bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Lactate Exposure Decreases Mitochondrial Function by Inhibition of Fatty Acid Uptake and Cardiolipin Alterations in Neonatal Rat Cardiomyocytes
Authors: San-Millan Iñigo , Sparagna Genevieve C. , Chapman Hailey L. , Warkins Valerie L. , Chatfield Kathryn C. , Shuff Sydney R. , Martinez Janel L. , Brooks George A.
Published: March 2022

Introduction

Lactate is an important signaling molecule with autocrine, paracrine and endocrine properties involved in multiple biological processes including regulation of gene expression and metabolism. Levels of lactate are increased chronically in diseases associated with cardiometabolic disease such as heart failure, type 2 diabetes, and cancer. Using neonatal ventricular myocytes, we tested the hypothesis that chronic lactate exposure could decrease the activity of cardiac mitochondria that could lead to metabolic inflexibility in the heart and other tissues.

Methods

Neonatal rat ventricular myocytes (NRVMs) were treated for 48 h with 5, 10, or 20 mM lactate and CPT I and II activities were tested using radiolabelled assays. The molecular species profile of the major mitochondrial phospholipid, cardiolipin, was determined using electrospray ionization mass spectrometry along with reactive oxygen species (ROS) levels measured by Amplex Red and mitochondrial oxygen consumption using the Seahorse analyzer.

Results

CPT I activity trended downward (p = 0.07) and CPT II activity significantly decreased with lactate exposure (p < 0.001). Cardiolipin molecular species containing four 18 carbon chains (72 carbons total) increased with lactate exposure, but species of other sizes decreased significantly. Furthermore, ROS production was strongly enhanced with lactate (p < 0.001) and mitochondrial ATP production and maximal respiration were both significantly down regulated with lactate exposure (p < 0.05 and p < 0.01 respectively).

Conclusions

Chronic lactate exposure in cardiomyocytes leads to a decrease in fatty acid transport, alterations of cardiolipin remodeling, increases in ROS production and decreases in mitochondrial oxygen consumption that could have implications for both metabolic health and flexibility. The possibility that both intra-, or extracellular lactate levels play roles in cardiometabolic disease, heart failure, and other forms of metabolic inflexibility needs to be assessed in vivo.
Antimicrobial Activity of Films and Coatings Containing Lactoperoxidase System: A Review
Authors: Yousefi Mojtaba , Nematollahi Amene , Shadnoush Mahdi , Mortazavian Amir M. , Khorshidian Nasim
Published: March 2022

The production of safe and healthy foodstuffs is considered as one of the most important challenges in the food industry, and achieving this important goal is impossible without using various processes and preservatives. However, recently, there has been a growing concern about the use of chemical preservatives and attention has been focused on minimal process and/or free of chemical preservatives in food products. Therefore, researchers and food manufacturers have been induced to utilize natural-based preservatives such as antimicrobial enzymes in their production. Lactoperoxidase, as an example of antimicrobial enzymes, is the second most abundant natural enzyme in the milk and due to its wide range of antibacterial activities, it could be potentially applied as a natural preservative in various food products. On the other hand, due to the diffusion of lactoperoxidase into the whole food matrix and its interaction and/or neutralization with food components, the direct use of lactoperoxidase in food can sometimes be restricted. In this regard, lactoperoxidase can be used as a part of packaging material, especially edible and coating, to keep its antimicrobial properties to extend food shelf-life and food safety maintenance. Therefore, this study aims to review various antimicrobial enzymes and introduce lactoperoxidase as a natural antimicrobial enzyme, its antimicrobial properties, and its functionality in combination with an edible film to extend the shelf-life of food products.
Association Between Na, K, and Lipid Intake in Each Meal and Blood Pressure
Authors: Imamura Momoko , Sasaki Hiroyuki , Shinto Takae , Tahara Yu , Makino Saneyuki , Kuwahara Mai , Tada Ayako , Abe Nanako , Michie Mikiko , Shibata Shigenobu
Published: March 2022

Cardiovascular diseases (CVDs) are one of the leading causes of death worldwide, and one of the most significant risk factors for CVDs is high blood pressure. Blood pressure is associated with various nutrients, such as sodium, potassium, and cholesterol. However, research focusing on the timing of intake of these nutrients and blood pressure has not been conducted. In this study, we used dietary data and a questionnaire asking about the sleep, physical activity, and blood pressure, collected from the food-log app “Asken” (total N = 2,402), to investigate the relationship between the dietary data of nutrient intake in the breakfast, lunch, and dinner and blood pressure. Daily total intake of various nutrients such as sodium, sodium-to-potassium ratio, total energy, lipid, carbohydrate, and saturated fat showed a significant association with blood pressure depending on the meal timing. From multiple regression analysis, eliminating the confounding factors, lunch sodium-to-potassium ratio, dinner energy, lipid, cholesterol, saturated fat, and alcohol intake were positively associated with blood pressure, whereas breakfast protein and lunch fiber intake showed a negative association with blood pressure. Our results suggest that nutrient intake timing is also an important factor in the prevention of high blood pressure. Our study provides possibilities to prevent hypertension by changing the timing of nutrient intake, especially sodium, together with potassium and lipids. However, because our research was limited to food-log app users, broader research regarding the general population needs to be conducted.
Comprehensive Analysis Identified Mutation-Gene Signature Impacts the Prognosis Through Immune Function in Hepatocellular Carcinoma
Authors: Lin Zhuo , Xu Qian , Song Xian , Zeng Yuan , Zeng Liuwei , Zhao Luying , Xu Jun , Miao Dan , Chen Zhuoyan , Yu Fujun
Published: March 2022

Background

Hepatocellular carcinoma (HCC) is a life-threatening and refractory malignancy with poor outcome. Genetic mutations are the hallmark of cancer. Thus far, there is no comprehensive prognostic model constructed by mutation-gene transcriptome in HCC. The prognostic value of mutation-gene signature in HCC remains elusive.

Methods

RNA expression profiles and the corresponding clinical information were recruited from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was employed to establish gene signature. Kaplan–Meier curve and time-dependent receiver operating characteristic curve were implemented to evaluate the prognostic value. The Wilcoxon test was performed to analyze the expression of immune checkpoint genes, cell cycle genes, and tumor drug resistance genes in different risk groups. Finally, quantitative real-time PCR (qRT-RCR) and immunohistochemistry (IHC) were performed to validate the mRNA and protein expression between HCC and adjacent nontumorous tissues in an independent cohort.

Results

A prognostic model consisting of five mutated genes was established by LASSO Cox regression analysis. The prognostic model classified patients into high- and low-risk groups. Compared with the low‐risk group, patients in the high‐risk group had significantly worse survival results. The prognostic model can accurately predict the overall survival of HCC patients and predict overall survival more accurately when combined with stage. Furthermore, the immune checkpoint genes, cell cycle genes, and tumor drug resistance genes were higher expressed in the high-risk group compared in the low-risk group. In addition, the expression level of prognostic signature genes was validated in an independent sample cohort, which was consistent with RNA sequencing expression in the TCGA database.

Conclusion

The prediction model of HCC constructed using mutation-related genes is of great significance for clinical decision making and the personalized treatment of patients with HCC.
Palliative Care and End-of-Life Issues in Elderly Cancer Patients With Head and Neck Cancer
Authors: Schrijvers Dirk , Charlton Rodger
Published: March 2022

The number of elderly patients with incurable head and neck cancer will increase. They are in need of geriatric palliative care, that takes into account oncology, palliative care and geriatric medicine. In this review of the most recent and relevant literature and includes the expert opinion of the authors, several physical problems (e.g. pain, fatigue, malnutrition, and loco-regional problems) encountered by the elderly head and neck cancer patients are addressed. In addition end-of life issues in this patient population are discussed.
TGF-β1-Mediated PD-L1 Glycosylation Contributes to Immune Escape via c-Jun/STT3A Pathway in Nasopharyngeal Carcinoma
Authors: Ma Xue-Min , Luo Yun-Fan , Zeng Fang-Fang , Su Chang , Liu Xiong , Li Xiang-Ping , Lu Juan
Published: March 2022

Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. However, the molecular mechanisms underlying how PD-1/PD-L1 expression is regulated still remain unclear in nasopharyngeal carcinoma (NPC). Here, we found N-glycosylation of PD-L1 in NPC cells and tissues. Mechanistically, we showed that STT3A transferred N-linked glycans to PD-L1, and TGF-β1 could positively regulate STT3A expression through activating c-Jun to bind to STT3A promoter. Functional assays showed that inhibition of TGF-β1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. Analysis of clinical specimens revealed that the expression of STT3A was positively correlated with TGF-β1 and c-Jun, and high STT3A expression was positively correlated with a more advanced clinical stage. Altogether, TGF-β1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies.
Association of HER-2/CEP17 Ratio and HER-2 Copy Number With pCR Rate in HER-2-Positive Breast Cancer After Dual-Target Neoadjuvant Therapy With Trastuzumab and Pertuzumab
Authors: Li Fanfan , Ju Qian , Gao Cong , Li Jingjing , Wang Xiaolei , Yan Min , Zhang Liying , Huang Meiling , Long Qihe , Jin Xiangting , Li Nanlin
Published: March 2022

Objective

To explore the correlation between HER-2 status and pathological complete response (pCR) in HER-2-positive breast cancer after dual anti-HER-2 neoadjuvant therapy with trastuzumab and pertuzumab.

Methods

A total of 57 HER-2-positive breast cancer patients admitted to the Second Affiliated Hospital of Anhui Medical University and Xijing Hospital Affiliated to Air Force Military Medical University, between January 1, 2019 and September 30, 2020, were enrolled in this multicenter retrospective study. HER-2 status, including HER-2/CEP17 ratio and HER-2/cell number ratio, was detected by FISH. The correlation between HER-2 status/clinicopathological data and pCR was analyzed. The ROC curve was drawn to determine the cutoff value.

Results

IHC assessment revealed 40 (70.18%) patients with IHC 3+ and 17 (29.82%) with IHC 2+. 41/57 (71.93%) patients achieved pCR. FISH revealed that the ratio of HER-2/chromosome 17 centromere (HER-2/CEP17) (p<0.001) and the ratio of HER-2/cell number (p<0.001) was significantly correlated with the pCR rate. ROC analysis showed that patients with an HER-2/CEP17 ratio ≥4.495 or HER-2/cell number ≥11.650 have a high pCR rate after dual anti-HER-2 neoadjuvant therapy, suggesting its predictive significance.

Conclusion

The response to dual-targeted neoadjuvant therapy with trastuzumab and pertuzumab was adequate in hormone receptor-negative, HER-2-positive breast cancer patients. HER-2/CEP17 ratio and HER-2/cell number ratio were crucial for predicting efficacy.
Cervical Cancer Recurrence and Patient Survival After Radical Hysterectomy Followed by Either Adjuvant Chemotherapy or Adjuvant Radiotherapy With Optional Concurrent Chemotherapy: A Systematic Review and Meta-Analysis
Authors: Zhang Yu-fei , Fan Yu , Zhang Peng , Ruan Jia-ying , Mu Yi , Li Jin-ke
Published: March 2022

Objective

To compare cervical cancer recurrence and patient survival after radical hysterectomy followed by either adjuvant chemotherapy (AC) or adjuvant radiotherapy with or without concurrent chemotherapy (AR/CCRT).

Methods

We systematically searched PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov to identify studies reporting recurrence or survival of cervical cancer patients who received AC or AR/CCRT after radical hysterectomy. Data were meta-analyzed using a random-effects model, and heterogeneity was evaluated using the I2 test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity.

Results

The meta-analysis included 14 non-randomized studies and two randomized controlled trials, altogether involving 5,052 cervical cancer patients. AC and AR/CCRT groups did not differ significantly in rates of total or local recurrence or mortality. Nevertheless, AC was associated with significantly lower risk of distant recurrence [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.55-0.81] and higher rates of overall survival [hazard ratio (HR) 0.69, 95%CI 0.54-0.85] and disease-free survival rate (HR 0.77, 95%CI 0.62-0.92).

Conclusions

AC may be an effective alternative to AR/CCRT for cervical cancer patients after radical hysterectomy, especially younger women who wish to preserve their ovaries and protect them from radiation damage.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021252518).
Expression Patterns of Ezrin and AJAP1 and Clinical Significance in Breast Cancer
Authors: Xu Cong , Wang Feng , Hao Li , Liu Jing , Shan Benjie , Lv Shuhua , Han Xinghua , Pan Yueyin , Niu Yun
Published: March 2022

Ezrin and adherens junction-associated protein 1 (AJAP1) are structural proteins which are involved in numerous human malignancies. However, little is known about the relationship between them in breast cancer. This study was set out to investigate the relationship between them and to further explore the mechanism of AJAP1-mediating cytoskeleton in breast cancer progression. Ezrin and AJAP1 expressions were detected in 377 samples of breast cancer by immunohistochemistry, and different expression patterns between AJAP1 and Ezrin with clinicopathological parameters were analyzed. Besides, univariate and multivariate Cox models were used to evaluate their prognostic potential. Enzyme-linked immunosorbent assay, Western blot, qRT-PCR, and phalloidin staining of F-actin were used to explore the relationship and the mechanism between AJAP1 and Ezrin in cytoskeleton arrangement. 377 cases of breast cancer results showed that AJAP1 expression was negatively related with histological grade and lymph node involvement and could be an independent prognosis marker of breast cancer. AJAP1 expression tended to be higher in the Ezrin-negative expression case. Patients with AJAP1negative and Ezrinpositive expression had a worse prognosis (p < 0.0001) and shorter DFS (p = 0.015). More importantly, AJAP1 depletion increased the cell ability of F-actin formation through promoting Ezrin expression. AJAP1 depletion might mediate breast cancer malignancy potential through promoting Ezrin expression and cytoskeleton formation.
Diagnostic Value, Prognostic Value, and Immune Infiltration of LOX Family Members in Liver Cancer: Bioinformatic Analysis
Authors: Sun Chenyu , Ma Shaodi , Chen Yue , Kim Na Hyun , Kailas Sujatha , Wang Yichen , Gu Wenchao , Chen Yisheng , Tuason John Pocholo W. , Bhan Chandur , Manem Nikitha , Huang Yuting , Cheng Ce , Zhou Zhen , Zhou Qin , Zhu Yanzhe
Published: March 2022

Background

Liver cancer (LC) is well known for its prevalence as well as its poor prognosis. The aberrant expression of lysyl oxidase (LOX) family is associated with liver cancer, but their function and prognostic value in LC remain largely unclear. This study aimed to explore the function and prognostic value of LOX family in LC through bioinformatics analysis and meta-analysis.

Results

The expression levels of all LOX family members were significantly increased in LC. Area under the receiver operating characteristic curve (AUC) of LOXL2 was 0.946 with positive predictive value (PPV) of 0.994. LOX and LOXL3 were correlated with worse prognosis. Meta-analysis also validated effect of LOX on prognosis. Nomogram of these two genes and other predictors was also plotted. There was insufficient data from original studies to conduct meta-analysis on LOXL3. The functions of LOX family members in LC were mostly involved in extracellular and functions and structures. The expressions of LOX family members strongly correlated with various immune infiltrating cells and immunomodulators in LC.

Conclusions

For LC patients, LOXL2 may be a potential diagnostic biomarker, while LOX and LOXL3 have potential prognostic and therapeutic values. Positive correlation between LOX family and infiltration of various immune cells and immunomodulators suggests the need for exploration of their roles in the tumor microenvironment and for potential immunotherapeutic to target LOX family proteins.
A Promising Preoperative Prediction Model for Microvascular Invasion in Hepatocellular Carcinoma Based on an Extreme Gradient Boosting Algorithm
Authors: Liu Weiwei , Zhang Lifan , Xin Zhaodan , Zhang Haili , You Liting , Bai Ling , Zhou Juan , Ying Binwu
Published: March 2022

Background

The non-invasive preoperative diagnosis of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is vital for precise surgical decision-making and patient prognosis. Herein, we aimed to develop an MVI prediction model with valid performance and clinical interpretability.

Methods

A total of 2160 patients with HCC without macroscopic invasion who underwent hepatectomy for the first time in West China Hospital from January 2015 to June 2019 were retrospectively included, and randomly divided into training and a validation cohort at a ratio of 8:2. Preoperative demographic features, imaging characteristics, and laboratory indexes of the patients were collected. Five machine learning algorithms were used: logistic regression, random forest, support vector machine, extreme gradient boosting (XGBoost), and multilayer perception. Performance was evaluated using the area under the receiver operating characteristic curve (AUC). We also determined the Shapley Additive exPlanation value to explain the influence of each feature on the MVI prediction model.

Results

The top six important preoperative factors associated with MVI were the maximum image diameter, protein induced by vitamin K absence or antagonist-II, α-fetoprotein level, satellite nodules, alanine aminotransferase (AST)/aspartate aminotransferase (ALT) ratio, and AST level, according to the XGBoost model. The XGBoost model for preoperative prediction of MVI exhibited a better AUC (0.8, 95% confidence interval: 0.74–0.83) than the other prediction models. Furthermore, to facilitate use of the model in clinical settings, we developed a user-friendly online calculator for MVI risk prediction based on the XGBoost model.

Conclusions

The XGBoost model achieved outstanding performance for non-invasive preoperative prediction of MVI based on big data. Moreover, the MVI risk calculator would assist clinicians in conveniently determining the optimal therapeutic remedy and ameliorating the prognosis of patients with HCC.
Surfactant Therapy for Respiratory Distress Syndrome in High- and Ultra-High-Altitude Settings
Authors: Duan Xudong , Li Jiujun , Chen Long , Shi Yuan , Chen Xianyang , Xue Teng , Liu Chongde , Wang Xiaorong , Qiu Quanfang , Yu Zhen , Qiang Bacuozhen , Wu Hong , Wu Tianqi , Zhang Lihong , Chen Zhangsheng , Jigme Dobje , Xu Aili , Mima Zhuoga , Da Zhen , Ren Min , Gesang Deji , Pubu Zhaxi , Li Chun , Lv Yanchao , Zhou Haoquan , Zhang Xue , Dawa Zhuoma , Gongjue Wujin , Wang Li , Wu Li , Li Xuelian
Published: March 2022

Objective

The objective of this study is to investigate the therapeutic effect of surfactant replacement therapy (SRT) on respiratory distress syndrome (RDS) in premature infants in the Qinghai-Tibet Plateau.

Materials and Methods

This multi-center retrospective cohort study collected and screened reasonable clinical data of 337 premature infants with RDS from 10 hospitals in the Qinghai-Tibet Plateau from 2015 to 2017. We grouped the cases by rationally analyzing their baseline characteristics, using logistic analysis to evaluate each factor's effect on the prognosis of the infants, and comparing the short-term improvement in blood gas and mortality after SRT treatment at different altitudes, in high-altitude (1,500–3,500 m) and ultra-high-altitude (3,500–5,500 m) groups.

Results

Independent of altitude, the mortality rate of children with RDS in the SRT group was significantly lower than that of children in the non-SRT group (both P < 0.05). The effect of SRT on preterm infants with RDS in the high-altitude group [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.22–0.87, P = 0.02] was better than that in the infants in the ultra-high-altitude group (OR = 0.26, 95% CI = 0.13–0.58, P < 0.01), with death rates of 34.34 and 49.71%, respectively. Similarly, after SRT, the improvement of PaO2/FiO2 and pH of children at high altitude was significantly better than those of children at ultra-high altitude (all P < 0.01).

Conclusions

SRT plays a prominent role in curing infants with RDS in both high- and ultra-high-altitude regions, although with better effects at high rather than ultra-high altitude. This study provides a basis for further large-scale studies on SRT for RDS treatment at high altitudes.
Case Report: Clinical and Pathological Findings of a Recurrent C3 Glomerulopathy With Superimposed Membranoproliferative Glomerulonephritis Pattern and Cryoglobulinemia Associated With COVID-19
Authors: Daneshgar Nastaran , Liang Peir-In , Michels Christina J. , Nester Carla M. , Harshman Lyndsay A. , Dai Dao-Fu
Published: March 2022

Coronavirus disease 2019 (COVID-19) may cause a wide spectrum of kidney pathologies. The impact of COVID-19 is unclear in the context of the complement system abnormalities, including C3 glomerulopathy (C3G). In this report, we describe a young adult receiving a kidney transplant for C3 glomerulopathy (C3G), a disorder of the alternative complement pathway. The patient developed a recurrent C3G ~7 months after transplantation. His post-transplant course was complicated by SARS-CoV-2 infection. There was a progression of glomerulonephritis, characterized by de novo immune-complex mediated membranoproliferative glomerulonephritis pattern of injury with crescentic and necrotizing features, along with positive immunoglobulins, persistent IgM staining and the presence of cryoglobulinemia. COVID-19 may have aggravated the inherent complement dysregulation and contributed to cryoglobulinemia observed in this patient. Our study of 5 sequential kidney allograft biopsy series implicates that COVID-19 in this patient promoted a superimposed immune complex-mediated glomerulonephritis with membranoproliferative glomerulonephritis (MPGN) pattern and cryoglobulinemia, which was a potentiating factor in allograft loss. This work represents the first report of cryoglobulinemic GN after COVID-19.
Natural Products Against Renal Fibrosis via Modulation of SUMOylation
Authors: Liu Peng , Zhang Jing , Wang Yun , Wang Chen , Qiu Xinping , Chen Dan-Qian
Published: March 2022

Renal fibrosis is the common and final pathological process of kidney diseases. As a dynamic and reversible post-translational modification, SUMOylation and deSUMOylation of transcriptional factors and key mediators significantly affect the development of renal fibrosis. Recent advances suggest that SUMOylation functions as the promising intervening target against renal fibrosis, and natural products prevent renal fibrosis via modulating SUMOylation. Here, we introduce the mechanism of SUMOylation in renal fibrosis and therapeutic effects of natural products. This process starts by summarizing the key mediators and enzymes during SUMOylation and deSUMOylation and its regulation role in transcriptional factors and key mediators in renal fibrosis, then linking the mechanism findings of SUMOylation and natural products to develop novel therapeutic candidates for treating renal fibrosis, and concludes by commenting on promising therapeutic targets and candidate natural products in renal fibrosis via modulating SUMOylation, which highlights modulating SUMOylation as a promising strategy for natural products against renal fibrosis.
FGF4, A New Potential Regulator in Gestational Diabetes Mellitus
Authors: Fan Miaojuan , Pan Tongtong , Jin Wei , Sun Jian , Zhang Shujun , Du Yali , Chen Xinwei , Chen Qiong , Xu Wenxin , Choo Siew Woh , Zhu Guanghui , Chen Yongping , Zhou Jie
Published: March 2022

Background: Gestational diabetes mellitus (GDM) is associated with adverse maternal and neonatal outcomes, however the underlying mechanisms remain elusive. The aim of this study was to find efficient regulator of FGFs in response to the pathogenesis of GDM and explore the role of the FGFs in GDM.

Methods: We performed a systematic screening of placental FGFs in GDM patients and further in two different GDM mouse models to investigate their expression changes. Significant changed FGF4 was selected, engineered, purified, and used to treat GDM mice in order to examine whether it can regulate the adverse metabolic phenotypes of the diabetic mice and protect their fetus.

Results: We found FGF4 expression was elevated in GDM patients and its level was positively correlated to blood glucose, indicating a physiological relevance of FGF4 with respect to the development of GDM. Recombinant FGF4 (rFGF4) treatment could effectively normalize the adverse metabolic phenotypes in high fat diet induced GDM mice but not in STZ induced GDM mice. However, rFGF4 was highly effective in reduce of neural tube defects (NTDs) of embryos in both the two GDM models. Mechanistically, rFGF4 treatment inhibits pro-inflammatory signaling cascades and neuroepithelial cell apoptosis of both GDM models, which was independent of glucose regulation.

Conclusions/interpretation: Our study provides novel insight into the important roles of placental FGF4 and suggests that it may serve as a promising diagnostic factor and therapeutic target for GDM.
Controlling Nutritional Status (CONUT) Predicts Survival in Gastric Cancer Patients With Immune Checkpoint Inhibitor (PD-1/PD-L1) Outcomes
Authors: Chen Li , Sun Hao , Zhao Ruihu , Huang Rong , Pan Hongming , Zuo Yanjiao , Zhang Lele , Xue Yingwei , Song Hongjiang , Li Xingrui
Published: March 2022

Objective: The controlling nutritional status (CONUT), based on total lymphocyte count (TL), total cholesterol level (T-CHOL), and serum albumin (ALB), can provide a useful immunological prognostic biomarker for cancer patients. The present study aims to investigate the correlation between CONUT and prognosis in gastric cancer patients receiving immune checkpoint inhibitor (ICI) treatment.

Methods: We retrospectively enrolled 146 patients with gastric cancer treated with ICIs (PD-1/PD-L1 inhibitors) from August 2016 to December 2020. The clinicopathologic characteristics were analyzed by Chi-square test or Fisher’s exact test. The Kaplan–Meier and log-rank test were used to calculate and compare progression-free survival (PFS) and overall survival (OS). The prognostic and predictive factors of PFS and OS were identified by univariate and multivariate analyses. A nomogram was developed to estimate 1-, 3-, and 5-year PFS and OS probability.

Results: Through the CONUT score, there were 75 (51.37%) patients in the low CONUT group and 71 (48.63%) patients in the high CONUT group. There was a correlation between the CONUT score and age (p = 0.005), pathology (p = 0.043), ALB (p = 0.020), PALB (p = 0.032), and Hb (p = 0.001). The CA724, TNM stage, and treatment (ICIs vs. chemotherapy) were the independent prognostic factors for PFS and OS by multivariate analyses. Patients with high CONUT score had poorer PFS and OS (χ2 = 3.238, p = 0.072, and χ2 = 4.298, p = 0.038). In the subgroup analysis, the patients with high CONUT score were associated with shorter PFS and OS with ICIs or chemotherapy. With the PD-1/PD-L1 positive expression, the patients with high CONUT score had shorter PFS and OS than those with low CONUT score. Furthermore, the patients with high CA724 value were associated with shorter PFS and OS. The toxicity assessment in ICIs or chemotherapy was significantly associated with anemia. The nomograms were constructed to predict the probability of 1-, 3-, and 5-year PFS, and 1-, 3-, and 5-year OS with C-indices of 0.749 and 0.769, respectively.

Conclusion: The CONUT, as a novel immuno-nutritional biomarker, may be useful in identifying gastric cancer patients who are unlikely to benefit from ICI treatment.
Vanillin Derivatives Reverse Fusobacterium nucleatum-Induced Proliferation and Migration of Colorectal Cancer Through E-Cadherin/β-Catenin Pathway
Authors: Zhou Zhongkun , Wang Yiqing , Ji Rui , Zhang Dekui , Ma Chi , Ma Wantong , Ma Yunhao , Jiang Xinrong , Du Kangjia , Zhang Rentao , Chen Peng
Published: March 2022

Colorectal cancer (CRC) is a common clinical malignant tumor and closely related to intestinal microbiome disorders. Especially, Fusobacterium nucleatum (F. nucleatum) is one of the most prevalent pathogens in CRC. However, its change in CRC patients of Northwest China, an area with a high incidence of gastrointestinal tumors, is unclear, and therapeutic strategies targeting F. nucleatum remain unresolved. Here, fecal samples of healthy people and CRC patients were studied using 16S rRNA sequencing to explore microbial community alterations. Additionally, vanillin derivate (IPM711 and IPM712) intervention by coculture with CRC cells and potential mechanism were investigated. Results showed that intestinal microbial homeostasis was gradually dysregulated, and the abundance of Fusobacterium was higher in CRC patients. Moreover, IPM711 and IPM712 showed better anti-F. nucleatum activity than vanillin by increasing cell membrane permeability and destroying bacterial integrity. In addition, IPM711 and IPM712 could downregulate the expression of E-cadherin and β-catenin, thus, suppressing the migration of HCT116. Collectively, IPM711 and IPM712 have both anticolorectal cancer and anti-F. nucleatum activities, providing potential natural product drug candidates for microbe-targeted strategies for the treatment of CRC.
Automatic Detection of Osteochondral Lesions of the Talus via Deep Learning
Authors: Wang Gang , Li Tiefeng , Zhu Lei , Sun Siyuan , Wang Juntao , Cui Yidong , Liu Ben , Sun Yuliang , Xu Qingjia , Li Jianmin
Published: March 2022

Screening of osteochondral lesions of the talus (OLTs) from MR imags usually requires time and efforts, and in most case lesions with small size are often missed in clinical practice. Thereore, it puts forward higher requirements for a more efficient OLTs screening method. To develop an automatic screening system for osteochondral lesions of the talus (OLTs), we collected 92 MRI images of patients with ankle pain from Qilu Hospital of Shandong University and proposed an AI (artificial intelligence) aided lesion screening system, which is automatic and based on deep learning method. A two-stage detection method based on the cascade R-CNN model was proposed to significantly improve the detection performance by taking advantage of multiple intersection-over-union thresholds. The backbone network was based on ResNet50, which was a state-of-art convolutional neural network model in image classification task. Multiple regression using cascaded detection heads was applied to further improve the detection precision. The mean average precision (mAP) that is adopted as major metrics in the paper and mean average recall (mAR) was selected to evaluate the performance of the model. Our proposed method has an average precision of 0.950, 0.975, and 0.550 for detecting the talus, gaps and lesions, respectively, and the mAP, mAR was 0.825, 0.930. Visualization of our network performance demonstrated the effectiveness of the model, which implied that accurate detection performance on these tasks could be further used in real clinical practice.
Exploring for New Insights in the Performance of a 3D Orbital Angular Momentum Mode-Sorter
Authors: Lightman Shlomi , Wengrowitcz Jonathan M. , Teitelboim Ayelet , Gvishi Raz , Hurvitz Gilad
Published: March 2022

Optical vortex beams are light beams that can carry orbital angular momentum (OAM). Hence, such beams may serve as potential candidates for carriers of information in optical communication and quantum optics applications. This is owing to their spatial orthogonality, as these beams can be combined (multiplex) or separated (demultiplexed). We recently demonstrated a new method to detect OAM states by using a 3D-direct laser printing fabrication process. Measuring the mode-sorter performance was challenging, mainly due to mechanical and optical sensitivities originated from misalignments. In this work, this sensitivity was thoroughly examined. Pure OAM states having lateral and angular misalignments relative to the mode-sorter were introduced, and cross-talk between resolved states was theoretically simulated. The system is relatively vulnerable to small misalignments, which challenge its implementations in free-space communication systems. However, this might be an advantage for counseled communication, in which eavesdropping becomes more challenging, due to the angle-dependent increased modal cross-talk.
Near-Infrared Dual-Gas Sensor System for Methane and Ethane Detection Using a Compact Multipass Cell
Authors: Xi Zhenhai , Zheng Kaiyuan , Zheng Chuantao , Zhang Haipeng , Song Fang , Li Chunguang , Ye Weilin , Zhang Yu , Wang Yiding , Tittel Frank K.
Published: March 2022

In this invited paper, a compact dense-pattern multipass cell-based near-infrared sensor system was demonstrated for detection of parts-per-billion in volume (ppbv)-level methane (CH4) and ethane (C2H6). The dimension size of the fabricated gas cell is 18.5 × 8 × 9 cm3 with an absorption path length of 9.39 m. CH4 measurement was realized within a spectral range of 6,046–6,048 cm−1 and an absorption line of 6,046.95 cm−1. The spectral range for C2H6 detection is 5,951–5,953 cm−1 with an absorption line of 5,951.73 cm−1. Allan deviation analysis was used for evaluating the dual-gas sensing performance, and a detection limit of 78 ppbv for CH4 and 190 ppbv for C2H6 were achieved, respectively, with an averaging time of 0.8 s. Furthermore, CH4 measurement in the indoor and outdoor atmosphere was both performed to verify the field sensing capability of the sensor system. Compared with two separate sensor systems for CH4/C2H6 sensing, the proposed dual-gas sensor system using two near-infrared lasers and one multipass cell has the advantages of low-cost, compact-size without decreasing the selectivity and sensitivity.
Extended ECG Improves Classification of Paroxysmal and Persistent Atrial Fibrillation Based on P- and f-Waves
Authors: Zink Matthias Daniel , Laureanti Rita , Hermans Ben J. M. , Pison Laurent , Verheule Sander , Philippens Suzanne , Pluymaekers Nikki , Vroomen Mindy , Hermans Astrid , van Hunnik Arne , Crijns Harry J. G. M. , Vernooy Kevin , Linz Dominik , Mainardi Luca , Auricchio Angelo , Zeemering Stef , Schotten Ulrich
Published: March 2022

Background

The standard 12-lead ECG has been shown to be of value in characterizing atrial conduction properties. The added value of extended ECG recordings (longer recordings from more sites) has not been systematically explored yet.

Objective

The aim of this study is to employ an extended ECG to identify characteristics of atrial electrical activity related to paroxysmal vs. persistent atrial fibrillation (AF).

Methods

In 247 participants scheduled for AF ablation, an extended ECG was recorded (12 standard plus 3 additional leads, 5 min recording, no filtering). For patients presenting in sinus rhythm (SR), the signal-averaged P-wave and the spatiotemporal P-wave variability was analyzed. For patients presenting in AF, f-wave properties in the QRST (the amplitude complex of the ventricular electrical activity: Q-, R-, S-, and T-wave)-canceled ECG were determined.

Results

Significant differences between paroxysmal (N = 152) and persistent patients with AF (N = 95) were found in several P-wave and f-wave parameters, including parameters that can only be calculated from an extended ECG. Furthermore, a moderate, but significant correlation was found between echocardiographic parameters and P-wave and f-wave parameters. There was a moderate correlation of left atrial (LA) diameter with P-wave energy duration (r = 0.317, p < 0.001) and f-wave amplitude in lead A3 (r = −0.389, p = 0.002). The AF-type classification performance significantly improved when parameters calculated from the extended ECG were taken into account [area under the curve (AUC) = 0.58, interquartile range (IQR) 0.50–0.64 for standard ECG parameters only vs. AUC = 0.76, IQR 0.70–0.80 for extended ECG parameters, p < 0.001].

Conclusion

The P- and f-wave analysis of extended ECG configurations identified specific ECG features allowing improved classification of paroxysmal vs. persistent AF. The extended ECG significantly improved AF-type classification in our analyzed data as compared to a standard 10-s 12-lead ECG. Whether this can result in a better clinical AF type classification warrants further prospective study.
Simulation Modeling of Reduced Glycosylation Effects on Potassium Channels of Mouse Cardiomyocytes
Authors: Kim Haedong , Yang Hui , Ednie Andrew R. , Bennett Eric S.
Published: March 2022

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure and the primary reason for heart transplantation; upward of 70% of DCM cases are considered idiopathic. Our in-vitro experiments showed that reduced hybrid/complex N-glycosylation in mouse cardiomyocytes is linked with DCM. Further, we observed direct effects of reduced N-glycosylation on Kv gating. However, it is difficult to rigorously determine the effects of glycosylation on Kv activity, because there are multiple Kv isoforms in cardiomyocytes contributing to the cardiac excitation. Due to complex functions of Kv isoforms, only the sum of K+ currents (IKsum) can be recorded experimentally and decomposed later using exponential fitting to estimate component currents, such as IKto, IKslow, and IKss. However, such estimation cannot adequately describe glycosylation effects and Kv mechanisms. Here, we propose a framework of simulation modeling of Kv kinetics in mouse ventricular myocytes and model calibration using the in-vitro data under normal and reduced glycosylation conditions through ablation of the Mgat1 gene (i.e., Mgat1KO). Calibrated models facilitate the prediction of Kv characteristics at different voltages that are not directly observed in the in-vitro experiments. A model calibration procedure is developed based on the genetic algorithm. Experimental results show that, in the Mgat1KO group, both IKto and IKslow densities are shown to be significantly reduced and the rate of IKslow inactivation is much slower. The proposed approach has strong potential to couple simulation models with experimental data for gaining a better understanding of glycosylation effects on Kv kinetics.
Low Ambient Temperature Exposition Impairs the Accuracy of a Non-invasive Heat-Flux Thermometer
Authors: Masè Michela , Werner Andreas , Putzer Gabriel , Avancini Giovanni , Falla Marika , Brugger Hermann , Micarelli Alessandro , Strapazzon Giacomo
Published: March 2022

Background

Indirect core body temperature (CBT) monitoring from skin sensors is gaining attention for in-field applications thanks to non-invasivity, portability, and easy probe positioning. Among skin sensors, heat-flux devices, such as the so-called Double Sensor (DS), have demonstrated reliability under various experimental and clinical conditions. Still, their accuracy at low ambient temperatures is unknown. In this randomized cross-over trial, we tested the effects of cold temperature exposition on DS performance in tracking CBT.

Methods

Twenty-one participants were exposed to a warm (23.2 ± 0.4°C) and cold (−18.7 ± 1.0°C) room condition for 10 min, following a randomized cross-over design. The accuracy of the DS to estimate CBT in both settings was assessed by quantitative comparison with esophageal (reference) and tympanic (comparator) thermometers, using Bland–Altman and correlation analyses (Pearson’s correlation coefficient, r, and Lin’s concordance correlation coefficient, CCC).

Results

In the warm room setting, the DS showed a moderate agreement with the esophageal sensor [bias = 0.09 (−1.51; 1.69) °C, r = 0.40 (p = 0.069), CCC = 0.22 (−0.006; 0.43)] and tympanic sensor [bias = 2.74 (1.13; 4.35) °C, r = 0.54 (p < 0.05), CCC = 0.09 (0.008; 0.16)]. DS accuracy significantly deteriorated in the cold room setting, where DS temperature overestimated esophageal temperature [bias = 2.16 (−0.89; 5.22) °C, r = 0.02 (0.94), CCC = 0.002 (−0.05; 0.06)]. Previous exposition to the cold influenced temperature values measured by the DS in the warm room setting, where significant differences (p < 0.00001) in DS temperature were observed between randomization groups.

Conclusion

DS accuracy is influenced by environmental conditions and previous exposure to cold settings. These results suggest the present inadequacy of the DS device for in-field applications in low-temperature environments and advocate further technological advancements and proper sensor insulation to improve performance in these conditions.
Updates in the Diagnosis of Intraductal Neoplasms of the Pancreas
Authors: Assarzadegan Naziheh , Babaniamansour Sepideh , Shi Jiaqi
Published: March 2022

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer worldwide. There are many reasons for this dismal prognosis, including the advanced stage at the time of diagnosis and the lack of effective therapeutic approaches. Intraductal papillary mucinous neoplasms (IPMNs) represent detectable and treatable precursor lesions of PDAC. Our understanding of the pathology of IPMNs has evolved over the past few decades, and new advances in diagnostic tools have emerged. The new World Health Organization (WHO) classification scheme now recognizes the previously considered variants of IPMNs, such as intraductal oncocytic papillary neoplasms (IOPNs) and intraductal tubulopapillary neoplasms (ITPNs), as distinct neoplasms. New imaging and molecular diagnostic tests are being developed to recognize these PDAC precursor lesions better. Here, we review the advances in diagnostic tools for IPMNs, IOPNs, and ITPNs, emphasizing the new (5th edition, 2019) WHO classification for pathological diagnosis, molecular markers, new laboratory tests, and imaging tools.
Cross-Year Reuse of Historical Samples for Crop Mapping Based on Environmental Similarity
Authors: Liu Zhe , Zhang Lin , Yu Yaoqi , Xi Xiaojie , Ren Tianwei , Zhao Yuanyuan , Zhu Dehai , Zhu A-xing
Published: March 2022

Crop classification maps are fundamental data for global change research, regional agricultural regulation, fine production, and insurance services. The key to crop classification is samples, but it is very time-consuming in annual field sampling. Therefore, how to use historical samples in crop classification for future years at a lower cost is a research hotspot. By constructing the spectral feature vector of each historical sample in the historical year and its neighboring pixels in the target year, we produced new samples and classified them in the target year. Specifically, based on environmental similarity, we first calculated the similarities of every two pixels between each historical year and target year and took neighboring pixels with the highest local similarity as potential samples. Then, cluster analysis was performed on those potential samples of the same crop, and the class with more pixels is selected as newly generated samples for classification of the target year. The experiment in Heilongjiang province, China showed that this method can generate new samples with the uniform spatial distribution and that the proportion of various crops is consistent with field data in historical years. The overall accuracy of the target year by the newly generated sample and the real sample is 61.57 and 80.58%, respectively. The spatial pattern of maps obtained by two models is basically the same, and the classification based on the newly generated samples identified rice better. For areas with majority fields having no rotation, this method overcomes the problem of insufficient samples caused by difficulties in visual interpretation and high cost on field sampling, effectively improves the utilization rate of historical samples, and provides a new idea for crop mapping in areas lacking field samples of the target year.
Transcriptome Analysis Revealed a Cold Stress-Responsive Transcription Factor, PaDREB1A, in Plumbago auriculata That Can Confer Cold Tolerance in Transgenic Arabidopsis thaliana
Authors: Li Wenji , Gao Suping , Lei Ting , Jiang Liqiong , Duan Yifan , Zhao Zian , Li Jiani , Shi Lisha , Yang Lijuan
Published: March 2022

The tropical plant Plumbago auriculata can tolerate subzero temperatures without induction of apoptosis after cold acclimation in autumn, making it more cold tolerant than conventional tropical plants. In this study, we found that low temperatures significantly affected the photosynthetic system of P. auriculata. Using transcriptome sequencing, PaDREB1A was identified as a key transcription factor involved in the response to cold stress in P. auriculata. This transcription factor may be regulated by upstream JA signaling and regulates downstream ERD4 and ERD7 expression to resist cold stress. Overexpression of PaDREB1A significantly enhanced freezing resistance, protected the photosynthetic system, and enhanced the ROS scavenging mechanism under cold stress in Arabidopsis thaliana. Additionally, PaDREB1A significantly enhanced the expression of CORs and CAT1 in A. thaliana, which further activated the downstream pathway to enhance plant cold tolerance. This study explored the possible different regulatory modes of CBFs in tropical plants and can serve as an important reference for the introduction of tropical plants to low-temperature regions.