Triangulation supports agricultural spread of the Transeurasian languages.

The origin and early dispersal of speakers of Transeurasian languages-that is, Japanese, Korean, Tungusic, Mongolic and Turkic-is among the most disputed issues of Eurasian population history1-3. A key problem is the relationship between linguistic dispersals, agricultural expansions and population movements4,5. Here we address this question by 'triangulating' genetics, archaeology and linguistics in a unified perspective. We report wide-ranging datasets from these disciplines, including a comprehensive Transeurasian agropastoral and basic vocabulary; an archaeological database of 255 Neolithic-Bronze Age sites from Northeast Asia; and a collection of ancient genomes from Korea, the Ryukyu islands and early cereal farmers in Japan, complementing previously published genomes from East Asia. Challenging the traditional 'pastoralist hypothesis'6-8, we show that the common ancestry and primary dispersals of Transeurasian languages can be traced back to the first farmers moving across Northeast Asia from the Early Neolithic onwards, but that this shared heritage has been masked by extensive cultural interaction since the Bronze Age. As well as marking considerable progress in the three individual disciplines, by combining their converging evidence we show that the early spread of Transeurasian speakers was driven by agriculture.

CWAS-Plus: estimating category-wide association of rare noncoding variation from whole-genome sequencing data with cell-type-specific functional data.

Variants in cis-regulatory elements link the noncoding genome to human pathology; however, detailed analytic tools for understanding the association between cell-level brain pathology and noncoding variants are lacking. CWAS-Plus, adapted from a Python package for category-wide association testing (CWAS), enhances noncoding variant analysis by integrating both whole-genome sequencing (WGS) and user-provided functional data. With simplified parameter settings and an efficient multiple testing correction method, CWAS-Plus conducts the CWAS workflow 50 times faster than CWAS, making it more accessible and user-friendly for researchers. Here, we used a single-nuclei assay for transposase-accessible chromatin with sequencing to facilitate CWAS-guided noncoding variant analysis at cell-type-specific enhancers and promoters. Examining autism spectrum disorder WGS data (n = 7280), CWAS-Plus identified noncoding de novo variant associations in transcription factor binding sites within conserved loci. Independently, in Alzheimer's disease WGS data (n = 1087), CWAS-Plus detected rare noncoding variant associations in microglia-specific regulatory elements. These findings highlight CWAS-Plus's utility in genomic disorders and scalability for processing large-scale WGS data and in multiple-testing corrections. CWAS-Plus and its user manual are available at https://github.com/joonan-lab/cwas/ and https://cwas-plus.readthedocs.io/en/latest/, respectively.

Adolescent Parvalbumin Expression in the Left Orbitofrontal Cortex Shapes Sociability in Female Mice.

The adolescent social experience is essential for the maturation of the prefrontal cortex in mammalian species. However, it still needs to be determined which cortical circuits mature with such experience and how it shapes adult social behaviors in a sex-specific manner. Here, we examined social-approaching behaviors in male and female mice after postweaning social isolation (PWSI), which deprives social experience during adolescence. We found that the PWSI, particularly isolation during late adolescence, caused an abnormal increase in social approaches (hypersociability) only in female mice. We further found that the PWSI female mice showed reduced parvalbumin (PV) expression in the left orbitofrontal cortex (OFCL). When we measured neural activity in the female OFCL, a substantial number of neurons showed higher activity when mice sniffed other mice (social sniffing) than when they sniffed an object (object sniffing). Interestingly, the PWSI significantly reduced both the number of activated neurons and the activity level during social sniffing in female mice. Similarly, the CRISPR/Cas9-mediated knockdown of PV in the OFCL during late adolescence enhanced sociability and reduced the social sniffing-induced activity in adult female mice via decreased excitability of PV+ neurons and reduced synaptic inhibition in the OFCL Moreover, optogenetic activation of excitatory neurons or optogenetic inhibition of PV+ neurons in the OFCL enhanced sociability in female mice. Our data demonstrate that the adolescent social experience is critical for the maturation of PV+ inhibitory circuits in the OFCL; this maturation shapes female social behavior via enhancing social representation in the OFCL SIGNIFICANCE STATEMENT Adolescent social isolation often changes adult social behaviors in mammals. Yet, we do not fully understand the sex-specific effects of social isolation and the brain areas and circuits that mediate such changes. Here, we found that adolescent social isolation causes three abnormal phenotypes in female but not male mice: hypersociability, decreased PV+ neurons in the left orbitofrontal cortex (OFCL), and decreased socially evoked activity in the OFCL Moreover, parvalbumin (PV) deletion in the OFCL in vivo caused the same phenotypes in female mice by increasing excitation compared with inhibition within the OFCL Our data suggest that adolescent social experience is required for PV maturation in the OFCL, which is critical for evoking OFCL activity that shapes social behaviors in female mice.

Recent asymmetric synthesis of natural products bearing an α-tertiary amine moiety via temporary chirality induction strategies.

Covering: 2013 to 2023The α-tertiary amine moiety is a common structural motif in natural alkaloids and is frequently associated with intriguing biological activities and inherent synthetic challenges. A major hurdle in the total synthesis of these alkaloids is the asymmetric construction of the α-tertiary amine moiety. Temporary chirality inductions have been effective strategies employed to address this issue, particularly in natural product synthesis. The temporary chirality induction strategies in α-tertiary amine synthesis can be broadly classified into three categories based on the types of temporary chirality involved: Seebach's self-regeneration of stereocenters (SRS), C-to-N-to-C chirality transfer, and memory of chirality (MOC). This review highlights the recent advancements in temporary chirality induction strategies for the total synthesis of α-tertiary amine-containing natural products between 2013 and 2023.

Compact Solid Electrolyte Interface Realization Employing Surface-Modified Fillers for Long-Lasting, High-Performance All-Solid-State Li-Metal Batteries.

The implementation of polymer-based Li-metal batteries is hindered by their low coulombic efficiency and poor cycling stability attributed to continuous electrolyte decomposition. Enhancement of the solid electrolyte interface (SEI) stability is key to mitigating electrolyte decomposition. This study proposes surface-functionalized silica mesoball fillers to fabricate a composite polymer electrolyte (MSBM-CPE). As a result of surface modification, the polyethylene oxide matrix benefits from the uniform distribution of the filler, which provides a large surface area and Lewis acid sites. Molecular dynamics simulations reveal that the dissociation energy of lithium bis(trifluoromethanesulfonyl)imide in the filler is fourfold higher (-1.95 eV) than that of the filler-free electrolyte. Consequently, the MSMB-CPE diffusivity is 30 times higher than its filler-free counterpart. The MSMB-CPE of ionic conductivity of 1.16 × 10-2 S cm-1 @60 °C and a venerable Li-ion transference number of 0.81. The excellent compatibility of MSMB-CPE with the Li anode is demonstrated by its stable symmetric cell performance under high current density (200 µA cm-2 @60 °C) for over 5000 h. Approximately 85.60% retention capacity of the [Li/MSMB-CPE/LiFePO4] full cell after 700 cycles. Furthermore, compositional analysis reveals that the SEI layer in MSMB-CPE is smooth with fewer by-products at the electrolyte/Li interface.

Enhancing gadoxetic acid-enhanced liver MRI: a synergistic approach with deep learning CAIPIRINHA-VIBE and optimized fat suppression techniques.

OBJECTIVE: To investigate whether a deep learning (DL) controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-volumetric interpolated breath-hold examination (VIBE) technique can improve image quality, lesion conspicuity, and lesion detection compared to a standard CAIPIRINHA-VIBE technique in gadoxetic acid-enhanced liver MRI. METHODS: This retrospective single-center study included 168 patients who underwent gadoxetic acid-enhanced liver MRI at 3 T using both standard CAIPIRINHA-VIBE and DL CAIPIRINHA-VIBE techniques on pre-contrast and hepatobiliary phase (HBP) images. Additionally, high-resolution (HR) DL CAIPIRINHA-VIBE was obtained with 1-mm slice thickness on the HBP. Three abdominal radiologists independently assessed the image quality and lesion conspicuity of pre-contrast and HBP images. Statistical analyses involved the Wilcoxon signed-rank test for image quality assessment and the generalized estimation equation for lesion conspicuity and detection evaluation. RESULTS: DL and HR-DL CAIPIRINHA-VIBE demonstrated significantly improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE (p < 0.001), with a shorter acquisition time (DL vs standard, 11 s vs 17 s). However, the former presented a more synthetic appearance (both p < 0.05). HR-DL CAIPIRINHA-VIBE showed superior lesion conspicuity to standard and DL CAIPIRINHA-VIBE on HBP images (p < 0.001). Moreover, HR-DL CAIPIRINHA-VIBE exhibited a significantly higher detection rate of small (< 2 cm) solid focal liver lesions (FLLs) on HBP images compared to standard CAIPIRINHA-VIBE (92.5% vs 87.4%; odds ratio = 1.83; p = 0.036). CONCLUSION: DL and HR-DL CAIPIRINHA-VIBE achieved superior image quality compared to standard CAIPIRINHA-VIBE. Additionally, HR-DL CAIPIRINHA-VIBE improved the lesion conspicuity and detection of small solid FLLs. DL and HR-DL CAIPIRINHA-VIBE hold the potential clinical utility for gadoxetic acid-enhanced liver MRI. CLINICAL RELEVANCE STATEMENT: DL and HR-DL CAIPIRINHA-VIBE hold promise as potential alternatives to standard CAIPIRINHA-VIBE in routine clinical liver MRI, improving the image quality and lesion conspicuity, enhancing the detection of small (< 2 cm) solid focal liver lesions, and reducing the acquisition time. KEY POINTS: • DL and HR-DL CAIPIRINHA-VIBE demonstrated improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE, in addition to a shorter acquisition time. • DL and HR-DL CAIPIRINHA-VIBE yielded a more synthetic appearance than standard CAIPIRINHA-VIBE. • HR-DL CAIPIRINHA-VIBE showed improved lesion conspicuity than standard CAIPIRINHA-VIBE on HBP images, with a higher detection of small (< 2 cm) solid focal liver lesions.

Radiation Major Hepatectomy Using Ablative Dose Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma 5 cm or Larger.

PURPOSE: To evaluate the safety and effectiveness of ablative radioembolization for large hepatocellular carcinoma (HCC) while preserving a small future liver remnant (FLR). MATERIALS AND METHODS: Twenty-five patients with large HCC of ≥5 cm requiring treatment for >60% of the total liver volume and having well-preserved liver function were treated with ablative glass microsphere radioembolization at a single institution from January 2017 to December 2021. Radioembolization was performed with a mean absorbed dose of >150 Gy, and the FLR per nontumor liver volume (NTLV) was set at >30%. Changes in liver function, adverse events, duration of response (DoR) in a treated area, time-to-progression (TTP), and overall survival (OS) were retrospectively investigated. RESULTS: The largest tumor diameter and planned dose per treated volume were 11.4 cm ± 3.9 and 242.3 Gy ± 63.6 (169.4 Gy ± 45.9 per whole liver volume), respectively. All patients remained at Child-Pugh Class A for 90 days. No patient experienced Grade 3‒4 hyperbilirubinemia or new ascites. One patient (lung dose, 27.8 Gy) developed radiation pneumonitis requiring transient steroid treatment. According to the posttreatment dosimetry, the tumorous and nontumorous liver absorbed doses were 418.8 Gy ± 227.4 and 69.0 Gy ± 32.1, respectively. The median DoR in a treated area and TTP were 22.0 and 17.1 months, respectively. The 5-year OS rate was 83.2%. CONCLUSIONS: Ablative radioembolization of large HCC of ≥5 cm can be performed safely and effectively in patients with preserved liver function when FLR/NTLV exceeds 30%.

Syntheses of the ω-pyridinium-containing very-long-chain ceramides PyrCer(24:1(15Z)) and PyrCer(24:0) and their anticancer activity.

Ceramides, crucial sphingolipids in cellular biology, play various roles ranging from structural membrane integrity to signaling pathway regulation. Structurally, a ceramide consists of a fatty acid connected to a sphingoid base. The characteristics of the fatty acid chain, including length and saturation, determine the physiological properties of the ceramide. Ceramides typically fall into the following categories based on chain length: medium, long, very-long, and ultra-long. Among them, two very-long-chain ceramides, Cer(24:1(15Z)) and Cer(24:0), have been extensively studied, and they are known for their regulatory functions. However, the hydrophobic natures of ceramides, arising from their long hydrocarbon chain impedes their solubilities and levels of cellular delivery. Although ω-pyridinium ceramide analogs (ω-PyrCers) have been developed to address this issue, ω-PyrCers with very-long fatty acid chains or unsaturation have not been developed, presumably due to limited access to the corresponding ω-bromo fatty acids required in their syntheses. In this study, we prepared the ω-PyrCers of Cer(24:1(15Z)) and Cer(24:0), PyrCer(24:1(15Z)) and PyrCer(24:0), respectively. The key in the synthesis is the Wittig reaction to prepare the ω-bromo fatty acid with an appropriate chain length and (Z)-double bond position. Preliminary evaluation of the PyrCer(24:1(15Z)) and PyrCer(24:0) revealed their potential in hepatocellular carcinoma treatment.

Utility of abbreviated MRI in the post-treatment evaluation of rectal cancer.

BACKGROUND: Post-treatment evaluation of patients with rectal cancer (RC) using magnetic resonance imaging (MRI) burdens medical resources, necessitating an exploration of abbreviated protocols. PURPOSE: To evaluate the diagnostic performance of abbreviated MRI (A-MRI) for the post-treatment evaluation of RC patients. MATERIAL AND METHODS: This retrospective study included RC patients who underwent non-contrast rectal MRI and standard liver MRI, as well as abdominal contrast-enhanced computed tomography (CECT) for post-treatment evaluation. A-MRI comprised diffusion-weighted imaging (DWI) and T2-weighted imaging of the upper abdomen and the pelvic cavity. Three radiologists independently reviewed A-MRI, CECT, and standard liver MRI in the detection of viable disease. The diagnostic performances were compared using a reference standard considering all available information, including pathology, FDG-PET, endoscopic results, and clinical follow-up. RESULTS: We included 78 patients (50 men, 28 women; mean age=60.9 ± 10.2 years) and observed viable disease in 34 (43.6%). On a per-patient-basis analysis, A-MRI showed significantly higher sensitivity (95% vs. 81%, P = 0.04) and higher accuracy (93% vs. 82%, P < 0.01), compared to those of CECT, while A-MRI showed comparable sensitivity (91% vs. 91%, P = 0.42) and accuracy (97% vs. 98%, P = 0.06) to that of standard liver MRI. On a per-lesion-based analysis, A-MRI exhibited significantly superior lesion detectability than that of CECT (figure of merit 0.91 vs. 0.77, P < 0.01) and comparable to that of standard liver MRI (figure of merit 0.91 vs. 0.92, P = 0.75). CONCLUSION: A-MRI exhibited higher sensitivity and diagnostic accuracy than those of CECT in the post-treatment evaluation of RC, while it showed comparable performances with standard liver MRI. A-MRI provides diagnostic added value in the follow-up of RC patients.

Risk of Cerebral Aneurysm Rupture After Liver Transplantation: Development and Validation of a Hemorrhagic Stroke Scoring Model.

BACKGROUND: Liver transplantation (LT) patients appear to be more prone to neurological events compared to individuals undergoing other types of solid-organ transplantation. The aims of the present study were to analyze the prevalence of unruptured intracranial aneurysms (UIAs) in patients undergoing liver transplantation (LT) and to examine the perioperative occurrence of subarachnoid hemorrhage (SAH). Also, it intended to systematically identify the risk factors of SAH and hemorrhagic stroke (HS) within a year after LT and to develop a scoring system which involves distinct clinical features of LT patients. METHODS: Patients who underwent LT from January 2012 to March 2022 were analyzed. All included patients underwent neurovascular imaging within 6 months before LT. We conducted an analysis of prevalence and radiological features of UIA and SAH. The clinical factors that may have an impact on HS within one year of LT were also reviewed. RESULTS: Total of 3,487 patients were enrolled in our study after applying inclusion and exclusion criteria. The prevalence of UIA was 5.4%. The incidence of SAH and HS within one year following LT was 0.5% and 1.6%, respectively. We developed a scoring system based on multivariable analysis to predict the HS within 1-year after LT. The variables were a poor admission mental status, the diagnosis of UIA, serum ammonia levels, and Model for End-stage Liver Disease (MELD) scores. Our model showed good discrimination among the development (C index, 0.727; 95% confidence interval [CI], 0.635-0.820) and validation (C index, 0.719; 95% CI, 0.598-0.801) cohorts. CONCLUSION: The incidence of UIA and SAH was very low in LT patients. A poor admission mental status, diagnosis of UIA, serum ammonia levels, and MELD scores were significantly associated with the risk of HS within one year after LT. Our scoring system showed a good discrimination to predict the HS in LT patients.

Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder.

AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.

Impact of Additive Manufacturing Materials on Thermal Performance of Silicon Reference Cells.

Additive manufacturing, or 3D printing, is quickly becoming a widespread manufacturing method offering timely and cost-effective build times for unique part geometries with an increasing range of material offerings. One unique use for additive manufacturing is constructing the housing for reference solar cells, which are crucial instruments for evaluating the electrical performance of photovoltaic solar cells and modules. These instruments, which require good thermal conduction, are costly to manufacture because they are usually machined from aluminum using precision milling machines. In this work, we set out to evaluate several presently available additive manufacturing materials for their thermal properties when used to house reference solar cells. We fabricated several types of reference cell instruments with a tabletop, filament-based 3D printer using polylactic acid (PLA) and composite PLA/metal materials with different infill percentages. Furthermore, we fabricated several all-metal 3D printed reference cells using a binder jet printed stainless steel-bronze material blend and compared the thermal properties of all 3D printed instruments against a standard aluminum housing reference cell. Measurements included temperature monitoring of an embedded thermocouple sensor on an isothermal plate under the ambient environment and when exposed to high irradiation under a solar simulator. Current vs voltage measurements were also taken under the solar simulator and the open circuit voltage results were used to verify the actual silicon cell temperature. Our findings indicate that the stainless steel-bronze option can function well as an alternative to traditional aluminum-based housings, while the lower-cost metal-PLA composite can only be used under indoor light spectra or when used in a flash-type solar simulator when the instrument is not exposed to excessive radiation and heat.

Association between Perceived Activity Restriction Due to People's Perception of Aging and Unmet Medical Needs among Middle-Aged and Elderly People: A Population-Based Study.

Background and Objectives: The older members of a population might experience unmet medical needs, despite desiring medical care due to activity limitations driven by their perception of aging. This study conducted a cross-sectional analysis of the association between perceived activity restriction (PAR) due to people's own perception of aging and unmet medical needs (UMN) in late middle-aged and older Koreans based on the Korean National Health and Nutrition Examination Survey (KNHANES). Materials and Methods: The 2016-2020 KNHANES was used to analyze a total of 2008 participants among groups aged 45 years or older by applying individual weights imposed from the raw data. The independent variable of PAR was assessed using self-reported questionnaires based on the global activity limitation indicator. Also, the dependent variable of UMN, referring to the state in which a patient's medical care or service was insufficient, inadequate, or lacking, was assessed using a single question. After excluding missing values, the data on 2008 individuals were analyzed using a chi-square test, weighted logistic regression, and a stratified analysis of gender, age, and the presence of chronic illnesses. Results: The group that experienced PAR had an OR 2.13 higher (odds ratio [OR]: 2.13; 95% confidence interval [CI]: 1.27-3.56) to present UMN than the group that did not experience PAR. Furthermore, the results of the stratified analysis indicated that, in the group of female participants with chronic illness and in the group of elderly people, experiencing PAR was associated with a higher experience of UMN. Conclusions: There was a close association between PAR and UMN. In particular, when PAR occurred in the group of female participants with chronic illness and in the group of elderly people, the incidence rate of UMN was also found to be high. This finding highlights the need for policies and institutional measures to reduce UMN within vulnerable groups with an increased risk of medical inaccessibility due to activity restriction.

Effect of intensity of persistent social isolation on mental health in the late middle-aged and older population: results of the Korea Longitudinal Study of Ageing (2006-2020).

BACKGROUND: Social isolation (SI) was recently identified as a significant public health issue in the United States. Consequently, several studies on the association between SI and mental health were conducted. However, few studies have considered the duration and intensity of SI. In the present study, a longitudinal analysis was conducted to determine the effect of the intensity of persistent SI on the mental health status of late middle-aged and older Koreans. METHODS: After excluding missing values, data on 6200 participants were analyzed using the group-based trajectory model (GBTM) from the first to fifth Korean Longitudinal Study of Ageing (KLoSA) to categorise the SI trajectory (SIT). The Chi-square test, t-test, analysis of variance, and time-lagged generalised estimation equations were utilised from the fifth to eighth KLoSA to determine the association between SIT and the incidence of cognitive decline (the group with a Korean version Mini-Mental State Examination score of 23 or lower), cognitive function score, and depression score. RESULTS: Four SIT groups were identified in the GBTM analysis. These were the non-SIT (21.7%), mild (46.8%), moderate (21.1%), and severe SIT (10.4%) groups. Compared to the non-SIT group, the severe SIT group experienced a greater incidence of cognitive decline (odds ratio = 1.57, P < 0.0001) as well as poorer cognitive function scores (B = -0.63, P < 0.0001) and depression scores (B = 0.90, P < 0.0001). Furthermore, stratified analysis by sex and age showed that mental health status was inversely proportionate to the intensity of SIT, particularly in males and patients, aged 65 years and above. CONCLUSION: A close association was observed between SIT and mental health. This finding highlighted the need for policies and institutional measures to reduce the incidence of mental health deterioration among vulnerable groups due to the intensity of SI.

Alicyclic-Amine-Derived Imine-BF3 Complexes: Easy-to-Make Building Blocks for the Synthesis of Valuable α-Functionalized Azacycles.

A new strategy to access α-functionalized alicyclic amines via their corresponding imine-BF3 complexes is reported. Isolable imine-BF3 complexes, readily prepared via dehydrohalogenation of N-bromoamines in a base-promoted/18-crown-6 catalyzed process followed by addition of boron trifluoride etherate, undergo reactions with a wide range of organometallic nucleophiles to afford α-functionalized azacycles. Organozinc and organomagnesium nucleophiles add at ambient temperatures, obviating the need for cryogenic conditions. In situ preparation of imine-BF3 complexes provides access to α-functionalized morpholines and piperazines directly from their parent amines in a single operation. α-Functionalized morpholines can be elaborated further, for instance by installing a second substituent in the α'-position.

Polymer-Grafted, Gold Nanoparticle-Based Nano-Capsules as Reversible Colorimetric Tensile Strain Sensors.

Colloidal colorimetric microsensors enable the in-situ detection of mechanical strains within materials. Enhancing the sensitivity of these sensors to small scale deformation while enabling reversibility of the sensing capability would expand their utility in applications including biosensing and chemical sensing. In this study, we introduce the synthesis of colloidal colorimetric nano-sensors using a simple and readily scalable fabrication method. Colloidal nano sensors are prepared by emulsion-templated assembly of polymer-grafted gold nanoparticles (AuNP). To direct the adsorption of AuNP to the oil-water interface of emulsion droplets, AuNP (≈11nm) are functionalized with thiol-terminated polystyrene (PS, Mn  = 11k). These PS-grafted gold nanoparticles are suspended in toluene and subsequently emulsified to form droplets with a diameter of ≈30µm. By evaporating the solvent of the oil-inwater emulsion, we form nanocapsules (AuNC) (diameter < 1µm) decorated by PS-grafted AuNP. To test mechanical sensing, the AuNC are embedded in an elastomer matrix. The addition of a plasticizer reduces the glass transition temperature of the PS brushes, and in turn imparts reversible deformability to the AuNC. The plasmonic peak of the AuNC shifts towards lower wavelengths upon application of uniaxial tensile tension, indicating increased inter-nanoparticle distance, and reverts back as the tension is released.

High-resolution MR imaging with gadoxetate disodium for the comprehensive evaluation of potential living liver donors.

Several major transplantation centers have used composite multimodality evaluation for the preoperative evaluation of potential living liver donors. This approach can be time-consuming and, although rare, can cause complications. We aimed to demonstrate the clinical feasibility of our comprehensive preoperative MR protocol for the preoperative assessment of living liver donor candidates instead of composite multimodality evaluation. Thirty-five consecutive living liver donor candidates underwent multiphasic liver CT and comprehensive donor protocol MR examinations for preoperative evaluation in a single large-volume liver transplantation (LT) center. Three blinded abdominal radiologists reviewed the CT and MR images for vascular and biliary variations. The strength of agreement between CT and MR angiography was assessed using the kappa index. The detection rate of biliary anatomical variations was calculated. The sensitivity and specificity for detecting significant steatosis (>5%) were calculated. The estimated total volume and right lobe volumes measured by MR volumetry were compared with the corresponding CT volumetry measurements using the intraclass correlation coefficient (ICC). Among the 35 patients, 26 underwent LT. The measurement of agreement showed a moderate to substantial agreement between CT and MR angiography interpretations (kappa values, 0.47-0.79; p < 0.001). Combining T2-weighted and T1-weighted MR cholangiography techniques detected all biliary anatomical variations in 9 of the 26 patients. MR-proton density fat fraction showed a sensitivity of 100% (3/3) and a specificity of 91.3% (21/23) for detecting pathologically determined steatosis (>5%). MR volumetry reached an excellent agreement with CT volumetry (reviewers 1 and 2: ICC, 0.92; 95% CI, 0.84-0.96). Our one-stop comprehensive liver donor MR imaging protocol can provide complete information regarding hepatic vascular and biliary anatomies, hepatic parenchymal quality, and liver volume for living liver donor candidates and can replace composite multimodality evaluation.

Proteomic analysis predicts anti-angiogenic resistance in recurred glioblastoma.

BACKGROUND: Recurrence is common in glioblastoma multiforme (GBM) because of the infiltrative, residual cells in the tumor margin. Standard therapy for GBM consists of surgical resection followed by chemotherapy and radiotherapy, but the median survival of GBM patients remains poor (~ 1.5 years). For recurrent GBM, anti-angiogenic treatment is one of the common treatment approaches. However, current anti-angiogenic treatment modalities are not satisfactory because of the resistance to anti-angiogenic agents in some patients. Therefore, we sought to identify novel prognostic biomarkers that can predict the therapeutic response to anti-angiogenic agents in patients with recurrent glioblastoma. METHODS: We selected patients with recurrent GBM who were treated with anti-angiogenic agents and classified them into responders and non-responders to anti-angiogenic therapy. Then, we performed proteomic analysis using liquid-chromatography mass spectrometry (LC-MS) with formalin-fixed paraffin-embedded (FFPE) tissues obtained from surgical specimens. We conducted a gene-ontology (GO) analysis based on protein abundance in the responder and non-responder groups. Based on the LC-MS and GO analysis results, we identified potential predictive biomarkers for anti-angiogenic therapy and validated them in recurrent glioblastoma patients. RESULTS: In the mass spectrometry-based approach, 4957 unique proteins were quantified with high confidence across clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic patterns (n = 269 proteins) between responders and non-responders. The GO term enrichment analysis revealed a cluster of genes related to immune cell-related pathways (e.g., TMEM173, FADD, CD99) in the responder group, whereas the non-responder group had a high expression of genes related to nuclear replisome (POLD) and damaged DNA binding (ERCC2). Immunohistochemistry of these biomarkers showed that the expression levels of TMEM173 and FADD were significantly associated with the overall survival and progression-free survival of patients with recurrent GBM. CONCLUSIONS: The candidate biomarkers identified in our protein analysis may be useful for predicting the clinical response to anti-angiogenic agents in patients with recurred GBM.

Photolithographic patterning on multi-wavelength quantum dot film of the improved conversion efficiency for digital holography.

A triple-wavelength patterned quantum dot film was fabricated for the light source of digital holography to improve both the axial measurement range and noise reduction. The patterned quantum dot film was fabricated after optimizing the photolithography process condition based on the UV-curable quantum dot solution, which was capable of multiple patterning processes. In addition, an optimized pattern structure was developed by adding TiO2 nanoparticles to both the quantum dot and bank layers to increase the scattering effect for the improved photoluminescence intensity. Finally, the newly developed light source with the balanced spectral distribution was applied to the digital holography, rendering it applicable as an improved light source.

Non-coding de novo mutations in chromatin interactions are implicated in autism spectrum disorder.

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD). We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions. Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development. Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.