Molecular insights into the development of hepatic metastases in colorectal cancer: a metastasis prediction study.

OBJECTIVE: Colorectal cancer is presently the third most commonly diagnosed cancer in the United States. In this study, we identified molecular differences between hepatic and non-hepatic metastases in colorectal cancer and evaluated their prognostic significance. MATERIALS AND METHODS: We downloaded primary data from the NCBI Gene Expression Omnibus (GSE6988, GSE62321, GSE50760, and GSE28722). To identify the molecular differences, we used the Significance Analysis of Microarray method. We selected nine prognostic genes (SYTL2, PTPLAD1, CDS1, RNF138, PIGR, WDR78, MYO7B, TSPAN3, and ATP5F1) with hepatic metastasis prediction score in colorectal cancer (hereafter referred to as LASSO Score). We confirmed the prognostic significance of the LASSO Score by using Kaplan-Meier survival analysis, multivariate analysis, the time-dependent area under the curve (AUC) of Uno's C-index, and the AUC of the receiver operating characteristic curve at 1-5 years. RESULTS: Survival analysis revealed that a high LASSO Score is associated with a poor prognosis in colorectal cancer patients with hepatic metastases (p = 0). Analysis of C-indices and AUC values from the receiver operating characteristic curve further supported this prediction by the LASSO Score. Multivariate analysis confirmed the prognostic significance of the LASSO Score (p = 1.13e-06). CONCLUSIONS: This study reveals the biological mechanisms underlying hepatic metastases in colorectal cancer and will help in developing targeted therapies for colorectal cancer.

Cytoprotective Effect of Echinochrome A in Primary Culture of Pulmonary Fibroblasts from Albino Rats under Conditions of Oxidative Stress.

We studied the effect of echinochrome A on the primary culture of pulmonary fibroblasts under normal conditions and under oxidative stress. Exposure to echinochrome A (100 µM, 6 h) did not affect the production of superoxide radical by fibroblasts, area of their nuclei, and number of nucleoli, but reduced the total area of nucleolar organizer regions against the background of stable proliferative activity of the culture. Two-hour oxidative stress induced by hydrogen peroxide solution (60 µM) increased the generation of superoxide radical, decreased DNA-synthetic activity of fibroblasts, area of fibroblast nuclei, and total area of nucleolar organizer regions. Preliminary administration of echinochrome A significantly attenuated the damaging effect of oxidative stress: the intensity of production of superoxide radicals decreased, DNA-synthetic activity and nucleus area of fibroblasts partially recovered; normalization of the total area of nucleoli was accompanied by an increase in their number.

Interpret with caution: An evaluation of the commercial AusDiagnostics versus in-house developed assays for the detection of SARS-CoV-2 virus.

INTRODUCTION: There is limited data on the analytical performance of commercial nucleic acid tests (NATs) for laboratory confirmation of COVID-19 infection. METHODS: Nasopharyngeal, combined nose and throat swabs, nasopharyngeal aspirates and sputum was collected from persons with suspected SARS-CoV-2 infection, serial dilutions of SARS-CoV-2 viral cultures and synthetic positive controls (gBlocks, Integrated DNA Technologies) were tested using i) AusDiagnostics assay (AusDiagnostics Pty Ltd); ii) in-house developed assays targeting the E and RdRp genes; iii) multiplex PCR assay targeting endemic respiratory viruses. Discrepant SARS-CoV-2 results were resolved by testing the N, ORF1b, ORF1ab and M genes. RESULTS: Of 52 clinical samples collected from 50 persons tested, respiratory viruses were detected in 22 samples (42 %), including SARS CoV-2 (n = 5), rhinovirus (n = 7), enterovirus (n = 5), influenza B (n = 4), hMPV (n = 5), influenza A (n = 2), PIV-2 (n = 1), RSV (n = 2), CoV-NL63 (n = 1) and CoV-229E (n = 1). SARS-CoV-2 was detected in four additional samples by the AusDiagnostics assay. Using the in-house assays as the "gold standard", the sensitivity, specificity, positive and negative predictive values of the AusDiagnostics assay was 100 %, 92.16 %, 55.56 % and 100 % respectively. The Ct values of the real-time in-house-developed PCR assay targeting the E gene was significantly lower than the corresponding RdRp gene assay when applied to clinical samples, viral culture and positive controls (mean 21.75 vs 28.1, p = 0.0031). CONCLUSIONS: The AusDiagnostics assay is not specific for the detection SARS-CoV-2. Any positive results should be confirmed using another NAT or sequencing. The case definition used to investigate persons with suspected COVID-19 infection is not specific.

Mechanically controllable nonlinear dielectrics.

Strain-sensitive Ba x Sr1-x TiO3 perovskite systems are widely used because of their superior nonlinear dielectric behaviors. In this research, new heterostructures including paraelectric Ba0.5Sr0.5TiO3 (BSTO) and ferroelectric BaTiO3 (BTO) materials were epitaxially fabricated on flexible muscovite substrate. Through simple bending, the application of mechanical force can regulate the dielectric constant of BSTO from -77 to 36% and the channel current of BTO-based ferroelectric field effect transistor by two orders. The detailed mechanism was studied through the exploration of phase transition and determination of band structure. In addition, the phase-field simulations were implemented to provide theoretical support. This research opens a new avenue for mechanically controllable components based on high-quality oxide heteroepitaxy.

Vectorizing the spatial structure of high-harmonic radiation from gas.

Strong field laser physics has primarily been concerned with controlling beams in time while keeping their spatial profiles invariant. In the case of high harmonic generation, the harmonic beam is the result of the coherent superposition of atomic dipole emissions. Therefore, fundamental beams can be tailored in space, and their spatial characteristics will be imparted onto the harmonics. Here we produce high harmonics using a space-varying polarized fundamental laser beam, which we refer to as a vector beam. By exploiting the natural evolution of a vector beam as it propagates, we convert the fundamental beam into high harmonic radiation at its focus where the polarization is primarily linear. This evolution results in circularly polarized high harmonics in the far field. Such beams will be important for ultrafast probing of magnetic materials.

Desflurane reduces intraoperative remifentanil requirements more than sevoflurane: comparison using surgical pleth index-guided analgesia.

BACKGROUND: Sevoflurane and desflurane are widely used in balanced anaesthesia in combination with opioid analgesics. The opioid remifentanil is frequently chosen because of its extremely rapid pharmacokinetics. However, intraoperative high-dose remifentanil is associated with increased postoperative pain and rescue analgesic use owing to acute tolerance and opioid-induced hyperalgesia. This study aimed to compare intraoperative remifentanil requirements during equi-minimum alveolar concentration (MAC) sevoflurane and desflurane anaesthesia via surgical pleth index-guided remifentanil administration. METHODS: Eighty-two subjects undergoing laparoscopic cholecystectomy were randomly allocated to two groups receiving either sevoflurane (n=40) or desflurane (n=42). Anaesthesia was maintained with the assigned inhaled anaesthetics and remifentanil. End-tidal anaesthetic concentration was maintained at age-corrected 1.0 MAC, and remifentanil infusion was continuously adjusted to achieve a surgical pleth index of 20-50. Mean remifentanil infusion rate, which was the primary outcome of the study, was calculated as the total infused remifentanil dose per kg body weight per minute of total operative time. RESULTS: Mean remifentanil infusion rate [mean (standard deviation)] was significantly higher in the sevoflurane group than in the desflurane group [0.192 (0.064) vs. 0.099 (0.033) µg kg-1 min-1; difference, 0.093 (95% confidence interval, 0.071-0.115); P<0.001]. CONCLUSIONS: During equi-MAC anaesthesia of 1.0 MAC, sevoflurane and desflurane did not show similar intraoperative remifentanil consumption under surgical pleth index-guided opioid administration. Further studies using other monitors with different measuring mechanisms are warranted to determine the cause of this difference. CLINICAL TRIAL REGISTRATION: NCT02830243 (ClinicalTrials.gov).

Evolving affinity between Coulombic reversibility and hysteretic phase transformations in nano-structured silicon-based lithium-ion batteries.

Nano-structured silicon is an attractive alternative anode material to conventional graphite in lithium-ion batteries. However, the anode designs with higher silicon concentrations remain to be commercialized despite recent remarkable progress. One of the most critical issues is the fundamental understanding of the lithium-silicon Coulombic efficiency. Particularly, this is the key to resolve subtle yet accumulatively significant alterations of Coulombic efficiency by various paths of lithium-silicon processes over cycles. Here, we provide quantitative and qualitative insight into how the irreversible behaviors are altered by the processes under amorphous volume changes and hysteretic amorphous-crystalline phase transformations. Repeated latter transformations over cycles, typically featured as a degradation factor, can govern the reversibility behaviors, improving the irreversibility and eventually minimizing cumulative irreversible lithium consumption. This is clearly different from repeated amorphous volume changes with different lithiation depths. The mechanism behind the correlations is elucidated by electrochemical and structural probing.

A Study of Piezoelectric Field Related Strain Difference in GaN-Based Blue Light-Emitting Diodes Grown on Silicon(111) and Sapphire Substrates.

We investigate the strain difference in InGaN/GaN multiple quantum wells of blue light-emitting diode (LED) structures grown on silicon(1 11) and c-plane sapphire substrates by comparing the strength of piezo-electric fields in MQWs. The piezo-electric fields for two LED samples grown on silicon and sapphire substrates are measured by using the reverse-bias electro-reflectance (ER) spectroscopy. The flat-band voltage is obtained by measuring the applied reverse bias voltage that induces a phase inversion in the ER spectra, which is used to calculate the strength of piezo-electric fields. The piezo-electric field is determined to be 1.36 MV/cm for the LED on silicon substrate and 1.83 MV/cm for the LED on sapphire substrate. The ER measurement results indicate that the strain-induced piezo-electric field is greatly reduced in the LED grown on silicon substrates consistent with previous strain measurement results by micro-Raman spectroscopy and high-resolution transmission electron microscopy.

Competitive Market Analysis of Transplant Centers and Discrepancy of Wait-Listing of Recipients for Kidney Transplantation.

BACKGROUND: There are over 250 kidney transplant programs in the USA. OBJECTIVE: To determine if highly competitive regions, defined as regions with a higher number of transplant centers, will approve and wait-list more end-stage renal disease (ESRD) candidates for transplant despite consistent incidence and prevalence of ESRD nationwide. METHODS: ESRD Network and OPTN data completed in 2011 were obtained from all transplant centers including listing data, market saturation, market share, organs transplanted, and ESRD prevalence. Herfindahl-Hirschman Index (HHI) was used to measure the size of firms in relation to the industry to determine the amount of competition. RESULTS: States were separated into 3 groups (HHI<1000 considered competitive; HHI 1000-1800 considered moderate competition; and HHI>1800 considered highly concentrated). The percentage of ESRD patients listed in competitive, moderate, and highly concentrated regions were 19.73%, 17.02%, and 13.75%, respectively. The ESRD listing difference between competitive versus highly concentrated was significant (p<0.05). CONCLUSION: When there is strong competition without a dominant center as defined by the HHI, the entire state tends to list more patients for transplant to drive up their own center's market share. Our analysis of the available national data suggests a discrepancy in access for ESRD patient to transplantation due to transplant center competition.

Comparison of Strain in GaN-Based Blue Light-Emitting Diode Grown on Silicon(111) and Sapphire Substrates.

We compare the strain states and device performances of GaN-based blue light-emitting diodes (LEDs) grown on Si(111) and sapphire substrates. The strain characteristics are investigated using micro-Raman spectroscopy and high-resolution transmission electron microscopy. These analyses reveal that GaN layer grown on Si has a residual tensile strain in contrast to a compressive strain for GaN on sapphire, and quantum wells (QWs) on GaN/Si experience reduced lattice mismatch than those of GaN/sapphire. When external quantum efficiencies of LED on sapphire and Si substrates are compared, the LED on Si shows better efficiency droop characteristics and this is attributed to a decrease in piezo-electric field strength in InGaN/GaN layers owing to reduced lattice mismatch.

Quality improvement of transgenic cloned bovine embryos using an aggregation method: Effects on cell number, cell ratio, embryo perimeter, mitochondrial distribution, and gene expression profile.

The production of cloned embryos using conventional methods has extremely low success rates owing to low embryo quality. To improve the quality of cloned bovine embryos expressing enhanced green fluorescent protein (EGFP), we applied an aggregation culture method. The EGFP gene was transfected into bovine fetal fibroblasts using a retroviral vector system. Somatic cell nuclear transfer was performed using these cells, and the resulting embryos were cultured in aggregates or individually. Gene expression was analyzed by a microarray, and differentially expressed genes were validated by quantitative real-time polymerase chain reaction. The total number of cells per blastocyst and the ratio of inner cell mass cells to trophectoderm cells were higher in aggregated transgenic cloned blastocysts (agBL; 368.7 ± 109.6 and 1:4.8, respectively) than in in vitro-fertilized blastocysts (ivfBL; 189.8 ± 65.8 and 1:2.6, respectively) and nonaggregated transgenic cloned blastocysts (sBL; 113.1 ± 36.3 and 1:1.5, respectively; P < 0.05 and P < 0.01, respectively). Moreover, the blastocyst perimeter was larger in the agBL group than in the ivfBL and sBL groups (1168.8 ± 200.23 vs. 887.33 ± 187.62 and 678 ± 226.1 µm; P < 0.05). In addition, mitochondrial fluorescence intensity was higher in the agBL group than in the ivfBL and sBL groups (P < 0.05). The number of apoptotic cells per blastocyst was lower in the ivfBL and agBL groups than in the sBL group (3.7 ± 2.2 and 3.4 ± 2.1 vs. 6.7 ± 6.8; P < 0.05). The genes identified in the microarray belonged to 18 categories. Expression of the Krüppel-like factor 4 gene, which is associated with cell proliferation, development, and transcription, was 7.2-fold higher in the agBL group than in the ivfBL group (P < 0.05) but did not differ between the sBL and ivfBL groups (P > 0.05). Expression of the heat shock 70-kDa protein 1A gene, which is associated with apoptosis, was 12-fold higher in the sBL group than in the ivfBL and agBL groups (P < 0.05). Expression of a stemness-related gene (octamer-binding transcription factor 4) and trophectoderm-specific genes (homeobox protein CDX2 and keratin 18) was higher in the agBL group than in the sBL group (P < 0.05). However, expression of the stemness gene homeobox protein NANOG did not differ among the groups (P > 0.05). Taken together, these data suggest that the aggregation method improves the quality of cloned embryos expressing EGFP and might be helpful in animal cloning.

Nomogram for Predicting Time to Death After Withdrawal of Life-Sustaining Treatment in Patients With Devastating Neurological Injury.

Reliable prediction of time of death after withdrawal of life-sustaining treatment in patients with devastating neurological injury is crucial to successful donation after cardiac death. Herein, we conducted a study of 419 neurocritical patients who underwent life support withdrawal at four neurosurgical centers in China. Based on a retrospective cohort, we used multivariate Cox regression analysis to identify prognostic factors for patient death, which were then integrated into a nomogram. The model was calibrated and validated using data from an external retrospective cohort and a prospective cohort. We identified 10 variables that were incorporated into a nomogram. The C-indexes for predicting the 60-min death probability in the training, external validation and prospective validation cohorts were 0.96 (0.93-0.98), 0.94 (0.91-0.97), and 0.99 (0.97-1.00), respectively. The calibration plots after WLST showed an optimal agreement between the prediction of time to death by the nomogram and the actual observation for all cohorts. Then we identified 22, 26 and 37 as cut-points for risk stratification into four groups. Kaplan-Meier curves indicated distinct prognoses between patients in the different risk groups (p < 0.001). In conclusion, we have developed and validated a nomogram to accurately identify potential cardiac death donors in neurocritical patients in a Chinese population.

Effects of flunixin meglumine and prostaglandin F2 α treatments on the development and quality of bovine embryos in vitro.

Assisted reproduction procedures, such as embryo transfer (ET) and artificial insemination (AI), in cattle could induce the secretion of prostaglandin F2 -alpha (PGF2 α) from uterine horns which may in turn interrupt embryo development and implantation. This study investigated the effect of flunixin meglumine (FM), prostaglandin F2 alpha (PGF2α) and FM combined with PGF2α supplementation in culture medium (IVC-II) on the development and quality of in vitro produced bovine embryos. The development rate of embryos was significantly higher in the FM group (33.3%) than in control (24.3%), PGF2 α (23.9%) and FM + PGF2 α groups (24.5%). The percentage of hatched blastocysts was also higher (p < 0.05) in the FM group (41.2%) than in the control (27.8%) and PGF2 α groups (19.8%). While, there was no significant difference in total cell number in all experimental groups, the number of apoptotic cells was significantly higher in the PGF2 α group (8.2 ± 6.6) than in the control (4.7 ± 3.2), FM (4.7 ± 2.5) and FM + PGF2 α (4.9 ± 3.4) groups. Detected by real-time PCR, secreted vesicle seminal protein 1 (SSLP1) and prostaglandin G/H synthase 2 (PTGS2) gene expression decreased (p < 0.05) in the PGF2 α group. However, SSLP1 and PTGS2 gene expression in the FM + PGF2 α group returned to their baseline levels, similar to the control and FM groups. Caspase 3 (CAPS3) gene expression increased in the PGF2 α group compared with other groups (p < 0.05). In conclusion, addition of FM in vitro culture significantly improved embryo development as well as alleviated the negative impact of PGF2 α.

Fractional erbium: YAG laser-assisted photodynamic therapy for facial actinic keratoses: a randomized, comparative, prospective study.

BACKGROUND: Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is effective for treating multiple actinic keratoses (AKs). Ablative fractional laser (FL) creates vertical channels that may facilitate MAL delivery and improve PDT response. OBJECTIVE: To evaluate the efficacy of FL-assisted PDT (FL-PDT) in treating facial AKs in Korean patients. METHODS: A prospective randomized non-blinded trial initially evaluated 271 facial AKs in 45 patients. All patients underwent one session of MAL-PDT using a red light-emitting diode lamp at 37 J/cm(2) , and 23 patients with 135 AK lesions were randomly assigned to pre-treatment with a 2940-nm ablative fractional erbium:Yag laser. Patients were followed up at 1, 2 and 4 weeks and every month until 6 and 12 months post-treatment. Response, adverse events, cosmetic outcome and patient satisfaction were documented. Finally, a total of 236 facial AKs in 40 patients were enrolled and analysed in this study. RESULTS: FL-PDT was significantly more effective than MAL-PDT at treating all AK grades (86.9% vs. 61.2%; P < 0.001). The efficacy of FL-PDT was most pronounced in treating Olsen grade III AKs (69.4% vs. 32.5%; P = 0.001). FL-PDT also showed a lower lesion recurrence rate than MAL-PDT (9.7% vs. 26.6%; P = 0.004). Excellent or good cosmetic outcome was reported in >90% cases. Erythema and hyperpigmentation intensities were higher in the FL-PDT group (P > 0.05). Side-effects were more frequent in the FL-PDT group, but these were mild and well tolerated (P > 0.05). CONCLUSION: FL-PDT is effective for treating AKs, especially moderate-to-thick lesions.

A randomized trial comparing methyl aminolaevulinate photodynamic therapy with and without Er:YAG ablative fractional laser treatment in Asian patients with lower extremity Bowen disease: results from a 12-month follow-up.

BACKGROUND: Methyl aminolaevulinate photodynamic therapy (MAL-PDT) is an effective treatment for Bowen disease (BD) of the lower extremities. Er:YAG (erbium:yttrium-aluminium-garnet) ablative fractional laser (AFL) treatment removes the stratum corneum to increase MAL uptake and may improve efficacy. However, no studies have directly compared the efficacy of MAL-PDT with and without Er:YAG AFL therapy in treating BD of the lower extremities in Asians. OBJECTIVES: To compare the efficacy, recurrence rate, cosmetic outcomes and safety between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL-PDT) and standard MAL-PDT. METHODS: Twenty-one patients with a total of 58 BD lesions randomly received either one session of Er:YAG AFL-PDT or two sessions of MAL-PDT in two symmetrical areas. Er:YAG AFL therapy was performed with 550-600 µm ablation depth, level 1 coagulation, 22% treatment density and a single pulse. MAL cream was then applied under occlusion for 3 h and illuminated with a red light-emitting diode lamp at 37 J cm(-2) . A second session of MAL-PDT was administered 7 days later. Overall response rate, recurrence rate, cosmetic outcomes and safety were assessed at 1 week, 3 and 12 months after treatment. RESULTS: After 3 months, Er:YAG AFL-PDT was significantly more effective (93.8%) than MAL-PDT (73.1%; P = 0.031), and the recurrence rate was significantly lower for Er:YAG AFL-PDT (6.7%) than MAL-PDT (31.6%) at 12 months (P = 0.022). No significant difference was found between Er:YAG AFL-PDT and MAL-PDT in terms of cosmetic outcomes or safety. CONCLUSIONS: Er:YAG AFL-PDT showed significantly higher efficacy and lower recurrence rate than did standard MAL-PDT for treating lower extremity BD in an Asian population.

[The process of bacterial population splitting into dissociants and long-term batch cultivation of bacteria].

The growth and composition of a population were studied during long-term (up to 50 days) batch cultivation of mono and mixed cultures of Pseudomonas aeruginosa S- and M-dissociants and Rhodobacter sphaeroides R- and M-dissociants without the addition of nutrients. During the cultivation of P. aeruginosa on a glucose-containing mineral medium, periodic lysis followed by polyculture growth resumption in the late stationary phase occurred on account of the M-dissociant: the change in its cell number corresponded to the change in the total cell number of the association. It was shown that the periodic occurrence of reducing sugars in the medium preceded the resumption ofpolyculture growth.

Size and shape effect of SiC source/drain on strained Si.

Strained Si is used to enhance carrier mobility in MOSFET devices. Epi-grown Si(1-x)C(x) as a source/drain induces strain on a channel because its lattice constant is smaller than Si. The distribution of stress varies with the layout of the device and can involve gate length, source/drain width, elevation height, etc. In this work, we report on how these parameters effect channel strain by employing the Finite Element Method. A 3-dimensional model and anisotropic properties such as the elastic constant and Poisson's ratio were adopted for high accuracy. Si0.983C0.017 was used as the source/drain on a Si substrate. The lateral channel strain was calculated based on a 30-90 nm gate length, a 30-90 nm source/drain width and 0-30 nm elevated source/drain shapes. The results showed that, when the gate length is longer, the channel strain is lower. On the other hand, source/drain width affects channel strain in a reverse manner. For models with the same gate length and source/drain width: 30, 60, 90 nm, the average channel strain is lower when the gate length and source/drain width are shorter. An additional parameter, namely, source/drain elevation height, was also studied. Interestingly, the effect of elevated shape is dependent on gate length and source/drain width.

Native portal vein embolization for persistent hyperoxaluria following kidney and auxiliary partial liver transplantation.

Type 1 primary hyperoxaluria (PH1) causes renal failure, for which isolated kidney transplantation (KT) is usually unsuccessful treatment due to early oxalate stone recurrence. Although hepatectomy and liver transplantation (LT) corrects PH1 enzymatic defect, simultaneous auxiliary partial liver transplantation (APLT) and KT have been suggested as an alternative approach. APLT advantages include preservation of the donor pool and retention of native liver function in the event of liver graft loss. However, APLT relative mass may be inadequate to correct the defect. We here report the first case of native portal vein embolization (PVE) to increase APLT to native liver mass ratio (APLT/NLM-R). Following initial combined APLT-KT, both allografts functioned well, but oxalate plasma levels did not normalize. We postulated the inadequate APLT/NLM-R could be corrected by trans-hepatic native PVE. The resulting increased APLT/NLM-R decreased serum oxalate to normal levels within 1 month following PVE. We conclude that persistently elevated oxalate levels after combined APLT-KT for PH1 treatment, results from inadequate relative functional capacity. This can be reversed by partial native PVE to decrease portal flow to the native liver. This approach might be applicable to other scenarios where partial grafts have been transplanted to replace native liver function.