Numerous pathogenic
exon 9 mutations have been identified in myeloproliferative neoplasms (MPN), with type 1 (52bp deletion;
) and type 2 (5bp insertion;
) being the most prevalent. Despite the ...universal pathobiology of MPN driven by various
mutants, it is unclear why different
mutations result in diverse clinical phenotypes. Through RNA sequencing followed by validation at the protein and mRNA levels, we found that S100A8 was specifically enriched in
but not in
MPN-model cells. The expression of
could be regulated by STAT3 based on luciferase reporter assay complemented with inhibitor treatment. Pyrosequencing demonstrated relative hypomethylation in two CpG sites within the potential pSTAT3-targeting
promoter region in
cells as compared to
cells, suggesting that distinct epigenetic alteration could factor into the divergent S100A8 levels in these cells. The functional analysis confirmed that S100A8 non-redundantly contributed to accelerated cellular proliferation and reduced apoptosis in
cells. Clinical validation showed significantly enhanced
expression in
-mutated MPN patients compared to
-mutated cases, and thrombocytosis was less prominent in those with
upregulation. This study provides indispensable insights into how different
mutations discrepantly drive the expression of specific genes that contributes to unique phenotypes in MPN.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Facing the emerging COVID viral variants and the uneven distribution of vaccine worldwide, imported pre-symptomatic COVID-19 cases play a pivotal role in border control strategies. A stochastic ...disease process and computer simulation experiments with Bayesian underpinning was therefore developed to model pre-symptomatic disease progression during incubation period on which we were based to provide precision strategies for containing the resultant epidemic caused by imported COVID-19 cases. We then applied the proposed model to data on 1051 imported COVID-19 cases among inbound passengers to Taiwan between March 2020 and April 2021. The overall daily rate (per 100,000) of pre-symptomatic COVID-19 cases was estimated as 106 (95% credible interval (CrI): 95-117) in March-June 2020, fell to 37 (95% CrI: 28-47) in July-September 2020 (p < 0.0001), resurged to 141 (95% CrI: 118-164) in October-December 2020 (p < 0.0001), and declined to 90 (95% CrI: 73-108) in January-April 2021 (p = 0.0004). Given the median dwelling time, over 82% cases would progress from pre-symptomatic to symptomatic phase in 5-day quarantine. The time required for quarantine given two real-time polymerase chain reaction (RT-PCR) tests depends on the risk of departing countries, testing and quarantine strategies, and whether the passengers have vaccine jabs. Our proposed four-compartment stochastic process and computer simulation experiments design underpinning Bayesian MCMC algorithm facilitated the development of precision strategies for imported COVID-19 cases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The prevalence of inflammatory bowel disease (IBD) has increased worldwide. The prevalence of metabolic dysfunction associated fatty liver disease (MAFLD) has also risen. However, there is limited ...research on the connection between MAFLD and IBD in the Asian population. This study aims to analyze the prevalence and clinical significance of MAFLD in Taiwanese IBD patients with clinical remission. We retrospectively analyzed IBD patients who received transient elastography for liver fibrosis and controlled attenuation parameter evaluation for liver steatosis. This study enrolled 120 patients with IBD, including 45 Crohn’s disease (CD) and 75 ulcerative colitis (UC). MAFLD prevalence in IBD was 29.2%. Patients with MAFLD had a shorter disease duration (2.8 years vs. 5.3 years, p = 0.017), higher alanine aminotransferase levels (24 U/L vs. 17 U/L, p = 0.003), a lower estimated glomerular filtration rate (91.37 mL/min/1.73 m2 vs. 103.92 mL/min/1.73 m2, p = 0.004), and higher γ-glutamyl transferase (γ-GT) (24 mg/dL vs. 13 mg/dL, p < 0.001). The prevalence of significant fibrosis in IBD with MAFLD was 17.1%. Significant fibrosis was found in older age (58.5 years vs. 40 years, p = 0.004) and the high type 2 diabetes mellitus proportion (50.0% vs. 10.3%, p = 0.049). A trend of longer disease duration was found in significant fibrosis (4.9 years vs. 1.6 years, p = 0.051). The prevalence of MALFD in IBD was 29.2%. and 17.1% of them had significant fibrosis. In addition to the intestinal manifestation, the study findings remind clinicians that they should be aware of the possibility of hepatic complications for IBD patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by ...measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death.
Methods
Among 549,091 women, covering approximately 30% of the Swedish screening‐eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression.
Results
Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51‐0.68 P < .001) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66‐0.84 P < .001).
Conclusions
Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.
Substantial and significant reductions in the incidence rates of fatal breast cancer and advanced breast cancer with 10 years of follow‐up are observed in this analysis of greater than one‐half million Swedish women participating and not participating in breast cancer screening. These comparisons are contemporaneous, and thus are not influenced by changes in therapeutic regimens.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Neuromorphic computation possesses the advantages of self‐learning, highly parallel computation, and low energy consumption, and is of great promise to overcome the bottleneck of von Neumann ...computation. In this work, a series of poly(3‐hexylthiophene) (P3HT)‐based block copolymers (BCPs) with different coil segments, including polystyrene, poly(2‐vinylpyridine) (P2VP), poly(2‐vinylnaphthalene), and poly(butyl acrylate), are utilized in photosynaptic transistor to emulate paired‐pulse facilitation, spike time/rate‐dependent plasticity, short/long‐term neuroplasticity, and learning−forgetting−relearning processes. P3HT serves as a carrier transport channel and a photogate, while the insulating coils with electrophilic groups are for charge trapping and preservation. Three main factors are unveiled to govern the properties of these P3HT‐based BCPs: i) rigidity of the insulating coil, ii) energy levels between the constituent polymers, and iii) electrophilicity of the insulating coil. Accordingly, P3HT‐b‐P2VP‐based photosynaptic transistor with a sought‐after BCP combination demonstrates long‐term memory behavior with current contrast up to 105, short‐term memory behavior with high paired‐pulse facilitation ratio of 1.38, and an ultralow energy consumption of 0.56 fJ at an operating voltage of −0.0003 V. As far as it is known, this is the first work to utilize conjugated BCPs in an electret‐free photosynaptic transistor showing great potential to the artificial intelligence technology.
A series of poly(3‐hexylthiophene) (P3HT)‐based block copolymers with different coil segments, including polystyrene, poly(2‐vinylpyridine) (P2VP), poly(2‐vinylnaphthalene), and poly(butyl acrylate), are utilized in photosynaptic transistor to emulate pair‐pulse facilitation, spike time/rate‐dependent plasticity, short/long‐term neuroplasticity, and learning−forgetting−relearning processes. Accordingly, P3HT‐b‐P2VP‐based device shows an ultralow energy consumption of 0.56 fJ at an operating voltage of −0.0003 V.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Hepatitis B surface antigen (HBsAg) seroclearance, an indicator of recovery from hepatitis B virus (HBV) infection, is uncommon in long-term nucleos(t)ide analog (NUC) therapy. We compared the ...incidence of HBsAg seroclearance in patients with and without NUC discontinuation to identify predictors of HBsAg seroclearance. This retrospective study enrolled adult patients with a chronic HBV infection followed for ≥12 months after NUC discontinuation (finite group) and those treated with NUCs for >3 years (non-finite group). Demographic, clinical, and laboratory data were analyzed. The study cohort included 978 patients, including 509 and 469 patients in the finite and non-finite groups, respectively. Cumulative HBsAg seroclearance incidence was significantly higher in the finite group than in the non-finite group (p = 0.006). The 5- and 10-year cumulative HBsAg seroclearance incidence were 6.6% and 18.9% in the finite group and 3% and 14.6% in the non-finite group, respectively. The likelihood of HBsAg seroclearance was higher in those with end of treatment (EOT) HBsAg levels of <100 IU/mL and in those without clinical relapse (CR). The cumulative 3-year CR incidence was 16.8%. The incidence of liver decompensation and hepatocellular carcinoma were 4.1 and 0.4 per 1000 person-years, respectively. The hepatocellular carcinoma incidence did not significantly differ between the finite and non-finite groups (p = 0.941). In conclusion, higher HBsAg seroclearance incidence in patients receiving finite therapy, and the increased likelihood of HBsAg seroclearance in those with EOT HBsAg levels of <100 IU/mL and in those without CR should be considered during decision-making of treatment options.
Background Afatinib is one of the standard treatments for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). However, data on the use of afatinib in ...patients with poor performance status (PS greater than or equai to 2) are limited. This study aimed to retrospectively review the clinical outcomes and safety of afatinib treatment in EGFR-mutation-positive (EGFRm+) NSCLC patients with PS greater than or equai to 2. Methods The data for 62 patients who were treated at Linkou Chang Gung Memorial Hospital from January 2010 to August 2019 were retrospectively reviewed. Patients' clinicopathological features were obtained, and univariate and multivariate analyses were performed to identify possible prognostic factors. Data on adverse events were collected to evaluate general tolerance for afatinib therapy. Results Until February 2020, the objective response rate, disease control rate, median progression-free survival (PFS), and overall survival (OS) were 58.1% (36/62), 69.4% (43/62), 8.8 months, and 12.9 months, respectively. The absence of liver metastasis (PFS: p = 0.044; OS: p = 0.061) and good disease control (p < 0.001 for PFS and OS) were independent favorable prognostic factors for PFS and OS. Bone metastasis (p = 0.036) and dose modification (reduction/interruption, p = 0.021) were predictors of disease control. Conclusion Afatinib demonstrated acceptable efficacy and safety in the current cohort. This study provided evidence to support the use of afatinib as a first-line treatment in EGFRm+ NSCLC patients with poor PS. Keywords: Lung cancer, Afatinib, EGFR, TKI, Performance status
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With the maturity and popularity of Internet of Things (IoT), the notion of Social Internet of Things (SIoT) has been proposed to support novel applications and networking services for the IoT in ...more effective and efficient ways. Although there are many works for SIoT, they focus on designing the architectures and protocols for SIoT under the specific schemes. How to efficiently utilize the collaboration capability of SIoT to complete complex tasks remains unexplored. Therefore, we propose a new problem family, namely, Task-Optimized SIoT Selection (TOSS) , to find the best group of IoT objects for a given set of tasks in the task pool. TOSS aims to select the target SIoT group such that the target SIoT group is able to easily communicate with each other while maximizing the accuracy of performing the given tasks. We propose two problem formulations, named Bounded Communication-loss TOSS (BC-TOSS) and Robustness Guaranteed TOSS (RG-TOSS) , for different scenarios and prove that they are both NP-hard and inapproximable. We propose a polynomial-time algorithm with a performance guarantee for BC-TOSS, and an efficient polynomial-time algorithm to obtain good solutions for RG-TOSS. Moreover, as RG-TOSS is NP-hard and inapproximable within any factor, we further propose Structure-Aware Reinforcement Learning (SARL) to leverage the Graph Convolutional Networks (GCN) and Deep Reinforcement Learning (DRL) to effectively solve RG-TOSS. Further, since we use graph models to simulate the problem instance for DRL, which is different from the real ones, we propose Structure-Aware Meta Reinforcement Learning (SAMRL) for fast adapting to new domains. Experimental results on multiple real datasets indicate that our proposed algorithms outperform the other deterministic and learning-based baseline approaches.
Sediment flushing and the morphological responses to the procedure of check dam removal are still unclear. Following laboratory experiments that revealed three stages (deepening, widening, and volume ...release) of check dam adjustment, a check dam built in 2007 at Landao Creek in central Taiwan was adjusted in 2015 by removing central bars and cutting 2.5 m from the middle two piers (stage 1 + 2), with the purpose of regulating sediment transfer and keeping the thalweg at the center of the channel, while also preventing hill slope toe erosion. In 2019, four central piers were removed (stage 3) to increase the volume of sediment released. Annual surveys were conducted after the initial adjustment in 2015 through to 2020 using unmanned aerial vehicles (UAVs). The check dam adjustments revealed that the channel had narrowed and stabilized as indicated by regenerating riparian vegetation. Additionally, distinct terraces had formed on the hill slope toes of the creek channel in proximity to the check dam. The meander upstream weakened following the dam adjustments. This study combining laboratory experiments with actual field observation contributed immensely to check dam decommissioning. Additionally, this study illustrated how an adjustable check dam may aid regulation of sediment transport and thereby sediment balance. It can be adjusted accordingly based on the prevailing channel condition.
The check dam removal guide consists of three stages.
Stage 1: cutting the central portion deeper.
Stage 2: widens the opening.
Stage 3: complete removal. While the adjustable check dam can be adjusted freely in each stage according to the demand of the sediment budget.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Chronic hepatitis B (CHB) relapse occurs after the cessation of nucleos(t)ide analogues (NUC) therapy due to the waning of viral suppression. Few studies have investigated the viral relapse rate and ...clinical relapse rate after tenofovir alafenamide (TAF) therapy. We compared the CHB relapse rate between TAF and entecavir therapy. We enrolled patients with chronic hepatitis B who underwent TAF or entecavir therapy. NUC therapy was terminated after HBeAg loss for 1 year in HBeAg-positive patients and after undetectable serum HBV DNA on three separate tests each >6 months apart in HBeAg-negative patients. After cessation of NUC therapy, we followed alanine aminotransferase (ALT) levels at 12, 24, and 48 weeks. Serum HBV DNA levels were checked if patients showed a two-fold elevation from the upper limit of normal ALT levels (41 IU/mL). Clinical relapse (CR) was defined as a two-fold elevation in ALT levels and HBV DNA levels > 2000 IU/mL. We then investigated the CR rate of HBV after cessation of TAF and entecavir therapy at 12, 24, and 48 weeks. Of the 117 patients enrolled, 78 were in the entecavir group and 39 were in the TAF group. At 12 weeks after cessation of NUC therapy, no patients had HBV CR in the entecavir group. However, three patients (CR cumulative rate 7.9%) had CR in the TAF group. At 24 weeks, the CR cumulative rate in the entecavir and TAF groups were 1.3% and 13.2%, respectively (
< 0.05). At 48 weeks, the CR cumulative rates were 9.2% and 24.2%, respectively (
= 0.055). Patients in the TAF group had a higher cumulative rate of CR than those in the entecavir group (log-rank
= 0.023). Furthermore, patients in the TAF group had earlier CR times than those in the entecavir group, especially in the first 24 weeks after cessation of therapies (
< 0.05). The cessation of TAF therapy had significantly earlier and higher CR rates than that of entecavir therapy. Close monitoring of liver function and HBV DNA levels may be necessary, especially within 24 weeks after cessation of TAF therapy.
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