patient survival. The benefits of PCI in the treatment of limited-stage SCLC have been confirmed. However, there has been continuous controversy about the indications and advantages of PCI for extensive-stage SCLC (ES-SCLC) because of the conflicting results from two prospective trials. In this review, we aimed to discuss the relevant controversy and progress made in the clinical application of PCI in ES-SCLC.
The Styryl Benzoic Acid Derivative DC10 Potentiates Radiotherapy by Targeting the xCT-Glutathione Axis
Authors: Sarowar Shahin , Cirillo Davide , Játiva Pablo , Nilsen Mette Hartmark , Otragane Sarah-Muheha Anni , Heggdal Jan , Selheim Frode , Ceña Valentín , Bjørsvik Hans-René , Enger Per Øyvind
Published: February 2022

Metastatic tumors with moderate radiosensitivity account for most cancer-related deaths, highlighting the limitations of current radiotherapy regimens. The xCT-inhibitor sulfasalazine (SAS) sensitizes cancer cells to radiotherapy by blocking cystine uptake via the xCT membrane antiporter, and thereby glutathione (GSH) synthesis protecting against radiation-induced oxidative stress. The expression of xCT in multiple tumor types implies it as a target generic to cancer rather than confined to few subtypes. However, SAS has limited clinical potential as a radiosensitizer due to side effects and low bioavailability. Using SAS as a starting point, we previously developed synthetic xCT-inhibitors through scaffold hopping and structure optimization aided by structure-activity relationship analysis (SAR). Notably, the compound DC10 exhibited inhibition of GSH synthesis. In this study, we validated DC10 as a radiosensitizer in the xCT-expressing cancer cell lines A172, A375 and MCF7, and mice harboring melanoma xenografts. After DC10 treatment, we measured 14C-cystine uptake in the cancer cells using liquid scintillation counting, and intracellular GSH levels and reactive oxygen species (ROS) using luminescence assays. We performed immunoblotting of H2AX and ATM to assess DNA damage after treatment with DC10 and radiotherapy. We then assessed the effect of adding DC10 to radiation upon cancer cell colony formation. Blood samples from mice treated with DC10 underwent biochemical analysis to assess toxicity. Finally, mice with A375 melanomas in the flank, received DC10 and radiotherapy in combination, as monotherapies or no treatment. Notably, DC10 reduced cystine uptake and GSH synthesis and increased ROS levels in a dose-dependent manner. Furthermore, DC10 interacted synergistically with radiation to increase DNA damage and reduce tumor cell colony formation. Mice receiving DC10 were clinically unaffected, whereas blood samples analysis to assess bone marrow suppression, liver or kidney toxicity revealed no significant differences between treated mice and untreated controls. Importantly, DC10 potentiated the anti-tumor efficacy of radiation in mice with melanoma xenografts. We conclude that DC10 is well tolerated and acts as a radiosensitizer by inhibiting cystine uptake, leading to GSH depletion and increased oxidative stress. Our findings demonstrate the feasibility of using synthetic xCT-inhibitors to overcome radioresistance.
ARID1A Downregulation Predicts High PD-L1 Expression and Worse Clinical Outcome in Patients With Gallbladder Cancer
Authors: Nan Lingxi , Wang Changcheng , Wang Jie , Zhang Shulong , Bo Xiaobo , Wang Yueqi , Liu Houbao
Published: February 2022

Background

Recent studies have confirmed that AT-rich interactive domain-containing protein 1A (ARID1A) plays a critical role in tumorigenesis, but its role in gallbladder cancer (GBC) remains unclear.

Methods

In total, 224 patients from Zhongshan Hospital were recruited for this retrospective study. The clinicopathological and baseline characteristics of the patients were collected. Bioinformatics analysis was performed to reveal variations in genes and signaling pathways, and ARID1A and PD-L1 expression and the number of PD1+ tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemical staining.

Results

ARID1A expression was negatively correlated with overall survival in patients with GBC, and multivariate analysis identified ARID1A as an independent prognostic factor for overall survival. A heatmap and gene set enrichment analysis suggested that cytotoxic T lymphocyte signatures and immune-related signaling pathways were downregulated in ARID1A low tumors. Subsequent immunohistochemical staining confirmed that ARID1A expression was negatively correlated with PD-L1 expression and PD1+ TILs in the tumor microenvironment. The Kaplan–Meier analysis suggested that high ARID1A expression combined with low PD-L1 expression or low PD1+ TIL counts is associated with the best prognosis in patients with GBC.

Conclusion

ARID1A inactivation can lead to a worse prognosis in patients with GBC, potentially by mediating immune evasion through the PD1/PD-L1 pathway.
Pyroptosis: A Developing Foreland of Ovarian Cancer Treatment
Authors: Liu Tianyi , Hou Min , Li Manyu , Qiu Cheng , Cheng Lin , Zhu Tianyu , Qu Jinfeng , Li Lanyu
Published: February 2022

Ovarian cancer (OVCA) has the second highest mortality among all gynecological cancers worldwide due to its complexity and difficulty in early-stage diagnosis and a lack of targeted therapy. Modern strategies of OVCA treatment involve debulking surgery combined with chemotherapy. Nonetheless, the current treatment is far from satisfactory sometimes and therefore the demand for novel therapeutic measures needs to be settled. Pyroptosis is a notable form of programmed cell death characterized by influx of sodium with water, swelling of cells, and finally osmotic lysis, which is distinctive from numerous classes of programmed cell death. So far, four major pathways underlying mechanisms of pyroptosis have been identified and pyroptosis is indicated to be connected with a variety of disorders including cancerous diseases. Interestingly enough, pyroptosis plays an important role in ovarian cancer with regard to long non-coding RNAs and several regulatory molecules, as is shown by previously published reports. In this review, we summarized major pathways of pyroptosis and the current research foundations of pyroptosis and ovarian cancer, anticipating enriching the thoughts for the treatment of ovarian cancer. What is more, some problems yet unsolved in this field were also raised to hopefully propose several potential threads of OVCA treatment and research directions in future.
Plasma Metabolomics Reveals Diagnostic Biomarkers and Risk Factors for Esophageal Squamous Cell Carcinoma
Authors: Yu Mengjie , Wen Wei , Yi Xin , Zhu Wei , Aa Jiye , Wang Guangji
Published: February 2022

Esophageal squamous carcinoma (ESCC) has a high morbidity and mortality rate. Identifying risk metabolites associated with its progression is essential for the early prevention and treatment of ESCC. A total of 373 ESCC, 40 esophageal squamous dysplasia (ESD), and 218 healthy controls (HC) subjects were enrolled in this study. Gas chromatography-mass spectrometry (GC/MS) was used to acquire plasma metabolic profiles. Receiver operating characteristic curve (ROC) and adjusted odds ratio (OR) were calculated to evaluate the potential diagnosis and prediction ability markers. The levels of alpha-tocopherol and cysteine were progressively decreased, while the levels of aminomalonic acid were progressively increased during the various stages (from precancerous lesions to advanced-stage) of exacerbation in ESCC patients. Alpha-tocopherol performed well for the differential diagnosis of HC and ESD/ESCC (AUROC>0.90). OR calculations showed that a high level of aminomalonic acid was not only a risk factor for further development of ESD to ESCC (OR>13.0) but also a risk factor for lymphatic metastasis in ESCC patients (OR>3.0). A low level of alpha-tocopherol was a distinguished independent risk factor of ESCC (OR< 0.5). The panel constructed by glycolic acid, oxalic acid, glyceric acid, malate and alpha-tocopherol performed well in distinguishing between ESD/ESCC from HC in the training and validation set (AUROC>0.95). In conclusion, the oxidative stress function was impaired in ESCC patients, and improving the body’s antioxidant function may help reduce the early occurrence of ESCC.
Multiparametric MRI and Machine Learning Based Radiomic Models for Preoperative Prediction of Multiple Biological Characteristics in Prostate Cancer
Authors: Fan Xuhui , Xie Ni , Chen Jingwen , Li Tiewen , Cao Rong , Yu Hongwei , He Meijuan , Wang Zilin , Wang Yihui , Liu Hao , Wang Han , Yin Xiaorui
Published: February 2022

Objectives

This study aims to develop and evaluate multiparametric MRI (MP-MRI)-based radiomic models as a noninvasive diagnostic method to predict several biological characteristics of prostate cancer.

Methods

A total of 252 patients were retrospectively included who underwent radical prostatectomy and MP-MRI examinations. The prediction characteristics of this study were as follows: Ki67, S100, extracapsular extension (ECE), perineural invasion (PNI), and surgical margin (SM). Patients were divided into training cohorts and validation cohorts in the ratio of 4:1 for each group. After lesion segmentation manually, radiomic features were extracted from MP-MRI images and some clinical factors were also included. Max relevance min redundancy (mRMR) and recursive feature elimination (RFE) based on random forest (RF) were adopted to select features. Six classifiers were included (SVM, KNN, RF, decision tree, logistic regression, XGBOOST) to find the best diagnostic performance among them. The diagnostic efficiency of the construction models was evaluated by ROC curves and quantified by AUC.

Results

RF performed best among the six classifiers for the four groups according to AUC values (Ki67 = 0.87, S100 = 0.80, ECE = 0.85, PNI = 0.82). The performance of SVM was relatively the best for SM (AUC = 0.77). The number and importance of DCE features ranked first in the models of each group. The combined models of MP-MRI and clinical characteristics showed no significant difference compared with MP-MRI models according to Delong’s tests.

Conclusions

Radiomics models based on MP-MRI have the potential to predict biological characteristics and are expected to be a noninvasive method to evaluate the risk stratification of prostate cancer.
Gynecologists Need to Be Vigilant—Two Case Reports of Intravascular Leiomyomatosis and Literature Review
Authors: Li Xiang , Ma Ning-Ye , Zhang Yao , Jiao Yi-Sheng
Published: February 2022

Background

Intravascular leiomyomatosis is a rare benign lesion with malignant potential. The cases are sporadic. Most patients have no clinical symptoms, and the preoperative diagnostic rate is low. Case 1 was misdiagnosed, passively managed during operation, recurred quickly, and underwent a secondary operation. We learned lessons from case 1 and treated the case 2 patient differently. The case 2 patient had a good prognosis. We hope the report will be helpful to other gynecologists.

Case Summary

Case 1: a 49-year-old woman complained of dysmenorrhea. Traditional ultrasound showed adenomyosis and a solid mass 6 * 3 cm in the right appendix. After routine examination, the patient underwent transabdominal total hysterectomy + bilateral salpingectomy + IVL tumor resection, with both ovaries kept. No medication was used after operation. Routine ultrasound was performed every 3 months. The disease recurred, and the patient underwent a secondary surgery 9 months after the first time. So far, 25 months after the secondary surgery, there is no sign of recurrence. Case 2: a 41-year-old woman underwent a routine body examination, where a left adnexal mass 7 cm was found. The patient underwent contrast-enhanced ultrasonography and was diagnosed and prepared well preoperatively. The patient underwent transabdominal total hysterectomy + bilateral salpingectomy + IVL tumor resection. GnRH-a drugs were used after operation for 3 cycle. Now, there is no sign of recurrence after operation for 23 months.

Conclusion

The incidence rate of IVL is low, and there are no typical clinical symptoms. It is easy to be ignored by gynecologists. Contrast-enhanced ultrasound is helpful to diagnose preoperatively and reduce misdiagnosis. Good preparation, full exploration of the pelvic and abdominal vessels, removal of lesions completely as much as possible, and anti-estrogen therapy after operation can reduce the recurrence of disease.
Excellent Outcome Following Sibling Peripheral Blood Hematopoietic Stem Cell Transplantation for Glanzmann Thrombasthenia: A Case Report
Authors: Li Jian hua , Sun Shu wen , Ai Yuan , Yang Xue , Zhu Yi ping
Published: February 2022

Glanzmann thrombasthenia (GT) is a rare autosomal recessive platelet disorder due to a qualitative or quantitative anomaly of the platelet membrane glycoprotein GPIIb/IIIa. Its clinical manifestations include mild to severe bleeding. GT diagnosis mainly depends on platelet function analysis, flow cytometry, and gene detection. Treatment methods include conservative symptomatic treatment and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT is the only clinical radical method for GT. Herein, we report a 2-year-old boy with GT successfully cured by related identical peripheral blood stem cell transplantation (PBSCT). The platelet disorder was corrected to a normal level after PBSCT, with no significant complication related to the transplantation. Hematopoietic stem cell transplantation with full-matched donor in early stage could be a treatment option for GT.
Sex and Rate Change Differences in QT/RR Hysteresis in Healthy Subjects
Authors: Andršová Irena , Hnatkova Katerina , Šišáková Martina , Toman Ondřej , Smetana Peter , Huster Katharina M. , Barthel Petra , Novotný Tomáš , Schmidt Georg , Malik Marek
Published: February 2022

While it is now well-understood that the extent of QT interval changes due to underlying heart rate differences (i.e., the QT/RR adaptation) needs to be distinguished from the speed with which the QT interval reacts to heart rate changes (i.e., the so-called QT/RR hysteresis), gaps still exist in the physiologic understanding of QT/RR hysteresis processes. This study was designed to address the questions of whether the speed of QT adaptation to heart rate changes is driven by time or by number of cardiac cycles; whether QT interval adaptation speed is the same when heart rate accelerates and decelerates; and whether the characteristics of QT/RR hysteresis are related to age and sex. The study evaluated 897,570 measurements of QT intervals together with their 5-min histories of preceding RR intervals, all recorded in 751 healthy volunteers (336 females) aged 34.3 ± 9.5 years. Three different QT/RR adaptation models were combined with exponential decay models that distinguished time-based and interval-based QT/RR hysteresis. In each subject and for each modelling combination, a best-fit combination of modelling parameters was obtained by seeking minimal regression residuals. The results showed that the response of QT/RR hysteresis appears to be driven by absolute time rather than by the number of cardiac cycles. The speed of QT/RR hysteresis was found decreasing with increasing age whilst the duration of individually rate corrected QTc interval was found increasing with increasing age. Contrary to the longer QTc intervals, QT/RR hysteresis speed was faster in females. QT/RR hysteresis differences between heart rate acceleration and deceleration were not found to be physiologically systematic (i.e., they differed among different healthy subjects), but on average, QT/RR hysteresis speed was found slower after heart rate acceleration than after rate deceleration.
Fine-Root Decomposition and Nutrient Return in Moso Bamboo (Phyllostachys pubescens J.Houz.) Plantations in Southeast China
Authors: Xu Yaowen , Huang Runxia , Zhou Benzhi , Ge Xiaogai
Published: February 2022

Plant fine-root decomposition is an important pathway for the reentry of nutrients into the soil. Studies have mainly focused on the loss of fine-root mass and the release characteristics of major elements, including, C, N, and P, but there are few reports on trace elements. In this study, in situ decomposition experiments were conducted to study the dynamic characteristics of mass loss and residual rates of 10 mineral elements in two diameter classes (<2 mm and 2–5 mm) of moso bamboo in the process of fine-root decomposition. The results of the year-long experiment reported herein showed that: (1) fine roots with diameters of less than 2 mm decomposed faster than those with diameters of 2–5 mm; (2) C, N, P, K, Ca, and Mg were released, whereas Fe, Mn, Zn, and Cu were enriched or changed little; (3) decomposition time and root diameter had significant effects on the remaining percentages of C, N, K, Ca, Mg, Mn, Zn, and Cu, and there were interactions among the elements (P < 0.05). The remaining percentages of P and Fe were only affected by decomposition time. This is the first comprehensive report on the variation in 10 elements during the fine-root decomposition of moso bamboo. The study expands our understanding of the release of mineral nutrients during fine-root decomposition, laying a solid theoretical foundation for further research on fine-root decomposition and plant–soil nutrient cycling.
Does Fair Coach Behavior Predict the Quality of Athlete Leadership Among Belgian Volleyball and Basketball Players: The Vital Role of Team Identification and Task Cohesion
Authors: De Backer Maarten , Van Puyenbroeck Stef , Fransen Katrien , Reynders Bart , Boen Filip , Malisse Florian , Vande Broek Gert
Published: February 2022

A vast stream of empirical work has revealed that coach and athlete leadership are important determinants of sport teams’ functioning and performance. Although coaches have a direct impact on individual and team outcomes, they should also strive to stimulate athletes to take up leadership roles in a qualitative manner. Yet, the relation between coach leadership behavior and the extent of high-quality athlete leadership within teams remains underexposed. Based on organizational justice theory and the social identity approach, the present research tested whether perceived justice of the coach positively predicts the quality of athlete leadership. Furthermore, we examined the role of group dynamic processes (i.e., team identification and task cohesion) within this relation. Belgian volleyball (N = 161) and basketball players (N = 78) were asked to rate the justice of their coach, their team identification, the task cohesion, and the athlete leadership quality in the team. Structural equation modeling indicated that coaches’ perceived justice positively predicted the quality of athletes’ leadership, and that this relation was established through three intermediate steps (i.e., from team identification to task cohesion, to athlete leadership quality). These results suggest that fair coach behavior does not only bridge the gap between leadership and followership, it also has the potential to improve the quality of athletes’ leadership within sport teams. More specifically, findings suggest that coaches’ perceived justice cultivates a shared social identity characterized by high levels of players’ identification with their team, which in turn increased their perceptions of the team’s task cohesion. Finally, this increased task cohesion encouraged the athlete leaders to demonstrate high-quality leadership.