Harnessing cold adaptation for postglacial colonisation: Galactinol synthase expression and raffinose accumulation in a polyploid and its progenitors.

Allotetraploid white clover (Trifolium repens) formed during the last glaciation through hybridisation of two European diploid progenitors from restricted niches: one coastal, the other alpine. Here, we examine which hybridisation-derived molecular events may have underpinned white clover's postglacial niche expansion. We compared the transcriptomic frost responses of white clovers (an inbred line and an alpine-adapted ecotype), extant descendants of its progenitor species and a resynthesised white clover neopolyploid to identify genes that were exclusively frost-induced in the alpine progenitor and its derived subgenomes. From these analyses we identified galactinol synthase, the rate-limiting enzyme in biosynthesis of the cryoprotectant raffinose, and found that the extant descendants of the alpine progenitor as well as the neopolyploid white clover rapidly accumulated significantly more galactinol and raffinose than the coastal progenitor under cold stress. The frost-induced galactinol synthase expression and rapid raffinose accumulation derived from the alpine progenitor likely provided an advantage during early postglacial colonisation for white clover compared to its coastal progenitor.

Insight into the structural and electrochemical properties of the interface between a Na6SOI2 solid electrolyte and a metallic Na anode.

Solid electrolytes (SE) have attracted a great deal of interest as they can not only mitigate the safety issues related to currently used liquid organic electrolytes but also enable the introduction of a metallic Na anode with extreme energy density in sodium-ion batteries. For such application, SE should exhibit high interfacial stability against metallic Na as well as high ionic conductivity, and Na6SOI2 with a Na-rich double anti-perovskite structure was recently identified as a promising SE candidate. In this work, we performed first principles calculations to investigate the structural and electrochemical properties of the interface between Na6SOI2 and a metallic Na anode. Our calculations revealed that interfaces could be formed safely, keeping the ultra-fast ionic conductivity of the bulk phase near the interface. Through the electronic structure analysis of the interface models, we found the change of upward valence band bending at the surface to downward band bending at the interface, being accompanied by electronic charge transfer from a metallic Na anode to Na6SOI2 SE at the interface. This work provides valuable atomistic insight into the formation and properties of the interface between SE and alkali metal for enhancing battery performance.

The whale shark genome reveals how genomic and physiological properties scale with body size.

The endangered whale shark (Rhincodon typus) is the largest fish on Earth and a long-lived member of the ancient Elasmobranchii clade. To characterize the relationship between genome features and biological traits, we sequenced and assembled the genome of the whale shark and compared its genomic and physiological features to those of 83 animals and yeast. We examined the scaling relationships between body size, temperature, metabolic rates, and genomic features and found both general correlations across the animal kingdom and features specific to the whale shark genome. Among animals, increased lifespan is positively correlated to body size and metabolic rate. Several genomic traits also significantly correlated with body size, including intron and gene length. Our large-scale comparative genomic analysis uncovered general features of metazoan genome architecture: Guanine and cytosine (GC) content and codon adaptation index are negatively correlated, and neural connectivity genes are longer than average genes in most genomes. Focusing on the whale shark genome, we identified multiple features that significantly correlate with lifespan. Among these were very long gene length, due to introns being highly enriched in repetitive elements such as CR1-like long interspersed nuclear elements, and considerably longer neural genes of several types, including connectivity, activity, and neurodegeneration genes. The whale shark genome also has the second slowest evolutionary rate observed in vertebrates to date. Our comparative genomics approach uncovered multiple genetic features associated with body size, metabolic rate, and lifespan and showed that the whale shark is a promising model for studies of neural architecture and lifespan.

Impact of COVID-19 on Out-of-Hospital Cardiac Arrest in Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global public health crisis that has had a significant impact on emergency medical services (EMS). Several studies have reported an increase in the incidence of out-of-hospital cardiac arrest (OHCA) and a decreased survival due to COVID-19, which has been limited to a short period or has been reported in some regions. This study aimed to investigate the effect of COVID-19 on OHCA patients using a nationwide database. METHODS: We included adult OHCA patients treated by EMS providers from January 19, 2019 to January 20, 2021. The years before and after the first confirmed case in Korea were set as the non-COVID-19 and COVID-19 periods, respectively. The main exposure of interest was the COVID-19 period, and the primary outcome was prehospital return of spontaneous circulation (ROSC). Other OHCA variables were compared before and after the COVID-19 pandemic and analyzed. We performed a multivariable logistic regression analysis to understand the independent effect of the COVID-19 period on prehospital ROSC. RESULTS: The final analysis included 51,921 eligible patients, including 25,355 (48.8%) during the non-COVID-19 period and 26,566 (51.2%) during the COVID-19 period. Prehospital ROSC deteriorated during the COVID-19 period (10.2% vs. 11.1%, P = 0.001). In the main analysis, the adjusted odds ratios (AORs) for prehospital ROSC showed no significant differences between the COVID-19 and non-COVID-19 periods (AOR [95% confidence interval], 1.02 [0.96-1.09]). CONCLUSION: This study found that the proportion of prehospital ROSC was lower during the COVID-19 period than during the non-COVID-19 period; however, there was no statistical significance when adjusting for potential confounders. Continuous efforts are needed to restore the broken chain of survival in the prehospital phase and increase the survival rate of OHCA patients.

Interfacial Strain-Modulated Nanospherical Ni2 P by Heteronuclei-Mediated Growth on Ti3 C2 Tx MXene for Efficient Hydrogen Evolution.

Interface modulation of nickel phosphide (Ni2 P) to produce an optimal catalytic activation barrier has been considered a promising approach to enhance the hydrogen production activity via water splitting. Herein, heteronuclei-mediated in situ growth of hollow Ni2 P nanospheres on a surface defect-engineered titanium carbide (Ti3 C2 Tx ) MXene showing high electrochemical activity for the hydrogen evolution reaction (HER) is demonstrated. The heteronucleation drives intrinsic strain in hexagonal Ni2 P with an observable distortion at the Ni2 P@Ti3 C2 Tx MXene heterointerface, which leads to charge redistribution and improved charge transfer at the interface between the two components. The strain at the Ni2 P@Ti3 C2 Tx MXene heterointerface significantly boosts the electrochemical catalytic activities and stability toward HER in an acidic medium via a combination between experimental results and theoretical calculations. In a 0.5 m H2 SO4 electrolyte, the Ni2 P@Ti3 C2 Tx MXene hybrid shows excellent HER catalytic performance, requiring an overpotential of 123.6 mV to achieve 10 mA cm-2 with a Tafel slope of 39 mV dec-1 and impressive durability over 24 h operation. This approach presents a significant potential to rationally design advanced catalysts coupled with 2D materials and transition metal-based compounds for state-of-the-art high efficiency energy conversions.

Localization of Cracks in Concrete Structures Using an Unmanned Aerial Vehicle.

Active research on crack detection technology for structures based on unmanned aerial vehicles (UAVs) has attracted considerable attention. Most of the existing research on localization of cracks using UAVs mounted the Global Positioning System (GPS)/Inertial Measurement Unit (IMU) on the UAVs to obtain location information. When such absolute position information is used, several studies confirmed that positioning errors of the UAVs were reflected and were in the order of a few meters. To address these limitations, in this study, without using the absolute position information, localization of cracks was defined using relative position between objects in UAV-captured images to significantly reduce the error level. Through aerial photography, a total of 97 images were acquired. Using the point cloud technique, image stitching, and homography matrix algorithm, 5 cracks and 3 reference objects were defined. Importantly, the comparative analysis of estimated relative position values and ground truth values through field measurement revealed that errors in the range 24-84 mm and 8-48 mm were obtained on the x- and y-directions, respectively. Also, RMSE errors of 37.95-91.24 mm were confirmed. In the future, the proposed methodology can be utilized for supplementing and improving the conventional methods for visual inspection of infrastructures and facilities.

FOXO3a Mediates Homologous Recombination Repair (HRR) via Transcriptional Activation of MRE11, BRCA1, BRIP1, and RAD50.

To test whether homologous recombination repair (HRR) depends on FOXO3a, a cellular aging model of human dermal fibroblast (HDF) and tet-on flag-h-FOXO3a transgenic mice were studied. HDF cells transfected with over-expression of wt-h-FOXO3a increased the protein levels of MRE11, BRCA1, BRIP1, and RAD50, while knock-down with siFOXO3a decreased them. The protein levels of MRE11, BRCA1, BRIP1, RAD50, and RAD51 decreased during cellular aging. Chromatin immunoprecipitation (ChIP) assay was performed on FOXO3a binding accessibility to FOXO consensus sites in human MRE11, BRCA1, BRIP1, and RAD50 promoters; the results showed FOXO3a binding decreased during cellular aging. When the tet-on flag-h-FOXO3a mice were administered doxycycline orally, the protein and mRNA levels of flag-h-FOXO3a, MRE11, BRCA1, BRIP1, and RAD50 increased in a doxycycline-dose-dependent manner. In vitro HRR assays were performed by transfection with an HR vector and I-SceI vector. The mRNA levels of the recombined GFP increased after doxycycline treatment in MEF but not in wt-MEF, and increased in young HDF comparing to old HDF, indicating that FOXO3a activates HRR. Overall, these results demonstrate that MRE11, BRCA1, BRIP1, and RAD50 are transcriptional target genes for FOXO3a, and HRR activity is increased via transcriptional activation of MRE11, BRCA1, BRIP1, and RAD50 by FOXO3a.

Exponentially Weighted Multivariate HAR Model with Applications in the Stock Market.

This paper considers a multivariate time series model for stock prices in the stock market. A multivariate heterogeneous autoregressive (HAR) model is adopted with exponentially decaying coefficients. This model is not only suitable for multivariate data with strong cross-correlation and long memory, but also represents a common structure of the joint data in terms of decay rates. Tests are proposed to identify the existence of the decay rates in the multivariate HAR model. The null limiting distributions are established as the standard Brownian bridge and are proven by means of a modified martingale central limit theorem. Simulation studies are conducted to assess the performance of tests and estimates. Empirical analysis with joint datasets of U.S. stock prices illustrates that the proposed model outperforms the conventional HAR models via OLSE and LASSO with respect to residual errors.

Exclusion and multiplicity for stable communities in Lotka-Volterra systems.

For classic Lotka-Volterra systems governing many interacting species, we establish an exclusion principle that rules out the existence of linearly asymptotically stable steady states in subcommunities of communities that admit a stable state which is internally D-stable. This type of stability is known to be ensured, e.g., by diagonal dominance or Volterra-Lyapunov stability conditions. By consequence, the number of stable steady states of this type is bounded by Sperner's lemma on anti-chains in a poset. The number of stable steady states can nevertheless be very large if there are many groups of species that strongly inhibit outsiders but have weak interactions among themselves. By examples we also show that in general it is possible for a stable community to contain a stable subcommunity consisting of a single species. Thus a recent empirical finding to the contrary, in a study of random competitive systems by Lischke and Löffler (Theor Popul Biol 115:24-34, 2017), does not hold without qualification.

Development and operation of a digital platform for sharing pathology image data.

BACKGROUND: Artificial intelligence (AI) research is highly dependent on the nature of the data available. With the steady increase of AI applications in the medical field, the demand for quality medical data is increasing significantly. We here describe the development of a platform for providing and sharing digital pathology data to AI researchers, and highlight challenges to overcome in operating a sustainable platform in conjunction with pathologists. METHODS: Over 3000 pathological slides from five organs (liver, colon, prostate, pancreas and biliary tract, and kidney) in histologically confirmed tumor cases by pathology departments at three hospitals were selected for the dataset. After digitalizing the slides, tumor areas were annotated and overlaid onto the images by pathologists as the ground truth for AI training. To reduce the pathologists' workload, AI-assisted annotation was established in collaboration with university AI teams. RESULTS: A web-based data sharing platform was developed to share massive pathological image data in 2019. This platform includes 3100 images, and 5 pre-processing algorithms for AI researchers to easily load images into their learning models. DISCUSSION: Due to different regulations among countries for privacy protection, when releasing internationally shared learning platforms, it is considered to be most prudent to obtain consent from patients during data acquisition. CONCLUSIONS: Despite limitations encountered during platform development and model training, the present medical image sharing platform can steadily fulfill the high demand of AI developers for quality data. This study is expected to help other researchers intending to generate similar platforms that are more effective and accessible in the future.

Efficacy of biodegradable collagen matrix (Ologen® CM) in augmenting the success rate of Ahmed glaucoma valve implantation in canine glaucoma.

OBJECTIVE: To prospectively assess the efficacy of a biodegradable collagen matrix (ologen) in dogs with uncontrolled glaucoma receiving an Ahmed glaucoma valve (AGV) implant. ANIMAL STUDIED: Five client-owned dogs with glaucoma (five eyes). PROCEDURES: Five eyes treated for uncontrolled glaucoma underwent AGV implantation with ologen. Ologen was placed on the AGV plate and tube with a scleral flap. Complete ophthalmological examinations were performed preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1, 2, 3, and 6 months postoperatively. Surgical outcomes were assessed based on the intraocular pressure (IOP), vision, frequency of anti-glaucoma eye drops, and bleb morphology; complications, if any, were recorded. The number of dogs with an IOP <20 mmHg with or without topical medications were tabulated and compared to those with an IOP ≥20 mmHg or those requiring surgery to maintain the IOP at <20 mmHg. RESULTS: The IOP significantly decreased from 47.00 ± 5.09 mmHg preoperatively to 17.00 ± 0.71 mmHg 6 months postoperatively (p = .008). IOP was controlled (<20 mmHg) in 5/5 dogs at 6 months postoperatively. Brief periods of elevated IOP (IOP ≥ 20 mmHg, IOP spike) occurred in one eye (case 5) at 1 month (35 mmHg) and 2 months (33 mmHg) postoperatively. The anti-glaucoma eye drop frequency decreased from 3.2 ± 0.44 preoperatively to 1.6 ± 0.90 at 6 months postoperatively (p = .007). CONCLUSIONS: To our knowledge, this is the first study to assess the potential safety of AGV implantation with ologen for canine glaucoma. This method effectively controlled the IOP, without any adverse effects.

Estimation of Cavities beneath Plate Structures Using a Microphone: Laboratory Model Tests.

The objective of this study is to detect a cavity and estimate its size using sound waves in a laboratory model chamber filled with dry sand. One side of the chamber is covered with an acrylic plate, and a cavity is placed between the plate and sand. Sound waves are generated by impacting the plate with an instrumented hammer, and are measured using a microphone. The measured sound waves are analyzed with four comprehensive analyses including the measured area under the rectified signal envelope (MARSE) energy, flexibility, peak magnitude of wavelet transform, and frequency corresponding to the peak magnitude. The test results show that the accuracy of cavity detection using the MARSE energy is higher for thicker plates, whereas that using flexibility is higher for thinner plates. The accuracies of cavity detection using the peak magnitude of wavelet transform, and frequency corresponding to the peak magnitude are consistently high regardless of the plate thickness. Moreover, the cavity size may be under- or overestimated depending on the plate thickness and the selected analysis method. The average of the cavity sizes estimated by these methods, however, is slightly larger than the actual cavity size regardless of the plate thickness. This study demonstrates that microphones may be effectively used for the identification of a cavity and the estimation of its size.

Effect of Extract and Synthesized Derivatives of Isolated Compound from Symplocos chinensis f. Pilosa Ohwi on Neuropathic Pain in Mice.

Neuropathic pain is described as the "most terrible of all tortures that a nerve wound may inflict." The aim of the present study was to demonstrate the antinociceptive effect of Symplocos chinensis f. pilosa Ohwi water extract (SCW) and synthesized derivatives of the isolated compound. The antinociceptive effect was tested using the acetic acid-induced writhing and 5% formalin tests. Antinociceptive effects on neuropathic pain were evaluated using the von Frey test with chronic constriction injury (CCI) and surgical nerve injury (SNI) models and tail-flick test with a vincristine-induced pain model. An Ames test was also conducted. 5-hydroxymethylfurfural (5-HMF) was isolated and derivatives were synthesized with various acid groups. Among the plant water extracts, SCW showed significantly effective activity. Additionally, SCW presented antinociceptive effects in the neuropathic pain models. The SCW water fraction resulted in fewer writhes than the other fractions, and isolated 5-HMF was identified as an effective compound. Because 5-HMF revealed a positive response in the Ames test, derivatives were synthesized. Among the synthesized derivations, 5-succinoxymethylfurfural (5-SMF) showed the best effect in the neuropathic pain model. Our data suggest that SCW and the synthesized compound, 5-SMF, possess effective antinociceptive activity against neuropathic pain.

The changes of nociception and the signal molecules expression in the dorsal root ganglia and the spinal cord after cold water swimming stress in mice.

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4°C) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice. Here, we show that 3 min of CWSS was sufficient to produce antinociception in tailflick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS. CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.

Association Between Post-Resuscitation Coronary Angiography With and Without Intervention and Neurological Outcomes After Out-of-Hospital Cardiac Arrest.

Objective: This study aimed to investigate the association between coronary angiography (CAG) with and without percutaneous coronary intervention (PCI) after out-of-hospital cardiac arrest (OHCA) and neurological recovery and to determine the influence of primary electrocardiogram or patient age on the effects of CAG. Methods: Adult patients with OHCA with cardiac etiology who were admitted to PCI-capable hospitals from 2016 to 2017 were enrolled in this study from the nationwide OHCA registry of Korea. Coronary intervention was categorized into three groups: No CAG, CAG without PCI, and CAG with PCI. The endpoint was good neurological recovery. Multivariable logistic regression and interaction analyses (intervention × electrocardiogram and intervention × age) were conducted by calculating adjusted odds ratios (aORs) and 95% confidence intervals (CI). Results: Of a total of 6,802 eligible OHCA patients, 1,218 (17.9%) underwent CAG without PCI and 1,136 (16.7%) underwent CAG with PCI. The CAG without PCI and CAG with PCI groups were more likely to have good neurological recovery than the No CAG group (57.4% vs. 61.6% vs. 16.3%; 3.39 [2.83-4.06] for CAG without PCI and 3.32 [2.74-4.01] for CAG with PCI). Interaction analysis showed that although the effect size differed according to patient characteristics, both CAG groups were associated with an increased likelihood of good neurological recovery, regardless of primary electrocardiogram and age group. In younger patients, CAG with PCI had greater outcome benefits than CAG without PCI (8.54 [4.31-16.95] vs. 4.10 [2.69-6.24]), whereas CAG without PCI had a larger effect size than CAG with PCI in elderly patients (4.46 [2.59-7.68] vs. 2.92 [1.80-4.73]) (p value for interaction 0.02). Conclusions: Post-resuscitation CAG with and without PCI are associated with better neurological recovery in patients with OHCA, regardless of primary electrocardiogram and patient age.

End stage renal disease modifies the effect of targeted temperature management after out-of-hospital cardiac arrest.

INTRODUCTION: Kidney function can affect the permeability of the blood-brain barrier; thus, end-stage renal disease (ESRD) may alter the effects of targeted temperature management (TTM) on the neurological outcomes of out-of-hospital cardiac arrest (OHCA) patients. We aimed to investigate whether the interaction effect of TTM on outcomes after OHCA was observed among patients with and without ESRD. METHODS: Adult OHCA patients with presumed cardiac etiology who attained sustained return of spontaneous circulation from 2013 to 2017 were included using nationwide OHCA registry. The main exposure variable was TTM. The primary endpoint was survival with good neurological recovery. Multivariable logistic regression analysis was performed after adjustment for potential confounders. To compare the effect of ESRD on TTM, an interaction term (TTM × ESRD) was added to the model. RESULTS: A total of 21,250 patients were included in the analysis; 2693 (12.7%) patients underwent TTM. ESRD was observed in 128 (4.8%) in the TTM group and 767 (4.1%) in the no-TTM group. The TTM group showed better outcomes than the no-TTM group (32.4% vs. 17.2%, p < 0.01). The adjusted odds ratio of TTM for good neurological recovery in the entire study group was 1.15 (95% CI, 1.03-1.29). In the interaction model, the adjusted odds ratio of TTM for good neurological recovery was 0.47 (95% CI, 0.23-0.98) in the ESRD group vs. 1.54 (95% CI, 1.00-2.39) in the no-ESRD group. CONCLUSIONS: The interaction effect between ESRD and TTM on neurologic outcome was positive in adult OHCA initial survivors with presumed cardiac etiology.

Production of adipic acid by short- and long-chain fatty acid acyl-CoA oxidase engineered in yeast Candida tropicalis.

In this study, to produce adipic acid, mutant strains of Candida tropicalis KCTC 7212 deficient of AOX genes encoding acyl-CoA oxidases which are important in the ß-oxidation pathway were constructed. Production of adipic acid in the mutants from the most favorable substrate C12 methyl laurate was significantly increased. The highest level of production of adipic acid was obtained in the C. tropicalis ΔAOX4::AOX5 mutant of 339.8 mg L-1 which was about 5.4-fold higher level compared to the parent strain. The C. tropicalis ΔAOX4::AOX5 mutant was subjected to fed-batch fermentation at optimized conditions of agitation rate of 1000 rpm, pH 5.0 and methyl laurate of 3% (w/v), giving the maximum level of adipic acid of 12.1 g L-1 and production rate of 0.1 g L-1 h-1.

Dynamic Cone Penetrometer Incorporated with Time Domain Reflectometry (TDR) Sensors for the Evaluation of Water Contents in Sandy Soils.

Ground moisture content and strength properties are the most important factors for a proper assessment of ground stability. This study developed a dynamic cone penetrometer incorporated with time domain reflectometry (TDR) sensors (TDCP). The TDCP is composed of an anvil, a driving rod, and a TDCP probe. Three wave guides and a K-type thermocouple are installed on the TDCP probe. For utilization of TDCP, relationships between relative permittivities measured by TDCP and those measured by standard TDR probe, temperature, and volumetric water content of the soils were investigated. In addition, the relationship between penetration indices by TDCP (TPI) and by standard dynamic cone penetrometer was established. In the field application test, relative permittivity, ground temperature, and TPI were measured along the depth. Moreover, gravimetric water contents were also measured for comparison. The experimental results showed that volumetric water contents compensated by ground temperature showed good agreement with the volumetric water contents estimated from the gravimetric water contents of the soil samples and TPI. This study suggests that the TDCP may be effectively used for the evaluation moisture contents and for the strength characterization of the subsurface.

Risk factors for erlotinib-induced hepatotoxicity: a retrospective follow-up study.

BACKGROUND: Erlotinib is a drug used for the treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer. Severe hepatotoxicity was observed in 4% to 31% of patients receiving erlotinib treatment prompting delay or termination of treatment. Only a few factors related to hepatotoxicity of erlotinib have been reported. No study has investigated the role of concomitant medications and erlotinib-induced hepatotoxicity. The aim of this study was to investigate the association between erlotinib-induced hepatotoxicity and various factors including concomitant medications in patients with NSCLC and pancreatic cancer. METHODS: From January 2014 to June 2017, a retrospective study was conducted in patients with NSCLC and pancreatic cancer, who were treated with erlotinib. Various data were reviewed, including sex, age, body weight, height, body surface area (BSA), underlying disease, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), smoking history, erlotinib dose, EGFR mutation, and concomitant drugs. RESULTS: The incidence of grade 2 or higher hepatotoxicity in the study group of patients was 17.2%. Multivariate analysis showed a 2.7-fold increase in hepatotoxicity with the concomitant use of CYP3A4 inducers. In NSCLC patients, co-administration of H2-antagonist/PPI increased hepatotoxicity 3.5-fold. Among the demographic factors, liver metastasis and age ≥ 65 years were significant risk factors in all study patients and NSCLC patients, respectively; the attributable risks for liver metastasis and age were 46.3% and 71.8%, respectively. Subgroup analysis using pancreatic cancer patients yielded marginally significant results with CYP3A4 inducers and erlotinib-induced hepatotoxicity. Liver metastasis and CYP3A4 inducers also shortened time to hepatotoxicity 2.1 and 2.3-fold, respectively. CONCLUSIONS: Our study showed that concomitant use of CYP3A4 inducers and H2-antagonist/PPI, liver metastasis, and age ≥ 65 were associated with erlotinib-induced hepatotoxicity. Thus, close monitoring of liver function is recommended, especially in patients using CYP3A4 inducers and anti-acid secreting agents.

Simultaneous cell disruption and lipid extraction of wet aurantiochytrium sp. KRS101 using a high shear mixer.

Microalgae are regarded as a promising source of biofuels, and the concept of a microalgae-based biorefinery has attracted increasing attention in recent years. From an economic perspective, however, the process remains far from competitive with fossil fuels. This is particularly true of lipid extraction, due in part to the energy-intensive drying step. As a result, wet extraction methods have been studied as an economic alternative. In the present study, a novel extraction approach which utilizes high shear stress mixing was adopted and demonstrated for simultaneous lipid extraction and cell disruption to enable the retrieval of lipids directly from concentrated wet biomass. When a high shear mixer (HSM) was used to extract lipid from a dense biomass (> 350 g/L) of the oleaginous algae Aurantiochytrium sp., it exhibited a yield of esterifiable lipids which exceeded 80% in 10 min at 15,000 rpm with various solvent types. The HSM was found to improve the lipid yields substantially with solvents less miscible with either lipids or water, such that the range of Hansen solubility parameters for the usable solvents became 3.3 times wider (14.9-26.5 MPa1/2). The HSM, which appeared effectively to loosen the water barrier that prevents solvent molecules from penetrating through the cell envelope, was found to be more efficient with hexane, hexane/isopropanol, and ethanol, all of which showed nearly identical lipid yields compared to the dry extraction process. The HSM can, indeed, offer a powerful mechanical means of lipid extraction with non-polar and less toxic solvents from wet biomass.