- A kriging-calibrated machine learning method for estimating daily ground-level NO2 in mainland China. [Journal Article]
- STSci Total Environ 2019 Jun 26; 690:556-564
- It is unclear how to develop a model based on the combined satellite data and ground monitoring data to accurately estimate daily NO2 levels. Furthermore, the conventional cross-validation (CV) resul…
It is unclear how to develop a model based on the combined satellite data and ground monitoring data to accurately estimate daily NO2 levels. Furthermore, the conventional cross-validation (CV) results represent average levels but the model performance may vary greatly from grid to grid. It is an essential issue to evaluate model's prediction ability in different grids and determine the factors affecting model extrapolating ability, which have never been well examined to date. The aim of this study was to compare the ability of three different methods to estimate the daily NO2 across mainland China during 2014-2016; and to develop a novel two-stage meta-analysis method for exploring the influence of the number and the distribution of nearby sites on grid-level prediction accuracy. For better estimating the daily NO2 level, we developed and compared three methods, including universal kriging model, satellite-based method (Non-linear exposure-lag-response model & Extreme gradient boosting combined technique) and the kriging-calibrated satellite method. For exploring influencing factors, the two-stage meta-analysis method was purposed. The kriging-calibrated satellite method had an overall CV R-square and root mean square error (RMSE) of 0.85 and 7.87μg/m3, better than the Universal Kriging model and the satellite-based method (CV R2 = 0.57 and 0.81). The two-stage meta-analysis method revealed that the model performance did decrease with the sparser distribution of nearby sites. And adding 5 sites within 50 km in the random mode can bring 17.51% improvement in model extrapolating ability. The kriging-calibration can help satellite-based machine learning to provide more accurate NO2 prediction. Our novel evaluation method can provide the suggestion of adding new sites effectively within a limit budget.
- Snapshot: Socioeconomic Competence in US Neurosurgery Residents. [Journal Article]
- WNWorld Neurosurg 2019 Jul 10
- CONCLUSIONS: With the increasing complexity of neurosurgery practice, solid knowledge of socioeconomic topics is essential. The study confirms suspected deficiencies in socioeconomic proficiency among neurosurgery residents, despite the availability of a validated curriculum. This knowledge gap will likely impact career success and satisfaction. Nevertheless, this survey had a significantly low response rate, and it may be an incomplete representation of the neurosurgical resident mind. Focused educational initiatives through the neurosurgical Residency Review Committee and individual training programs must facilitate an action plan that ensures the effective implementation of socioeconomic curricula.
- Hectd1 is essential for embryogenesis in mice. [Journal Article]
- GEGene Expr Patterns 2019 Jul 10; :119064
- Many aspects of the functional role of the E3 ubiquitin ligase Hectd1 in embryogenesis and in cell biology still remain to be elucidated. In order to contribute to this task we now report the generat…
Many aspects of the functional role of the E3 ubiquitin ligase Hectd1 in embryogenesis and in cell biology still remain to be elucidated. In order to contribute to this task we now report the generation of a new transgenic mouse model for Hectd1 using the gene trap strategy. The HECT domain deletion mutant mouse was created by inserting a β-geo cassette into the Hectd1 locus. Mice homozygous for Hectd1-mutant showed early embryonic lethality with abnormal placental development and defective of neural tube closure resulting in exencephaly. The thickness of the placenta of both Hectd1-mutant homozygous and heterozygous mice was distinctly thinner than that of wildtype mice, the difference being most pronounced in the labyrinth layer of the placenta. We also addressed the temporal and spatial expression profiles of Hectd1 in adult tissues by X-gal staining. Hectd1 expression was detected in specific cell populations of most but not all tissues of the adult organism. Furthermore, the expression of Hectd1 was regulated by insulin and by both heat and hypoxia. Thus, our studies reveal that Hectd1 is indispensable for normal embryogenesis and fetal survival. The generation of this new Hectd1 mutant mouse model provides ample opportunities to study the function of Hectd1 in mammalian cells in detail.
- Structural insights into the recognition of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) by HIV-1 reverse transcriptase: First crystal structures with RT and the active triphosphate forms of lamivudine and emtricitabine. [Journal Article]
- PSProtein Sci 2019 Jul 13
- The retrovirus HIV-1 has been a major health issue since its discovery in the early 80s. In 2017, over 37 million people were infected with HIV-1, of which 1.8 million were new infections that year. …
The retrovirus HIV-1 has been a major health issue since its discovery in the early 80s. In 2017, over 37 million people were infected with HIV-1, of which 1.8 million were new infections that year. Currently, the most successful treatment regimen is the highly active anti-retroviral therapy (HAART), which consists of a combination of three to four of the current 26 FDA-approved HIV-1 drugs. Half of these drugs target the reverse transcriptase (RT) enzyme that is essential for viral replication. One class of RT inhibitors are nucleoside reverse transcriptase inhibitors (NRTIs), a crucial component of the HAART therapy. Once incorporated into DNA, NRTIs function as a chain terminator to stop viral DNA replication. Unfortunately, treatment with NRTIs is sometimes linked to toxicity caused by off-target side effects. NRTIs may also target the replicative human mitochondrial DNA polymerase (Pol γ), causing long-term severe drug toxicity. The goal of this work is to understand the discrimination mechanism of different NRTI analogs by RT. Crystal structures and kinetic experiments are essential for the rational design of new molecules that are able to bind selectively to RT and not Pol γ. Structural comparison of NRTI-binding modes with both RT and Pol γ enzymes highlights key amino acids that are responsible for the difference in affinity of these drugs to their targets. Therefore, the long-term goal of this research is to develop safer, next generation therapeutics that can overcome off-target toxicity. This article is protected by copyright. All rights reserved.
- Inter-rater reliability and variability of ultrasound measurements of abdominal muscle and fasciae thickness. [Journal Article]
- CAClin Anat 2019 Jul 13
- CONCLUSIONS: Knowledge of the fascial anatomy of the abdominal wall is essential for accurate ultrasound examinations and for improving reliability. These findings confirm that US imaging is a reliable, non-invasive, cost-effective instrument for evaluating the abdominal muscles/fasciae. This article is protected by copyright. All rights reserved.
- Comparing Treatments for Basal Cell Carcinoma in Terms of Long-term Treatment-Failure: A Network Meta-analysis. [Review]
- JEJ Eur Acad Dermatol Venereol 2019 Jul 13
- Although many variations of guidelines have been released, there is limited research that compares multiple treatment strategies for basal cell carcinoma (BCC). The aim of this study was to systemati…
Although many variations of guidelines have been released, there is limited research that compares multiple treatment strategies for basal cell carcinoma (BCC). The aim of this study was to systematically review the studies reporting on multiple treatments for BCC with systematic review and network meta-analyses. Search formulas for databases, such as PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials, were created with the support of Cochrane Japan. The patient-level and tumor-level meta-analyses were performed for both the long-term treatment-failure and treatment-success. Of the 1464 studies identified from the database and hand searches, 14 met our inclusion criteria. These 14 studies included 2524 patients and 1738 tumors. Our study indicated that the incidence of treatment-failure of invasive treatments such as surgery and Mohs micrographic surgery (MMS) was significantly lower than that of superficial therapies such as: cryotherapy, photodynamic therapy, radiotherapy, or topical therapies, in the patient-level and the tumor-level analyses, despite histological-type and pretreatment. Relapse of BCC may be a low life-threatening risk and there are merits of non-surgical treatment. However, the significant difference of the recurrence rate is essential. Our study can provide useful guidance to clinicians in selecting treatment options for BCC. This article is protected by copyright. All rights reserved.
- Adenosine triphosphate enhances osteoblast differentiation of rat dental pulp stem cells via the PLC-IP3 pathway and intracellular Ca 2+ signaling. [Journal Article]
- JCJ Cell Physiol 2019 Jul 12
- Intracellular Ca2+ signals are essential for stem cell function and play a significant role in the differentiation process. Dental pulp stem cells (DPSCs) are a potential source of stem cells; howeve…
Intracellular Ca2+ signals are essential for stem cell function and play a significant role in the differentiation process. Dental pulp stem cells (DPSCs) are a potential source of stem cells; however, the mechanisms controlling cell differentiation remain largely unknown. Utilizing rat DPSCs, we examined the effect of adenosine triphosphate (ATP) on osteoblast differentiation and characterized its mechanism of action using real-time Ca 2+ imaging analysis. Our results revealed that ATP enhanced osteogenesis as indicated by Ca 2+ deposition in the extracellular matrix via Alizarin Red S staining. This was consistent with upregulation of osteoblast genes BMP2, Mmp13, Col3a1, Ctsk, Flt1, and Bgn. Stimulation of DPSCs with ATP (1-300 µM) increased intracellular Ca 2+ signals in a concentration-dependent manner, whereas histamine, acetylcholine, arginine vasopressin, carbachol, and stromal-cell-derived factor-1α failed to do so. Depletion of intracellular Ca 2+ stores in the endoplasmic reticulum by thapsigargin abolished the ATP responses which, nevertheless, remained detectable under extracellular Ca 2+ free condition. Furthermore, the phospholipase C (PLC) inhibitor U73122 and the inositol triphosphate (IP 3) receptor inhibitor 2-aminoethoxydiphenyl borate inhibited the Ca 2+ signals. Our findings provide a better understanding of how ATP controls osteogenesis in DPSCs, which involves a Ca 2+ -dependent mechanism via the PLC-IP 3 pathway. This knowledge could help improve osteogenic differentiation protocols for tissue regeneration of bone structures.
- A Comprehensive Update of Current Anesthesia Perspectives on Therapeutic Hypothermia. [Review]
- ATAdv Ther 2019 Jul 12
- Normal thermal regulation is a result of the integration of afferent sensory, central control, and efferent responses to temperature change. Therapeutic hypothermia (TH) is a technique utilized durin…
Normal thermal regulation is a result of the integration of afferent sensory, central control, and efferent responses to temperature change. Therapeutic hypothermia (TH) is a technique utilized during surgery to protect vital organs from ischemia; however, in doing so leads to other physiological changes. Indications for inducing hypothermia have been described for neuroprotection, coronary artery bypass graft (CABG) surgery, surgical repair of thoracoabdominal and intracranial aneurysms, pulmonary thromboendarterectomy, and arterial switch operations in neonates. Initially it was thought that induced hypothermia worked exclusively by a temperature-dependent reduction in metabolism causing a decreased demand for oxygen and glucose. Induced hypothermia exerts its neuroprotective effects through multiple underlying mechanisms including preservation of the integrity and survival of neurons through a reduction of extracellular levels of excitatory neurotransmitters dopamine and glutamate, therefore reducing central nervous system hyperexcitability. Risks of hypothermia include increased infection risk, altered drug pharmacokinetics, and systemic cardiovascular changes. Indications for TH include ischemia-inducing surgeries and diseases. Two commonly used methods are used to induce TH, surface cooling and endovascular cooling. Core body temperature monitoring is essential during induction of TH and rewarming, with central venous temperature as the gold standard. The aim of this review is to highlight current literature discussing perioperative considerations of TH including risks, benefits, indications, methods, and monitoring.
- Biological functions and clinical applications of exosomal non-coding RNAs in hepatocellular carcinoma. [Review]
- CMCell Mol Life Sci 2019 Jul 12
- Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a high mortality rate. Its dismal prognosis is attributed to late diagnosis, high risk of recurrence and drug res…
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a high mortality rate. Its dismal prognosis is attributed to late diagnosis, high risk of recurrence and drug resistance. To improve the survival of patients with HCC, new approaches are required for early diagnosis, real-time monitoring and effective treatment. Exosomes are small membranous vesicles released by most cells that contain biological molecules and play a great role in intercellular communication under physiological or pathological conditions. In cancer, exosomes from tumor cells or non-tumor cells can be taken up by neighboring or distant target cells, and the cargoes in exosomes are functional to modulate the behaviors of tumors or reshape tumor microenvironment (TME). As essential components, non-coding RNAs (ncRNAs) are selectively enriched in exosomes, and exosomal ncRNAs participate in regulating specific aspects of tumor development, including tumorigenesis, tumor metastasis, angiogenesis, immunomodulation and drug resistance. Besides, dysregulated exosomal ncRNAs have emerged as potential biomarkers, and exosomes can serve as natural vehicles to deliver tumor-suppressed ncRNAs for treatment. In this review, we briefly summarize the biology of exosomes, the functions of exosomal ncRNAs in HCC development and their potential clinical applications, including as biomarkers and therapeutic tools.
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- Wisteria floribunda agglutinin-positive mac-2 binding protein as an age-independent fibrosis marker in nonalcoholic fatty liver disease. [Journal Article]
- SRSci Rep 2019 Jul 12; 9(1):10109
- The assessment of liver fibrosis is essential because it correlates with mortality risk in nonalcoholic fatty liver disease (NAFLD). This study aims to examine whether serum fibrosis markers could id…
The assessment of liver fibrosis is essential because it correlates with mortality risk in nonalcoholic fatty liver disease (NAFLD). This study aims to examine whether serum fibrosis markers could identify candidate patients likely to have advanced fibrosis. We enrolled 352 patients with NAFLD and performed liver biopsies in 97 patients. The area under the receiver operating characteristic curve (AUROC) of liver stiffness by magnetic resonance elastography for histological advanced fibrosis was 0.910, and the optimal cutoff value was 4.07 kPa. To predict severe liver stiffness (≥4.07 kPa), the AUROC for Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) and FIB-4 were 0.897 (cutoff value, 1.08) and 0.880 (cutoff value, 2.53), respectively. After stratification of patients into four age groups as quartile, the optimal cutoff values of WFA+-M2BP for predicting severe liver stiffness were similar in each group (1.09, 1.08, 1.10, and 1.12). On the other hand, those of FIB-4 increased in parallel with age (1.47, 2.19, 2.99, and 3.88). In conclusion, WFA+-M2BP was precise for estimating severe liver stiffness in NAFLD with single cutoff value independent of age. Hence, identifying high-risk cases using WFA+-M2BP from a large number of NAFLD patients is clinically significant.