A Review of Multi-Modal Learning from the Text-Guided Visual Processing Viewpoint.

For decades, co-relating different data domains to attain the maximum potential of machines has driven research, especially in neural networks. Similarly, text and visual data (images and videos) are two distinct data domains with extensive research in the past. Recently, using natural language to process 2D or 3D images and videos with the immense power of neural nets has witnessed a promising future. Despite the diverse range of remarkable work in this field, notably in the past few years, rapid improvements have also solved future challenges for researchers. Moreover, the connection between these two domains is mainly subjected to GAN, thus limiting the horizons of this field. This review analyzes Text-to-Image (T2I) synthesis as a broader picture, Text-guided Visual-output (T2Vo), with the primary goal being to highlight the gaps by proposing a more comprehensive taxonomy. We broadly categorize text-guided visual output into three main divisions and meaningful subdivisions by critically examining an extensive body of literature from top-tier computer vision venues and closely related fields, such as machine learning and human-computer interaction, aiming at state-of-the-art models with a comparative analysis. This study successively follows previous surveys on T2I, adding value by analogously evaluating the diverse range of existing methods, including different generative models, several types of visual output, critical examination of various approaches, and highlighting the shortcomings, suggesting the future direction of research.

Characterization of early postzygotic somatic mutations through multi-organ analysis.

Mosaicisms caused by postzygotic mutational events are of increasing interest because of their potential association with various human diseases. Postzygotic somatic mutations have not been well characterized however in terms of their developmental lineage in humans. We conducted whole-genome sequencing (WGS) and targeted deep sequencing in 15 organs across three developmental lineages from a single male fetus with polycystic kidney disease (PKD) of 21 weeks gestational age. This fetus had no detectable neurological abnormalities at autopsy but germline mutations in the PKHD1 gene were identified that may have been associated with the PKD. Eight early embryonic mosaic variants with no alteration of protein function were detected. These variants were thought to have occurred at the two or four cell stages after fertilization with a mutational pattern involving frequent C>T and T>C transitions. In our current analyses, no tendency toward organ-specific mutation occurrences was found as the eight variants were detected in all 15 organs. However different allele fractions of these variants were found in different organs, suggesting a tissue-specific asymmetric growth of cells that reflected the developmental germ layer of each organ. This indicated that somatic mutation occurrences, even in early embryogenesis, can affect specific organ development or disease. Our current analyses demonstrate that multi-organ analysis is helpful for understanding genomic mosaicism. Our results also provide insights into the biological role of mosaicism in embryonic development and disease.

Immunogenomic landscape of hepatocellular carcinoma with immune cell stroma and EBV-positive tumor-infiltrating lymphocytes.

BACKGROUND & AIMS: The immunogenomic characteristics of hepatocellular carcinomas (HCCs) with immune cell stroma (HCC-IS), defined histologically, have not been clarified. We investigated the clinical and molecular features of HCC-IS and the prognostic impact of Epstein-Barr virus (EBV) infection. METHODS: We evaluated 219 patients with conventional HCC (C-HCC) and 47 with HCC-IS using in situ hybridization for EBV, immunohistochemistry, multiplex immunofluorescence staining, and whole exome and transcriptome sequencing. Human leukocyte antigen types were also extracted from the sequencing data. Genomic and prognostic parameters were compared between HCC-IS and C-HCC. RESULTS: CD8 T cell infiltration was more frequent in HCC-IS than C-HCC (mean fraction/sample, 22.6% vs. 8.9%, false discovery rate q <0.001), as was EBV positivity in CD20-positive tumor-infiltrating lymphocytes (TILs) (74.5% vs. 4.6%, p <0.001). CTNNB1 mutations were not identified in any HCC-IS, while they were present in 24.1% of C-HCC (p = 0.016). Inhibitory and stimulatory immune modulators were expressed at similar levels in HCC-IS and EBV-positive C-HCC. Global hypermethylation, and expression of PD-1 and PD-L1 in TILs, and PD-L1 in tumors, were also associated with HCC-IS (p <0.001), whereas human leukocyte antigen type did not differ according to HCC type or EBV positivity. HCC-IS was an independent factor for favorable recurrence-free survival (adjusted hazard ratio [aHR] 0.23; p = 0.002). However, a subgroup of tumors with a high density of EBV-positive TILs had poorer recurrence-free (aHR 25.48; p <0.001) and overall (aHR 9.6; p = 0.003) survival, and significant enrichment of CD8 T cell exhaustion signatures (q = 0.0296). CONCLUSIONS: HCC-IS is a distinct HCC subtype associated with a good prognosis and frequent EBV-positive TILs. However, paradoxically, a high density of EBV-positive TILs in tumors is associated with inferior prognostic outcomes. Patients with HCC-IS could be candidates for immunotherapy. LAY SUMMARY: Hepatocellular carcinomas with histologic evidence of abundant immune cell infiltration are characterized by frequent activation of Epstein-Barr virus in tumor-infiltrating lymphocytes and less aggressive clinical behavior. However, a high density of Epstein-Barr virus-positive tumor-infiltrating lymphocytes is associated with inferior prognostic outcomes, possibly as a result of immune escape due to significant CD8 T cell exhaustion.

Analysis of Flow Characteristics between Tandem Flexible Structures Based on PIV: Substantial Applications for the Removal of Microplastics.

This study emphasizes the potential risk posed by microplastics, particularly in tap water. Numerous studies have reported the removal of microplastics, but the limitations in addressing this issue remain challenging. To tackle this problem, a new method is introduced using tandem flexible structures (FSs) for microplastic removal. The present study focused on understanding the hydrodynamic characteristics between FSs to utilize microplastic removal. This comprehension of fluid flow and FSs offers valuable insights for improving the efficiency of microplastic removal methods. Therefore, the optimal conditions for removing microplastics were experimentally investigated inside the FSs gap region. Based on the gap distance and height, the flow structures between FSs were investigated. A small secondary vortex structure that could trap particles from upstream was continuously maintained behind the upstream FSs under certain geometric conditions. It is shown that this vortex structure has an effective way of confining the particles from upstream. The persistency of a small secondary vortex was also evaluated. This study may be helpful to researchers working on microplastic removal and FSs with a tandem arrangement.

ELOVL2-AS1 suppresses tamoxifen resistance by sponging miR-1233-3p in breast cancer.

Tamoxifen (Tam) has long been a top treatment option for breast cancer patients, but the challenge of eliminating cancer recurrence remains. Here, we identify a signalling pathway involving ELOVL2, ELOVL2-AS1, and miR-1233-3p, which contributes to drug resistance in Tam-resistant (TamR) breast cancer. ELOVL2-AS1, a long noncoding RNA, was significantly upregulated by its antisense gene, ELOVL2, which is known to be downregulated in TamR cells. Additionally, ELOVL2-AS1 underwent the most hypermethylation in MCF-7/TamR cells. Furthermore, patients with breast cancer who developed TamR during chemotherapy had significantly lower expression of ELOVL2-AS1 compared to those who responded to Tam. Ectopic downregulation of ELOVL2-AS1 by siRNA both stimulated cancer cell growth and deteriorated TamR. We also found that ELOVL2-AS1 sponges miR-1233-3p, which has pro-proliferative activity and elevates TamR, leading to the activation of potential target genes, such as MYEF2, NDST1, and PIK3R1. These findings suggest that ELOVL2-AS1, in association with ELOVL2, may contribute to the suppression of drug resistance by sponging miR-1233-3p in breast cancer.

Learning-Based Ordering Characters on Ancient Document.

Digitalizing and translating a scanned document image entails detecting the characters using a detector and translating the characters in the order they were detected with a translator. However, it is impossible to translate these characters correctly because the detector often detects them in any order. As a result, since it is critical to organize the recognized characters for proper translation, we propose ordering characters from documents with multiple variations using the strength of the learning-based model that learns the necessary operations from the data. In this task, it is difficult to order the characters written on antique handwritten documents that have deviations such as a bent or split line, as opposed to official records that have lines placed uprightly one by one. Because dealing with these many variants using a human-designed algorithm is problematic, we arrange characters printed on papers with diverse variations by taking advantage of a training model that can learn the appropriate function from data. Our method outputs both line id and y-axis and combines them to assign the sequential index. It is difficult to train using simply local regions because sequential character indexes in a large range include long-range dependencies. To solve this problem, we use network architecture to expand the receptive field as wide as possible. The network must learn to give various indexes to characters in similar places for each document because the number and area of characters vary for each document. We offer the ground truth assign method based on the absolute position to assign similar indexes to characters in similar places. Furthermore, even if the network uses absolute ground truth, the network may assign the incorrect line if the center coordinates of characters are biased in one direction. As a result, we employed the Region of Interest (ROI) from the pretrained coordinate layer, which contains position and trend information. We used the modified edit distance to compare the similarity of character indexes from the ground truth and our technique. In addition, we computed the modified fisher criterion to assess the degree of the clustering line. Consequently, our edit distance is just 0.43 times that of the human-designed algorithm, and our fisher criterion is 1.46 times that of the human-designed algorithm, improving the performance of human-designed algorithm.

Immuno-genomic classification of colorectal cancer organoids reveals cancer cells with intrinsic immunogenic properties associated with patient survival.

BACKGROUND: The intrinsic immuno-ge7nomic characteristics of colorectal cancer cells that affect tumor biology and shape the tumor immune microenvironment (TIM) are unclear. METHODS: We developed a patient-derived colorectal cancer organoid (CCO) model and performed pairwise analysis of 87 CCOs and their matched primary tumors. The TIM type of the primary tumor was classified as immuno-active, immuno-exhausted, or immuno-desert. RESULTS: The gene expression profiles, signaling pathways, major oncogenic mutations, and histology of the CCOs recapitulated those of the primary tumors, but not the TIM of primary tumors. Two distinct intrinsic molecular subgroups of highly proliferative and mesenchymal phenotypes with clinical significance were identified in CCOs with various cancer signaling pathways. CCOs showed variable expression of cancer-specific immune-related genes such as those encoding HLA-I and HLA-II, and molecules involved in immune checkpoint activation/inhibition. Among these genes, the expression of HLA-II in CCOs was associated with favorable patient survival. K-means clustering analysis based on HLA-II expression in CCOs revealed a subgroup of patients, in whom cancer cells exhibited Intrinsically Immunogenic Properties (Ca-IIP), and were characterized by high expression of signatures associated with HLA-I, HLA-II, antigen presentation, and immune stimulation. Patients with the Ca-IIP phenotype had an excellent prognosis, irrespective of age, disease stage, intrinsic molecular type, or TIM status. Ca-IIP was negatively correlated with intrinsic E2F/MYC signaling. Analysis of the correlation between CCO immuno-genotype and TIM phenotype revealed that the TIM phenotype was associated with microsatellite instability, Wnt/ß-catenin signaling, APC/KRAS mutations, and the unfolded protein response pathway linked to the FBXW7 mutation in cancer cells. However, Ca-IIP was not associated with the TIM phenotype. CONCLUSIONS: We identified a Ca-IIP phenotype from a large set of CCOs. Our findings may provide an unprecedented opportunity to develop new strategies for optimal patient stratification in this era of immunotherapy.

T cell receptor repertoires of ex vivo-expanded tumor-infiltrating lymphocytes from breast cancer patients.

A higher level of tumor-infiltrating lymphocytes (TILs) is associated with better prognosis in breast cancer patients. Adoptive transfer of lymphocytes coupled with conventional therapies has appealed to many clinicians and investigators as an effective treatment strategy for cancer patients, which necessitates efficient activation and expansion of cytotoxic T lymphocytes precisely targeting cancer cells. To comprehensively understand composition of TILs and to provide a grounding in adoptive T cell therapy, we analyzed the T cell receptor (TCR) repertoires in ex vivo-expanded TILs from nine breast cancer patients via next-generation sequencing. For the three of them, TCR repertoires of TILs gathered after the initial culture during 2 weeks were additionally analyzed and compared to those of TILs that underwent ex vivo rapid expansion procedure (REP). Diversity of TCR repertoire was variable among the patients. V/J segment usage in the clonotypes was similar among patients, with variable distribution of read counts for each V/J segment. The top 50% of most frequently observed VJ combinations was present in > 80% of the total clonotypes. Compared with TCGA data, the samples contained a similar amount of recurrent CDR3 sequences, but clonotype expansion was variable among the samples. In terms of clinicopathologic factor, presence of in vitro reactivity among triple-negative breast cancer cases seemed to be related to lower Shannon's index, but p value was not statistically significant. In addition, the proportion of CD45RO+ cells out of CD8+ T cells were negatively correlated with Shannon's diversity index for both TCRα and TCRß chains (p = 0.010) via Spearman test. In this study, we identified a heterogeneous pattern of expanded T cell clones and stable usage of V/J segments in ex vivo-expanded TILs from breast cancer patients. Further large-scale studies are requisite to elucidate the clinical significance of TCR repertoires.

Advantage of the go/no-go task over the yes/no lexical decision task: ERP indexes of parameters in the diffusion model.

Previous research findings supporting the advantages of the go/no-go choice over the yes/no choice in lexical decision task (LDT) have suggested that the go/no-go choice might require less cognitive resources in the non-decisional processes. This study aims to test such an idea using the event-related potential method. In this study, the tasks (yes/no LDT and go/no-go LDT) and word frequency (high and low) were manipulated, and the difference between the go/no-go choice and yes/no choice were examined with BP, pN, pN1, P200, N400, and P3 components that were assumed to be closely related with the various parameters in the diffusion model. The results showed that BP, pN and pN1 amplitudes reflecting the preparation stage were not differently affected by word frequency and the task type. However, ERPs after stimulus onset showed differences. The P200 amplitudes were smaller in the go/no-go task than in the yes/no task only for low-frequency words. N400 and P3 amplitudes were only affected by word frequency. The results suggest that the go/no-go task and the yes/no task differ in sub-lexical processes, which is indicated in the Tencoding parameter in the diffusion model. This study is important as it offers the first electrophysiological evidence supporting the assumption in the diffusion model that explains the advantage of the go/no-go choice over the yes/no choice.

Retained or altered expression of major histocompatibility complex class I in patient-derived xenograft models in breast cancer.

The expression of major histocompatibility complex class I (MHC I) in tumor cells is regulated by interferon signaling, and it is an important factor in the efficacy of cytotoxic T cell-dependent immunotherapy. To determine the impact of immune cells in MHC I expression on tumor cells, we compared the expression of MHC I in tumor cells derived from primary breast cancers and patient-derived xenograft (PDX) models. MHC I and myxovirus resistance gene A (MxA) expression were analyzed using immunohistochemistry in 23 cases of tumor tissue and corresponding primary and secondary PDXs. The median H score of MHC I was 210 (0-300) in patient tumor tissues, 197.5 (0-300) in primary PDX tumors, and 157.5 (5-300) in secondary PDX tumors. Cases were divided into four groups based on the difference in MHC I expression between the patient tumor tissues and secondary PDXs. Eleven cases constituted the high MHC I group, four constituted the low MHC I group, six comprised the decreased MHC I group, and two comprised the increased MHC I group. MHC I and MxA expressions in each tumor were weakly correlated within patients' tumors, while strongly correlated within PDX models. Retained or altered expression of MHC I in breast cancer PDXs reveals the presence of intrinsic and extrinsic interferon signaling pathways in tumor cells. Thus, considering MHC I expression in PDX is important when using PDX models to evaluate the efficacy of cancer immunotherapy in a preclinical setting.

Language and False-Belief Task Performance in Children With Autism Spectrum Disorder.

Purpose: Language is related to false-belief (FB) understanding in both typically developing children and children with autism spectrum disorder (ASD). The current study examined the role of complementation and general language in FB understanding. Of interest was whether language plays similar or different roles in the groups' FB performance. Method: Participants were 16 typically developing children (mean age = 5.0 years; mental age = 6.7) and 18 with ASD (mean age = 7.3 years; mental age = 8.3). Children were administered FB and language tasks (say- and think-complements), receptive and expressive vocabulary tests, and relative clauses. Results: When mental age and receptive and expressive vocabulary were used as separate covariates, the typical control group outperformed the children with ASD in FB task performance. Chi-square analyses indicated that passing both complementation tasks was linked to the FB understanding of children with ASD. Children with ASD who passed FB tasks all passed say- and think-complement tasks. However, some children in the control group were able to pass the FB tasks, even if they failed the say- and think-complement tasks. Conclusion: The results indicate that children with ASD relied more on complement understanding to pass FB than typically developing children. Results are discussed regarding the developmental pathways for FB understanding.

Visible Light-Triggered On-Demand Drug Release from Hybrid Hydrogels and its Application in Transdermal Patches.

On-demand release from stimuli-responsive hydrogels has received great attention due to an increasing clinical need. Here, we have prepared spherical hydrogel beads showing visible light-induced volume change at body temper-ature. By spray injection of the monomer solution using the alginate templ-ating method, hybrid beads of several hundred micrometers, consisting of temperature-responsive poly(N-isopropylacrylamide-co-vinyl-2-pyrrolidinone) hydrogel and magnetite nanoparticles (MNP), are produced. MNP dispersed in the hydrogel matrix absorbed visible light and generated heat, increasing the temperature of the matrix and resulting in shrinkage of the beads proportional to light intensity. It is demonstrated that light-induced volume change of dexamethasone-loaded hybrid beads result in on-demand and localized release of the drug by exposure to moderate visible light. As a potential application of the light-sensitive hybrid hydrogel beads, a transdermal patch is developed that incorporates drug-loaded hydrogel beads in multiple drug reservoirs, achieving enhanced release of a model drug when exposed to visible light. This platform should be applicable to on-demand, sequential, and long-term release of drugs via light exposure.

Examination of the Korean Modified Checklist of Autism in Toddlers: Item Response Theory.

The study examined the clinical utility and psychometric properties of the Korean Modified Checklist of Autism in Toddlers (K-M-CHAT)-2. A sample of 2300 parents of 16- to 36-month-old children was recruited across South Korea. A phone interview was utilized to follow up with participants who initially screened positive for autism spectrum disorder (ASD). Item response theory was applied to assess the psychometric properties of the K-M-CHAT-2. Parents' responses were substantially changed after the follow-up, and the final screen-positive rate was 2.3 %. Results indicated that the psychometric properties of items 1, 3, 11, 18 and 22 were not as strong as the other items. The K-M-CHAT-2 is a useful ASD screening test when implemented with a follow-up.

Photothermally triggered fast responding hydrogels incorporating a hydrophobic moiety for light-controlled microvalves.

Iron oxide nanoparticles dispersed within a thermally responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel matrix effectively convert the photo energy of visible light of modest intensity into thermal energy, providing the efficient means to trigger changes in volumetric swelling of hydrogels. However, long irradiation time (on the order of minutes) and modest volume change limit their applications that need fast response and/or large volume change. In this work, we found that the degree of volume change triggered by light could be maximized by adjusting the lower critical solution temperature (LCST) of the hydrogels. On the basis of the evidence in this investigation, we can develop highly responsive hydrogels that show rapid and significant light-induced volume change, which could be achieved by incorporating a hydrophobic N,N-diethylacrylamide moiety in the PNIPAm network. This enhanced responsiveness led to the successful application of this material in a remote-controllable microvalve for microfluidic devices operated by light illumination within a few seconds.

Anthocyanin compositions and biological activities from the red petals of Korean edible rose (Rosa hybrida cv. Noblered).

The objectives of the present study were to investigate anthocyanin profiles and their biological properties, including antioxidant, anticancer, and antiallergic, from the red petals of Korean edible rose (Rosa hybrida cv. Noblered). The acidic methanol extract of this species showed potent biological activities at a concentration of 50µg/mL. Its anthocyanins were characterised as cyanidin 3,5-di-O-glucoside and pelargonidin 3,5-di-O-glucoside using reversed-phase C18 column chromatography, NMR spectroscopy, and HPLC-DAD-ESI/MS analysis. Cyanidin 3,5-di-O-glucoside was the predominant constituent (375mg/100g), representing about 85% of total content. Cyanidin 3,5-di-O-glucoside exhibited good scavenging activity against DPPH radical with IC50 value of 55.2µg/mL; pelargonidin 3,5-di-O-glucoside showed potent anticancer effects against LNCap (human prostate cell line), ACHN (human renal cell line) and MOLT-4F (human leukaemia cell line) cell cultures, with IC50 values of 6.43, 18.3, and 6.78µg/mL, respectively. Antiallergic activities were only moderate.