bluuebunny/crossref_metadata_2025 huggingface dataset:
Bi-Directionality of the Microbiota-Gut-Brain Axis in Patients With Functional Dyspepsia: Relevance of Psychotherapy and Probiotics
Authors: Rupp Sophia Kristina , Stengel Andreas
Published: February 2022

Functional dyspepsia is one of the most commonly diagnosed disorders of the gut-brain interaction worldwide. The precise pathogenesis of functional dyspepsia is complex and remains incompletely understood. Therefore, advances in the understanding of functional dyspepsia could change clinical practice. The aim of this review is to highlight the relevance of psychotherapy and probiotics in the context of the microbiota-gut-brain axis in the pathophysiology and especially in the treatment of functional dyspepsia. Therefore, studies which have been conducted to investigate the role of psychotherapy and probiotics in FD and the microbiota-gut-brain axis in the pathophysiology of functional dyspepsia were examined, and the outcomes of this research summarized. There might be a link between changes in the microbiome and functional dyspepsia. Even though, specific alterations in the microbiome that may be pathognomonic in functional dyspepsia remain unclear, the use of probiotics became a viable treatment option for patients with functional dyspepsia. Since mental illness also plays an important role in the pathophysiology of functional dyspepsia, psychotherapy is a useful treatment method, with additional study results indicating that psychotherapy may also shift the microbiome in a favorable direction. Moreover, other findings suggest that probiotics can be used not only to alleviate gastrointestinal symptoms in functional dyspepsia, but also to treat or even prevent mental disorders in these patients. In summary, in this review we highlight the bi-directionality of the microbiota-gut-brain axis in the pathophysiology of functional dyspepsia. Although there are multiple treatment approaches, the burden of disease in patients with functional dyspepsia is still enormous and a definitive therapy to cure this disease does not (yet) exist. Lastly, there is a lack of studies on the impact of dysbiosis, mental health and probiotics on pathophysiology and symptomatology in functional dyspepsia which should be investigated in future studies.
Blood Plasma Metabolites in Diabetes-Associated Chronic Kidney Disease: A Focus on Lipid Profiles and Cardiovascular Risk
Authors: Lecamwasam Ashani , Mansell Toby , Ekinci Elif I. , Saffery Richard , Dwyer Karen M.
Published: February 2022

Background

We investigated a cross-sectional metabolomic analysis of plasma and urine of patients with early and late stage diabetes associated chronic kidney disease (CKD), inclusive of stages 1–5 CKD, to identify potential metabolomic profiles between the two groups.

Methods

This cross-sectional study recruited 119 adults. Metabolomic biomarkers were quantified in 119 non-fasted plasma and 57 urine samples using a high-throughput proton Nuclear Magnetic Resonance platform. Analyses were conducted using R with the ggforestplot package. Linear regression models were minimally adjusted for age, sex, and body mass index and p-values were adjusted for multiple comparisons using the Benjamini-Hockberg method with a false discovery rate of 0.05.

Results

Apolipoprotein A1 concentration (ApoA1) was reduced (adj. p = 0.04) and apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) was increased (adj. p = 0.04) in late CKD compared with early CKD. Low-density lipoprotein triglyceride (LDL-TG) had an increased concentration (adj. p = 0.01), while concentrations of high-density lipoprotein cholesterol (HDL-C) were reduced (adj. p = 0.04) in late CKD compared to early stages of disease.

Conclusion

Our results highlight the presence of abnormal lipid metabolism namely significant reduction in the protective ApoA1 and significant increase in atherogenic ApoB/ApoA1 ratio. The study also demonstrates significantly elevated levels of triglyceride-rich lipoproteins such as LDL-TG. We illustrate the significant reduction in protective HDL-C in individuals with diabetic CKD. It explores a detailed plasma lipid profile that significantly differentiates between the late and early CKD groups as well as each CKD stage. The study of complex metabolite profiles may provide additional data required to enable more specific cardiovascular risk stratification.
Metabolome and Whole-Transcriptome Analyses Reveal the Molecular Mechanisms Underlying Hypoglycemic Nutrient Metabolites Biosynthesis in Cyclocarya paliurus Leaves During Different Harvest Stages
Authors: Zheng Xuehai , Xiao Huibao , Chen Jiannan , Zhu Jinmao , Fu Yajuan , Ouyang Songying , Chen Youqiang , Chen Duo , Su Jingqian , Xue Ting
Published: February 2022

Cyclocarya paliurus, a well-known nutrient and beverage plant, is under development for use in functional health care products best and natural and organic foods. We hypothesis that the composition and metabolic accumulation of hypoglycemic nutrient metabolites exhibit significant differences depending on harvest time. Therefore, it is of great significance to establish the best harvest time for C. paliurus leaves for the further development of healthy teas and other products. However, the detail compositions and molecular mechanisms of nutrients biosynthesis in C. paliurus leaves during different harvest stages remain largely unclear. Metabolome analysis showed that a suitable leaf-harvesting strategy for C. paliurus could be in September or October each year due to the high content of hypoglycemic nutrient metabolites. We found that two of the seven differentially accumulated phenolic acid metabolites have a relatively good inhibitory effect on α-amylase, indicating that they may play a role in the hypoglycemic function. Combined analysis of coexpression, ceRNA network, and weighted gene correlation network analysis (WGCNA) showed that several genes or transcription factors (TFs) in three modules correlated highly with hypoglycemic nutrient metabolites, including CpPMM, CpMan, CpFK, CpSUS, CpbglX, Cp4CL, CpHCT, and CpWRKY1. These findings help in the understanding of the molecular mechanisms and regulatory networks of the hypoglycemic nutrient metabolites in C. paliurus leaves which are dependent on harvest time and provide theoretical guidance in the development of functional health care products and foods from C. paliurus.
The Dark Pigment in the Sesame (Sesamum indicum L.) Seed Coat: Isolation, Characterization, and Its Potential Precursors
Authors: Dossou Senouwa Segla Koffi , Luo Zishu , Wang Zhijian , Zhou Wangyi , Zhou Rong , Zhang Yanxin , Li Donghua , Liu Aili , Dossa Komivi , You Jun , Wang Linhai
Published: February 2022

Sesame is a worldwide oilseed crop used in the food pharmacy. Its seed phenotypes determine the seed quality values. However, a thorough assessment of seed coat metabolites is lacking, and the dark pigment in the seed coat is not well-characterized. Herein, we report the isolation of melanin by the alkali method from the black and brown sesame seeds. Physicochemical methods, including scanning electron microscopy (SEM), solubility, precipitation, UV-Vis spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, and thermogravimetric-differential scanning calorimetry (TG-DSC), were used to characterize the sesame melanins. The results clearly showed that the isolated pigments were similar to melanin from other sources. Both melanins were heat-stable and exhibited numerous characteristic absorption peaks. Through a comprehensible LC-MS/MS-based metabolome profiles analysis of NaOH and methanol extracts of black and white sesame seeds, caffeic, protocatechuic, indole-carboxylic, homogentisic, ferulic, vanillic, and benzoic acids were identified as the potential precursors of the sesame melanin. Our findings widen our understanding of dark seeds pigmentation in sesame. Furthermore, they show that black sesame seeds are promising sources of edible melanin for food and biotechnological applications.
High-Grade Glioma Treatment Response Monitoring Biomarkers: A Position Statement on the Evidence Supporting the Use of Advanced MRI Techniques in the Clinic, and the Latest Bench-to-Bedside Developments. Part 2: Spectroscopy, Chemical Exchange Saturation, Multiparametric Imaging, and Radiomics
Authors: Booth Thomas C. , Wiegers Evita C. , Warnert Esther A. H. , Schmainda Kathleen M. , Riemer Frank , Nechifor Ruben E. , Keil Vera C. , Hangel Gilbert , Figueiredo Patrícia , Álvarez-Torres Maria Del Mar , Henriksen Otto M.
Published: February 2022

Objective

To summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and to highlight the latest bench-to-bedside developments.

Methods

The current evidence regarding the potential for monitoring biomarkers was reviewed and individual modalities of metabolism and/or chemical composition imaging discussed. Perfusion, permeability, and microstructure imaging were similarly analyzed in Part 1 of this two-part review article and are valuable reading as background to this article. We appraise the clinic readiness of all the individual modalities and consider methodologies involving machine learning (radiomics) and the combination of MRI approaches (multiparametric imaging).

Results

The biochemical composition of high-grade gliomas is markedly different from healthy brain tissue. Magnetic resonance spectroscopy allows the simultaneous acquisition of an array of metabolic alterations, with choline-based ratios appearing to be consistently discriminatory in treatment response assessment, although challenges remain despite this being a mature technique. Promising directions relate to ultra-high field strengths, 2-hydroxyglutarate analysis, and the use of non-proton nuclei. Labile protons on endogenous proteins can be selectively targeted with chemical exchange saturation transfer to give high resolution images. The body of evidence for clinical application of amide proton transfer imaging has been building for a decade, but more evidence is required to confirm chemical exchange saturation transfer use as a monitoring biomarker. Multiparametric methodologies, including the incorporation of nuclear medicine techniques, combine probes measuring different tumor properties. Although potentially synergistic, the limitations of each individual modality also can be compounded, particularly in the absence of standardization. Machine learning requires large datasets with high-quality annotation; there is currently low-level evidence for monitoring biomarker clinical application.

Conclusion

Advanced MRI techniques show huge promise in treatment response assessment. The clinical readiness analysis highlights that most monitoring biomarkers require standardized international consensus guidelines, with more facilitation regarding technique implementation and reporting in the clinic.
Application of Anesthetics in Cancer Patients: Reviewing Current Existing Link With Tumor Recurrence
Authors: Liu Xiaotian , Wang Qian
Published: February 2022

Surgery remains the most effective cancer treatment, but residual disease in the form of scattered micro-metastases and tumor cells is usually unavoidable. Whether minimal residual disease results in clinical metastases is a function of host defense and tumor survival and growth. The much interesting intersection of anesthesiology and immunology has drawn increasing clinical interest, particularly, the existing concern of the possibility that the perioperative and intraoperative anesthetic care of the surgical oncology patient could meaningfully influence tumor recurrence. This paper examines current data, including recent large clinical trials to determine whether the current level of evidence warrants a change in practice. Available pieces of evidence from clinical studies are particularly limited, largely retrospective, smaller sample size, and often contradictory, causing several questions and providing few answers. Recent randomized controlled clinical trials, including the largest study (NCT00418457), report no difference in cancer recurrence between regional and general anesthesia after potentially curative surgery. Until further evidence strongly implicates anesthesia in future clinical trials, clinicians may continue to choose the optimum anesthetic-analgesic agents and techniques in consultation with their cancer patients, based on their expertise and current best practice.
Serum Abnormal Metabolites for Evaluating Therapeutic Response and Prognosis of Patients With Multiple Myeloma
Authors: Wei Yujun , Wang Jinying , Chen Fei , Li Xin , Zhang Jiajia , Shen Man , Tang Ran , Huang Zhongxia
Published: February 2022

Aims

To evaluate abnormal metabolites related to treatment response and prognosis of multiple myeloma (MM) patients through ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS).

Methods

Forty-six symptomatic MM patients were included in this study who had a prior high level of positive monoclonal proteins before receiving targeted therapy with bortezomib-based regimens. UPLC-MS along with traditional immunofixation was performed on MM diagnostic samples and effective serum samples, and UPLC-MS was used to target valuable metabolic markers related to M protein.MM patients were segregated into pre-therapy (pre-T) and post-therapy (post-T) groups according to the response after chemotherapy. A monoclonal protein could be detected at baseline in 33 newly diagnosed MM (NDMM), 13 refractory and relapsed MM (RRMM) patients and 20 healthy controls (HC) by immunofixation.

Results

Between pre-T and post-T patients, the data showed that 32, 28 and 3 different metabolites were significantly correlated with M protein in IgG, IgA and light chain-type MM, respectively. These identified metabolites were significantly enriched in arginine and proline metabolism as well as glycerophospholipid metabolism pathways. Among them, PC (19:0/22:2) was displayed to increase significantly and consistently with M protein in each subtype of MM after treatment, which obviously indicated that it was related to the treatment response of MM. Further survival analysis of metabolic markers found that aspartic acid, LysoPE (16:0), SM (d18:1/17:0), PC (18:0/24:1), PC (16:0/16:0), TG (18:1/18:1/22:5) and LysoPE (18:2) reaching a certain cutoff value may be associated with shorter progression free survival (PFS). Finally, Cox multivariate regression analysis identified three factors were independent prognostic factors of MM. Moreover, there were significantly different in PC (19:0/22:2) and in aspartic acid between MM patients and healthy people.

Conclusion

This work identified significant metabolic disorders in 46 pairs off pre- and post-therapy MM patients, specifically in arginine, proline and glycerophospholipid pathways. The abnormal metabolites have the potential to serve as new biomarkers for evaluating treatment response and prognosis, as well as early monitoring of disease activity. Therefore, these systematic studies on abnormal metabolites as biomarkers for diagnosis and treatment will provide the evidence for future precise treatment of MM.
The Lymph Node Microenvironment May Invigorate Cancer Cells With Enhanced Metastatic Capacities
Authors: Li Tianhang , Liu Tianyao , Zhao Zihan , Xu Xinyan , Zhan Shoubin , Zhou Shengkai , Jiang Ning , Zhu Wenjie , Sun Rui , Wei Fayun , Feng Baofu , Guo Hongqian , Yang Rong
Published: February 2022

Cancer metastasis, a typical malignant biological behavior involving the distant migration of tumor cells from the primary site to other organs, contributed majorly to cancer-related deaths of patients. Although constant efforts have been paid by researchers to elucidate the mechanisms of cancer metastasis, we are still far away from the definite answer. Recently, emerging evidence demonstrated that cancer metastasis is a continuous coevolutionary process mediated by the interactions between tumor cells and the host organ microenvironment, and epigenetic reprogramming of metastatic cancer cells may confer them with stronger metastatic capacities. The lymph node served as the first metastatic niche for many types of cancer, and the appearance of lymph node metastasis predicted poor prognosis. Importantly, multiple immune cells and stromal cells station and linger in the lymph nodes, which constitutes the complexity of the lymph node microenvironment. The active cross talk between cancer cells and immune cells could happen unceasingly within the metastatic environment of lymph nodes. Of note, diverse immune cells have been found to participate in the formation of malignant properties of tumor, including stemness and immune escape. Based on these available evidence and data, we hypothesize that the metastatic microenvironment of lymph nodes could drive cancer cells to metastasize to further organs through epigenetic mechanisms.
Ex Vivo Near-Infrared Molecular Imaging of Human Upper Urinary Tract Urothelial Carcinoma With a CD47-Based Targeted Tracer
Authors: Yan Pengyu , Chen Dan , Yan Xutao , Yan Xiaoting , Wang Yingpeng , Liu Chao , Yang Xiaofeng
Published: February 2022

Objective

The low detection rate of early and small tumors remains a clinical problem that urgently needs to be solved in the accurate diagnosis and treatment of upper urinary tract urothelial carcinoma (UTUC). The objective of this study is to evaluate the feasibility of CD47 as a target for optical molecular imaging of human UTUC and conduct preliminary ex vivo imaging experiments.

Methods

We firstly analyzed the genome-wide mRNA expression data from Gene Expression Omnibus (GEO). Paraffin-embedded tissue specimens comprising UTUC and normal urothelium were collected. All tissue specimens were used for immunohistochemistry to compare CD47 protein expression in normal and cancer tissue. Meanwhile, 12 patients undergoing radical nephroureterectomy were prospectively included in ex vivo imaging experiments. Freshly isolated upper urinary tract specimens were incubated with anti-CD47-Alexa Fluor 790 and then imaged under white light and near-infrared (NIR) light. Standard histopathologic evaluation was performed, and findings were correlated with CD47-targeted NIR molecular imaging.

Results

The GEO data revealed that CD47 mRNA expression was higher in UTUC specimens than that in paracancer normal tissue. In immunohistochemical analysis, the CD47 protein expression level was higher in both non-muscle-invasive and muscle-invasive (stage ≥T2) UTUCs than that in normal uroepithelium, and the localization of CD47 protein was the tumor cell membrane. In the ex vivo imaging experiments, all patients were pathologically diagnosed with UTUC, and no adverse effects of anti-CD47-Alexa Fluor 790 on the histological structure of the tumor and normal uroepithelium were observed. In the NIR grayscale images, the mean fluorescence intensity of the tumor tissue was significantly higher than that of the adjacent normal background tissue, which greatly improved the visualization of the tumor.

Conclusions

CD47-targeted NIR molecular imaging could be a feasible and powerful strategy for the accurate diagnosis of UTUC. Larger-scale randomized trials are needed.
Value of 18F-FDG PET/MRI in the Preoperative Assessment of Resectable Esophageal Squamous Cell Carcinoma: A Comparison With 18F-FDG PET/CT, MRI, and Contrast-Enhanced CT
Authors: Wang Fei , Guo Rui , Zhang Yan , Yu Boqi , Meng Xiangxi , Kong Hanjing , Yang Yang , Yang Zhi , Li Nan
Published: February 2022

Objectives

To investigate the value of 18F-FDG PET/MRI in the preoperative assessment of esophageal squamous cell carcinoma (ESCC) and compare it with 18F-FDG PET/CT, MRI, and CECT.

Methods

Thirty-five patients with resectable ESCC were prospectively enrolled and underwent PET/MRI, PET/CT, and CECT before surgery. The primary tumor and regional lymph nodes were assessed by PET/MRI, PET/CT, MRI, and CECT, respectively, and the diagnostic efficiencies were determined with postoperative pathology as a reference standard. The predictive role of imaging and clinical parameters on pathological staging was analyzed.

Results

For primary tumor staging, the accuracy of PET/MRI, MRI, and CECT was 85.7%, 77.1%, and 51.4%, respectively. For lymph node assessment, the accuracy of PET/MRI, PET/CT, MRI, and CECT was 96.2%, 92.0%, 86.8%, and 86.3%, respectively, and the AUCs were 0.883, 0.745, 0.697, and 0.580, respectively. PET/MRI diagnosed 13, 7, and 6 more stations of lymph node metastases than CECT, MRI, and PET/CT, respectively. There was a significant difference in SUVmax, TLG, and tumor wall thickness between T1-2 and T3 tumors (p = 0.004, 0.024, and < 0.001, respectively). Multivariate analysis showed that thicker tumor wall thickness was a predictor of a higher T stage (p = 0.040, OR = 1.6).

Conclusions

18F-FDG PET/MRI has advantages over 18F-FDG PET/CT, MRI, and CECT in the preoperative assessment of primary tumors and regional lymph nodes of ESCC. 18F-FDG PET/MRI may be a potential supplement or alternative imaging method for preoperative staging of ESCC.
DNMT3A R882 Mutations Confer Unique Clinicopathologic Features in MDS Including a High Risk of AML Transformation
Authors: Jawad Majd , Afkhami Michelle , Ding Yi , Zhang Xiaohui , Li Peng , Young Kim , Xu Mina Luqing , Cui Wei , Zhao Yiqing , Halene Stephanie , Al-Kali Aref , Viswanatha David , Chen Dong , He Rong , Zheng Gang
Published: February 2022

DNMT3A mutations play a prominent role in clonal hematopoiesis and myeloid neoplasms with arginine (R)882 as a hotspot, however the clinical implications of R882 vs. non-R882 mutations in myeloid neoplasms like myelodysplastic syndrome (MDS) is unclear. By data mining with publicly accessible cancer genomics databases and a clinical genomic database from a tertiary medical institution, DNMT3A R882 mutations were found to be enriched in AML (53% of all DNMT3A mutations) but decreased in frequency in clonal hematopoiesis of indeterminate potential (CHIP) (10.6%) or other myeloid neoplasms including MDS (27%) (p<.001). Next with the largest cohort of patients with DNMT3A R882 mutant MDS known to date from multiple institutions, DNMT3A R882 mutant MDS cases were shown to have more severe leukopenia, enriched SRSF2 and IDH2 mutations, increased cases with excess blasts (47% vs 22.5%, p=.004), markedly increased risk of AML transformation (25.8%, vs. 1.7%, p=.0001) and a worse progression-free survival (PFS) (median 20.3, vs. >50 months, p=.009) than non-R882 mutant MDS cases. DNMT3A R882 mutation is an independent risk factor for worse PFS, and importantly the differences in the risk of AML transformation between R882 vs. non-R882 mutant patients cannot be explained by different treatment approaches. Interestingly the higher risk of AML transformation and the worse PFS in DNMT3A R882 mutant MDS cases are mitigated by coexisting SF3B1 or SRSF2 mutations. The unique clinicopathologic features of DNMT3A R882 mutant MDS shed light on the prognostic and therapeutic implications of DNMT3A R882 mutations.
Quality of Life in Chinese Patients With Large Congenital Melanocytic Nevi
Authors: Wang Huijing , Yu Qingxiong , Li Qingfeng , Wang Zhichao
Published: February 2022

Background

Large congenital melanocytic nevus (LCMN) is a rare skin disease that deeply affects an individual's appearance, may influence patients' self-evaluation and social relationships, and further affects their quality of life (QoL). The Skindex-29 and 36-Item Short Form Survey (SF-36) are valid instruments used to evaluate QoL specifically. It is necessary to assess the QoL of patients with LCMN and summarize potentially impactful factors to help people understand LCMN patients and assist doctors in offering professional advice.

Methods

Twenty-five patients were recruited from Shanghai Ninth People's Hospital from July 1st, 2019, to March 31st, 2021. Both males and females were included, and the age groups were divided into infants (0–6 y), children (7–12 y), teenagers (13–17 y) and youths (18–45 y). The Skindex-29 and SF-36 were applied as questionnaires for the assessment of QoL. Clinical information was acquired by physical examination.

Results

QoL in patients with LCMN was diminished, especially in the emotional aspect. However, different genders, ages and distribution patterns of LCMN did not significantly influence QoL, but the patterns of “Bonce” and “Body” affected QoL the most and the severest. The results of Skindex-29 and SF-36 were consistent in that LCMN mainly reduced QoL from an emotional perspective.

Conclusions

This research shows that LCMN has the strongest impact on patients' emotional wellbeing but weakly influences the whole fettle of QoL. The gender, age and distribution patterns of lesions all have no direct effect on QoL, although a larger proportion of LCMNs probably insinuates worse QoL. Even though patients with LCMN show better QoL than those with other visible skin conditions, their general mental health still requires ample attention from surroundings and professional doctors.
Esophageal Diameter as a Function of Weight in Neonates, Children and Adolescents: Reference Values for Dilatation of Esophageal Stenoses
Authors: Loff Steffan , Diez Oliver , Ho Wei , Kalle Thekla v. , Hetjens Svetlana , Boettcher Michael
Published: February 2022

Introduction

Esophageal stenoses are frequent complications after esophageal atresia surgery as well as after acid, alkali and battery ingestion. Worldwide, repeated balloon dilatations are the most frequently performed procedures for these stenoses. In most cases the stenoses can be dilated sufficiently to allow adequate enteral nutrition. Until recently, age dependent esophageal lumen size has not been established; which was aim of the current study.

Methods

All children in whom an esophageal contrast imaging was performed between 1/2011 and 5/2021 were included. The width was measured by two investigators at two measuring points in two planes, the diameter was calculated and plotted against the respective weight of the child. Bland-Altmann plots have confirmed the validity of the measurements of both investigators.

Results

Esophagus diameter was measured in more than 100 children. The resulting curves show a very good correlation with weight (upper measuring point: r = 0.86743, p < 0.0001; lower measuring point: r = 0.80593, p < 0.0001).

Conclusion

These results are the first to define the esophageal diameter in children. The results of this study may guide physicians performing esophageal interventions including dilatations in future.
Patients' Perception of the Use of the EasyPod™ Growth Hormone Injector Device and Impact on Injection Adherence: A Multi-Center Regional Study
Authors: Deeb Asma , Al Yaarubi Saif , Abbas Bassam Bin , Al Jubeh Jamal , Chaturvedi Deepti , Al Hassani Noura , Mutair Angham , Al Masri Neamat , Al Sanad Yazan , Al Shidhani Azza , Mahmoud Noha Samir , Alherbish Abdullah , Savage Martin O.
Published: February 2022

Objective

This study aimed to assess patient perceptions of the use of the EasyPod™ growth hormone delivery device and its association with compliance.

Methods

This cross-sectional, multicenter study was conducted in six centers from three countries (United Arab Emirates, Oman, and Saudi Arabia,) between March 2020 and June 2020. Children and adolescents aged 3–18 years, diagnosed with growth disorders and receiving rhGH through the EasyPod™ device were enrolled. Patients and caregivers were given a pre-set questionnaire that evaluated patient satisfaction, preference for technical and personalized features, and device drawbacks. The results were analyzed using independent measures of analysis of variance to evaluate the association of higher satisfaction with device features and better compliance.

Results

A total of 186 patients were enrolled in the study. Of these, 45.7% had GH deficiency. The mean age (±SD) of patients was 11.8 (±2.76) years; 117 (62.90%) were males. Average compliance was 87%. One hundred patients (53.76%) had injection compliance of ≥90%. Amongst these patients, 74%, 68%, and 77% top-scored (5/5) the technical features of hidden needle, skin sensor, and pre-set dosing, respectively, compared to top scores by 39%, 34%, and 51% patients in the <90% compliance group (p-value <0.05). Similarly, a statistically significant difference was observed between the groups (p-value <0.05) in the perception of the usefulness of the tracking features such as display of history of injected doses (78% vs. 47.7%), a reminder for medicine remaining (46% vs. 23.3%) and battery power indicator (48% vs. 20.9%). Personal screen messages were associated with higher compliance while the requirement to keep the device in the fridge was reported as the most inconvenient feature by 56% of patients in the higher compliance group as against 39.5% in the lower compliance group (p-value <0.05). There was no statistically significant difference in the intensity of pain reported in the two compliance groups.

Conclusion

Our study showed that there is a statistically significant association between better perception of device features and higher compliance.
β-Sitosterol Inhibits Rheumatoid Synovial Angiogenesis Through Suppressing VEGF Signaling Pathway
Authors: Qian Kai , Zheng Xue-Xia , Wang Chen , Huang Wen-Guang , Liu Xiao-Bao , Xu Shu-Di , Liu Dan-Kai , Liu Min-Ying , Lin Chang-Song
Published: February 2022

Background: Rheumatoid arthritis (RA) is a chronic disabling inflammatory disease that causes synovial angiogenesis in an invasive manner and leads to joint destruction. Currently available pharmacotherapy for RA has unwanted side effects and limitations. Although anti-angiogenic therapy is regarded as a new potential treatment for RA, only a few anti-angiogenic drugs are available. An increasing number of studies have shown that β-sitosterol (BSS) may exert inhibitory effects against angiogenesis. However, the mechanisms involved are still unclear.

Methods: Based on the results of the gene set enrichment analysis (GSEA) of the transcriptome data of endothelial cells from RA patients, we evaluated the pharmacological effects of BSS on the tube formation, cell proliferation, and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, the effects of BSS treatment on vascular endothelial growth factor receptor 2 (VEGFR2) were determined using molecular docking and Western blotting. Additionally, in the presence or absence of BSS, synovial angiogenesis and joint destruction of the ankle were investigated in collagen-induced arthritis (CIA) mice. The effect of BSS treatment on VEGFR2/p-VEGFR2 expression was verified through immunohistochemical staining.

Results: The immunohistochemistry results revealed that BSS treatment inhibited angiogenesis both in vitro and in vivo. In addition, the results of 5-ethynyl-2′-deoxyuridine and cell cycle analysis showed that BSS treatment suppressed the proliferation of HUVECs, while the Transwell migration and stress fiber assays demonstrated that BSS treatment inhibited the migration of HUVECs. Notably, the inhibitory effect of BSS treatment on VEGFR2/p-VEGFR2 was similar to that of axitinib. In CIA mice, BSS also exerted therapeutic effects on the ankles by reducing the degree of swelling, ameliorating bone and cartilage damage, preventing synovial angiogenesis, and inhibiting VEGFR2 and p-VEGFR2 expression.

Conclusion: Therefore, our findings demonstrate that BSS exerts an inhibitory effect on synovial angiogenesis by suppressing the proliferation and migration of endothelial cells, thereby alleviating joint swelling and bone destruction in CIA mice. Furthermore, the underlying therapeutic mechanisms may involve the inhibition of VEGF signaling pathway activation.
Transforming Growth Factor-Beta (TGF-β) Signaling in Cancer-A Betrayal Within
Authors: Baba Abdul Basit , Rah Bilal , Bhat Gh. Rasool , Mushtaq Ifra , Parveen Sabra , Hassan Rukhsana , Hameed Zargar Mahrukh , Afroze Dil
Published: February 2022

A ubiquitously expressed cytokine, transforming growth factor-beta (TGF-β) plays a significant role in various ongoing cellular mechanisms. The gain or loss-of-function of TGF-β and its downstream mediators could lead to a plethora of diseases includes tumorigenesis. Specifically, at the early onset of malignancy TGF-β act as tumour suppressor and plays a key role in clearing malignant cells by reducing the cellular proliferation and differentiation thus triggers the process of apoptosis. Subsequently, TGF-β at an advanced stage of malignancy promotes tumorigenesis by augmenting cellular transformation, epithelial-mesenchymal-transition invasion, and metastasis. Besides playing the dual roles, depending upon the stage of malignancy, TGF-β also regulates cell fate through immune and stroma components. This oscillatory role of TGF-β to fight against cancer or act as a traitor to collaborate and crosstalk with other tumorigenic signaling pathways and its betrayal within the cell depends upon the cellular context. Therefore, the current review highlights and understands the dual role of TGF-β under different cellular conditions and its crosstalk with other signaling pathways in modulating cell fate.
Case Report: Tackling Complement Hyperactivation With Eculizumab in Atypical Hemolytic Uremic Syndrome Triggered by COVID-19
Authors: Leone Valentina Fanny , Imeraj Amantia , Gastoldi Sara , Mele Caterina , Liguori Lucia , Condemi Carmelita , Ruggenenti Piero , Remuzzi Giuseppe , Carrara Camillo
Published: February 2022

Hemolytic uremic syndrome (HUS) is a rare life-threatening disease of unrestrained complement system dysregulation, microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure in genetically predisposed individuals. In this report, we describe two cases of SARS-CoV-2–associated HUS treated with eculizumab, a C5-blocking monoclonal antibody reported to be remarkably effective in the treatment of HUS. Detailed biochemical and genetic complement system analysis is reported, and the prompt clinical response after C5 pharmacological blockade is documented. Our report provides the rationale and supports the use of terminal complement pathway inhibition for the treatment of SARS-CoV-2–associated HUS.
A Broadband Low-RCS Circularly Polarized Meta-Antenna
Authors: Zhou Hongkun , Wang Yuchao , Liu Chengguo , Zhang Cheng
Published: February 2022

A low-profile circularly polarized (CP) meta-antenna with a broadband low-RCS feature is proposed in this article. Our design is the combination of a CP antenna with a chessboard polarization conversion metasurface (CPCM) for balancing the radiation property and stealth feature. To relieve the adverse effect of the CPCM on the entire radiation performance, several redundant meta-atoms with the opposite phase state were removed to enhance the realized gain within the operation bandwidth (8.0–9.0 GHz). The proposed meta-antenna showed excellent radiation performance: −10 dB impedance relative bandwidth was 26.48% (6.78–8.85 GHz), and 3-dB axial ratio relative bandwidth was 22.03% (7.27–9.07 GHz). In addition, RCS reduction over 5 dB was achieved via our design from 8.5 to 21.5 GHz (86.67%) with the help of the deliberately designed CPCM. The final measured results demonstrate great consistency with the simulated ones.
Studies on the Manner of Collateral Regeneration From Nerve Stem to Motor Endplate
Authors: Qi Zhidan , Li Dongdong , Li Li , Meng Dexuan , Deng Jin , Jin Bo , Gu Xinyi , Wang Shen , Huang Chen , Yin Xiaofeng
Published: February 2022

Despite recent evidence suggesting that nerve transfer techniques help improve clinical outcomes, the underlying manner by which collateral-regenerated nerve enters skeletal muscles to restore an organized pattern of the neuromuscular junction (NMJ) is unclear. To construct the animal models of collateral regeneration, the proximal peroneal nerve was fixed to the distal tibial nerve stump. Three months after surgery, the spatial distribution of motor endplates (MEPs) and corresponding in-muscle nerve branches in long flexor digitorum muscles were observed with tissue optical clearing combined with light-sheet microscopy in transgenic fluorescent mice. The results showed that the number of fibers in the proximal donor peroneal nerve was 415 ± 11, while regenerated nerve fibers in the distal tibial stump were 781 ± 43, which indicates a collateral regeneration ratio of 1.88. The spatial distribution of MEPs was restored to an organized pattern of the lamella, and the corresponding in-muscle nerve branches reverted to the normal manner such as after collateral regeneration. Beyond this, the numbers of MEPs dominated by the single distal nerve fiber were 25.58 ± 0.50 and 26.42 ± 0.94, respectively (n = 6, p > 0.05, collateral regeneration group vs. normal group). However, the numbers of distal-regenerated nerve fibers were less than those in normal control groups (781 ± 43 vs. 914 ± 55, n = 6, p < 0.05), and the number and perforations of MEPs were lower than those in normal control groups as such. In summary, this is the first study to show the manner of collateral regeneration of the peripheral nerve that the smaller proximal donor nerve can sprout more axonal buds to connect distal larger nerves and finally restore to an organized pattern of lamella dominated by corresponding in-muscle nerve branches.
CCAAT/Enhancer-Binding Protein Alpha Is a Novel Regulator of Vascular Smooth Muscle Cell Osteochondrogenic Transition and Vascular Calcification
Authors: Chen Pengyuan , Hong Wanzi , Chen Ziying , Gordillo-Martinez Flora , Wang Siying , Fan Hualin , Liu Yuanhui , Dai Yining , Wang Bo , Jiang Lei , Yu Hongjiao , He PengCheng
Published: February 2022

Aims

Vascular calcification is a common clinical complication of chronic kidney disease (CKD), atherosclerosis (AS), and diabetes, which is associated with increased cardiovascular morbidity and mortality in patients. The transdifferentiation of vascular smooth muscle cells (VSMCs) to an osteochondrogenic phenotype is a crucial step during vascular calcification. The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) plays an important role in regulating cell proliferation and differentiation, but whether it regulates the calcification of arteries and VSMCs remains unclear. Therefore, this study aims to understand the role of C/EBPα in the regulation of vascular calcification.

Methods and Results

Both mRNA and protein expression levels of C/EBPα were significantly increased in calcified arteries from mice treated with a high dose of vitamin D3 (vD3). Upregulation of C/EBPα was also observed in the high phosphate- and calcium-induced VSMC calcification process. The siRNA-mediated knockdown of C/EBPα significantly attenuated VSMC calcification in vitro. Moreover, C/EBPα depletion in VSMCs significantly reduced the mRNA expression of the osteochondrogenic genes, e.g., sex-determining region Y-box 9 (Sox9). C/EBPα overexpression can induce SOX9 overexpression. Similar changes in the protein expression of SOX9 were also observed in VSMCs after C/EBPα depletion or overexpression. In addition, silencing of Sox9 expression significantly inhibited the phosphate- and calcium-induced VSMC calcification in vitro.

Conclusion

Findings in this study indicate that C/EBPα is a key regulator of the osteochondrogenic transdifferentiation of VSMCs and vascular calcification, which may represent a novel therapeutic target for vascular calcification.
Antisense Oligonucleotide Technologies to Combat Obesity and Fatty Liver Disease
Authors: Keating Michael F. , Drew Brian G. , Calkin Anna C.
Published: February 2022

Synthetic oligonucleotide technologies are DNA or RNA based molecular compounds that are utilized to disrupt gene transcription or translation in target tissues or cells. Optimally, oligonucleotides are 10–30 base pairs in length, and mediate target gene suppression through directed sequence homology with messenger RNA (mRNA), leading to mRNA degradation. Examples of specific oligonucleotide technologies include antisense oligonucleotides (ASO), short hairpin RNAs (shRNA), and small interfering RNAs (siRNA). In vitro and in vivo studies that model obesity related disorders have demonstrated that oligonucleotide technologies can be implemented to improve the metabolism of cells and tissues, exemplified by improvements in fat utilization and hepatic insulin signaling, respectively. Oligonucleotide therapy has also been associated with reductions in lipid accumulation in both the liver and adipose tissue in models of diet-induced obesity. Recent advances in oligonucleotide technologies include the addition of chemical modifications such as N-acetylgalactosamine (GalNAc) conjugates that have been successful at achieving affinity for the liver, in turn improving specificity, and thus reducing off target effects. However, some challenges are still yet to be overcome relating to hepatic injury and off-target effects that have been reported with some compounds, including ASOs. In summary, oligonucleotide-based therapies are an effective tool to elucidate mechanistic insights into metabolic pathways and provide an attractive avenue for translational research into the clinic.
Rice Genotypes Express Compensatory Root Growth With Altered Root Distributions in Response to Root Cutting
Authors: Kawai Tsubasa , Chen Yinglong , Takahashi Hirokazu , Inukai Yoshiaki , Siddique Kadambot H. M.
Published: February 2022

Root systems play a pivotal role in water and nutrient uptake from soil. Lateral root (LR) growth is promoted to compensate for inhibited main root growth. Compensatory LR growth contributes to maintaining total root length (TRL) and hence water and nutrient uptake in compacted soils. However, it remains unclear how shoot and root phenotypic traits change during the compensatory growth and whether there are genotypic variations in compensatory root growth. This study analyzed shoot and root morphological traits of 20 rice genotypes, which includes mutants with altered root morphology, during the vegetative stage using a semihydroponic phenotyping system. The phenotyping experiment detected large variation in root and shoot traits among the 20 genotypes. Morphological changes induced by root cutting were analyzed in six selected genotypes with contrasting root system architecture. Root cutting significantly affected root distribution along vertical sections and among diameter classes. After root cutting, more roots distributed at shallower depth and thicker LRs developed. Furthermore, genotypes with deeper root growth without root cutting allocated more compensatory roots to deeper sections even after root cutting than the genotypes with shallower rooting. Due to the compensatory LR growth, root cutting did not significantly affect TRL, root dry weight (RDW), or shoot dry weight (SDW). To analyze the interaction between crown root (CR) number and compensatory root growth, we removed half of the newly emerged CRs in two genotypes. TRL of YRL38 increased at depth with CR number manipulation (CRM) regardless of root tip excision, which was attributed to an increase in specific root length (SRL), despite no change in RDW. Taken together, the tested rice genotypes exhibited compensatory root growth by changing root distribution at depth and in diameter classes. Reducing CR number promoted root development and compensatory growth by improving the efficiency of root development [root length (RL) per resource investment].
EST-SSR Primer Development and Genetic Structure Analysis of Psathyrostachys juncea Nevski
Authors: Li Zhen , Yun Lan , Gao Zhiqi , Wang Tian , Ren Xiaomin , Zhao Yan
Published: February 2022

Psathyrostachys juncea is a perennial forage grass which plays an important role in soil and water conservation and ecological maintenance in cold and dry areas of temperate regions. In P. juncea, a variety of biotic and abiotic stress related genes have been used in crop improvement, indicating its agronomic, economic, forage, and breeding value. To date, there have been few studies on the genetic structure of P. juncea. Here, the genetic diversity and population structure of P. juncea were analyzed by EST-SSR molecular markers to evaluate the genetic differentiation related to tillering traits in P. juncea germplasm resources. The results showed that 400 simple sequence repeat (SSR) loci were detected in 2,020 differentially expressed tillering related genes. A total of 344 scored bands were amplified using 103 primer pairs, out of which 308 (89.53%) were polymorphic. The Nei’s gene diversity of 480 individuals was between 0.092 and 0.449, and the genetic similarity coefficient was between 0.5008 and 0.9111, with an average of 0.6618. Analysis of molecular variance analysis showed that 93% of the variance was due to differences within the population, and the remaining 7% was due to differences among populations. Psathyrostachys juncea materials were clustered into five groups based on population genetic structure, principal coordinate analysis and unweighted pair-group method with arithmetic means (UPGMA) analysis. The results were similar between clustering methods, but a few individual plants were distributed differently by the three models. The clustering results, gene diversity and genetic similarity coefficients showed that the overall genetic relationship of P. juncea individuals was relatively close. A Mantel test, UPGMA and structural analysis also showed a significant correlation between genetic relationship and geographical distribution. These results provide references for future breeding programs, genetic improvement and core germplasm collection of P. juncea.
Identifying Quantitative Trait Loci and Candidate Genes Conferring Resistance to Soybean Mosaic Virus SC7 by Quantitative Trait Loci-Sequencing in Soybean
Authors: Zhang Yong , Song Jiling , Wang Lei , Yang Mengping , Hu Kaifeng , Li Weiwei , Sun Xuhong , Xue Hong , Dong Quanzhong , Zhang Mingming , Lou Shubao , Yang Xingyong , Du Hao , Li Yongli , Dong Lidong , Che Zhijun , Cheng Qun
Published: February 2022

Soybean mosaic virus (SMV) is detrimental to soybean (Glycine max) breeding, seed quality, and yield worldwide. Improving the basic resistance of host plants is the most effective and economical method to reduce damage from SMV. Therefore, it is necessary to identify and clone novel SMV resistance genes. Here, we report the characterization of two soybean cultivars, DN50 and XQD, with different levels of resistance to SMV. Compared with XQD, DN50 exhibits enhanced resistance to the SMV strain SC7. By combining bulked-segregant analysis (BSA)-seq and fine-mapping, we identified a novel resistance locus, RSMV-11, spanning an approximately 207-kb region on chromosome 11 and containing 25 annotated genes in the reference Williams 82 genome. Of these genes, we identified eleven with non-synonymous single-nucleotide polymorphisms (SNPs) or insertion-deletion mutations (InDels) in their coding regions between two parents. One gene, GmMATE68 (Glyma.11G028900), harbored a frameshift mutation. GmMATE68 encodes a multidrug and toxic compound extrusion (MATE) transporter that is expressed in all soybean tissues and is induced by SC7. Given that MATE transporter families have been reported to be linked with plant disease resistance, we suggest that GmMATE68 is responsible for SC7 resistance in DN50. Our results reveal a novel SMV-resistance locus, improving understanding of the genetics of soybean disease resistance and providing a potential new tool for marker-assisted selection breeding in soybean.