Liver fibrosis MR images classification based on higher-order interaction and sample distribution rebalancing.

The fractal features of liver fibrosis MR images exhibit an irregular fragmented distribution, and the diffuse feature distribution lacks interconnectivity, result- ing in incomplete feature learning and poor recognition accuracy. In this paper, we insert recursive gated convolution into the ResNet18 network to introduce spatial information interactions during the feature learning process and extend it to higher orders using recursion. Higher-order spatial information interactions enhance the correlation between features and enable the neural network to focus more on the pixel-level dependencies, enabling a global interpretation of liver MR images. Additionally, the existence of light scattering and quantum noise during the imaging process, coupled with environmental factors such as breathing artifacts caused by long time breath holding, affects the quality of the MR images. To improve the classification performance of the neural network and better cap- ture sample features, we introduce the Adaptive Rebalance loss function and incorporate the feature paradigm as a learnable adaptive attribute into the angular margin auxiliary function. Adaptive Rebalance loss function can expand the inter-class distance and narrow the intra-class difference to further enhance discriminative ability of the model. We conduct extensive experiments on liver fibrosis MR imaging involving 209 patients. The results demonstrate an average improvement of two percent in recognition accuracy compared to ResNet18. The github is at https://github.com/XZN1233/paper.git.

MRI Features for Predicting Microvascular Invasion and Postoperative Recurrence in Hepatocellular Carcinoma Without Peritumoral Hypointensity.

Purpose: To identify MRI features of hepatocellular carcinoma (HCC) that predict microvascular invasion (MVI) and postoperative intrahepatic recurrence in patients without peritumoral hepatobiliary phase (HBP) hypointensity. Patients and Methods: One hundred and thirty patients with HCC who underwent preoperative gadoxetate-enhanced MRI and curative hepatic resection were retrospectively reviewed. Two radiologists reviewed all preoperative MR images and assessed the radiological features of HCCs. The ability of peritumoral HBP hypointensity to identify MVI and intrahepatic recurrence was analyzed. We then assessed the MRI features of HCC that predicted the MVI and intrahepatic recurrence-free survival (RFS) in the subgroup without peritumoral HBP hypointensity. Finally, a two-step flowchart was constructed to assist in clinical decision-making. Results: Peritumoral HBP hypointensity (odds ratio, 3.019; 95% confidence interval: 1.071-8.512; P=0.037) was an independent predictor of MVI. The sensitivity, specificity, positive predictive value, negative predictive value, and AUROC of peritumoral HBP hypointensity in predicting MVI were 23.80%, 91.04%, 71.23%, 55.96%, and 0.574, respectively. Intrahepatic RFS was significantly shorter in patients with peritumoral HBP hypointensity (P<0.001). In patients without peritumoral HBP hypointensity, the only significant difference between MVI-positive and MVI-negative HCCs was the presence of a radiological capsule (P=0.038). Satellite nodule was an independent risk factor for intrahepatic RFS (hazard ratio,3.324; 95% CI: 1.733-6.378; P<0.001). The high-risk HCC detection rate was significantly higher when using the two-step flowchart that incorporated peritumoral HBP hypointensity and satellite nodule than when using peritumoral HBP hypointensity alone (P<0.001). Conclusion: In patients without peritumoral HBP hypointensity, a radiological capsule is useful for identifying MVI and satellite nodule is an independent risk factor for intrahepatic RFS.

Complete Coding Sequence of Lumpy Skin Disease Virus Isolated from Kinmen Island, Taiwan, in 2020.

We reported the complete coding sequence of a lumpy skin disease virus (LSDV) isolated from cattle from Kinmen, Taiwan, in 2020. The nucleotide sequence of LSDV/KM/Taiwan/2020 was most closely related to strains from an outbreak in China and Vietnam in 2020 and clustered within the vaccine or vaccine-derived clade.

Genetic diversity of avian paramyxoviruses isolated from wild birds and domestic poultry in Taiwan between 2009 and 2020.

Avian paramyxoviruses (APMVs) belonging to the subfamily Avulavirinae within the family Paramyxoviridae. APMVs consist of twenty-two known species and are constantly isolated from a wide variety of avian species around the world. In this study, the APMV isolates obtained from wild birds and domestic poultry during 2009-2020 in Taiwan were genetically characterized by phylogenetic analysis of their complete fusion protein gene or full-length genome. As a result, 57 APMV isolates belonging to seven different species were obtained during this period and subsequently identified as APMV-1 (n=17), APMV-2 (n=1), APMV-4 (n=25), APMV-6 (n=8), APMV-12 (n=2), APMV-21 (n=2) and APMV-22 (n=2). Sanger sequencing was performed to provide 22 full-length genome sequences and 35 complete fusion protein gene sequences for the APMV isolates. Phylogenetic analysis showed that the recovered viruses were closely related to Eurasian strains, except five class I APMV-1 and four APMV-4 isolates were related to North America strains. Our findings provided more evidence for the intercontinental transmission of APMVs between Eurasia and North America by wild birds. In addition, according to the criteria of the classification system based on complete fusion protein gene sequences, three novel genotypes within APMV-2, APMV-12, and APMV-22 were identified. Together, this investigation provided a broader perspective on the genetic diversity, evolution, and distribution of APMVs in multiple avian host species sampled in Taiwan.

Erlotinib protests against LPS-induced parthanatos through inhibiting macrophage surface TLR4 expression.

Sepsis is a life-threatening cascading systemic inflammatory response syndrome on account of serve infection. In inflamed tissues, activated macrophages generate large amounts of inflammatory cytokines reactive species, and are exposed to the damaging effects of reactive species. However, comparing with necroptosis and pyroptosis, so far, there are few studies focusing on the overproduction-related cell death, such as parthanatos in macrophage during sepsis. In LPS-treated macrophage, we observed PARP-1 activation, PAR formation and AIF translocation. All these phenomena could be inhibited by both erlotinib and 3-AB, indicating the presence of parthanatos in endotoxemia. We further found that LPS induced the increase of cell surface TLR4 expression responsible for the production of ROS and subsequent parthanatos in endotoxemia. All these results shed a new light on how TLR4 regulating the activation of PARP-1 by LPS in macrophage.

Evolutionary history of H5 highly pathogenic avian influenza viruses (clade 2.3.4.4c) circulating in Taiwan during 2015-2018.

The highly pathogenic avian influenza (HPAI) virus A/goose/Guangdong/1/96 H5N1 (Gs/GD) lineage has been transmitted globally and has caused deaths in wild birds, poultry, and humans. Clade 2.3.4.4c, one of the subclades of the Gs/GD lineage, spread through Taiwan in late 2014 and become an endemic virus. We analyzed 239 newly sequenced HPAI clade H5Nx isolates to explore the phylogenetic relationships, divergence times, and evolutionary history of Taiwan HPAI H5Nx viruses from 2015 to 2018. Overall, 15 reassortant genotypes were identified among H5N2, H5N3, and H5N8 viruses. Maximum likelihood and Bayesian phylogenies based on homologous hemagglutinin (HA) and matrix protein (MP) genes suggest that Taiwan HPAI H5Nx viruses share a most recent common ancestor that has diversified since October 2014 and is closely related to two HPAI H5N8 viruses identified from wild birds in Japan. Two waves of HPAI caused by multiple reassortants were identified, the first occurring in late 2014 and the second beginning in late 2016. The first wave consisted of seven H5Nx reassortants that spread through Taiwan. In the second wave, eight novel reassortants were detected which had newly introduced internal genes, mostly derived from the avian influenza virus gene pool maintained in wild birds in Asia. Phylodynamic reconstruction using the Bayesian Skygrid model revealed varied fluctuating patterns of relative genetic diversity among reassortants. The mean evolutionary rate also varied among reassortants and subtypes. The neuraminidase (NA) gene evolved faster than the HA gene in H5N2 viruses, while HA evolved faster than NA in H5N8 viruses. The HA mean evolutionary rate ranged from 6.10 × 10-3 to 7.73 × 10-3 and from 5.81 × 10-3 to 9.45 × 10-3 substitutions/site/year for H5N2 and H5N8 viruses, respectively. The continuous circulation of HPAI H5Nx variants and the emergence of novel reassortants in Taiwan highlight that the surveillance, biosecurity, and management systems of poultry farms need to be improved and carefully executed.

Lower-Grade Gliomas: Predicting DNA Methylation Subtyping and its Consequences on Survival with MR Features.

RATIONALE AND OBJECTIVES: To explore associations between MR imaging features, DNA methylation subtyping, and survival in lower-grade gliomas (LGG). MATERIALS AND METHODS: The MR data from 170 patients generated with the Cancer Imaging Archive were reviewed. The correlation was evaluated by Fisher's Exact Test, Pearson Chi-Square and binary regression analysis. Survival analysis was conducted by using time-dependent ROC analysis and the Kaplan-Meier method (the worst prognosis subgroup). RESULTS: Identified were 9 (5.3%) M1-subtype, 18 (10.6%) M2-subtype, 48 (28.2%) M3-subtype, 31 (18.2%) M4-subtype and 64 (37.6%) M5-subtype. Patients with M4-subtype had the shortest median OS (49.3 vs. 28.4) months(p < 0.05). The time-dependent ROC for the M4-subtype was 0.83 (95% confidence interval 0.72-0.95) for survival at 12 months, 0.82 (95% confidence interval 0.70-0.94) for survival at 24 months, and 0.74 (95% confidence interval 0.62-0.86) for survival at 36 months. After uni- and multivariate analysis, a nomogram was built based on proportion contrast-enhanced (CE) tumor, extranodular growth, volume_cutoff_median, and location. For the prediction of M4-subtype, the nomogram showed good discrimination, with an area under the curve (AUC) of 0.886 (95% CI: 0.820-952) and was well calibrated. On multivariate logistic regression analysis, volume ≥60cm3 (OR: 0.200; p < 0.001; 95%CI: 0.048-0.834) was associated with M1-subtype (AUC: 0.690). Hemorrhage (OR: 5.443; p = 0.002; 95%CI: 1.844-16.069) and volume > median (OR: 3.256; p = 0.05; 95%CI: 0.992-10.686) were associated with M2-subtype (AUC: 0.733). Proportion CE tumor<=5% (OR: 3.968; P=0.002; 95%CI: 1.634-9.635) was associated with M3-subtype (AUC: 0.632). Poorly-defined (OR: 2.258; p = 0.05; 95%CI: 1.000-5.101) and volume > median (OR: 2.447; p = 0.01; 95%CI: 1.244-4.813) were associated with M5-subtype (AUC: 0.645). Decision curve analysis indicated predictions for all models were clinically useful. CONCLUSION: This preliminary radiogenomics analysis of lower-grade gliomas demonstrated associations between MR features and DNA methylation subtyping. The shortest survival was observed in patients with M4-subtype. And we have constructed nomogram that enables more accurate predictions of M4-subtype.

FDG PET/CT Findings of Melanoma in a Renal Allograft.

Renal melanoma is rare. We present a case with FDG-avid melanoma arising from renal allograft. This case indicates that melanoma can occur in the allograft, and it should be considered as a differential diagnosis of focal abnormal FDG uptake in the renal allograft.

Phylogenetic analysis of avian paramyxoviruses 1 isolated in Taiwan from 2010 to 2018 and evidence for their intercontinental dispersal by migratory birds.

Avian paramyxovirus 1 (APMV-1), synonymous with Newcastle disease virus (NDV), is a worldwide viral agent that infects various avian species and responsible for outbreaks of Newcastle disease. In this study, 40 APMV-1 isolates collected from poultry, migratory birds, and resident birds during 2010-2018 in Taiwan were characterized genetically. Our phylogenetic analysis of complete fusion protein gene of the APMV-1 isolates revealed that 39 of the 40 Taiwanese isolates were closely related to APMV-1 of class I genotype 1 or class II genotypes I, VI or VII, and one isolate belonged to a group that can be classified as a novel genotype 2 within class I. The fusion protein gene sequences of a branch (former 1d) nested within class I sub-genotype 1.2 were closely related to those isolated from wild birds in North America. Viruses placed in class II sub-genotype VI.2.1.1.2.1 and sub-genotype VI.2.1.1.2.2 were the dominant pigeon paramyxovirus 1 (PPMV-1) circulating in the last decade in Taiwan. All the Newcastle disease outbreak-associated isolates belonged to class II sub-genotype VII.1.1, which was mainly responsible for the present epizootic of Newcastle disease in Taiwan. We conclude that at least five sub/genotypes of APMV-1 circulate in multiple avian host species in Taiwan. One genetically divergent group of APMV-1 should be considered as a novel genotype within class I. Migratory birds may play an important role in intercontinental spread of lentogenic APMV-1 between Eurasia and North America.

Novel avian metaavulavirus isolated from birds of the family Columbidae in Taiwan.

Avian paramyxoviruses (APMVs) consist of twenty known species and have been isolated from domestic and wild birds around the world. In 2009, the isolate APMV/dove/Taiwan/AHRI33/2009 was isolated from swabs of red turtle doves (Streptopelia tranquebarica) during active surveillance of avian influenza in resident birds in Taiwan, and it was initially identified as paramyxovirus based on electron microscopy. Hemagglutination inhibition assays indicated antigenic heterogeneity of AHRI33 with the known APMV-1, -2, -3, -4, -6, -8, and -9 species, only showing weak but measurable cross-reactivity with APMV-7. Pathogenicity ICPI test revealed that the virus was avirulent for chickens. The AHRI33 virus genome revealed a typical APMV structure consisting of six genes 3'-NP-P-M-F-HN-L-5', and the length of the genome was 16,914 nucleotides, the third longest among the members of the subfamily Avulavirinae. Estimates of the nucleotide sequence identities of the genome between each prototype of APMVs had shown AHRI33 to be more closely related to APMV-7 than to the others, with a sequence identity of 62.8%. Based on topology of the phylogenetic tree of RdRp genes and the branch length between the nearest node and the tip of the branch, AHRI33 met the criteria for designation as distinct species. Together, the data suggest that the isolate APMV/dove/Taiwan/AHRI33/2009 should be considered as the prototype strain of the new species Avian metaavulavirus 21 in the genus Metaavulavirus in the subfamily Avulavirinae.

Covalent chemistry on nanostructured substrates enables noninvasive quantification of gene rearrangements in circulating tumor cells.

Well-preserved mRNA in circulating tumor cells (CTCs) offers an ideal material for conducting molecular profiling of tumors, thereby providing a noninvasive diagnostic solution for guiding treatment intervention and monitoring disease progression. However, it is technically challenging to purify CTCs while retaining high-quality mRNA.Here, we demonstrate a covalent chemistry-based nanostructured silicon substrate ("Click Chip") for CTC purification that leverages bioorthogonal ligation-mediated CTC capture and disulfide cleavage-driven CTC release. This platform is ideal for CTC mRNA assays because of its efficient, specific, and rapid purification of pooled CTCs, enabling downstream molecular quantification using reverse transcription Droplet Digital polymerase chain reaction. Rearrangements of ALK/ROS1 were quantified using CTC mRNA and matched with those identified in biopsy specimens from 12 patients with late-stage non-small cell lung cancer. Moreover, CTC counts and copy numbers of ALK/ROS1 rearrangements could be used together for evaluating treatment responses and disease progression.

FDG PET/CT in a Case of Dural Amyloidoma.

Dural amyloidoma is an unusual presentation of central nervous system amyloidosis. A 49-year-old woman presented with 1-month history of repeated episodes of vertigo. Precontrast MRI showed dural thickening over right frontal convexity with signal intensity similar to white matter. Postcontrast T1-weighted images showed remarkable enhancement of the lesion. Dural amyloidoma was confirmed by partial resection of the lesion. The patient underwent no further treatment. A follow-up FDG PET/CT showed increased FDG uptake of the residual dural amyloidoma. This case indicates dural amyloidoma should be included in the differential diagnosis of abnormal FDG uptake in dural lesions.

Reassortant Clade 2.3.4.4 of Highly Pathogenic Avian Influenza A(H5N6) Virus, Taiwan, 2017.

A highly pathogenic avian influenza A(H5N6) virus of clade 2.3.4.4 was detected in a domestic duck found dead in Taiwan during February 2017. The endemic situation and continued evolution of various reassortant highly pathogenic avian influenza viruses in Taiwan warrant concern about further reassortment and a fifth wave of intercontinental spread.

Detection of reassortant H5N6 clade 2.3.4.4 highly pathogenic avian influenza virus in a black-faced spoonbill (Platalea minor) found dead, Taiwan, 2017.

A H5N6 highly pathogenic avian influenza virus (HPAIV) was detected in a black-faced spoonbill (Platalea minor) found dead in Taiwan during December 2017. Genome sequencing and phylogenetic analyses suggest the hemagglutinin gene belongs to H5 clade 2.3.4.4 Group B. All genes except neuraminidase gene shared high levels of nucleotide identity with H5N8 HPAIV identified from Europe during 2016-2017. Genetically similar H5N6 HPAIV was also identified from Japan during November 2017. Enhanced surveillance is required in this region.

Sarcomatoid renal cell carcinoma: a case report and literature review.

BACKGROUND: The poorly differentiated renal cell carcinoma (RCC) with rhabdomyosarcomatous sarcomatoid differentiation shows a severely aggressive biological behavior characterized by rapid disease progression. Preoperative identification of the subtype with the prognostic factors and imaging features of sarcomatoid renal cell carcinoma (SRCC) would be of great clinical significance. CASE PRESENTATION: A 45-year-old male patient presented a nine day history of gross hematuria without any other symptoms. A computed tomography (CT) and a full-body fluorine-18 fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) - computed tomography (CT) scan urogram were performed. An initial diagnosis identified a space-occupying lesion of the right kidney, retroperitoneal and right renal hulum lymph node metastases, as well as a space-occupying lesion of the third thoracic vertebra (T3). A right radical nephrectomy was performed. Pathologic analysis revealed poorly differentiated RCC with rhabdomyosarcomatous sarcomatoid differentiation that extends into the renal sinus and the ureteral (T3N1M1). Five days later, the Magnetic Resonance imaging (MRI) evidenced a diffused osseous metastatic disease in the thoracic and lumbar vertebra and multiple retroperitoneal lymph node metastases. The disease progressed quickly to multiple organ dysfunction syndrome (MODS) in half a month and the patient died of respiratory failure two days later. The patient refused any chemoradiotherapy in the hospital. CONCLUSIONS: Our case presents a SRCC with severe, aggressive, and rapid disease progression. Classifying SRCC imaging features by CT, MRI as well as PET-CT techniques could potentially be helpful for preoperative identification of the subtype. The prognostic factors of SRCC would be of great clinical interest.

Computed Tomography and Magnetic Resonance Imaging Features of Primary and Secondary Hepatic Glycogenosis.

Glycogen storage disease type I and glycogenic hepatopathy are the most common type of primary and secondary hepatic glycogenosis, with presenting common radiological features of hepatomegaly, hepatic signal, or density change. Beyond that, glycogen storage disease type I shows hepatocellular adenomas or fatty liver, while glycogenic hepatopathy does not.

Sequence diversity and associated pathogenicity of the hemagglutinin cleavage site of H5N2 avian influenza viruses isolated from chickens in Taiwan during 2013-2015.

The sequence at the hemagglutinin (HA) cleavage site (CS) plays a key role in determining the pathogenicity of avian influenza viruses. Three types of HA CS sequences, QREKR/GL, QRKKR/GL and QRRKR/GL, were previously reported in Taiwanese H5N2 viruses that were isolated from chickens from 2003 to 2013. However, no HA CS sequence was reported for viruses isolated after 2013. This article presents the HA CS sequences and pathogenicity of H5N2 viruses that were isolated from chickens in Taiwan during 2013-2015. Two novel HA CS sequences, QKEKR/GL and KREKREKR/GL, were found in the viruses isolated in 2013 and 2014, and pathogenicity tests showed that the viruses with these novel HA CS sequences are low and high pathogenic viruses, respectively. In contrast, the HA CS sequence QREKR/GL was found in all viruses that were isolated in 2015, and all of these viruses were low pathogenic viruses. After 10 passages in embryonated chicken eggs, a virus strain that was isolated in 2003 evolved into a viral quasispecies that contained at least four distinct types of HA CS sequences. These results highlight the potential of Taiwanese H5N2 viruses to change their pathogenicity and HA CS sequences via mutations. Furthermore, viruses with the HA CS sequence QREKR/GL were more prevalent than others in 2015. These findings are useful for understanding the mechanism of sequence changes at the HA CS and for refining H5N2 virus control measures in Taiwan.

[Correlation between Fractional Anisotropy and Amyotrophic Lateral Sclerosis, and Effect of Inte- grative Medical Treatment on ALS].

OBJECTIVE: To explore whether fractional anisotropy (FA) value could be taken as a quantitative indicator for tracing and reexamining amyotrophic lateral sclerosis (ALS), and to analyze the correlation between FA value and integrative medical treatment. METHODS: Totally 18 ALS patients were recruited in this study. All patients received diffusion tensor imaging (DTI) using 3. OT (Propeller HD) MRI twice. Six regions of interest (ROI) were selected to measure FA values. Survival analyses were performed in 11 cases of end point events. RESULTS: (1) Three ROI (cerebral peduncle, posterior limb of internal capsule, and corona radiata) all indicated that FA value was the highest in patients with mild health status scale of amyotrophic lateral sclerosis (ALS/HSS). (2) There was statistical difference in the means of FA values in cerebral peduncle, posterior limb of internal capsule, and corona radiata of 18 cases between initial examination and reexamination (P < 0.01). (3) Kaplan-Meier survival curve showed the survival rate of ALS patients decreased as time went by, with the median survival time of 48 months. CONCLUSIONS: FA value was inversely proportional to the severity of ALS, the more severe, the lower FA values. FA value was an objective indicator for assessing the severity of ALS. ALS is an incurable disease till now. Integrative medical treatment might become one direction for ALS patients.

Highly pathogenic avian influenza viruses H5N2, H5N3, and H5N8 in Taiwan in 2015.

A severe epidemic, affecting mainly goose populations, broke out in early January 2015. The causative agents were identified as novel H5 avian influenza viruses carrying N2, N3, and N8 subtypes of the neuraminidase gene. From January 8 to February 11, 766 waterfowl and poultry farms were invaded by the H5 viruses, and more than 2.2 million geese died or were culled. Phylogenetic analysis suggested that these avian influenza viruses derived from the H5 viruses of clade 2.3.4.4 which were emerging in 2014 in East Asia, West Europe, and North America.