Nuclear factors NF-YC3 and NF-YBs positively regulate arbuscular mycorrhizal symbiosis in tomato.

The involvement of nuclear factor Y (NF-Y) in transcriptional reprogramming during arbuscular mycorrhizal symbiosis has been demonstrated in several plant species. However, a comprehensive picture is lacking. We showed that the spatial expression of NF-YC3 was observed in cortical cells containing arbuscules via the cis-regulatory element GCC boxes. Moreover, the NF-YC3 promoter was transactivated by the combination of CYCLOPS and autoactive calcium and calmodulin-dependent kinase (CCaMK) via GCC boxes. Knockdown of NF-YC3 significantly reduced the abundance of all intraradical fungal structures and affected arbuscule size. BCP1, SbtM1, and WRI5a, whose expression associated with NF-YC3 levels, might be downstream of NF-YC3. NF-YC3 interacted with NF-YB3a, NF-YB5c, or NF-YB3b, in yeast (Saccharomyces cerevisiae) and in planta, and interacted with NF-YA3a in yeast. Spatial expression of three NF-YBs was observed in all cell layers of roots under both mock and mycorrhizal conditions. Simultaneous knockdown of three NF-YBs, but not individually, reduced the fungal colonization level, suggesting that there might be functional redundancy of NF-YBs to regulate AM symbiosis. Collectively, our data suggest that NF-YC3 and NF-YBs positively regulate AM symbiosis in tomato, and arbuscule-related NF-YC3 may be an important downstream gene of the common symbiosis signaling pathway.

Enhanced Vascular-like Network Formation of Encapsulated HUVECs and ADSCs Coculture in Growth Factors Conjugated GelMA Hydrogels.

Tissue engineering primarily aimed to alleviate the insufficiency of organ donations worldwide. Nonetheless, the survival of the engineered tissue is often compromised due to the complexity of the natural organ architectures, especially the vascular system inside the organ, which allows food-waste transfer. Thus, vascularization within the engineered tissue is of paramount importance. A critical aspect of this endeavor is the ability to replicate the intricacies of the extracellular matrix and promote the formation of functional vascular networks within engineered constructs. In this study, human adipose-derived stem cells (hADSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured in different types of gelatin methacrylate (GelMA). In brief, pro-angiogenic signaling growth factors (GFs), vascular endothelial growth factor (VEGF165) and basic fibroblast growth factor (bFGF), were conjugated onto GelMA via an EDC/NHS coupling reaction. The GelMA hydrogels conjugated with VEGF165 (GelMA@VEGF165) and bFGF (GelMA@bFGF) showed marginal changes in the chemical and physical characteristics of the GelMA hydrogels. Moreover, the conjugation of these growth factors demonstrated improved cell viability and cell proliferation within the hydrogel construct. Additionally, vascular-like network formation was observed predominantly on GelMA@GrowthFactor (GelMA@GF) hydrogels, particularly on GelMA@bFGF. This study suggests that growth factor-conjugated GelMA hydrogels would be a promising biomaterial for 3D vascular tissue engineering.

Excess Mortality in Individuals with Autism Spectrum Disorder: A Population-Based Cohort Study.

Purpose: Autism spectrum disorder (ASD) may be associated with increased mortality, but relevant findings have been inconsistent. The modifying effects of gender and intellectual disability on excess mortality in individuals with ASD are underexplored. Patients and Methods: Using Taiwan's National Health Insurance Research Database and the National Death Registry, this population-based cohort study selected the data of 75,946 patients with ASD (ASD cohort) and 75,946 age group-, gender-, and income-matched (1:1) patients without ASD (non-ASD cohort). Cox proportional hazards models were used to compare mortality rates between the cohorts, and stratified analyses were used to evaluate the influence of gender and intellectual disability on mortality risk. Results: The ASD cohort had higher mortality rates for all causes of death than did the non-ASD cohort (adjusted hazard ratio 1.64, 95% confidence interval 1.54-1.75). Comorbid intellectual disability was associated with an increased risk of mortality, and this association was stronger in female patients than in male patients. Moreover, when focusing on deaths from natural causes, we found a significantly higher odds ratio for mortality in the ASD population with ID compared to those without ID. Conclusion: ASD is associated with increased mortality, especially among female individuals and those with intellectual disability.

Mandatory monthly outpatient visits could improve therapeutic inertia in patients with poorly controlled type 2 diabetes.

AIMS/INTRODUCTION: Delayed intensification of treatment, or therapeutic inertia, increases the risk of diabetic complications and death. The aim of this study was to determine the effect of mandatory monthly outpatient visits on therapeutic inertia in patients with suboptimal control of type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study used data from the Chang Gung Research Database and defined two study periods: the baseline period and the intervention period. The intervention period began when the Kaohsiung branch initiated a mandatory monthly outpatient visits program. Type 2 diabetes patients with baseline glycated hemoglobin (HbA1c) >7% and a follow-up HbA1c measurement were enrolled in each period, and divided into a Kaohsiung branch (intervention) group and the other branches (control) group. Therapy intensification was evaluated by comparing prescriptions after the follow-up HbA1c measurement with the prescriptions after the baseline HbA1c measurement. RESULTS: A total of 5,045 patients at the Kaohsiung branch and 13,400 participants at other branches were enrolled in the baseline period; and 5,573 and 15,603 patients, respectively, were enrolled in the intervention period. The adjusted odds ratio (AOR) for therapy intensification in patients with baseline HbA1c ≥9% was not significantly higher at 1.21 (95% CI, 1.00-1.47) in the intervention period at the Kaohsiung branch, but was significantly higher (AOR, 1.53; 95% CI, 1.02-2.30) in the subgroup with worsened HbA1c. CONCLUSIONS: Mandatory monthly outpatient visits could improve therapeutic inertia in patients with poorly controlled type 2 diabetes, especially in those with worsened control. The trajectory of HbA1c could significantly influence the assessment of the prevalence of therapeutic inertia.

Analysis of effectiveness and outcome of traumatic brain injury treatment in ED during COVID-19 pandemic: A multicenter in Taiwan.

The coronavirus disease 2019 has become a threat to global healthcare because of its rapid spread and evolution. In severe cases, the initial management of the disease is mainly supportive therapy and mechanical ventilation. Therefore, we investigated whether a modified emergency department workflow affects the efficacy will influence the efficacy and patient outcomes of traumatic brain injury (TBI) in Taiwan. This retrospective observational study used the Chang Gung Research Database in Taiwan from 7 hospitals in the Chang Gung Memorial Hospital System. Clinical index parameters and treatment efficiencies were analyzed between the locally transmitted period (January 20, 2020-June 7, 2020, period 2) and the community spread period (May 19, 2021-July 27, 2021, period 4) with the same interval of the pre-pandemic in 2019 as a reference period. During the locally transmitted period, only the time interval for patients who had to wait for a brain CT examination was, on average, 7.7 minutes shorter, which reached statistical significance. In addition, the number of TBI patients under 18 years of age decreased significantly during the community spread period. The "Door to the operating room (OR)," with polymerase chain reaction (PCR) testing, was on average 109.7 minutes slower than without the PCR testing in the reference period 2019. TBI treatment efficiency was delayed because of the PCR test. However, the surgical volume and functional outcome during these 2 periods were statistically insignificant compared to the pre-pandemic period because the spread of the virus was well controlled and hospital capacity was increased.

Acute heart failure with mildly reduced ejection fraction and myocardial infarction: a multi-institutional cohort study.

BACKGROUND: Little research has been done on ischemic outcomes related to left ventricular ejection fraction (EF) in acute decompensated heart failure (ADHF). METHODS: A retrospective cohort study was conducted between 2001 and 2021 using the Chang Gung Research Database. ADHF Patients discharged from hospitals between January 1, 2005, and December 31, 2019. Cardiovascular (CV) mortality and heart failure (HF) rehospitalization are the primary outcome components, along with all-cause mortality, acute myocardial infarction (AMI) and stroke. RESULTS: A total of 12,852 ADHF patients were identified, of whom 2,222 (17.3%) had HFmrEF, the mean (SD) age was 68.5 (14.6) years, and 1,327 (59.7%) were males. In comparison with HFrEF and HFpEF patients, HFmrEF patients had a significant phenotype comorbid with diabetes, dyslipidemia, and ischemic heart disease. Patients with HFmrEF were more likely to experience renal failure, dialysis, and replacement. Both HFmrEF and HFrEF had similar rates of cardioversion and coronary interventions. There was an intermediate clinical outcome between HFpEF and HFrEF, but HFmrEF had the highest rate of AMI (HFpEF, 9.3%; HFmrEF, 13.6%; HFrEF, 9.9%). The AMI rates in HFmrEF were higher than those in HFpEF (AHR, 1.15; 95% Confidence Interval, 0.99 to 1.32) but not in HFrEF (AHR, 0.99; 95% Confidence Interval, 0.87 to 1.13). CONCLUSION: Acute decompression in patients with HFmrEF increases the risk of myocardial infarction. The relationship between HFmrEF and ischemic cardiomyopathy, as well as optimal anti-ischemic treatment, requires further research on a large scale.

Cardiovascular outcomes in hepatitis C virus infected patients treated with direct acting antiviral therapy: a retrospective multi-institutional study.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with increased cardiovascular risks. We aimed to investigate the impact of direct acting antiviral (DAA) on HCV-associated cardiovascular events. METHODS: In this retrospective cohort study, patients with the diagnosis of chronic HCV were retrieved from multi-institutional electronic medical records, where diagnosis of HCV was based on serum HCV antibody and HCV-RNA test. The patients eligible for analysis were then separated into patients with DAA treatment and patient without DAA treatment. Primary outcomes included acute coronary syndrome, heart failure (HF), venous thromboembolism (VTE), stroke, cardiovascular death, major adverse cardiovascular event (MACE), and all-cause mortality. Outcomes developed during follow-up were compared between DAA treatment and non-DAA treatment groups. RESULTS: There were 41 565 patients with chronic HCV infection identified. After exclusion criteria applied, 1984 patients in the DAA treatment group and 413 patients in the non-DAA treatment group were compared for outcomes using inverse probability of treatment weighting. Compared to patients in non-DAA treatment group, patients in DAA treatment group were associated with significantly decreased HF (hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.44-0.97, P = 0.035), VTE (HR: 0.19, 95% CI: 0.07-0.49, P = 0.001), MACE (HR: 0.73, 95% CI 0.59-0.92, P = 0.007), and all-cause mortality (HR: 0.50, 95% CI: 0.38-0.67, P < 0.001) at 3-year follow-up. CONCLUSIONS: Chronic HCV patients treated with DAA experienced lower rates of cardiovascular events and all-cause mortality than those without treatment. The reduction of VTE was the most significant impact of DAA treatment among the cardiovascular outcomes.

High-Bonding-Strength Polyimide Films Achieved via Thermal Management and Surface Activation.

In this study, thermal and argon (Ar) plasma/wetting treatments were combined to enhance the bonding strength of polyimide (PI) films. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was used to analyze the changes in the PI imidization degrees. The contact angles of the PI films were also measured. The results show that the contact angles of the fully cured PI films markedly decreased from 78.54° to 26.05° after the Ar plasma treatments. X-ray photoelectron spectroscopy (XPS) analysis was also conducted on the PI surfaces. We found that the intensities of the C-OH and C-N-H bonds increased from 0% to 13% and 29% to 57%, respectively, after Ar plasma activation. Such increases in the C-OH and C-N-H intensities could be attributed to the generation of dangling bonds and the breakage of the imide ring or polymer long chains. Shear tests were also conducted to characterize the bonding strength of the PI films, which, after being treated with the appropriate parameters of temperature, plasma power, and wetting droplets, was found to be excellent at greater than 35.3 MPa.

Functional and Anatomical Outcomes of Anti-Vascular Endothelial Growth Factor Treatment for Exudative Age-Related Macular Degeneration with or without Obstructive Sleep Apnea.

(1) To investigate the functional and anatomical outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with exudative age-related macular degeneration (AMD) with or without obstructive sleep apnea (OSA); (2) In total, 65 patients with AMD with or without OSA who received three consecutive doses of intravitreal anti-VEGF injections were enrolled. The primary outcomes-best-corrected visual acuity (BCVA) and central macular thickness (CMT)-were assessed at 1 and 3 months. Moreover, morphological changes observed through optical coherence tomography were analyzed; (3) In total, 15 of the 65 patients had OSA and were included in the OSA group; the remaining 50 patients were included in the non-OSA (control) group. At 1 and 3 months after treatment, BCVA and CMT had improved but did not differ significantly between the groups. More patients in the OSA group demonstrated subretinal fluid (SRF) resorption at 3 months after treatment than in the non-OSA group (p = 0.009). Changes in other imaging biomarkers, such as intraretinal cysts, retinal pigment epithelium detachment, hyperreflective dots, and ellipsoid zone disruptions, did not differ significantly between the groups; (4) Our results suggest that the BCVA and CMT outcomes 3 months after anti-VEGF treatment are similar between patients with and without OSA. Moreover, patients with OSA may exhibit superior SRF resorption. A large-scale prospective study is mandatory to evaluate the association between SRF resorption and visual outcomes in AMD patients with OSA.

Loss of MBNL1-mediated retrograde BDNF signaling in the myotonic dystrophy brain.

Reduced brain volume including atrophy in grey and white matter is commonly seen in myotonic dystrophy type 1 (DM1). DM1 is caused by an expansion of CTG trinucleotide repeats in the 3' untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene. Mutant DMPK mRNA containing expanded CUG RNA (DMPK-CUGexp) sequesters cytoplasmic MBNL1, resulting in morphological impairment. How DMPK-CUGexp and loss of MBNL1 cause histopathological phenotypes in the DM1 brain remains elusive. Here, we show that BDNF-TrkB retrograde transport is impaired in neurons expressing DMPK-CUGexp due to loss of cytoplasmic MBNL1 function. We reveal that mature BDNF protein levels are reduced in the brain of the DM1 mouse model EpA960/CaMKII-Cre. Exogenous BDNF treatment did not rescue impaired neurite outgrowth in neurons expressing DMPK-CUGexp, whereas overexpression of the cytoplasmic MBNL1 isoform in DMPK-CUGexp-expressing neurons improved their responsiveness to exogenous BDNF. We identify dynein light chain LC8-type 2, DYNLL2, as an MBNL1-interacting protein and demonstrate that their interaction is RNA-independent. Using time-lapse imaging, we show that overexpressed MBNL1 and DYNLL2 move along axonal processes together and that MBNL1-knockdown impairs the motility of mCherry-tagged DYNLL2, resulting in a reduced percentage of retrograde DYNLL2 movement. Examination of the distribution of DYNLL2 and activated phospho-TrkB (pTrkB) receptor in EpA960/CaMKII-Cre brains revealed an increase in the postsynaptic membrane fraction (LP1), indicating impaired retrograde transport. Finally, our neuropathological analysis of postmortem DM1 tissue reveals that reduced cytoplasmic MBNL1 expression is associated with an increase in DYNLL2 and activated pTrkB receptor levels in the synaptosomal fraction. Together, our results support that impaired MBNL1-mediated retrograde BDNF-TrkB signaling may contribute to the histopathological phenotypes of DM1.

Sex-Specific Effect of Obesity on Epiblepharon in Different Age Groups: A Case-Control Study.

Obesity has been regarded as a risk factor for several ocular diseases. This study aims to investigate the age- and sex-specific relationship between epiblepharon and obesity in children. A retrospective case-control study was conducted using the Chang Gung Research Database. Children ≤ 18 years of age with epiblepharon were identified from 1 January 2009 to 31 December 2019. Children were classified into three groups: normal, overweight and obese groups. A total of 513 patients and 1026 controls (57.7% males) aged 1 to 18 matched by sex and age were included in the analysis. The median body mass index (BMI) of children with epiblepharon was significantly higher than that of children without epiblepharon (p < 0.001). In the subgroup analysis, among boys aged 4 to 9 years, the BMI in boys with epiblepharon was significantly higher than that in boys without epiblepharon (p < 0.05) and the risk of epiblepahron in overweight/obese boys was significantly higher than in non-overweight boys (OR = 1.74, 95% CI = 1.07-2.82 for age 4 to 6; OR = 3.06, 95% CI = 1.56-6.03 for age 7 to 9). On the other hand, among girls aged 13 to 18 years, the BMI in adolescent girls with epiblepharon was significantly higher than that in the control group (p < 0.05) and overweight/obese girls had a statistically higher risk of persistent epiblepharon than non-overweight girls (OR = 3.70, 95% CI = 1.38-9.97). The association between obesity and epiblepharon varies in strength according to age in a sex-specific manner.

Inferring Mechanisms of Auditory Attentional Modulation with Deep Neural Networks.

Humans have an exceptional ability to extract specific audio streams of interest in a noisy environment; this is known as the cocktail party effect. It is widely accepted that this ability is related to selective attention, a mental process that enables individuals to focus on a particular object. Evidence suggests that sensory neurons can be modulated by top-down signals transmitted from the prefrontal cortex. However, exactly how the projection of attention signals to the cortex and subcortex influences the cocktail effect is unclear. We constructed computational models to study whether attentional modulation is more effective at earlier or later stages for solving the cocktail party problem along the auditory pathway. We modeled the auditory pathway using deep neural networks (DNNs), which can generate representational neural patterns that resemble the human brain. We constructed a series of DNN models in which the main structures were autoencoders. We then trained these DNNs on a speech separation task derived from the dichotic listening paradigm, a common paradigm to investigate the cocktail party effect. We next analyzed the modulation effects of attention signals during all stages. Our results showed that the attentional modulation effect is more effective at the lower stages of the DNNs. This suggests that the projection of attention signals to lower stages within the auditory pathway plays a more significant role than the higher stages in solving the cocktail party problem. This prediction could be tested using neurophysiological experiments.

Unprecedented outbreak of respiratory syncytial virus in Taiwan associated with ON1 variant emergence between 2010 and 2020.

An outbreak of respiratory syncytial virus (RSV) has been observed in Taiwan since August 2020. We reviewed a central laboratory-based surveillance network established over 20 years by Taiwan Centres for Disease Control for respiratory viral pathogens between 2010 and 2020.A retrospective study of children <5 years old hospitalized with RSV infection at Chang Gung Memorial Hospital between 2018 and 2020 was conducted, and samples positive for RSV-A were sequenced. Clinical data were obtained and stratified by genotype and year.Data from 2020 showed an approximately 4-fold surge in RSV cases compared to 2010 in Taiwan, surpassing previous years during which ON1 was prevalent. Phylogenetic analysis of G protein showed that novel ON1 variants were clustered separately from those of 2018 and 2019 seasons and ON1 reference strains. The variant G protein carried six amino acid changes that emerged gradually in 2019; high consistency was observed in 2020. A unique substitution, E257K, was observed in 2020 exclusively. The F protein of the variant carried T12I and H514N substitutions, which weren't at antigenic sites. In terms of multivariate analysis, age (OR: 0.97; 95% CI: 0.94-0.99; p = 0.02) and 2020 ON1 variant (OR:2.52; 95% CI:1.13-5.63; p = 0.025) were independently associated with oxygen saturation <94% during hospitalization.The 2020 ON1 variant didn't show higher replication or virulence compared with those in 2018 in our study. The unprecedented 2020 RSV epidemic may attribute to antigenic changes and lack of interferon-stimulated immunity induced by seasonal circulating virus under non-pharmaceutical intervention.

Statins to prevent pacing-induced cardiomyopathy: Evidence from the bench applied to clinical studies.

BACKGROUND: Pacing-induced cardiomyopathy is an undesired outcome in patients with atrioventricular block (AVB), and our animal model showed lipotoxic cardiomyopathy after pacing. OBJECTIVES: The purpose of this study was to explore the mechanisms and clinical outcomes of statins in AVB patients receiving pacing. METHODS: Rat ventricular cardiomyocytes were treated with atorvastatin, liver X receptor (LXR) agonist, and LXR antagonist during pacing. Pigs were divided into 3 groups: right ventricular pacing, pacing with concomitant atorvastatin treatment, and sham control. Clinically, we enrolled 1717 AVB patients who had received a permanent pacemaker from Chang Gung Memorial Hospital Medical database. The primary outcome (cardiovascular death or heart failure [HF] hospitalization) and individual outcome were compared between statin and nonstatin groups after inverse probability of treatment weighting. RESULTS: Lipid accumulation in rat cardiomyocytes by pacing was significantly reduced by treatment with LXR agonist and atorvastatin, whereas LXR antagonist counteracted the atorvastatin effect on lipid expression. Left ventricular ejection fraction (LVEF) was significantly lower in the AVB pig pacing group compared to the group concomitantly treated with atorvastatin. Moreover, lipid accumulation and fibronectin expression were significantly ameliorated by concomitant treatment with atorvastatin. In the clinical study, the statin group had a significantly lower risk of the primary outcome event (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.56-0.84), less HF hospitalization (HR 0.45; 95% CI 0.30-0.67), and higher LVEF than the nonstatin group. CONCLUSION: In experimental models, atorvastatin ameliorated lipid accumulation in cardiomyocytes and fibrosis in left ventricular myocardium induced by pacing. Clinically, treatment with statins was associated with less HF hospitalization and cardiovascular death in AVB patients receiving pacemaker therapy.

Helical structure motifs made searchable for functional peptide design.

The systematic design of functional peptides has technological and therapeutic applications. However, there is a need for pattern-based search engines that help locate desired functional motifs in primary sequences regardless of their evolutionary conservation. Existing databases such as The Protein Secondary Structure database (PSS) no longer serves the community, while the Dictionary of Protein Secondary Structure (DSSP) annotates the secondary structures when tertiary structures of proteins are provided. Here, we extract 1.7 million helices from the PDB and compile them into a database (Therapeutic Peptide Design database; TP-DB) that allows queries of compounded patterns to facilitate the identification of sequence motifs of helical structures. We show how TP-DB helps us identify a known purification-tag-specific antibody that can be repurposed into a diagnostic kit for Helicobacter pylori. We also show how the database can be used to design a new antimicrobial peptide that shows better Candida albicans clearance and lower hemolysis than its template homologs. Finally, we demonstrate how TP-DB can suggest point mutations in helical peptide blockers to prevent a targeted tumorigenic protein-protein interaction. TP-DB is made available at http://dyn.life.nthu.edu.tw/design/ .

Prevalence and diversity of rotavirus A in pigs: Evidence for a possible reservoir in human infection.

BACKGROUND: Rotavirus A (RVA) are a group of diverse viruses causing acute gastroenteritis (AGE) in humans and animals. Zoonotic transmission is an important mechanism for rotavirus evolution and strain diversity in humans, but the extent of pigs as a major reservoir for human infection is not clear. METHODS AND FINDINGS: We have surveyed 153 pig farms across Taiwan with a total of 4588 porcine stool samples from three age groups from 2014 to 2017. Nursing piglets (less than one month of age) had higher detection rate for rotavirus than older age groups. Five VP7 (G) genotypes and 5 VP4 (P) genotypes were found in a total of 14 different G/P genotype combinations. In addition, porcine RVA strains had 2 NSP4 (E) genotypes and 3 VP6 (I) genotypes. A P[3]-like genotype was also discovered among strains collected in 2016 and 2017. CONCLUSIONS: Most of the genes from Taiwanese porcine strains clustered with each other and the lineages formed by these strains were distinct from the sequences of numerous regional variants or globally circulating porcine strains, suggesting an independent evolutionary history for Taiwanese rotavirus genotypes. The close relationship among porcine RVA strains and some unique porcine-like genotypes detected sporadically among human children in swine farms illustrates that pigs might serve as a reservoir for potential zoonotic transmission and novel genotype evolution in Taiwan's insular environment.

Transcriptional Start Site Coverage Analysis in Plasma Cell-Free DNA Reveals Disease Severity and Tissue Specificity of COVID-19 Patients.

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.

Investigation of anxiety and depressive disorders and psychiatric medication use before and after cancer diagnosis.

OBJECTIVE: Data regarding the prevalence of depression and anxiety among cancer patients, especially before cancer diagnosis, remains scarce. This study investigated the prevalence of these conditions and associated drug use among cancer patients pre- and post-diagnosis. METHODS: This population-based cohort study using data from Taiwan's National Health Insurance Research Database recruited patients with a registered cancer diagnosis and matched control between January 1, 2000, and December 31, 2011. We compared the prevalence of anxiety and depressive disorders between cancer patients and non-cancer participants during a 2-year period both pre- and post-diagnosis by Pearson's chi-square test. Psychiatric medication use was also examined for the associated mental condition. RESULTS: We examined participants diagnosed with liver (N = 17,154), colorectal (N = 30,391), breast (N = 40,036), gynecological (N = 23,218), and lung (N = 15,671) cancer. Before the cancer diagnosis, the prevalence of depression was higher in non-cancer participants than in gynecological cancer patients (p = 0.018) but anxiety is higher in liver, colorectal, and lung cancer patients when compared to non-cancer participants (p < 0.05). After the cancer diagnosis, the prevalence of anxiety and depression became significantly higher in all enrolled cancer patients than non-cancer participants (p < 0.05). Similar results were observed in psychiatric medication use trends. CONCLUSIONS: This study proposed that patients with liver, colorectal, and lung cancer had an increased risk of developing anxiety, which might be a sentinel diagnosis. The participants had a significantly higher level of anxiety and depressive disorder post-diagnosis, which highlights the importance of the care for both mental and physical conditions in cancer management.

Sapoviruses detected from acute gastroenteritis outbreaks and hospitalized children in Taiwan.

BACKGROUND/PURPOSE: Sapoviruses (SaVs) become important pathogens causing both sporadic and outbreaks of acute gastroenteritis (AGE) after rotavirus vaccination era worldwide. SaVs were included in AGE screening items when norovirus and rotavirus were negative in Taiwan CDC since 2008. However, no complete SaV genome sequence of any genotype detected in Taiwan was determined. This study aimed to investigate SaVs infection and complete genome sequences detected in Taiwan. METHODS: This prospective survey, SaVs samples with untyped or weak PCR result were selected for testing the new design qRT-PCR assay from AGE hospitalized children during 2008-2011, 2016-2017 and AGE outbreak in 2012-2014. Those were genetically characterized using long RT-PCR with different primer combinations as well as primer independent deep sequencing and with 5' RACE and 3' terminal region targeting RT-PCR. RESULTS: Overall, 14 SaV-AGE hospitalized children and 4 SaV-AGE outbreaks were enrolled in this study. In addition to the AGE symptoms, 6 children also showed URI symptoms (cough, pharyngitis, rhinorrhea and nasal congestion). The detected 19 SaVs were classified as eight genotypes (GI.1, GI.2, GI.3, GII.2, GII.3, GII.5, GII.8, and GIV.1) and the complete genome sequence of representative strain for each genotype were determined except GI.3. The GII.3 was the most major genotype following GI.1 and GIV.1. CONCLUSION: Our result confirmed that SaV is one of the pathogens detected from Taiwanese AGE patients. Multiple SaV genotype strains would associate with AGE as similar to those detected in different countries/areas. The whole genome of SaV strains detected including rarely reported GII.8 was firstly determined.