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A genetic Gaussian network of multiple phenotypes, constructed through the inverse matrix of the genetic correlation matrix, is informative for understanding the biological dependencies of the phenotypes. However, its estimation may be challenging because the genetic correlation estimates are biased due to estimation errors and idiosyncratic pleiotropy inherent in GWAS summary statistics. Here, we introduce a novel approach called estimation of genetic graph (EGG), which eliminates the estimation error bias and idiosyncratic pleiotropy bias with the same techniques used in multivariable Mendelian randomization. The genetic network estimated by EGG can be interpreted as shared common biological contributions between phenotypes, conditional on others. We use both simulations and real data to demonstrate the superior efficacy of our novel method in comparison with the traditional network estimators. [ABSTRACT FROM AUTHOR]

Carbon price fluctuations significantly impact the development of industries, energy, agriculture, and stock investments. The carbon price possesses the features of nonlinearity, non-stationarity, and high complexity as a time series. To overcome the negative impact of these characteristics on prediction and to improve the prediction accuracy of carbon price series, a combination prediction model named Lp-CNN-LSTM, which utilizes both convolutional neural networks and long short-term memory networks, has been proposed. Strategy one involved establishing distinct models of CNN-LSTM and LSTM to analyze high-frequency and low-frequency carbon price sequences; the combination of output was integrated to predict carbon prices more precisely. Strategy two comprehensively considered the economic and technical indicators of carbon price sequences based on the Pearson correlation coefficient, while the Multi-CNN-LSTM model selected explanatory variables that strongly correlated with carbon prices. Finally, a predictive model for a combination of carbon prices was developed using Lp-norm. The empirical study focused on China's major carbon markets, including Hubei, Guangdong, and Shanghai. According to the error indicators, the performance of the Lp-CNN-LSTM model was superior to individual strategy prediction models. The Lp-CNN-LSTM model has excellent accuracy, superiority, and robustness in predicting carbon prices, which can provide a necessary basis for revising carbon pricing strategies, regulating carbon trading markets, and making investment decisions. [ABSTRACT FROM AUTHOR]

The estimation of large functional and longitudinal data, which refers to the estimation of mean function, estimation of covariance function, and prediction of individual trajectory, is one of the most challenging problems in the field of high-dimensional statistics. Functional Principal Components Analysis (FPCA) and Functional Linear Mixed Model (FLMM) are two major statistical tools used to address the estimation of large functional and longitudinal data; however, the former suffers from a dramatically increasing computational burden while the latter does not have clear asymptotic properties. In this paper, we propose a computationally effective estimator of large functional and longitudinal data within the framework of FLMM, in which all the parameters can be automatically estimated. Under certain regularity assumptions, we prove that the mean function estimation and individual trajectory prediction reach the minimax lower bounds of all nonparametric estimations. Through numerous simulations and real data analysis, we show that our new estimator outperforms the traditional FPCA in terms of mean function estimation, individual trajectory prediction, variance estimation, covariance function estimation, and computational effectiveness. [ABSTRACT FROM AUTHOR]

Background In March 2020, the greater New York metropolitan area became an epicenter for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The initial evolution of case incidence has not been well characterized. Methods Northwell Health Laboratories tested 46 793 persons for SARS-CoV-2 from 4 March through 10 April. The primary outcome measure was a positive reverse transcription–polymerase chain reaction test for SARS-CoV-2. The secondary outcomes included patient age, sex, and race, if stated; dates the specimen was obtained and the test result; clinical practice site sources; geolocation of patient residence; and hospitalization. Results From 8 March through 10 April, a total of 26 735 of 46 793 persons (57.1%) tested positive for SARS-CoV-2. Males of each race were disproportionally more affected than females above age 25, with a progressive male predominance as age increased. Of the positive persons, 7292 were hospitalized directly upon presentation; an additional 882 persons tested positive in an ambulatory setting before subsequent hospitalization, a median of 4.8 days later. Total hospitalization rate was thus 8174 persons (30.6% of positive persons). There was a broad range (>10-fold) in the cumulative number of positive cases across individual zip codes following documented first caseincidence. Test positivity was greater for persons living in zip codes with lower annual household income. Conclusions Our data reveal that SARS-CoV-2 incidence emerged rapidly and almost simultaneously across a broad demographic population in the region. These findings support the premise that SARS-CoV-2 infection was widely distributed prior to virus testing availability. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that induction of a diverse repertoire of memory T cells ("immune education") affects responses to murine cecal ligation and puncture (CLP), the most widely – used animal model of sepsis. Among the documented effects of immune education on CLP are changes in T cell, macrophage and neutrophil activity, more pronounced organ dysfunction and reduced survival. Little is known, however, about the effects of CLP on B cell responses, and how these responses might be altered by immune education. Importantly, effective B cell responses are modulated by IL21 produced by CD4+/CXCR5+/PD1+ T follicular helper (Tfh) cells. We examined the B cell population in control and immune educated mice 24 h and 60 days after CLP. Education alone increased Tfh cells. Twenty-four hours after CLP, Tfh cells were depleted. However, this reduction was less pronounced in immune educated mice than in controls and the percentage of CD4 T cells expressing a Tfh phenotype increased in the animals. CLP did not alter splenic architecture and decreased numbers of follicular, marginal, and germinal center B cells. CLP induced changes were not, however, noted following CLP in immune educated mice. At 60 days post – CLP, numbers of follicular, germinal center and marginal zone B cells were increased; this increase was more pronounced in immune educated mice. Finally, while CLP reduced the induction of antigen specific B cells in controls, this response was maintained following CLP in immune educated mice. Our data suggest that preexisting Tfh assists in rescuing the B cell response to CLP. [ABSTRACT FROM AUTHOR]

Background. Risk of progressive disease of gastrointestinal stromal tumors (GISTs) relies on mitotic index, size, and location of the tumor. However, manual mitotic counting on hematoxylin and eosin–stained slides (MMC-HE) is inefficient with low reproducibility. Manual count of phospho-histone H3 (MC-PHH3)-positive cells on immunohistochemical stained slides has been shown to have comparable reliability with MMC-HE. This study aims to confirm the reliability of MC-PHH3 in GISTs compared with MMC-HE and then to further compare MC-PHH3 with computer-assisted image analysis of PHH3-positive cells (Comp-PHH3). Methods. The study included 119 patients with GISTs. PHH3 stains were performed. MC-PHH3 was assessed as counts/5 mm2 high-power fields. Whole slide images were captured and the tumor area with greatest mitotic activity was manually identified. The PHH3-positive cells were automatically counted in 0.5 mm2 using Ventana Virtuoso software. Results. MMC-HE ranged from 0 to 157/5 mm2. MC-PHH3 ranged from 0 to 35.6/5 mm2. Comp-PHH3 ranged from 0 to 66/0.5 mm2. Interclass correlation coefficient (ICC) indicates good agreement between the 3 pathologists for MC-PHH3 (ICC = 0.74, P =.42). There is a strong correlation between MMC-HE and MC-PHH3. The Spearman correlation coefficient was 0.63 (P <.0001). Lin's concordance further indicated a moderate diagnostic agreement between MC-PHH3 and Comp-PHH3. Conclusion. MC-PHH3 is proposed as a superior alternative to MMC-HE with potential application in GIST reporting and prognostication. Furthermore, Comp-PHH3 may be a valid alternative to MC-PHH3. [ABSTRACT FROM AUTHOR]

Tomato hot pot sauce (THPS) at different storage temperatures (0, 25, and 37°C) and with two kinds of packaging for 120 days was investigated in this study. High performance liquid chromatography was employed for detecting lycopene and 5-hydroxymethylfurfural (HMF). The changes of lycopene and HMF during storage were regressed with kinetic equation of both zero-order and first-order models, and the latter fitted better. The kinetic equation constant (k value) of lycopene or HMF at 37°C was higher than that at 25°C. The k value of lycopene of PET/PE (P1) packaged THPS was 1.60 times of that of PET/Al/EAA/PE (P2) packaged at 37°C, while it was 2.12 times at 25°C. The k value of HMF of P1 packaged THPS was 1.69 times of that of P2 packaged at 37°C, while it was 1.01 times at 25°C. Significant correlations between color index of L⁎, a⁎, and a⁎/b⁎ and lycopene or HMF were found at storage temperature. Browning color was attributed to both Maillard reaction and degradation of lycopene. In conclusion, lower storage temperature and stronger oxygen barrier property of package could maintain color stability and extend shelf life. [ABSTRACT FROM AUTHOR]

Purpose: Surgical resection of colorectal liver metastases is not achievable in more than 70% of the cases. Although the liver directed therapies have become a part of the stand of care, lack of a preclinical model impedes the assessment of toxicity and therapeutic benefits attributed several candidate drugs or treatment regimens that can be designed. In the present study we aim develop and characterize a rat colorectal liver metastasis model. Materials and Methods: Growth characteristics of CC-531 cells were determined in vitro followed by subcapsular liver implantation in syngeneic WAG/Rij rats. Tumor growth progression was followed over 3 weeks by ultrasound (US) and magnetic resonance imaging (MRI). Growth characteristics were also assessed by histopathology and immunohistochemistry in harvested tumor tissues. Results: The doubling time of CC-531 cells was found be under 24hrs and all the implanted rats grew tumors. US imaging showed hypoechoic masses and MRI showed contrast enhancement representing complex tumor microenvironments. Hematoxylin and Eosin staining confirmed tumor growth and uniform CD31 staining in tumor confirmed even vessel density. Conclusion: CC-531 can be used as a metastatic rat tumor colorectal liver metastases model with well-defined characteristics that can be readily followed by imaging whilst having a therapeutic window for interventions. [ABSTRACT FROM AUTHOR]

Objectives: Obesity is associated with cardiovascular diseases and has become the main public health issue in western countries and urban China. However, the prevalence and secular trends of obesity in rural China are currently unknown. The aim of this study was to investigate secular trends in the prevalence of overweight and obesity among rural adults in northern China between 1991 and 2011. Method: The prevalence of overweight and obesity was assessed in adults aged 35–74 years living in a rural area in northern China by comparing two surveys that were conducted in 1991 and 2011, respectively. Result: The age-adjusted prevalence of overweight increased from 24.5% in 1991 to 42.0% in 2011, and the prevalence of obesity increased from 5.7% in 1991 to 19.6% in 2011. Over the 21-year period, there were significant increases in the prevalence of overweight and obesity for both men and women in all age groups; however, the greatest increase was observed in men aged 35–44 years, with an 10.3-fold increase in obesity prevalence. The prevalence of obesity increased significantly in all risk factors categories, including education levels, blood pressure categories, diabetes previous history, current smoking situation and alcohol drinking situation over the past 21 years overall (p<0.05). The greatest increase in obesity prevalence appeared among those who consumed alcohol (increased by 8.0-fold). Next, there was a 5.3-fold increase in the prevalence of obesity in illiterate residents. Conclusion: The prevalence of overweight and obesity has increased rapidly among rural adults in Tianjin over the past 21 years, with the most dramatic increase observed in young men. Therefore, the burden of obesity should serve as a call for action. [ABSTRACT FROM AUTHOR]

Improved street lighting can provide better use of public space and helps to promote safety while driving or walking. In terms of balancing benefits and impacts, on the basis of cost saving, this research adopts two prominent mathematical models, the maximal coverage location problem and the location set covering problem, to optimize street light locations. By comparing with the currently installed lights following the rule of thumb, the mathematical models in this research achieve the effect of saving electric energy while meeting residents' traffic safety needs and living conditions. Furthermore, the models can provide greater coverage of illumination using the same amount of energy. [ABSTRACT FROM AUTHOR]

Context. To determine the clinical-pathological features associated with cholesterol embolic renal disease, and review of literature. Design. This retrospective case series includes patients with cholesterol embolic renal disease (10 of 3087 kidney biopsies) who were diagnosed at Northwell Health, New York, between July 2017 and October 2022. Results. Cholesterol embolic renal disease is a rare disease with a prevalence of 0.32%. Four of 10 patients had intravascular interventional radiology procedures within 6 months prior to kidney biopsy. Four patients had remote interventional radiology history (6 months to 4 years). Seven patients presented with acute kidney injury; 3 patients underwent renal biopsy due to proteinuria. The average baseline creatinine was 2.0 ± 0.9 mg/dL; the creatinine at kidney biopsy and at follow-up was 4.3 ± 3.0 mg/dL and 2.8 ± 1.3 mg/dL, respectively. Eight patients had elevated serum eosinophil counts. Three patients died (mortality rate 30%) in an average follow-up of 4 months (range: 1-10 months). One patient progressed to end-stage kidney disease. The presence of cholesterol clefts is a hallmark of atherosclerotic emboli. Cholesterol clefts were present on the specimen for light microscopy (H&E and special stains) in 9 biopsies; 7 patients had cholesterol clefts in vascular lumens and/or walls. Cholesterol clefts were present on semi-thin sections for electron microscopy examination in 4 biopsies. One patient had cholesterol clefts present in semi-thin sections only. Conclusions. The clinical manifestation of cholesterol embolic renal disease in patients without recent intravascular interventional radiology history can be indolent but is associated with high mortality. Careful examination of all levels with light microscopy, including the perirenal tissue, and semi-thin sections can increase the detection rate of cholesterol embolic renal disease. [ABSTRACT FROM AUTHOR]

Gastrointestinal neuroendocrine tumors, or GI-NETs are a highly diverse group of tumors derived from neuroendocrine cells of the GI tract. In GI-NET, a spectrum of histological and molecular parameters exists to predict prognosis and survival. Immunohistochemistry for Ki67, a nuclear antigen that is present in all but the G0 phase of the cell cycle with specificity for proliferating cells, can be used to determine a tumors proliferation index. With this in mind, grading of gastrointestinal neuroendocrine tumors is critical for prognosis and can impact clinical decision making. Recently, digital image analysis (DIA) has been shown in studies to be a superior and less time-consuming alternative to the manual scoring of Ki-67 in breast cancer, secondary to its theoretical diagnostic reproducibility. In DIA, the correct identification of tumor cells and non-tumor is paramount to avoid over or under calculation of biomarker expression. Additionally, DIA requires a pathologist to manually outline a tumor in large tissue areas of hematoxylin and eosin (H&E) sections, which is impractical. The findings in our study showed that ventana virtuoso software computer analyzed Ki-67 only correlated well with Neuroendocrine carcinomas while manual analysis of mitotic index and Ki67 were found to be gold standard. The performance of DIA in our study was plagued by software issues. In future, the advent of new digital imaging technologies such as virtual dual staining will hopefully improve diagnostic accuracy and reproducibility across different DIA platforms. Ultimately, determination of therapeutic strategies should be guided by an amalgamation of clinicopathologic characteristics not limited to mitotic index and Ki-67. As well, A visual check of the results should always be performed and correlated with other findings. [ABSTRACT FROM AUTHOR]