Histopathological growth pattern and vessel co-option in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) exhibits different blood imaging features and prognosis depending on histology. To clarity histopathological growth patterns (HGPs) and vascularization processes of iCCA, we collected 145 surgical specimens and histologically classified them into large bile duct (LBD) (20 cases), small bile duct (SBD) (54), cholangiolocarcinoma (CLC) (35), combined SBD-CLC (cSBD-CLC) (26), and ductal plate malformation (DPM) (10) (sub)types. According to the invasive pattern at the interface between tumor and adjacent background liver, HGPs were classified into desmoplastic, pushing, and replacing HGPs. Desmoplastic HGP predominated in LBD type (55.5%), while replacing HGP was common in CLC (82.9%) and cSBD-CLC (84.6%) subtypes. Desmoplastic HGP reflected angiogenesis, while replacing HGP showed vessel co-option in addition to angiogenesis. By evaluating microvessel density (MVD) using vascular markers, ELTD1 identified vessel co-option and angiogenesis, and ELTD1-positive MVD at invasive margin in replacing HGP was significantly higher than those in desmoplastic and pushing HGPs. REDD1, an angiogenesis-related marker, demonstrated preferably higher MVD in the tumor center than in other areas. iCCA (sub)types and HGPs were closely related to vessel co-option and immune-related factors (lymphatic vessels, lymphocytes, and neutrophils). In conclusion, HGPs and vascular mechanisms characterize iCCA (sub)types and vessel co-option linked to the immune microenvironment.

AMRomics: a scalable workflow to analyze large microbial genome collections.

Whole genome analysis for microbial genomics is critical to studying and monitoring antimicrobial resistance strains. The exponential growth of microbial sequencing data necessitates a fast and scalable computational pipeline to generate the desired outputs in a timely and cost-effective manner. Recent methods have been implemented to integrate individual genomes into large collections of specific bacterial populations and are widely employed for systematic genomic surveillance. However, they do not scale well when the population expands and turnaround time remains the main issue for this type of analysis. Here, we introduce AMRomics, an optimized microbial genomics pipeline that can work efficiently with big datasets. We use different bacterial data collections to compare AMRomics against competitive tools and show that our pipeline can generate similar results of interest but with better performance. The software is open source and is publicly available at https://github.com/amromics/amromics under an MIT license.

Hydrophobic binary mixtures containing amphotericin B as lipophilic solutions for the treatment of cutaneous leishmaniasis.

Cutaneous leishmaniasis, caused by Leishmania parasites, requires treatments with fewer side effects than those currently available. The development of a topical solution based on amphotericin B (AmB) was pursued. The considerable interest in deep eutectic solvents (DESs) and their remarkable advantages inspired the search for a suitable hydrophobic excipient. Various mixtures based on commonly used hydrogen bond donors (HBDs) and acceptors (HBAs) for DES preparations were explored. Initial physical and in-vitro screenings showed the potential of quaternary phosphonium salt-based mixtures. Through thermal analysis, it was determined that most of these mixtures did not exhibit eutectic behavior. X-ray scattering studies revealed a sponge-like nanoscale structure. The most promising formulation, based on a combination of trihexyl(tetradecyl)phosphonium chloride and 1-oleoyl-rac-glycerol, showed no deleterious effects through histological evaluation. AmB was fully solubilized at concentrations between 0.5 and 0.8 mg·mL-1, depending on the formulation. The monomeric state of AmB was observed by circular dichroism. In-vitro irritation tests demonstrated acceptable viability for AmB-based formulations up to 0.5 mg·mL-1. Additionally, an ex-vivo penetration study on pig ear skin revealed no transcutaneous passage, confirming AmB retention in healthy, unaffected skin.

Primary hepatobiliary mucoepidermoid carcinoma: a case report and review of literature.

Hepatobiliary mucoepidermoid carcinoma is a rare malignant tumor comprising mucous, intermediate, and epidermoid cells. Herein, we presented a case of primary liver mucoepidermoid carcinoma preoperatively misdiagnosed as conventional intrahepatic cholangiocarcinoma. A 67-year-old male was admitted to our hospital. Preoperative laboratory tests showed increased aspartate transaminase, alanine transaminase, and carbohydrate antigen 19-9. Abdominal Computer Tomography revealed a 4.8 × 4.9 cm liver mass in segment VI. A preliminary diagnosis of intrahepatic cholangiocarcinoma was made, with undergoing partial hepatectomy. However, on histopathology, the tumor comprised a mixture of epidermoid, mucous, and intermediate cells with diffuse infiltrating at the tumor margin. On special stains, mucous and intermedia cells were positive for mucicarmine and Alcian blue, whereas epidermoid cells were positive for Keratin 5/6 and p63. Intermediate cells are also positive for p63. All tumor cells were positive for Keratin 7. The Ki-67 index was 35%. The final diagnosis was primary hepatic mucoepidermoid carcinoma. Although rare, hepatic mucoepidermoid carcinoma should be considered in the intrahepatic cholangiocarcinoma differential diagnosis. We reviewed previous studies and found that hepatobiliary mucoepidermoid carcinoma is more likely to originate from the biliary tract adjacent to the tumor.

AMRViz enables seamless genomics analysis and visualization of antimicrobial resistance.

We have developed AMRViz, a toolkit for analyzing, visualizing, and managing bacterial genomics samples. The toolkit is bundled with the current best practice analysis pipeline allowing researchers to perform comprehensive analysis of a collection of samples directly from raw sequencing data with a single command line. The analysis results in a report showing the genome structure, genome annotations, antibiotic resistance and virulence profile for each sample. The pan-genome of all samples of the collection is analyzed to identify core- and accessory-genes. Phylogenies of the whole genome as well as all gene clusters are also generated. The toolkit provides a web-based visualization dashboard allowing researchers to interactively examine various aspects of the analysis results. Availability: AMRViz is implemented in Python and NodeJS, and is publicly available under open source MIT license at https://github.com/amromics/amrviz .

The genetic landscape of chromosomal aberrations in 3776 Vietnamese fetuses with clinical anomalies during pregnancy.

Background: Copy number variation sequencing (CNV-seq) is a powerful tool to discover structural genomic variation, but limitations associated with its retrospective study design and inadequate diversity of participants can be impractical for clinical application. Aim: This study aims to use CNV-seq to assess chromosomal aberrations in pregnant Vietnamese women. Materials & methods: A large-scale study was conducted on 3776 pregnant Vietnamese women with abnormal ultrasound findings. Results: Chromosomal aberrations were found in 448 (11.86%) women. Of these, 274 (7.26%) had chromosomal aneuploidies and 174 (4.61%) carried pathogenic/likely pathogenic CNVs. Correlations were established between chromosomal aberrations and various phenotypic markers. Conclusion: This comprehensive clinical study illuminates the pivotal role of CNV-seq in prenatal diagnosis for pregnancies featuring fetal ultrasound anomalies.

[Box: see text].

Differential requirement for IL-2 and IL-23 in the differentiation and effector functions of Th17/ILC3-like cells in a human T cell line.

A well-documented Achilles heel of current cancer immunotherapy approaches is T cell exhaustion within solid tumor tissues. The proinflammatory cytokine interleukin (IL)-23 has been utilized to augment chimeric antigen receptor (CAR) T cell survival and tumor immunity. However, in-depth interrogation of molecular events downstream of IL-23/IL-23 receptor signaling is hampered by a paucity of suitable cell models. The current study investigates the differential contribution of IL-2 and IL-23 to the maintenance and differentiation of the IL-23 responsive Kit225 T-cell line. We observed that IL-23 enhanced cellular fitness and survival but was insufficient to drive proliferation. IL-23 rapidly induced phosphorylation of STAT1, STAT3, and STAT4, and messenger RNA expression of IL17A, the archetypal effector cytokine of T helper 17 (Th17) cells, but not their lineage markers RORC and NCR1. These observations suggest that IL-23 endowed Th17/ILC3-like effector function but did not promote their differentiation. In contrast, spontaneous differentiation of Kit225 cells toward a Th17/ILC3-like phenotype was induced by prolonged IL-2 withdrawal. This was marked by strongly elevated basal IL17A and IL17F expression and the secretion of IL-17. Together, our data present Kit225 cells as a valuable model for studying the interplay between cytokines and their contribution to T cell survival, proliferation, and differentiation.

Pasa: leveraging population pangenome graph to scaffold prokaryote genome assemblies.

Whole genome sequencing has increasingly become the essential method for studying the genetic mechanisms of antimicrobial resistance and for surveillance of drug-resistant bacterial pathogens. The majority of bacterial genomes sequenced to date have been sequenced with Illumina sequencing technology, owing to its high-throughput, excellent sequence accuracy, and low cost. However, because of the short-read nature of the technology, these assemblies are fragmented into large numbers of contigs, hindering the obtaining of full information of the genome. We develop Pasa, a graph-based algorithm that utilizes the pangenome graph and the assembly graph information to improve scaffolding quality. By leveraging the population information of the bacteria species, Pasa is able to utilize the linkage information of the gene families of the species to resolve the contig graph of the assembly. We show that our method outperforms the current state of the arts in terms of accuracy, and at the same time, is computationally efficient to be applied to a large number of existing draft assemblies.

Deep learning-based phenotyping reclassifies combined hepatocellular-cholangiocarcinoma.

Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.

Genome characterization of Streptomyces sp. strain VNUA74, a potential biocontrol against pathogenic fungus Colletotrichum spp.

The whole genome sequence of Streptomyces sp. strain VNUA74, isolated from soil in a banana farm in Vietnam and exhibited fungicidal effects on banana Colletotrichum spp., was sequenced by PacBio RS II and DNBseq sequencing platforms. The complete circular genome is 7,250,076 bp with a GC content of 72.69%.

De novo variants of dominant monogenic disorders in Vietnam detected by a noninvasive prenatal test: a case series.

Background: Noninvasive prenatal tests for monogenic diseases (NIPT-SGG) have recently been reported as helpful in early-stage antenatal screening. Our study describes the clinical and genetic features of cases identified by NIPT-SGG. Materials & methods: In a cohort pregnancy with abnormal sonograms, affected cases were confirmed by invasive diagnostic tests concurrently, with NIPT-SGG targeting 25 common dominant single-gene diseases. Results: A total of 13 single-gene fetuses were confirmed, including Noonan and Costello syndromes, thanatophoric dysplasia, achondroplasia, osteogenesis imperfecta and Apert syndrome. Two novel variants seen were tuberous sclerosis complex (TSC2 c.4154G>A) and Alagille syndrome (JAG1 c.3452del). Conclusion: NIPT-SGG and standard tests agree on the results for 13 fetuses with monogenic disorders. This panel method of screening can benefit high-risk Vietnamese pregnancies, but further research is encouraged to expand on the causative gene panel.

Complete genome sequence of Streptomyces strain VNUA116, a potential biocontrol against phytopathogenic fusarium wilt fungus Fusarium oxysporum f. sp. cubense.

Here, we present the whole-genome sequence of Streptomyces strain VNUA116 was obtained by combining sequencing data from both PacBio RS II and DNBseq platforms. The complete circular genome is 8,306,919 bp with a GC content of 72.49%.

Does tourism reduce the shadow economy? An international evidence.

This paper investigates one of the positive contributions of tourism to the economy through the lens of its influences on the shadow economy. Specifically, our study analyzes the effects of five indicators of tourism consumption (including domestic tourism spending, international travel and tourism consumption, business tourism spending, leisure tourism spending, and outbound tourism spending on the percentage of shadow economy to GDP) in 129 economies between 1996 and 2015. We find interesting results that contribute to the existing literature about tourism economics. Firstly, the development of the inbound tourism industry reduces the shadow economy significantly, while outbound tourism causes higher underground economic activities. Secondly, the influence of tourism on the shadow economy is significant in both the short-run and long run with a stronger effect in the long run. Thirdly, the effect of tourism on the shadow economy is more significant in the 42 High-Income Economies and 54 Low and Lower-middle Income Economies, while it is less obvious in the 33 Upper-Middle Income Economies. These findings have been checked by a battery of robustness checks ensuring their statistical consistency.

Developing and validating noninvasive prenatal testing for de novo autosomal dominant monogenic diseases in Vietnam.

Background: Over 60% of single-gene diseases in newborns are autosomal dominant variants. Noninvasive prenatal testing for monogenic conditions (NIPT-SGG) is cost-effective and timesaving, but not widely applied. This study introduces and validates NIPT-SGG in detecting 25 monogenic conditions. Methods: NIPT-SGG with a 30-gene panel applied next-generation sequencing and trio assays to confirm de novo variants. Diagnostic tests confirmed NIPT-detected cases. Results: Among 93 pregnancies with ultrasound findings, 11 (11.8%) fetuses were screened and diagnosed with monogenic diseases, mostly with Noonan syndrome. NIPT-SGG determined >99.99% of actual positive and negative cases, confirmed by diagnostic tests. No false-negatives or false-positives were reported. Conclusion: NIPT-SGG effectively identifies the fetuses affected with monogenic diseases, which is a promisingly safe and timely antenatal screening option for high-risk pregnancies.

Complete genome sequence of Streptomyces sp. strain VNUA24, a potential antifungal bacterium isolated from soil.

Streptomyces species are important resources for secondary metabolites, including antimicrobial compounds. The Streptomyces sp. strain VNUA24 was isolated from a soil sample in Vietnam. The strain was identified as having antifungal activity against numerous fungal pathogens. Whole-genome sequencing was done to explore the biocontrol capability of this strain.

Endovascular management of severe lower gastrointestinal bleeding from angiodysplasia in the cecum: A case report.

Gastrointestinal angiodysplasias (GIADs) are rare disorder but can cause noticeable issue clinically. Their clinical characteristics can range from being an asymptomatic incidental finding to causing life-threatening bleeding. Many modalities are applied for treating bleeding GIADs include endoscopic therapies, angiography with embolization, surgical resection, and pharmacologic therapy. However, since patients with GIADs are often aged and have many comorbidities, endoscopic therapies may not be the best initial option. Angiography is suitable method for hemodynamically unstable patients with active bleeding, patients with an unknown active bleeding source, and patients who are poor surgical candidates. Angiography not only diagnose the bleeding point but also provide therapeutic endovascular intervention at the same time. We report a case of endovascular management of severe lower gastrointestinal bleeding from a GIAD in the cecum using a mixture of n-butyl cyanoacrylate and lipiodol to embolize the bleeding source. Clinical symptoms improved without prominent complications.

Conformal Cooling Channel Design for Improving Temperature Distribution on the Cavity Surface in the Injection Molding Process.

Mold heating is an essential process in plastic injection molding. Raising the temperature of the mold before injecting liquefied plastic can ease the mold-filling process. A cooling channel can be used to transport high-temperature fluids for this purpose, such as hot water or oil. This dual purpose is a cost-effective solution for heating the mold because the target temperature is easily achieved using this method. In addition, a conformal cooling channel (CCC) can provide more efficient mold heating than a straight cooling channel. This study used the response surface methodology to determine the optimum CCC shape for heat distribution in a mold, and the simulation results confirmed its optimization. The average temperature of the mold using a CCC was better than that using a straight cooling channel, and the heat zone was uniform across the mold surface.

Central-Smoothing Hypergraph Neural Networks for Predicting Drug-Drug Interactions.

Predicting drug-drug interactions (DDIs) is the problem of predicting side effects (unwanted outcomes) of a pair of drugs using drug information and known side effects of many pairs. This problem can be formulated as predicting labels (i.e., side effects) for each pair of nodes in a DDI graph, of which nodes are drugs and edges are interacting drugs with known labels. State-of-the-art methods for this problem are graph neural networks (GNNs), which leverage neighborhood information in the graph to learn node representations. For DDI, however, there are many labels with complicated relationships due to the nature of side effects. Usual GNNs often fix labels as one-hot vectors that do not reflect label relationships and potentially do not obtain the highest performance in the difficult cases of infrequent labels. In this brief, we formulate DDI as a hypergraph where each hyperedge is a triple: two nodes for drugs and one node for a label. We then present CentSmoothie , a hypergraph neural network (HGNN) that learns representations of nodes and labels altogether with a novel "central-smoothing" formulation. We empirically demonstrate the performance advantages of CentSmoothie in simulations as well as real datasets.

Optimization of 3D Cooling Channels in Plastic Injection Molds by Taguchi-Integrated Principal Component Analysis (PCA).

Injection molding has become an increasingly widely used method in the production of plastic parts. The injection process can be separated into five steps: mold closure, filling, packing, cooling, and product ejection. Before the melted plastic is loaded into the mold, the mold needs to be raised to a specified temperature, in order to increase the mold's filling capacity and improve the resultant product quality. One of the easy methods used to control a mold's temperature is to provide hot water through a cooling channel in the mold, to raise the temperature. In addition, this channel can be used for cooling the mold with cool fluid. This is simple, effective, and cost efficient, involving uncomplicated products. To improve the heating effectiveness of the hot water, a conformal cooling-channel design is considered in this paper. Through heat-transfer simulation using the CFX module in the Ansys software, an optimal cooling channel was defined according to the simulation result, using the Taguchi method integrated with principal component analysis. The comparison of traditional vs. conformal cooling channels revealed higher temperature rises in the first 100 s in both molds. During heating, conformal cooling produced higher temperatures compared with traditional cooling. Conformal cooling demonstrated better performance, with average temperature peaking at 58.78 °C and a range of 63.4 °C (max) to 54.66 °C (min). Traditional cooling resulted in an average steady-state temperature of 56.63 °C and a range of 61.74 °C (max) to 53.18 °C (min). Finally, the simulation results were verified experimentally.

A look beyond climate risk exposure: the impact of incapacity to cope with natural hazards on financial development.

We provide a comprehensive cross-country analysis on the impact of national incapacity to cope with natural hazards (i.e., social shocks, political stability, health care, infrastructure, and material security needed to reduce the harmful effects of natural disasters) on financial development. The panel quantile regression analyses on a global sample of 130 countries generally confirm that the financial development of countries with lower capacity to cope is indeed significantly hampered compared to their peers, especially in countries with low financial development levels. Seemingly unrelated regression (SUR) analyses, which acknowledge the dynamic co-existence between both financial institutions and financial market sectors in a given economy simultaneously, offer notable finer details. For example, the handicapping effect on both sectors tends to apply to only countries with higher climate risks. Lack of coping capacity also exert negative effects on the development of financial institutions in countries of all levels of income but only affect financial markets of high-income group. The more detailed look into different dimensions (financial efficiency, financial access, and financial depth) of financial development is also given in our study. Overall, our findings highlight the vital and complex role of "coping capacity" aspect of climate risk on the sustainable development of financial sectors.