Human and Murine Very Small Embryonic-Like Cells Represent Multipotent Tissue Progenitors, In Vitro and In Vivo

The purpose of this study was to determine the lineage progression of human and murine very small embryonic-like (HuVSEL or MuVSEL) cells in vitro and in vivo. In vitro, HuVSEL and MuVSEL cells differentiated into cells of all three embryonic germ layers. HuVSEL cells produced robust mineralized tissue of human origin compared with controls in calvarial defects. Immunohistochemistry demonstrated that the HuVSEL cells gave rise to neurons, adipocytes, chondrocytes, and osteoblasts within the calvarial defects. MuVSEL cells were also able to differentiate into similar lineages. First round serial transplants of MuVSEL cells into irradiated osseous sites demonstrated that ?60% of the cells maintained their VSEL cell phenotype while other cells differentiated into multiple tissues at 3 months. Secondary transplants did not identify donor VSEL cells, suggesting limited self renewal but did demonstrate VSEL cell derivatives in situ for up to 1 year. At no point were teratomas identified. These studies show that VSEL cells produce multiple cellular structures in vivo and in vitro and lay the foundation for future cell-based regenerative therapies for osseous, neural, and connective tissue disorders. Key Points HuVSEL and MuVSEL cells are capable of differentiating into multiple germline derivatives in vitro and in vivo. MuVSEL cells have limited capacity for self-renewal and neither HuVSEL nor MuVSEL cells formed tumors in immunodeficient animals.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140202/1/scd.2013.0362.pd

Emerging roles and potential application of PIWI-interacting RNA in urological tumors

The piRNA (PIWI-interacting RNA) is P-Element induced wimpy testis (PIWI)-interacting RNA which is a small molecule, non-coding RNA with a length of 24-32nt. It was originally found in germ cells and is considered a regulator of germ cell function. It can interact with PIWI protein, a member of the Argonaute family, and play a role in the regulation of gene transcription and epigenetic silencing of transposable factors in the nucleus. More and more studies have shown that piRNAs are abnormally expressed in a variety of cancer tissues and patient fluids, and may become diagnostic tools, therapeutic targets, staging markers, and prognostic evaluation tools for cancer. This article reviews the recent research on piRNA and summarizes the structural characteristics, production mechanism, applications, and its role in urological tumors, to provide a reference value for piRNA to regulate urological tumors

Dynamic Prognosis Prediction for Patients on DAPT After Drug-Eluting Stent Implantation: Model Development and Validation

BACKGROUND: The rapid evolution of artificial intelligence (AI) in conjunction with recent updates in dual antiplatelet therapy (DAPT) management guidelines emphasizes the necessity for innovative models to predict ischemic or bleeding events after drug-eluting stent implantation. Leveraging AI for dynamic prediction has the potential to revolutionize risk stratification and provide personalized decision support for DAPT management. METHODS AND RESULTS: We developed and validated a new AI-based pipeline using retrospective data of drug-eluting stent-treated patients, sourced from the Cerner Health Facts data set (n=98 236) and Optum\u27s de-identified Clinformatics Data Mart Database (n=9978). The 36 months following drug-eluting stent implantation were designated as our primary forecasting interval, further segmented into 6 sequential prediction windows. We evaluated 5 distinct AI algorithms for their precision in predicting ischemic and bleeding risks. Model discriminative accuracy was assessed using the area under the receiver operating characteristic curve, among other metrics. The weighted light gradient boosting machine stood out as the preeminent model, thus earning its place as our AI-DAPT model. The AI-DAPT demonstrated peak accuracy in the 30 to 36 months window, charting an area under the receiver operating characteristic curve of 90% [95% CI, 88%-92%] for ischemia and 84% [95% CI, 82%-87%] for bleeding predictions. CONCLUSIONS: Our AI-DAPT excels in formulating iterative, refined dynamic predictions by assimilating ongoing updates from patients\u27 clinical profiles, holding value as a novel smart clinical tool to facilitate optimal DAPT duration management with high accuracy and adaptability

miR-216b Post-Transcriptionally Downregulates Oncogene KRAS and Inhibits Cell Proliferation and Invasion in Clear Cell Renal Cell Carcinoma

Background/Aims: Increasing evidence has shown that miR-216b plays an important role in human cancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. Methods: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. Results: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3’untranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. Conclusion: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC

Effect of Humic Acid Addition on Buffering Capacity and Nutrient Storage Capacity of Soilless Substrates

Excessive application of fertilizers has become a major issue in croplands of intensive agricultural systems in China, resulting in severe non-point source pollution; thus, reduction in the use of chemical fertilizers has received significant attention. Improving the nutrient storage capacity of soils or substrates is an effective approach for solving this problem. Humic acids (HA) are excellent soil conditioners. Thus, in the present study, their ability to improve the physico-chemical properties of three substrates with different textures was evaluated. HA treatments included 1% HA root application in three different types of substrates, including pure sand, pure cocopeat, and a mixture of sand:cocopeat (1:1, v/v) and their relative controls. We examined the morphological parameters of cucumber seedlings as well as pH buffering capacity (pHBC), total organic carbon (TOC), organic matter (OM), cation exchange capacity (CEC), and nutrient storage capacity of the three substrates. The results show that HA application improved the morphological parameters of cucumber seedlings (plant height, stem diameter, and biomass) in pure cocopeat and cocopeat-sand mixture treatments. On the contrary, HA addition had harmful effects on the cucumber seedlings cultivated in sand due to the low pHBC of sand. The seedlings cultivated in pure cocopeat showed the best morphological parameter performances among the seedlings grown in the three substrates. Furthermore, pHBC, TOC, OM, and CEC were enhanced by HA application. Incorporation of HA improved ammonium (N

A Bayesian network to predict the risk of post influenza vaccination Guillain-Barré syndrome: Development and validation study

BACKGROUND: Identifying the key factors of Guillain-Barré syndrome (GBS) and predicting its occurrence are vital for improving the prognosis of patients with GBS. However, there are scarcely any publications on a forewarning model of GBS. A Bayesian network (BN) model, which is known to be an accurate, interpretable, and interaction-sensitive graph model in many similar domains, is worth trying in GBS risk prediction. OBJECTIVE: The aim of this study is to determine the most significant factors of GBS and further develop and validate a BN model for predicting GBS risk. METHODS: Large-scale influenza vaccine postmarketing surveillance data, including 79,165 US (obtained from the Vaccine Adverse Event Reporting System between 1990 and 2017) and 12,495 European (obtained from the EudraVigilance system between 2003 and 2016) adverse events (AEs) reports, were extracted for model development and validation. GBS, age, gender, and the top 50 prevalent AEs were included for initial BN construction using the R package bnlearn. RESULTS: Age, gender, and 10 AEs were identified as the most significant factors of GBS. The posttest probability of GBS suggested that male vaccinees aged 50-64 years and without erythema should be on the alert or be warned by clinicians about an increased risk of GBS, especially when they also experience symptoms of asthenia, hypesthesia, muscular weakness, or paresthesia. The established BN model achieved an area under the receiver operating characteristic curve of 0.866 (95% CI 0.865-0.867), sensitivity of 0.752 (95% CI 0.749-0.756), specificity of 0.882 (95% CI 0.879-0.885), and accuracy of 0.882 (95% CI 0.879-0.884) for predicting GBS risk during the internal validation and obtained values of 0.829, 0.673, 0.854, and 0.843 for area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy, respectively, during the external validation. CONCLUSIONS: The findings of this study illustrated that a BN model can effectively identify the most significant factors of GBS, improve understanding of the complex interactions among different postvaccination symptoms through its graphical representation, and accurately predict the risk of GBS. The established BN model could further assist clinical decision-making by providing an estimated risk of GBS for a specific vaccinee or be developed into an open-access platform for vaccinees\u27 self-monitoring

A high high-density lipoprotein level is associated with Gleason score upgrade in Chinese patients diagnosed with high-grade prostate carcinoma

Abstract Background The high incidence of Gleason score upgrading (GSU) made urologists underestimate the disease, leading to the inaccurate therapeutic decision. The study aimed to explore relevant laboratory examination evidence associated with GSU. Methods Patients diagnosed with prostate carcinoma undergoing radical prostatectomy in our center between January 2015 and December 2019 were included in this retrospective study. Patients were divided into GSU and NGSU groups according to the occurrence of GSU. Medical records were reviewed and analyzed between groups. Results A total of 130 patients were enrolled, including 52 patients diagnosed with GS = 6 (20 NGSU and 32 GSU) and 78 patients with GS = 7 (36 NGSU and 42 GSU). No significant differences in demographic characteristics were found between groups. An increased neutrophil count (OR = 1.326, 95% CI = 1.005–1.748) and a decreased percentage of lymphocytes (OR = 0.951, 95% CI = 0.904–1) were associated with GSU in the GS = 6 group, whereas a high HDL level (OR = 7.735, 95% CI = 0.998–59.957) was associated with GSU in GS = 7 group. Preoperative high neutrophile count and low lymphocyte percentage were correlated with GSU in patients with low-grade prostate cancer. In contrast, high HDL level was associated with GSU in patients with high-grade prostate cancer. Conclusions These laboratory examination data could provide urologists with information before making a therapeutic protocol

Characteristics and Management of Spinal Tuberculosis in Tuberculosis Endemic Area of Guizhou Province: A Retrospective Study of 597 Patients in a Teaching Hospital

Background. Tuberculosis (TB) is an endemic disease in Guizhou. Spinal TB accounts for approximately 50% cases of skeletal TB. The purpose of this study was to investigate the characteristics and management of patients treated for spinal TB in a certain hospital and to provide guidance for the prevention and treatment of spinal TB. Methods. The clinic records of all patients diagnosed with spinal tuberculosis in a teaching hospital between January 2010 and December 2018 were collected. The epidemiology, clinical characteristics, imaging and laboratory findings, treatment methods, and prognosis were recorded and analyzed. Results. During this nine-year period, 597 patients with spinal TB were identified. There were 313 males and 284 females with an average age of 43 years. The largest number of patients fell in the age group of 21–30 years; mean time from symptom onset to diagnosis in the hospital was 17 months. Back pain was the main clinical manifestation (89.34%). The most common imaging technique was computed tomography (CT, 96.80%), followed by magnetic resonance imaging (MRI, 84.01%). Majority of the lesions involved the lumbar spine (47.30%), followed by the thoracic spine (40.95%). 178 (29.82%) patients in this study had varying degrees of neurological impairment. 22.78% of the patients selected conservative treatment, and surgical treatment was performed in 483 patients (80.90%). Conclusions. The incidence of spinal TB was generally on the rise throughout the study period. After diagnosed with spinal TB, all patients got appropriate treatment and achieved good efficacy, but most of the patients did not pay much attention to the disease and receive timely treatment. Thus, it is essential to strengthen the TB preventive strategies, improve the health awareness of residents and universal resident health examination