Azimuthal rotation-controlled nanoinscribing for continuous patterning of period- and shape-tunable asymmetric nanogratings.

We present an azimuthal-rotation-controlled dynamic nanoinscribing (ARC-DNI) process for continuous and scalable fabrication of asymmetric nanograting structures with tunable periods and shape profiles. A sliced edge of a nanograting mold, which typically has a rectangular grating profile, slides over a polymeric substrate to induce its burr-free plastic deformation into a linear nanopattern. During this continuous nanoinscribing process, the "azimuthal angle," that is, the angle between the moving direction of the polymeric substrate and the mold's grating line orientation, can be controlled to tailor the period, geometrical shape, and profile of the inscribed nanopatterns. By modulating the azimuthal angle, along with other important ARC-DNI parameters such as temperature, force, and inscribing speed, we demonstrate that the mold-opening profile and temperature- and time-dependent viscoelastic polymer reflow can be controlled to fabricate asymmetric, blazed, and slanted nanogratings that have diverse geometrical profiles such as trapezoidal, triangular, and parallelogrammatic. Finally, period- and profile-tunable ARC-DNI can be utilized for the practical fabrication of diverse optical devices, as is exemplified by asymmetric diffractive optical elements in this study.

Hollow Microcavity Electrode for Enhancing Light Extraction.

Luminous efficiency is a pivotal factor for assessing the performance of optoelectronic devices, wherein light loss caused by diverse factors is harvested and converted into the radiative mode. In this study, we demonstrate a nanoscale vacuum photonic crystal layer (nVPCL) for light extraction enhancement. A corrugated semi-transparent electrode incorporating a periodic hollow-structure array was designed through a simulation that utilizes finite-difference time-domain computational analysis. The corrugated profile, stemming from the periodic hollow structure, was fabricated using laser interference lithography, which allows the precise engineering of various geometrical parameters by controlling the process conditions. The semi-transparent electrode consisted of a 15 nm thick Ag film, which acted as the exit mirror and induced microcavity resonance. When applied to a conventional green organic light-emitting diode (OLED) structure, the optimized nVPCL-integrated device demonstrated a 21.5% enhancement in external quantum efficiency compared to the reference device. Further, the full width at half maximum exhibited a 27.5% reduction compared to that of the reference device, demonstrating improved color purity. This study presents a novel approach by applying a hybrid thin film electrode design to optoelectronic devices to enhance optical efficiency and color purity.

Optimized Design of Hyaluronic Acid-Lipid Conjugate Biomaterial for Augmenting CD44 Recognition of Surface-Engineered NK Cells.

Triple-negative breast cancer (TNBC) presents treatment challenges due to a lack of detectable surface receptors. Natural killer (NK) cell-based adaptive immunotherapy is a promising treatment because of the characteristic anticancer effects of killing malignant cells directly by secreting cytokines and lytic granules. To maximize the cancer recognition ability of NK cells, biomaterial-mediated ex vivo cell surface engineering has been developed for sufficient cell membrane immobilization of tumor-targeting ligands via hydrophobic anchoring. In this study, we optimized amphiphilic balances of NK cell coating materials composed of CD44-targeting hyaluronic acid (HA)-poly(ethylene glycol) (PEG)-lipid to improve TNBC recognition and the anticancer effect. Changes in the modular design of our material by differentiating hydrophilic PEG length and incorporating lipid amount into HA backbones precisely regulated the amphiphilic nature of HA-PEG-lipid conjugates. The optimized biomaterial demonstrated improved anchoring into NK cell membranes and facilitating the surface presentation level of HA onto NK cell surfaces. This led to enhanced cancer targeting via increasing the formation of immune synapse, thereby augmenting the anticancer capability of NK cells specifically toward CD44-positive TNBC cells. Our approach addresses targeting ability of NK cell to solid tumors with a deficiency of surface tumor-specific antigens while offering a valuable material design strategy using amphiphilic balance in immune cell surface engineering techniques.

Networked Cluster Formation via Trigonal Lipid Modules for Augmented Ex Vivo NK Cell Priming.

Current cytokine-based natural killer (NK) cell priming techniques have exhibited limitations such as the deactivation of biological signaling molecules and subsequent insufficient maturation of the cell population during mass cultivation processes. In this study, we developed an amphiphilic trigonal 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-polyethylene glycol (PEG) material to assemble NK cell clusters via multiple hydrophobic lipid insertions into cellular membranes. Our lipid conjugate-mediated ex vivo NK cell priming sufficiently augmented the structural modulation of clusters, facilitated diffusional signal exchanges, and finally activated NK cell population with the clusters. Without any inhibition in diffusional signal exchanges and intrinsic proliferative efficacy of NK cells, effectively prime NK cell clusters produced increased interferon-gamma, especially in the early culture periods. In conclusion, the present study demonstrates that our novel lipid conjugates could serve as a promising alternative for future NK cell mass production.

Effects of micro-sized biodegradable plastics on Microcystis aeruginosa.

Plethora of plastics are being used in current society, generating huge amounts of plastic waste. Non-biodegradability of conventional plastics is one of the main challenges to treat plastic waste. In an effort to increase the efficiency of plastic waste treatment, biodegradable plastics have gained attention. Although the use of biodegradable plastics has been increased, their potential effects on the environments are not fully elucidated yet. In this study, the impacts of micro-sized non-biodegradable plastic (i.e., polystyrene (PS)) and micro-sized biodegradable plastics (i.e., polycaprolactone (PCL) and polylactic acid (PLA)) on Microcystis aeruginosa were investigated. Regardless of microplastic (MP) types, MP treatments inhibited the growth of M. aeruginosa at the beginning (4 days) while significant dose-dependent effect was not observed in the range of 0.1 to 10 mg/L. However, after long-term exposure (12 days), micro-sized biodegradable plastics stimulated the growth of M. aeruginosa (up to 73 % increase compared to the control). The photosynthetic activity showed a similar trend to the cell growth. The MP treatments induced the production of extracellular polymeric substances (EPS). Indeed, micro-sized PCL and PLA stimulated the production of protein compounds in EPS. These might have affected the releases of chemicals from PCL and PLA, suggesting that the chemicals in biodegradable plastic leachates would promote the growth of M. aeruginosa in long-term exposure. The MP treatments also induced cyanotoxin (microcystin-LR) productions. Our results give a new insight into the cyanobacterial blooming and suggest a novel relationship between harmful algal blooms (HABs) and biodegradable plastics.

Surveillance spilled Chironomidae (Diptera) larvae from drinking water treatment plants in South Korea using morphogenetic species analysis and eDNA metabarcoding.

Chironomid larvae (Diptera: Chironomidae) are tremendous indicator species that can tolerate a broad range of environmental conditions, from polluted to unimpaired water ecosystems. These species are ubiquitously observed in all bioregions and can even be found in drinking water treatment plants (DWTPs). Detection of chironomid larvae in DWTPs is a critical issue because their presence may be indicative of the water quality in the supply of tap water for human consumption. Therefore, the aim of the present study was to identify the chironomid communities that reflect the water quality of DWTPs and develop a biomonitoring tool to detect biological contamination of the chironomids in DWTPs. To do so, we investigated the identity and distribution of chironomid larvae in seven DWTP areas using morphological identification, DNA barcoding, and sediment environmental DNA (eDNA) analysis. A total of 7924 chironomid individuals encompassing three subfamilies and 25 species of 19 genera were identified in 33 sites within the DWTPs. The Gongchon and Bupyeong DWTPs were dominated by Chironomus spp. larvae, which were correlated with low levels of dissolved oxygen in the water. In the Samgye DWTP and Hwajeong DWTP, Chironomus spp. were almost absent, and instead, Tanytarsus spp. were abundant. Additionally, the Gangjeong DWTP was dominated by a Microtendipes sp., and two species of Orthocladiinae (a Parametriocnemus sp. and a Paratrichocladius sp.) were found only in the Jeju DWTP. We also identified the eight most abundant Chironomidae larvae found in the DWTPs. Furthermore, eDNA metabarcoding of DWTP sediment indicated the presence of different eukaryotic fauna and confirmed the presence of chironomids in DWTPs. These data provide useful morphological and genetic information regarding chironomid larvae that can be used for the water quality biomonitoring of DWTPs to support the supply of clean drinking water.

Ultrasonic Treatment Enhanced Astaxanthin Production of Haematococcus pluvialis.

In this study, effects of ultrasonic treatment on Haematococcus pluvialis (H. pluvialis) were investigated. It has been confirmed that the ultrasonic stimulation acted as stress resources in the red cyst stage H. pluvialis cells containing astaxanthin, resulting in additional astaxanthin production. With the increase in production of astaxanthin, the average diameter of H. pluvialis cells increased accordingly. In addition, to determine how ultrasonic stimulation had an effect on the further biosynthesis of astaxanthin, genes related to astaxanthin synthesis and cellular ROS level were measured. As a result, it was confirmed that astaxanthin biosynthesis related genes and cellular ROS levels were increased, and thus ultrasonic stimulation acts as an oxidative stimulus. These results support the notion on the effect of the ultrasonic treatment, and we believe our novel approach based on the ultrasonic treatment would help to enhance the astaxanthin production from H. pluvialis.

Facilitation of axonal transcriptome analysis with quantitative microfluidic devices.

Microfluidic chambers are powerful tools for studying axonal mRNA localization and translation in neurons. In addition to specific manipulation and measurements of axons, microfluidic chambers are used for collecting axonal materials to perform axonal transcriptome analysis. However, traditional bipartite and tripartite chambers have limitations either in purity or quantity of collected axons. Here, we improved the design of traditional chambers. Moreover, we developed two new quantitative chambers, multi-compartmental quantitative bipartite chamber (MQBC) and long quantitative tripartite chamber (LQTC). Compared with the traditional chambers, MQBC and LQTC could dramatically increase the efficiency in collecting axonal RNA. Finally, we applied these chambers to do comparative axon transcriptome analysis of different types of neurons. Thus, our newly designed quantitative chambers significantly improve axon collection efficiency and facilitate axonal transcriptome analysis.

Recent Advancements in Technologies to Detect Enterohaemorrhagic Escherichia coli Shiga Toxins.

Shiga toxin (Stxs)-producing enterohaemorrhagic Escherichia coli (EHEC) and Shigella dysenteriae serotype 1 are major causative agents of severe bloody diarrhea (known as hemorrhagic colitis) and hemolytic uremic syndrome (HUS) associated with extraintestinal complications such as acute renal failure and neurologic impairment in infected patients under 9 years of age. Extreme nephrotoxicity of Stxs in HUS patients is associated with severe outcomes, highlighting the need to develop technologies to detect low levels of the toxin in environmental or food samples. Currently, the conventional polymerase chain reaction (PCR) or immunoassay is the most broadly used assay to detect the toxin. However, these assays are laborious, time-consuming, and costly. More recently, numerous studies have described novel, highly sensitive, and portable methods for detecting Stxs from EHEC. To contextualize newly emerging Stxs detection methods, we briefly explain the basic principles of these methods, including lateral flow assays, optical detection, and electrical detection. We subsequently describe existing and newly emerging rapid detection technologies to identify and measure Stxs.

Monodisperse Micro-Droplet Generation in Microfluidic Channel with Asymmetric Cross-Sectional Shape.

Micro-droplets are widely used in the fields of chemical and biological research, such as drug delivery, material synthesis, point-of-care diagnostics, and digital PCR. Droplet-based microfluidics has many advantages, such as small reagent consumption, fast reaction time, and independent control of each droplet. Therefore, various micro-droplet generation methods have been proposed, including T-junction breakup, capillary flow-focusing, planar flow-focusing, step emulsification, and high aspect (height-to-width) ratio confinement. In this study, we propose a microfluidic device for generating monodisperse micro-droplets, the microfluidic channel of which has an asymmetric cross-sectional shape and high hypotenuse-to-width ratio (HTWR). It was fabricated using basic MEMS processes, such as photolithography, anisotropic wet etching of Si, and polydimethylsiloxane (PDMS) molding. Due to the geometric similarity of a Si channel and a PDMS mold, both of which were created through the anisotropic etching process of a single crystal Si, the microfluidic channel with the asymmetric cross-sectional shape and high HTWR was easily realized. The effects of HTWR of channels on the size and uniformity of generated micro-droplets were investigated. The monodisperse micro-droplets were generated as the HTWR of the asymmetric channel was over 3.5. In addition, it was found that the flow direction of the oil solution (continuous phase) affected the size of micro-droplets due to the asymmetric channel structures. Two kinds of monodisperse droplets with different sizes were successfully generated for a wider range of flow rates using the asymmetric channel structure in the developed microfluidic device.

The cytotoxicity of nano- and micro-sized graphene oxides on microalgae depends on the characteristics of cell wall and flagella.

Cytotoxic effects of emerging contaminants in aquatic environments have been widely studied using diverse microalgal species. However, the role of microalgal characteristics such as presence/absence of cell wall or flagella on cytotoxicity of contaminants was not elucidated yet. In this study, four different Chlamydomonas reinhardtii strains that have different characteristics were used to confirm how these characteristics affect toxicity of contaminants, nano-/micro-sized graphene oxide (GO). The nano-sized GO inhibited the growth of cell wall-deficient strains and reduced the photosynthetic activity. The micro-sized GO inhibited the growth of all strains, but the inhibition efficiency was higher in flagella-deficient strains, indicating that cell wall and flagella have different roles in response to contaminant exposure. The electron microscopy analysis demonstrated that nano-sized GO caused the cell rupture in cell wall-deficient strains. In flagella-deficient strains, the nano- and micro-sized GOs were parallelly attached on the surface of cells, covering the cells. The wrapping of flagella-deficient cells by GO led to the increase of reactive oxygen species (ROS) contents. These results indicate main cytotoxic mechanism of nano-sized GO was the membrane damage of cells, and the presence of cell wall can protect the cells from the attack of nano-sized GO. On the one hand, the presence of flagella might help to avoid the attachment of GO while the cell proliferation and photosynthesis were inhibited in flagella-deficient cells due to the GO wrapping. Overall, given that different microalgal species have different characteristics and these characteristics might affect the cytotoxic effect of the contaminants, it is of great importance to consider the characteristics of test microalgal species when evaluating the cytotoxic mechanism of the nano-/micro-sized pollutants.

Volatile fatty acid-treated mixotrophic cultivation of lipid/carbohydrate-rich cyanobacterial species, Pseudanabaena mucicola GO0704, for the enhancement of biofuel production.

Cyanobacteria-derived biofuels can be helpful in achieving a circular bioeconomy. To increase the production of biodiesel/bioethanol from cyanobacterium, Pseudanabaena mucicola GO0704, mixotrophic cultivation using volatile fatty acid (VFA), a cheap organic carbon source, was performed. The treatment of butyric acid or acetic acid enhanced the cell growth, particularly, the dry weight of the butyric acid-treated cells was 2.30-fold higher than the control. The enhancement of the growth led to the increase of metabolite (i.e., lipid and carbohydrate) productions, resulting in high amount of biodiesel and bioethanol to be produced. Butyric acid was more effective compared to acetic acid and the productions of biodiesel (52.2 mg/L) and bioethanol (132.6 mg/L) from the butyric acid-treated P. mucicola GO0704 were 2.34- and 2.17-fold higher compared to the control, respectively. This study will provide a foundation to commercialize the cyanobacteria-based carbon-neutral fuels, and ultimately, achieve a circular bioeconomy.

10-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory Activities.

Natural antimicrobial peptides (AMPs) are multifunctional host defense peptides (HDPs) that are valuable for various therapeutic applications. In particular, natural and artificial AMPs with dual antibacterial immunomodulatory functions emerged as promising candidates for the development of therapeutic agents to treat infectious inflammation. In an effort to develop useful AMP variants with short lengths and simple amino acid composition, we devised a de novo design strategy to generate a series of model peptide isomer sequences, named WALK peptides, i.e., tryptophan (W)-containing amphipathic-helical (A) leucine (L)/lysine (K) peptides. Here, we generated two groups of WALK peptide isomers: W2L4K4 (WALK244.01~WALK244.10) and W2L4K3 (WALK243.01~WALK243.09). Most showed apparent antibacterial activities against both Gram-positive and Gram-negative bacteria at a concentration of approximately 4 µg/mL along with varied hemolytic activities against human red blood cells. In addition, some exhibited significant anti-inflammatory activities without any significant cytotoxicity in macrophages. Collectively, these results suggest that the two selected peptides, WALK244.04 and WALK243.04, showed promise for the development of antibacterial and anti-inflammatory agents.

Identification of Bacterial Communities in Laboratory-Adapted Glyptotendipes tokunagai and Wild-Stream-Inhabiting Chironomus flaviplumus.

Chironomidae (chironomid) are one of the dominant families in freshwater ecosystems, and they plays an important role in the food web. They have been used as an indicator for water quality assessment, as they are resistant to diverse environmental pollutants. In this study, we identified the microbiomes of two chironomid species to see if there are any endogenous bacterial groups which could contribute to the host survival. The studied species are Glyptotendipes tokunagai, a model species cultivated in a laboratory-controlled environment, and Chironomus flaviplumus captured in a field stream in Yeosu, Korea. DNAs were extracted from the whole body of the individual species, and the 16S rRNA gene was amplified. The amplified products were sequenced using an Illumina MiSeq platform. The microbiomes of G. tokunagai were homogeneous, having 20% of the core amplicon sequence variants overlapping between replicates sampled from different water tanks. In contrast, none of the core amplicon sequence variants overlapped in C.flaviplumus. In both chironomid groups, potential symbionts were identified. Dysgonomonas, which can degrade complex carbon sources, was found in more than half of the total microbiomes of G. tokunagai. Tyzzerella and Dechloromonas, which have been suggested to detoxify environmental pollutants, were identified in the microbiome of C.flaviplumus. This study can help elucidate the life strategies of chironomids in polluted or organic-rich environments.

Strategies to control the growth of cyanobacteria and recovery using adsorption and desorption.

In this study, adsorption strategy using diethylenetriamine-modified cotton fiber (DETA-cotton) was investigated to control the target cells in aqueous phase. Adsorptive removal of M. aeruginosa using the DETA-cotton showed decrease in cell concentration from (100 ± 4.0) × 104 cells/mL to (32.1 ± 0.7) × 104 cells/mL in 24 h, and the concentration of microcystin did not increase during the removal process. Also, an increase in the amine groups on the surface was confirmed through the surface characterization by FT-IR and XPS. Desorption process was performed to analyze total lipid and fatty acid contents for potential use as bio-energy resources. About 90 % of the adsorbed cells were recovered through desorption, and the lipid content and composition were more suitable for use as biodiesel raw materials. Our adsorption-based approach might provide feasible solution not only to counteract environmental issue HABs but also to recover energy-resources from the harmful cyanobacterial species.

Profiling Analysis of Filter Feeder Polypedilum (Chironomidae) Gut Contents Using eDNA Metabarcoding Following Contrasting Habitat Types-Weir and Stream.

We analyzed the dietary composition of Polypedilum larvae among two contrasting habitats (river and weir). Our approach was (i) to apply eDNA-based sampling to reveal the gut content of the chironomid larvae, (ii) the diversity of gut contents in the two aquatic habitats, and (iii) assessment of habitat sediment condition with the food sources in the gut. The most abundant food was Chlorophyta in the gut of the river (20%) and weir (39%) chironomids. The average ratio of fungi, protozoa, and zooplankton in river chironomids gut was 5.9%, 7.2%, and 3.8%, while it was found decreased to 1.2%, 2.5%, and 0.1% in weir chironomids. Aerobic fungi in river midge guts were 3.6% and 10.34% in SC and IS, while they were in the range of 0.34-2.58% in weir midges. The hierarchical clustering analysis showed a relationship of environmental factors with food contents. Abiotic factors (e.g., pH) in the river and weir habitats correlated the clustered pattern with phytoplankton and minor groups of fungi. This study could help understand the food source diversity in the chironomid and habitat environmental conditions by using eDNA metabarcoding as an effective tool to determine dietary composition.

Transcriptional Responses of Stress-Related Genes in Pale Chub (Zacco platypus) Inhabiting Different Aquatic Environments: Application for Biomonitoring Aquatic Ecosystems.

Pale chub (Zacco platypus) is a dominant species in urban rivers and reservoirs, and it is used as an indicator to monitor the effects of environmental contaminants. Gene responses at the molecular level can reflect the health of fish challenged with environmental stressors. The objective of this study was to identify correlations between water quality factors and the expression of stress-related genes in Z. platypus from different lake environments (Singal and Juam Lakes). To do so, transcriptional responses of genes involving cellular homeostasis (heat-shock protein 70, HSP70; heat-shock protein 90, HSP90), metal detoxification (metallothionein, MT), and antioxidation (superoxide dismutase, SOD; catalase, CAT) were analyzed in the gill and liver tissues of Z. platypus. HSP70, HSP90, and MT genes were overall upregulated in Z. platypus from Singal Lake, which suffered from poorer water quality than Juam Lake. In addition, gene responses were significantly higher in Singal Lake outflow. Upregulation of HSP70, HSP90, and MT was significantly higher in Z. platypus gills than in the liver tissue. In addition, integrated biomarker response and heatmap analysis determined correlations between expression of biomarker genes or water quality factors and sampling sites of both lakes. These results suggest that stress-related genes used as multiple biomarkers may reflect spatial characteristics and water quality of different lake environments, and they can be used for biomonitoring and ecological risk assessment.

Metformin administration is associated with enhanced response to transarterial chemoembolization for hepatocellular carcinoma in type 2 diabetes patients.

Transarterial chemoembolization (TACE) is often used as a locoregional therapy for early hepatocellular carcinoma (HCC) when local ablation or resection are not feasible, but incomplete response and recurrence are commonly observed. In this study, we sought to determine the association between metformin administration and TACE outcomes for single nodular HCC in patients with type 2 diabetes mellitus (T2DM). The retrospective cohort analysis included 164 T2DM patients with single nodular HCC who underwent TACE as an initial treatment, and 91 were exposed to metformin before and after TACE. Propensity score (PS) matching was used to balance covariates. Logistic regression analysis was used to determine the predictors of tumor response after TACE, and Cox regression analysis assessed independent predictors of local tumor recurrence (LTR) in patients with complete response after TACE. Metformin use was associated with significantly higher objective response rate (ORR) in the overall and PS-matched cohort (79.1% vs. 60.3 and 78.7% vs. 57.5%; p = 0.008 and p = 0.029, respectively). Logistic regression analysis showed that metformin use was an independent predictor of ORR in all and PS-matched patients (odds ratio = 2.65 and 3.06; p = 0.016 and 0.034, respectively). Cox regression analysis showed metformin administration was an independent predictor for lower LTR in all and PS-matched patients (hazard ratio = 0.28 and 0.27; p = 0.001 and 0.007, respectively). Metformin administration is associated with better initial response and lower local recurrence after TACE for single nodular HCC in T2DM.

Incidence and Pattern of Aminotransferase Elevation During Anti-Hypertensive Therapy With Angiotensin-II Receptor Blockers.

BACKGROUND: Angiotensin type II receptor blockers (ARBs) are the most widely used anti-hypertensive drugs. This study aimed to elucidate the likelihood and pattern of ARB-induced liver injury in a hospital-based cohort. METHODS: Data of patients receiving fimasartan (n = 5,543), candesartan (n = 6,406), valsartan (n = 6,040), and losartan (n = 9,126) were retrieved from the clinical data warehouse of two tertiary hospitals. Patients with alanine aminotransferase (ALT) levels > 5 times the upper normal limit were assessed according to the Roussel Uclaf Causality Assessment Method (RUCAM). RESULTS: A total of 27,115 patients were enrolled, including 14,630 (54.0%) men, with a mean age of 64.6 years (standard deviation, 13.6). During 31,717 person-years of ARB therapy, serum ALT levels > 120 IU/L were found in 558 (2.1%) person-years, and levels > 200 IU/L were found in 155 (0.6%) person-years. The incidence of ALT elevation > 120 IU/L per 106 cumulative defined daily doses was 6.6, 3.6, 3.9, and 4.0 in the fimasartan, candesartan, valsartan, and losartan groups, respectively (P = 0.002). An ALT level > 200 IU/L with RUCAM score ≥ 6 was found in 20 patients, suggesting probable drug-induced liver injury for 11 (0.2%) patients receiving fimasartan, five (0.1%) receiving candesartan, four (0.1%) receiving valsartan, and none receiving losartan (P < 0.001). CONCLUSION: Approximately 2% of patients receiving ARB therapy had significant ALT elevation (4.24/106 cumulative defined daily doses [cDDDs]), which was associated with probable ARB-related liver injury in 0.07% of patients (0.15/106 cDDDs). Elevation of ALT was more commonly associated with fimasartan than the other ARBs. Clinicians should be aware of the possibility of ARB-related ALT elevation in patients with unexplained chronic abnormal ALT.

Multi-Phase, Contrast-Enhanced Computed Tomography-Based Radiomic Prognostic Marker of Non-Metastatic Pancreatic Ductal Adenocarcinoma.

Background/Aim: This study investigated the predictive ability of intra-tumor enhancement on computed tomography (CT) for the outcomes of patients with pancreatic ductal adenocarcinoma (PDA). Methods: Multi-phase, contrast-enhanced CT (including unenhanced, pancreatic parenchymal phase (PPP) and portal venous phase (PVP)) images of patients diagnosed with non-metastatic PDA were analyzed to investigate prognostic factors. Results: Two hundred ninety-eight patients with PDA (159 with resectable pancreatic cancer (RPC) and 139 with borderline resectable pancreatic cancer (BRPC)/locally advanced pancreatic cancer (LAPC)) were included. The attenuation values of PDA during the PPP (94.5 vs. 60.7 HU; p <0.001) and PVP (101.5 vs. 75.5 HU; p <0.001) were higher in patients with RPC than in those with BRPC/LAPC. Well-enhanced PDA during the PPP was associated with longer overall survival in the RPC group (27.9 vs. 15.4 months; p <0.001) and the BRPC/LAPC group (22.7 vs. 13.6 months; p = 0.024). Patients with BRPC/LAPC who underwent neoadjuvant treatment and had well-enhanced PDA during the PPP were more likely to undergo resection. Although tumor size was also an independent prognostic factor, it was not correlated with intra-tumoral enhancement during the PPP. Conclusions: Intra-tumoral contrast enhancement on CT is an independent prognostic factor in patients with non-metastatic PDA.