Neural substrates of marriage on self-parents processing and the association with a parents-oriented perspective shift in a collectivistic culture.

Relationship with parents is a special bond that shapes self-other representations and have an impact on adult-child's marriage, especially in the early stages of marriage. This study sought to investigate the neural mechanisms underlying self-parents processing as well as their relationship with marriage. Seventy-eight premarital Korean participants were scanned in functional MRI while evaluating traits of the self and parents. Then, 21 of them returned after being married to engage in the identical task three years later. The precuneus and temporoparietal junction were identified to activate stronger for parents than self at both marital statuses. The dorsal anterior cingulate cortex, posterior cingulate cortex, parietal operculum, and caudate activated more for self than parents before marriage, but their activities changed during marriage. The activation increase of the parietal operculum between marital statuses in the parents condition was negatively correlated with the level of marital dissatisfaction, and this association only appeared among participants with a child. Self-parents processing may recruit brain regions involved in autobiographical memory and self-other distinction, and marriage has an impact on the way individuals process rewards and multimodal sensory information during this processing. Marriage may lead to changes in brain function that affect the processing of emotions toward parents and a more parents-oriented perspective shift in collectivistic societies.

A long-term storable gel-laden chip composite built in a multi-well plate enablingin situcell encapsulation for high-throughput liver model.

Hydrogels are widely used as scaffold materials for constructingin vitrothree-dimensional microphysiological systems. However, their high sensitivity to various external cues hinders the development of hydrogel-laden, microscale, and high-throughput chips. Here, we have developed a long-term storable gel-laden chip composite built in a multi-well plate, which enablesin situcell encapsulation and facilitates high-throughput analysis. Through optimized chemical crosslinking and freeze-drying method (C/FD), we have achieved a high-quality of gel-laden chip composite with excellent transparency, uniform porosity, and appropriate swelling and mechanical characteristics. Besides collagen, decellularized extracellular matrix with tissue-specific biochemical compound has been applied as chip composite. As a ready-to-use platform,in situcell encapsulation within the gel has been achieved through capillary force generated during gel reswelling. The liver-mimetic chip composite, comprising HepG2 cells or primary hepatocytes, has demonstrated favorable hepatic functionality and high sensitivity in drug testing. The developed fabrication process with improved stability of gels and storability allows chip composites to be stored at a wide range of temperatures for up to 28 d without any deformation, demonstrating off-the-shelf products. Consequently, this provides an exceptionally simple and long-term storable platform that can be utilized for an efficient tissue-specific modeling and various biomedical applications.

Evaluation of the root dentin bond strength and intratubular biomineralization of a premixed calcium aluminate-based hydraulic bioceramic endodontic sealer.

PURPOSE: This study evaluated the dentin bonding strength and biomineralization effect of a recently developed premixed calcium aluminate-based endodontic sealer (Dia-Root Bio Sealer) in comparison with existing calcium silicate-based sealers. METHODS: The root canals of 80 mandibular premolars were filled with Dia-Root Bio Sealer, Endoseal MTA, EndoSequence BC Sealer, and AH Plus Bioceramic Sealer. Medial and apical specimens were then obtained by sectioning. The push-out bond strength was measured using the medial specimens, and the failure mode was recorded. Intratubular biomineralization in the apical specimens was analyzed using scanning electron microscopy and energy-dispersive X-ray spectroscopy (EDS). The data were analyzed using one-way analysis of variance followed by the Tukey test (P < 0.05). RESULTS: The push-out bond strength of Dia-Root Bio Sealer was significantly higher than that of the other tested materials, and a cohesive failure pattern was observed in all groups. Dia-Root Bio Sealer also exhibited a significantly higher degree of biomineralization than the other groups, and EDS analysis indicated that the biomineralized precipitates were amorphous calcium phosphate. CONCLUSION: The results of this study indicate that Dia-Root Bio Sealer has the potential to be used as an adequate root canal sealer due to its favorable bonding performance.

Application of plasma circulating KRAS mutations as a predictive biomarker for targeted treatment of pancreatic cancer.

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in circulating tumor deoxyribonucleic acid (ctDNA) have been reported as representative noninvasive prognostic markers for pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to evaluate single KRAS mutations as prognostic and predictive biomarkers, with an emphasis on potential therapeutic approaches to PDAC. A total of 128 patients were analyzed for multiple or single KRAS mutations (G12A, G12C, G12D, G12R, G12S, G12V, and G13D) in their tumors and plasma using droplet digital polymerase chain reaction (ddPCR). Overall, KRAS mutations were detected by multiplex ddPCR in 119 (93%) of tumor DNA and 68 (53.1%) of ctDNA, with a concordance rate of 80% between plasma ctDNA and tumor DNA in the metastatic stage, which was higher than the 44% in the resectable stage. Moreover, the prognostic prediction of both overall survival (OS) and progression-free survival (PFS) was more relevant using plasma ctDNA than tumor DNA. Further, we evaluated the selective tumor-suppressive efficacy of the KRAS G12C inhibitor sotorasib in a patient-derived organoid (PDO) from a KRAS G12C-mutated patient using a patient-derived xenograft (PDX) model. Sotorasib showed selective inhibition in vitro and in vivo with altered tumor microenvironment, including fibroblasts and macrophages. Collectively, screening for KRAS single mutations in plasma ctDNA and the use of preclinical models of PDO and PDX with genetic mutations would impact precision medicine in the context of PDAC.

A well plate-based GelMA photo-crosslinking system with tunable hydrogel mechanical properties to regulate the PTH-mediated osteogenic fate.

Versatile and efficient regulation of the mechanical properties of the extracellular matrix is crucial not only for understanding the dynamic changes in biological systems, but also for obtaining precise and effective cellular responses in drug testing. In this study, we developed a well plate-based hydrogel photo-crosslinking system to effectively control the mechanical properties of hydrogels and perform high-throughput assays. We improved cell biocompatibility by using gelatin methacryloyl (GelMA) with a visible light photo-crosslinking method. Multiple cell-laden GelMA hydrogels were simultaneously and uniformly created using multi-arrayed 520 nm light-emitting diodes in a well plate format. The elastic modulus of the hydrogels can be widely adjusted (0.5-30 kPa) using a photo-crosslinking system capable of independently controlling the light intensity or exposure time for multiple samples. We demonstrate the feasibility of our system by observing enhanced bone differentiation of human mesenchymal stem cells (hMSCs) cultured on stiffer hydrogels. Additionally, we observed that the osteogenic fate of hMSCs, affected by the different mechanical properties of the gel, was regulated by parathyroid hormone (PTH). Notably, in response to PTH, hMSCs in a high-stiffness microenvironment upregulate osteogenic differentiation while exhibiting increased proliferation in a low-stiffness microenvironment. Overall, the developed system enables the generation of multiple cell-laden three-dimensional cell culture models with diverse mechanical properties and holds significant potential for expansion into drug testing.

Clinical Features of Delirium among Patients in the Intensive Care Unit According to Motor Subtype Classification: A Retrospective Longitudinal Study.

PURPOSE: Delirium in the intensive care unit (ICU) poses a significant safety and socioeconomic burden to patients and caregivers. However, invasive interventions for managing delirium have severe drawbacks. To reduce unnecessary interventions during ICU hospitalization, we aimed to investigate the features of delirium among ICU patients according to the occurrence of hypoactive symptoms, which are not expected to require invasive intervention. MATERIALS AND METHODS: Psychiatrists assessed all patients with delirium in the ICU during hospitalization. Patients were grouped into two groups: a "non-hypoactive" group that experienced the non-hypoactive motor subtype once or more or a "hypoactive only" group that only experienced the hypoactive motor subtype. Clinical variables routinely gathered for clinical management were collected from electronic medical records. Group comparisons and logistic regression analyses were conducted. RESULTS: The non-hypoactive group had longer and more severe delirium episodes than the hypoactive only group. Although the non-hypoactive group was prescribed more antipsychotics and required restraints longer, the hypoactive only group also received both interventions. In multivariable logistic regression analysis, BUN [odds ratio (OR): 0.993, pH OR: 0.202], sodium (OR: 1.022), RASS score (OR: 1.308) and whether restraints were applied [OR: 1.579 (95% confidence interval 1.194-2.089), p<0.001] were significant predictors of hypoactive only group classification. CONCLUSION: Managing and predicting delirium patients based on whether patients experienced non-hypoactive delirium may be clinically important. Variables obtained during the initial 48 hours can be used to determine which patients are likely to require invasive interventions.

3D bioprinting of dECM-incorporated hepatocyte spheroid for simultaneous promotion of cell-cell and -ECM interactions.

The cell spheroid technology, which greatly enhances cell-cell interactions, has gained significant attention in the development of in vitro liver models. However, existing cell spheroid technologies still have limitations in improving hepatocyte-extracellular matrix (ECM) interaction, which have a significant impact on hepatic function. In this study, we have developed a novel bioprinting technology for decellularized ECM (dECM)-incorporated hepatocyte spheroids that could enhance both cell-cell and -ECM interactions simultaneously. To provide a biomimetic environment, a porcine liver dECM-based cell bio-ink was developed, and a spheroid printing process using this bio-ink was established. As a result, we precisely printed the dECM-incorporated hepatocyte spheroids with a diameter of approximately 160-220 µm using primary mouse hepatocyte (PMHs). The dECM materials were uniformly distributed within the bio-printed spheroids, and even after more than 2 weeks of culture, the spheroids maintained their spherical shape and high viability. The incorporation of dECM also significantly improved the hepatic function of hepatocyte spheroids. Compared to hepatocyte-only spheroids, dECM-incorporated hepatocyte spheroids showed approximately 4.3- and 2.5-fold increased levels of albumin and urea secretion, respectively, and a 2.0-fold increase in CYP enzyme activity. These characteristics were also reflected in the hepatic gene expression levels of ALB, HNF4A, CPS1, and others. Furthermore, the dECM-incorporated hepatocyte spheroids exhibited up to a 1.8-fold enhanced drug responsiveness to representative hepatotoxic drugs such as acetaminophen, celecoxib, and amiodarone. Based on these results, it can be concluded that the dECM-incorporated spheroid printing technology has great potential for the development of highly functional in vitro liver tissue models for drug toxicity assessment.

Liver dECM-Gelatin Composite Bioink for Precise 3D Printing of Highly Functional Liver Tissues.

In recent studies, liver decellularized extracellular matrix (dECM)-based bioinks have gained significant attention for their excellent compatibility with hepatocytes. However, their low printability limits the fabrication of highly functional liver tissue. In this study, a new liver dECM-gelatin composite bioink (dECM gBioink) was developed to overcome this limitation. The dECM gBioink was prepared by incorporating a viscous gelatin mixture into the liver dECM material. The novel dECM gBioink showed 2.44 and 10.71 times higher bioprinting resolution and compressive modulus, respectively, than a traditional dECM bioink. In addition, the new bioink enabled stable stacking with 20 or more layers, whereas a structure printed with the traditional dECM bioink collapsed. Moreover, the proposed dECM gBioink exhibited excellent hepatocyte and endothelial cell compatibility. At last, the liver lobule mimetic structure was successfully fabricated with a precisely patterned endothelial cell cord-like pattern and primary hepatocytes using the dECM gBioink. The fabricated lobule structure exhibited excellent hepatic functionalities and dose-dependent responses to hepatotoxic drugs. These results demonstrated that the gelatin mixture can significantly improve the printability and mechanical properties of the liver dECM materials while maintaining good cytocompatibility. This novel liver dECM gBioink with enhanced 3D printability and resolution can be used as an advanced tool for engineering highly functional liver tissues.

Dissemination of the high-risk cloneST147 carbapenem-resistant klebsiella pneumoniae from a local tertiary care hospital in the Republic of Korea.

BACKGROUND: The emergence of carbapenem-resistant Enterobacterales (CRE) infections is rapidly increasing and represents a serious public threat. In 2020, a total of 16,883 carbapenemase-producing Enterobacterales strains were collected; among these isolates, 21 strains were repeatedly isolated in a local tertiary care hospital. METHODS: Antimicrobial susceptibility testing was performed using the broth microdilution method. All 21 strains of CRKP were analyzed by PFGE after XbaI digestion. The 21 CRKP strains were sequenced on the Illumina Miseq and Oxford Nanopore GridION platforms. RESULTS: These 21 CRKP isolates showed an identical antimicrobial resistance profile, including resistance to ampicillin, carbapenems, cephems, chloramphenicol, fluoroquinolone, macrolides and trimethoprim/sulfamethoxazole. Based on whole-genome analysis, these 21 CRKP isolates shared a common genetic structure (ISAba125-IS630-blaNDM-1-bleMBL) and harbored additional resistance determinants (blaOXA-1, blaCTX-M-15, blaSHV-11, blaSHV-67, aac(6')-Ib-cr, qnrS1, OqxA, OqxB, catB3, mph(A), sul1, and dfrA12) and mutations in the quinolone resistance-determining regions of gyrA (S83I) and parC (S80I). These isolates belonged to the ST147 and KL64 capsular types, which were carried on IncFIB replicon plasmids. The 21 CRKP strains collected from one hospital were divided into five PFGE patterns, and they were closely related with a minimum similarity value of 95.2%. These isolates were found to be highly related based on the presence of between 2 and 27 SNPs. CONCLUSIONS: These findings indicate that NDM-1-producing K. pneumoniae ST147 may have been introduced via a common source, implying nosocomial transmission; furthermore, continuous monitoring is necessary to prevent endemic transmission.

Bone-on-a-Chip: Biomimetic Models Based on Microfluidic Technologies for Biomedical Applications.

With the increasing importance of preclinical evaluation of newly developed drugs or treatments, in vitro organ or disease models are necessary. Although various organ-specific on-chip (organ-on-a-chip, or OOC) systems have been developed as emerging in vitro models, bone-on-a-chip (BOC) systems that recapitulate the bone microenvironment have been less developed or reviewed compared with other OOCs. The bone is one of the most dynamic organs and undergoes continuous remodeling throughout its lifetime. The aging population is growing worldwide, and healthcare costs are rising rapidly. Since in vitro BOC models that recapitulate native bone niches and pathological features can be important for studying the underlying mechanism of orthopedic diseases and predicting drug responses in preclinical trials instead of in animals, the development of biomimetic BOCs with high efficiency and fidelity will be accelerated further. Here, we review recently engineered BOCs developed using various microfluidic technologies and investigate their use to model the bone microenvironment. We have also explored various biomimetic strategies based on biological, geometrical, and biomechanical cues for biomedical applications of BOCs. Finally, we addressed the limitations and challenging issues of current BOCs that should be overcome to obtain more acceptable BOCs in the biomedical and pharmaceutical industries.

Fermentation of Abelmoschus manihot Extract with Halophilic Bacillus licheniformis CP6 Results in Enhanced Anti-Inflammatory Activities.

Microbial fermentation provides a valorization strategy, through biotransformation, to convert plant-derived raw materials into health-promoting agents. In this study, we have investigated the antioxidative activity of Abelmoschus manihot fermented with various Bacillaceae strains from specific environments and demonstrated the anti-inflammatory effects of Bacillus licheniformis CP6 fermented A. manihot extract (FAME) in lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. Of 1500 bacteria isolated from various specific environments, 47 extracellular protease- and amylase-producing strains with qualified presumption safety status, belonging to the family Bacillaceae, were selected for A. manihot fermentation. Among them, strain CP6, a halophilic bacterium isolated from Tongyeong seawater in Korea and identified as B. licheniformis, showed the highest antioxidant activity. In particular, FAME exerted anti-inflammatory effects on LPS-stimulated Raw264.7 macrophages. Consequently, FAME had a potent inhibitory effect on nitric oxide (NO) production in LPS-stimulated macrophages, without cytotoxicity. Moreover, FAME downregulated LPS-induced pro-inflammatory mediator and enzyme levels in LPS-induced Raw264.7 cells, including IL-1ß, IL-6, TNF-α, iNOS, and COX-2, compared to levels when cells were incubated in A. manihot extract (IAME). Further detailed characterization indicated that FAME suppresses inflammation by blocking NF-κB via IKK phosphorylation inhibition and IκB-α degradation and by downregulating NO production, and inflammatory mediators also decreased NF-κB translocation. Furthermore, FAME inhibited LPS-stimulated activation of MAPKs, including ERK1/2, JNK, and p38, compared to that with either IAME. Therefore, we suggest that FAME could be used for inflammation-related disorders.

A high-throughput biomimetic bone-on-a-chip platform with artificial intelligence-assisted image analysis for osteoporosis drug testing.

Although numerous organ-on-a-chips have been developed, bone-on-a-chip platforms have rarely been reported because of the high complexity of the bone microenvironment. With an increase in the elderly population, a high-risk group for bone-related diseases such as osteoporosis, it is essential to develop a precise bone-mimicking model for efficient drug screening and accurate evaluation in preclinical studies. Here, we developed a high-throughput biomimetic bone-on-a-chip platform combined with an artificial intelligence (AI)-based image analysis system. To recapitulate the key aspects of natural bone microenvironment, mouse osteocytes (IDG-SW3) and osteoblasts (MC3T3-E1) were cocultured within the osteoblast-derived decellularized extracellular matrix (OB-dECM) built in a well plate-based three-dimensional gel unit. This platform spatiotemporally and configurationally mimics the characteristics of the structural bone unit, known as the osteon. Combinations of native and bioactive ingredients obtained from the OB-dECM and coculture of two types of bone cells synergistically enhanced osteogenic functions such as osteocyte differentiation and osteoblast maturation. This platform provides a uniform and transparent imaging window that facilitates the observation of cell-cell interactions and features high-throughput bone units in a well plate that is compatible with a high-content screening system, enabling fast and easy drug tests. The drug efficacy of anti-SOST antibody, which is a newly developed osteoporosis drug for bone formation, was tested via ß-catenin translocation analysis, and the performance of the platform was evaluated using AI-based deep learning analysis. This platform could be a cutting-edge translational tool for bone-related diseases and an efficient alternative to bone models for the development of promising drugs.

Alteration of resting-state functional connectivity network properties in patients with social anxiety disorder after virtual reality-based self-training.

Social anxiety disorder (SAD) is a mental disorder characterized by excessive anxiety in social situations. This study aimed to examine the alteration of resting-state functional connectivity in SAD patients related to the virtual reality-based self-training (VRS) which enables exposure to social situations in a controlled environment. Fifty-two SAD patients were randomly assigned to the experimental group who received the VRS, or the control group who did not. Self-report questionnaires and resting-state functional magnetic resonance imaging (fMRI) were performed to assess clinical symptoms and analyze the resting-state network properties, respectively. Significant decrease in social anxiety and an increase in self-esteem was found in the experimental group. From the resting-state fMRI analysis, alteration of local network properties in the left dorsolateral prefrontal gyrus (-10.0%, p = 0.025), left inferior frontal gyrus (-32.3%, p = 0.044), left insula (-17.2%, p = 0.046), left Heschl's gyrus (-21.2%, p = 0.011), bilateral inferior temporal gyrus (right: +122.6%, p = 0.045; left:-46.7%, p = 0.015), and right calcarine sulcus (+17.0%, p = 0.010) were found in the experimental group. Average shortest path length (+8.3%, p = 0.008) and network efficiency (-7.6%, p = 0.011) are found to be altered from the global network property analysis. In addition, the experimental group displayed more positive and more negative changes in the correlation trend of average shortest path length (p = 0.004) and global network efficiency (p = 0.014) with the severity of social anxiety, respectively. These results suggest potential effectiveness of the VRS, which is possibly related to the change of aberrant processing and control of visual and auditory linguistic stimuli and the adaptive change in rumination pattern.

Predicting social anxiety in young adults with machine learning of resting-state brain functional radiomic features.

Social anxiety is a symptom widely prevalent among young adults, and when present in excess, can lead to maladaptive patterns of social behavior. Recent approaches that incorporate brain functional radiomic features and machine learning have shown potential for predicting certain phenotypes or disorders from functional magnetic resonance images. In this study, we aimed to predict the level of social anxiety in young adult participants by training machine learning models with resting-state brain functional radiomic features including the regional homogeneity, fractional amplitude of low-frequency fluctuation, fractional resting-state physiological fluctuation amplitude, and degree centrality. Among the machine learning models, the XGBoost model achieved the best performance with balanced accuracy of 77.7% and F1 score of 0.815. Analysis of input feature importance demonstrated that the orbitofrontal cortex and the degree centrality were most relevant to predicting the level of social anxiety among the input brain regions and the input type of radiomic features, respectively. These results suggest potential validity for predicting social anxiety with machine learning of the resting-state brain functional radiomic features and provide further understanding of the neural basis of the symptom.

Development and Validation of Simplified Delirium Prediction Model in Intensive Care Unit.

Background: The intensive care unit (ICU) is where various medical staffs and patients with diverse diseases convene. Regardless of complexity, a delirium prediction model that can be applied conveniently would help manage delirium in the ICU. Objective: This study aimed to develop and validate a generally applicable delirium prediction model in the ICU based on simple information. Methods: A retrospective study was conducted at a single hospital. The outcome variable was defined as the occurrence of delirium within 30 days of ICU admission, and the predictors consisted of a 12 simple variables. Two models were developed through logistic regression (LR) and random forest (RF). A model with higher discriminative power based on the area under the receiver operating characteristics curve (AUROC) was selected as the final model in the validation process. Results: The model was developed using 2,588 observations (training dataset) and validated temporally with 1,109 observations (test dataset) of ICU patients. The top three influential predictors of the LR and RF models were the restraint, hospitalization through emergency room, and drainage tube. The AUROC of the LR model was 0.820 (CI 0.801-0.840) and 0.779 (CI 0.748-0.811) in the training and test datasets, respectively, and that of the RF model was 0.762 (CI 0.732-0.792) and 0.698 (0.659-0.738), respectively. The LR model showed better discriminative power (z = 4.826; P < 0.001). Conclusion: The LR model developed with brief variables showed good performance. This simplified prediction model will help screening become more accessible.

In vitrobreast cancer model with patient-specific morphological features for personalized medicine.

In vitrocancer models that can simulate patient-specific drug responses for personalized medicine have attracted significant attention. However, the technologies used to produce such models can only recapitulate the morphological heterogeneity of human cancer tissue. Here, we developed a novel 3D technique to bioprint anin vitrobreast cancer model with patient-specific morphological features. This model can precisely mimic the cellular microstructures of heterogeneous cancer tissues and produce drug responses similar to those of human cancers. We established a bioprinting process for generating cancer cell aggregates with ductal and solid tissue microstructures that reflected the morphology of breast cancer tissues, and applied it to develop breast cancer models. The genotypic and phenotypic characteristics of the ductal and solid cancer aggregates bioprinted with human breast cancer cells (MCF7, SKBR3, MDA-MB-231) were respectively similar to those of early and advanced cancers. The bioprinted solid cancer cell aggregates showed significantly higher hypoxia (>8 times) and mesenchymal (>2-4 times) marker expressions, invasion activity (>15 times), and drug resistance than the bioprinted ductal aggregates. Co-printing the ductal and solid aggregates produced heterogeneous breast cancer tissue models that recapitulated three different stages of breast cancer tissue morphology. The bioprinted cancer tissue models representing advanced cancer were more and less resistant, respectively, to the anthracycline antibiotic doxorubicin and the hypoxia-activated prodrug tirapazamine; these were analogous to the results in human cancer. The present findings showed that cancer cell aggregates can mimic the pathological micromorphology of human breast cancer tissue and they can be bioprinted to produce breast cancer tissuein vitrothat can morphologically represent the clinical stage of cancer in individual patients.

Targeted next generation sequencing of circulating tumor DNA provides prognostic information for management in breast cancer patients.

Background: Circulating tumor DNA (ctDNA) is a non-invasive biomarker for evaluating cancer prognosis. The aim of this study was to analyze the genomic profile of circulating tumor DNA (ctDNA) in breast cancer patients, and evaluate its clinical implications. Methods: Targeted sequencing of ctDNA was performed in 38 patients using commercially available Oncomine Breast cfDNA panel. Whole exome sequencing was performed on matched tumor DNA (n=20). Survival analysis and response to chemotherapy in the study population were evaluated. The detected genomic variants were validated and serially monitored with droplet digital polymerase chain reaction (ddPCR) in 5 patients. Results: At least one variant or copy number alteration was detected in the ctDNA of 31 of 38 (82%) breast cancer patients, with the most common variants being in TP53 (50%), PIK3CA (15%) and ESR1 (14%). When comparing genomic profiles of ctDNA and those of matched tumor DNA in 20 patients, the concordance rate was 9.7% among positives. The patients with variants in TP53 showed significantly poorer overall survival than those without [hazard ratio (HR) =3.90, 95% confidence interval (CI): 1.10-13.84, P=0.035] and its impact was also statistically significant in multivariate analysis with breast cancer subtype included. In serially monitored results, changes in the allele frequency of somatic variants (PI3KCA, TP53) of ctDNA were found to be reflective of response to chemotherapy. Conclusions: The genomic profile of ctDNA reflects and provides additional information to the tumor DNA genome profile. Follow-up monitoring of mutations detected in ctDNA is useful in the clinical management of breast cancer patients.

Power Reduction in Punch-Through Current-Based Electro-Thermal Annealing in Gate-All-Around FETs.

Device guidelines for reducing power with punch-through current annealing in gate-all-around (GAA) FETs were investigated based on three-dimensional (3D) simulations. We studied and compared how different geometric dimensions and materials of GAA FETs impact heat management when down-scaling. In order to maximize power efficiency during electro-thermal annealing (ETA), applying gate module engineering was more suitable than engineering the isolation or source drain modules.

Brain functional connectivity during and after imagery of gaming and alternative leisure activities in patients with internet gaming disorder.

BACKGROUND: The effect of gaming cue exposure on brain activity in patients with internet gaming disorder (IGD) has been investigated a lot, but the effect on brain connectivity has not. This study aimed to investigate the effects of imageries of gaming and alternative leisure activities on functional connectivity during the during-task and post-task states in patients with IGD. METHODS: Twenty-nine patients and 20 healthy controls were scanned in the 6-min states before, during, and after the imagery tasks for gaming and alternative leisure behaviors using fMRI. Seed-based functional connectivity during and after the tasks were analyzed. The seeds were the nucleus accumbens (NAcc), ventral tegmental area (VTA), caudate, putamen, anterior cingulate cortex (ACC), and posterior cingulate cortex. RESULTS: The group-by-state interaction effects for the during-tasks were found in caudate-, putamen-, and ACC-based connectivity, whereas those for the post-tasks were shown only in NAcc-based connectivity. In particular, patients showed that caudate-right parahippocampal gyrus connectivity and putamen-right orbitofrontal cortex connectivity increased during gaming and decreased during alternative, whereas NAcc-right precuneus connectivity decreased at baseline, increased in post-gaming, and were not different in post-alternative. CONCLUSION: Differences in during-task connectivity of the habit/motor and salience networks and post-task resting-state connectivity of the reward and limbic networks between the two imagery tasks may differ between the groups. In the treatment of IGD, when these network connections are reactive to alternative leisure activity, just as to gaming activity, they seem to be freed from gaming addiction.