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Adult T-cell leukemia/lymphoma (ATL) is a genetically complex hematological malignancy derived from mature T cells. Using an integrative approach, we previously identified genes recurrently associated with super-enhancers in ATL. One of those genes was TP73, a TP53 family gene; however, the roles and function of TP73 and its super-enhancer in ATL pathogenesis are poorly understood. Our study demonstrates that TP73 is highly activated under the control of a super-enhancer in ATL cells but not in normal T cells or other hematological malignancies examined. Full-length TP73 is required for ATL cell maintenance in vitro and in vivo via the regulation of cell proliferation and DNA damage response pathways. Notably, recurrent deletions of TP73 exons 2-3 were observed in a fraction of primary ATL cases that harbored the super-enhancer, while induction of this deletion in cell lines further increased proliferation and mutational burden. Our study suggests that formation of the TP73 intragenic super-enhancer and genetic deletion are likely sequentially acquired in relation to intracellular state of ATL cells, which leads to functional alteration of TP73 that confers additional clonal advantage.

INTRODUCTION: Dose escalation is one of the treatment approaches studied and suggested in advanced therapies for Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to identify and characterize the dosing escalation patterns of advanced therapies in CD and UC. METHODS: Two systematic literature reviews (SLRs) were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE®, Embase®, and Cochrane Library were searched for articles published between January 2011 and October 2021 and limited to non-interventional studies in English language. Congress and bibliographic searches were also conducted. Articles were screened by two independent researchers. Dose escalation patterns were described and summarized considering the regional regulatory label recommendation (in North America [NA] or outside of North America [ONA]). RESULTS: Among 3190 CD and 2116 UC articles identified in the Ovid searches, 100 CD and 54 UC studies were included in the SLR, with more studies conducted ONA. Most studies reported an initial maintenance dose pattern aligned with the lower starting dose per local regulatory label; however, several ONA studies (n = 13 out of 14) reported ustekinumab every 8 weeks as starting maintenance pattern in CD. In ONA studies, the median within-guideline escalation rates in CD and UC were 43% in ustekinumab (CD only), 33% and 32% for vedolizumab; 29% and 39% for adalimumab; and 14% and 10% for infliximab. Evidence regarding dose escalation patterns for tofacitinib, certolizumab pegol, and golimumab was limited. Some dose escalation patterns outside of label recommendations were observed including ustekinumab every 8 weeks to every 4 weeks and vedolizumab every 8 weeks to every 6 weeks. CONCLUSION: Dose escalation strategies are widely documented in the literature. The reported dose escalation patterns and escalation rates vary by region and by CD and UC. Most escalation patterns reported were aligned with regulatory recommendations while some reported more diverse or aggressive dose escalation. PROSPERO REGISTRATION: CRD42021289251.

Background Stroke may cause debilitating neurological deficiencies that result in motor, sensory, and cognitive deficits and poorer psychosocial functioning. Prior studies have provided some initial evidence for the significant roles of health literacy and poor oral health for old people. However, few studies have focused on the health literacy of individuals who had a stroke; therefore, the relationships between the health literacy and oral health-related quality of life (OHRQoL) among middle-aged and older adults who had a stroke are unknown. We aimed to assess the relationships between stroke prevalence, health literacy status, and OHRQoL in middle-aged and older adults. Methods We retrieved the data from The Taiwan Longitudinal Study on Aging, a population-based survey. For each eligible subject, we gathered data in 2015 on age, sex, level of education, marital status, health literacy, the activity daily living (ADL), stroke history and OHRQoL. We evaluated the respondents’ health literacy by using a nine-item health literacy scale and categorized their health literacy level as low, medium, or high. OHRQoL was identified based on the Taiwan version of the Oral Health Impact Profile (OHIP-7T). Results The final study contained 7702 community-based dwelling elderly people (3630 male and 4072 female) were analysis in our study. Stroke history was reported in 4.3% of participants, 25.3% reported low health literacy, and 41.9% had at least one ADL disability. Furthermore, 11.3% of participants had depression, 8.3% had cognitive impairment, and 3.4% had poor OHRQoL. Age, health literacy, ADL disability, stroke history, and depression status were significantly associated with poor OHRQoL after sex and marital status was adjusted. Medium (odds ratio [OR] = 1.784, 95% confidence interval [CI] = 1.177, 2.702) to low health literacy (OR = 2.496, 95% CI = 1.628, 3.828) was significantly associated with poor OHRQoL. Conclusions Base our study results, people with stroke history had poor OHRQoL. Lower health literacy and ADL disability were associated with worse QHRQoL. Further studies are necessary to define practical strategies for reducing the risk of stroke and oral health with constantly lower health literacy, thereby improving the quality of life and providing health care of older people.

Although multiple studies have shown that resettled refugee women are less likely to receive preventative cancer screenings like pap smears and mammograms, a small number have demonstrated the opposite. This retrospective chart review, conducted between January 2017 and October 2018, compares pap smear and mammogram rates of patients seen in a refugee-specific OB/GYN clinic with patients from the general OB/GYN clinic at the same institution. Data from 298 patients (149 refugee and 149 general clinic patients matched by age and date-of-visit) were analyzed. Pap smear screening rates were 90.60% in the refugee group and 73.83% in the general group [p

Abstract Fluoroscopy-induced chronic radiation dermatitis (FICRD) is a complication of fluoroscopy-guided intervention. Unlike acute radiation dermatitis, FICRD is different as delayed onset and usually appears without preexisting acute dermatitis. Unfortunately, the chronic and progressive pathology of FICRD makes it difficult to treat, and some patients need to receive wide excision and reconstruction surgery. Due to lack of standard treatment, investigating underlying mechanism is needed in order to develop an effective therapy. Herein, the Hippo pathway is specifically identified using an RNA-seq analysis in mild damaged skin specimens of patients with FICRD. Furthermore, specific increase of the Yes-associated protein (YAP1), an effector of the Hippo pathway, in skin region with mild damage plays a protective role for keratinocytes via positively regulating the numerous downstream genes involved in different biological processes. Interestingly, irradiated-keratinocytes inhibit activation of fibroblasts under TGF-β1 treatment via remote control by an exosome containing YAP1. More importantly, targeting one of YAP1 downstream genes, nuclear receptor subfamily 3 group C member 1 (NR3C1), which encodes glucocorticoid receptor, has revealed its therapeutic potential to treat FICRD by inhibiting fibroblasts activation in vitro and preventing formation of radiation ulcers in a mouse model and in patients with FICRD. Taken together, this translational research demonstrates the critical role of YAP1 in FICRD and identification of a feasible, effective therapy for patients with FICRD. Key messages • YAP1 overexpression in skin specimens of radiation dermatitis from FICRD patient. • Radiation-induced YAP1 expression plays protective roles by promoting DNA damage repair and inhibiting fibrosis via remote control of exosomal YAP1. • YAP1 positively regulates NR3C1 which encodes glucocorticoid receptor expression. • Targeting glucocorticoid receptor by prednisolone has therapeutic potential for FICRD patient.

With the increasing concerns for environmental pollution, photocatalysts have been attracting attention due to their environmentally friendly characteristics, low cost, and simple processing. Titanium dioxide (TiO2) has been commonly used as a photocatalyst owing to its white pigment, excellent photocatalytic activity and low cost; however, its poor pollutant adsorption properties and high electron-hole recombination ratio limit its practical application. Transition metals such as nickel exhibit excellent electron-trapping capability, lowering the rate of electron-hole recombination and facilitating the generation of oxygen free radicals. One-dimensional nanofibers fabricated by electrospinning methods not only develop mesopores but can also make photocatalytic materials with a relatively high specific surface area, thereby increasing the adsorption of pollutants. In this study, transition metal-embedded TiO2 was fabricated by an electrospinning method, and the influence of post-calcination in a reducing atmosphere on the photocatalytic activity was investigated. The photocatalytic properties were performed by decomposition of Rhodamine B under visible light irradiation using fabricated material. Among the investigated samples, Ni-embedded TiO2 nanofibers showed the fastest decomposition of Rhodamine B under visible light irradiation due to a relatively high number of oxygen vacancies, lower Fermi level, small particle size, well-developed mesopores and relatively high specific surface area.

Background Timely tracking of health outcomes is difficult in low- and middle-income countries without comprehensive vital registration systems. Community health workers (CHWs) are increasingly collecting vital events data while delivering routine care in low-resource settings. It is necessary, however, to assess whether routine programmatic data collected by CHWs are sufficiently reliable for timely monitoring and evaluation of health interventions. To study this, we assessed the consistency of vital events data recorded by CHWs using two methodologies—routine data collected while delivering an integrated maternal and child health intervention, and data from a birth history census approach at the same site in rural Nepal. Methods We linked individual records from routine programmatic data from June 2017 to May 2018 with those from census data, both collected by CHWs at the same site using a mobile platform. We categorized each vital event over a one-year period as ‘recorded by both methods,’ ‘census alone,’ or ‘programmatic alone.’ We further assessed whether vital events data recorded by both methods were classified consistently. Results From June 2017 to May 2018, we identified a total of 713 unique births collectively from the census (birth history) and programmatic maternal ‘post-delivery’ data. Three-fourths of these births (n = 526) were identified by both. There was high consistency in birth location classification among the 526 births identified by both methods. Upon including additional programmatic ‘child registry’ data, we identified 746 total births, of which 572 births were identified by both census and programmatic methods. Programmatic data (maternal ‘post-delivery’ and ‘child registry’ combined) captured more births than census data (723 vs. 595). Both methods consistently classified most infants as ‘living,’ while infant deaths and stillbirths were largely classified inconsistently or recorded by only one method. Programmatic data identified five infant deaths and five stillbirths not recorded in census data. Conclusions Our findings suggest that data collected by CHWs from routinely tracking pregnancies, births, and deaths are promising for timely program monitoring and evaluation. Despite some limitations, programmatic data may be more sensitive in detecting vital events than cross-sectional census surveys asking women to recall these events.

Supercapacitors are promising energy storage devices with high charging/discharging speeds and power densities. To improve their poor stability, we fabricated electrodes by integrating perovskite materials (La0.8Sr0.2Mn0.5Co0.5O3-δ, LSMCO) possessing redox reaction ability with graphene nanoplatelets exhibiting good electronic properties. One of the resultant composites (L25G70) demonstrated high capacitance and excellent capacitance retention (95% after 5000 cycles). These results are superior to other electrodes (L50G45 and L75G20) containing a larger ratio of LSMCO, even L75G20 did not exhibit supercapacitor behavior after 3000 cycles. GN can induce structural distortion in LSMCO, thereby the high amount of adsorbed oxygen per lattice oxygen can explain the best electrochemical performance of L25G70, while structural collapse rationalized the failure of L75G20. The findings of this study demonstrated that the use of LSMCO can improve the cycling stability of supercapacitors.

Groundwater plays an important role in mitigating drought. It is necessary to analyze the spatiotemporal variation characteristics of groundwater and establish an appropriate assessment for the risk of drought for disaster prevention. This study developed a novel approach for the drought risk assessment system based on the Hilbert Huang Transform (HHT) method to understand the spatial distribution of the risk of drought in terms of groundwater. We analyzed drought vulnerability applying the HHT to analyze the variation characteristics of groundwater level spatiotemporally and the physical mechanism of groundwater factors to quantify groundwater sensitivity to the environment, and present the resilience of each region. Furthermore, the drought hazard was determined using the standardized precipitation index and the dynamic drought intensity gave the durability characteristics of each region. The drought exposure was also investigated, which quantifies the water demand to satisfy people’s livelihoods for a certain population density. Based on the framework proposed in this study, an overall risk map of droughts in the Pingtung Plain was obtained. This study effectively classified the main time–frequency characteristics, the availability of groundwater, and the risk of drought in each region. A total of 11 of the 45 groundwater monitoring stations are located at the highest risk of level 5, most of which are located in the coastal area of Gaoping River and Linbian River. Over-pumping should be avoided in these areas. On the contrary, the alluvial fan area showed the lowest groundwater risk of drought. The results can be adopted for water management, drought resilience, sustainable development of groundwater resources, and decision making in determining drought risk.

Soft-hard magnetic composites have attracted much attention as magnetic materials for permanent magnets due to high coercivity and saturation magnetization in various fields such as motor, storage device and magnetic actuators. Hard magnetic materials with low saturation magnetization improve magnetic properties through exchange coupling effect with soft magnetic materials. Rare earth metals, which are used as magnetic materials in permanent magnetic, have issued such as high cost due to resource scarcity. Transition metals have been used for fabricating magnetic material with high magnetic properties due to low cost and abundant in the resource. Spinel magnetic materials with transition metals have excellent chemical, thermal stability, large magnetocrystalline anisotropy and magnetic properties. Composite magnetic materials in one dimensional (1D) morphology are effective in improving coercivity. In this work, soft-hard composite fiber has been fabricated by electrospinning method using iron oxide as soft magnetic material and cobalt ferrite as hard magnetic material. The change in the oxidation state of iron oxide can be controlled with sintering atmosphere and influences on the magnetic properties. In comparing with simple CoFe2O4, the fabricated Fe3O4–CoFe2O4 exhibits excellent saturation magnetization of 133.63 emu g−1 and enhanced coercivity of 2746.9 Oe.

IRF4 is a master regulator of immunity and is also frequently overexpressed in mature lymphoid neoplasms. Here, we demonstrate the oncogenicity of IRF4 in vivo, its potential effects on T-cell development and clonal evolution using a zebrafish model. IRF4-transgenic zebrafish develop aggressive tumors with massive infiltration of abnormal lymphocytes that spread to distal organs. Many late-stage tumors are mono- or oligoclonal, and tumor cells can expand in recipient animals after transplantation, demonstrating their malignancy. Mutation ofp53accelerates tumor onset, increases penetrance, and results in tumor heterogeneity. Surprisingly, single-cell RNA-sequencing reveals that the majority of tumor cells are double-negative T-cells, many of which expresstcr-γ that became dominant as the tumors progress, whereas double-positive T-cells are largely diminished. Gene expression and epigenetic profiling demonstrates thatgata3, mycb, lrrn1, patl1andpsip1are specifically activated in tumors, while genes responsible for T-cell differentiation includingid3are repressed.IRF4-driven tumors are sensitive to the BRD inhibitor.

The vision-based smart driving technologies to increase road safety are the popular research topics for modern automobile industries. The development of precise moving object detection with continuously tracking capability is the most important technology for such purpose nowadays. In this paper, we propose an improved object detection system, which combines a selected object detector with its enhancements and long short term memory (LSTM) modules, to improve the detection performance for smart driving systems. First, from a selected object detector, we combine all vehicle classes and bypassing low-level features to improve its detection performance. After the spatial association of the detected objects, the outputs of the improved objector are then fed into the proposed double-layer LSTM (dLSTM) modules to successfully improve the detection of the vehicles in various conditions, including the newly-appeared, the detected and the gradually-disappearing vehicles. With stage-by-stage evaluations, the experimental results show that the proposed vehicle detection system with the improved procedures and dLSTM modules can precisely detect the vehicles without increasing computations.

Flank wear is the most common wear that happens in the end milling process. However, the process of detecting the flank wear is cumbersome. To achieve comprehensively automatic detecting the flank wear area of the spiral end milling cutter, this study proposed a novel flank wear detection method of combining the template matching and deep learning techniques to expand the curved surface images into panorama images, which is more available to detect the flank wear areas without choosing a specific position of cutting tool image. You Only Look Once v4 model was employed to automatically detect the range of cutting tips. Then, popular segmentation models, namely, U-Net, Segnet and Autoencoder were used to extract the areas of the tool flank wear. To evaluate the segmenting performance among these models, U-Net model obtained the best maximum dice coefficient score with 0.93. Moreover, the predicting wear areas of the U-Net model is presented in the trend figure, which can determine the times of the tool change depend on the curve of the tool wear. Overall, the experiments have shown that the proposed methods can effectively extract the tool wear regions of the spiral cutting tool. With the developed system, users can obtain detailed information about the cutting tool before being worn severely to change the cutting tools in advance.

Based on the concept of an imagined future community, this article analyzes the relationship between the establishment of a national biobank (Taiwan Biobank) and nation-building. This article examines (1) the shift in state policy from pursuing a Sci-Tech Island to an Island of Biomedical Technology for the purpose of strengthening the national economy and Taiwan’s global competitiveness in biomedicine, (2) the discourses about the uniqueness of the Taiwanese genome as a niche in the competitive global biomedical market, and (3) scientists’ imaginary of the necessity of a national genetic project for the health of Taiwan’s future generations. By exploring how the discourse of the Taiwanese genome as a niche has been constructed, this article reveals that life science and scientists’ imaginary of the futurity who have played important roles in Taiwan’s nation-building. We argue that the future imaginaries contained in the scientific discourse regarding Taiwan Biobank reflect the ideas of global scientific competition, connections between genetic distinctness and nationality, and the health of future generations in Taiwan.

An ongoing novel coronavirus outbreak (COVID-19) started in Wuhan, China, in December 2019. Currently, the spatiotemporal epidemic transmission, prediction, and risk are insufficient for COVID-19 but we urgently need relevant information globally. We have developed a novel two-stage simulation model to simulate the spatiotemporal changes in the number of cases and estimate the future worldwide risk. Simulation results show that if there is no specific medicine for it, it will form a global pandemic. Taiwan, South Korea, Hong Kong, Japan, Thailand, and the United States are the most vulnerable. The relationship between each country's vulnerability and days before the first imported case occurred shows an exponential decrease. We successfully predicted the outbreak of South Korea, Japan, and Italy in the early stages of the global pandemic based on the information before February 12, 2020. The development of the epidemic is now earlier than we expected. However, the trend of spread is similar to our estimation.

As the glomerular filtration rate (GFR) decreases, it can cause imbalance in some divalent elements. These imbalances can cause increased oxidative stress in patients with renal impairment. The aim of present study was to investigate the changes of these divalent elements with CKD progression. One hundred and ninety-four patients with chronic kidney diseases (CKD) were divided into five stages, stage 1, 2, 3a, 3b, 4, and were recruited into this study. The divalent elements, calcium, magnesium, phosphorus, as well as iron, zinc, and copper were determined in clinical chemistry analyzer. Higher CKD stages were found to be associated with increased levels of phosphorus and copper; Ptrend values were 0.002 and 0.004, respectively. Also, higher CKD stages were associated with decreased levels of zinc; Ptrend value was 0.002, after adjustment for age, gender, smoke, education, diabetes, hypertension, and BMI. Decreased levels of zinc and elevated levels of phosphorus and copper might increase the oxidative stress and complications in CKD patients. Future randomized studies are needed to show whether adjusting dietary intake of phosphorus, copper, and zinc might affect the progression of CKD.

The need for greater interest in and the study of the pedestrian protection system is growing in the effort to minimize the human and material damages from traffic accidents and to improve traffic safety. Among the numerous methods for distinguishing key characteristics, particularly among those used for detecting pedestrians, the most frequently used method is the one that recognizes key characteristics using Histogram of Oriented Gradient (HOG). The method that relies on HOG for detecting pedestrians, however, requires a massive amount of calculations and is currently seeing a falling recognition rate owing to its unnecessary dimensions. As such, an algorithm with an improved pedestrian recognition rate was designed and realized in this study by reducing the number of dimensions for the characteristic vectors through the minimization of the unnecessary cell histogram calculations and the adoption of the UDP dimension reduction method. The developed algorithm was confirmed from such assessment that the algorithm demonstrated an about 11% processing speed improvement compared to HOG, the existing pedestrian recognition algorithm, and an about 3.98% recognition rate improvement and a 31% calculation speed improvement.

With the recent increased interest in atmospheric pollutants in South Korea, studies on the analysis and forecast of atmospheric pollution using Internet-of-Things technology have been actively conducted. To forecast atmospheric pollution, a multiple regression analysis technique based on statistical techniques, data mining, and an analysis technique combining time series models have typically been used. In terms of accuracy, however, multiple regression analysis is insufficient for analyzing atmospheric environment data in South Korea. In addition, although the time series analysis technique is appropriate for analyzing linear data, it is inappropriate for analyzing atmospheric environment data in South Korea, where linear and nonlinear data are mixed. Therefore, this study proposes a seasonal auto regressive integrated moving average–support vector machine (SARIMA–SVM) time series analysis algorithm, combining time series analysis and nonlinear analysis, for data analysis of atmospheric environment information and improvement of pollution forecast accuracy. The proposed algorithm analyzes the seasonality in environmental contamination by using the SARIMA model, and succeeds in improving accuracy in the contamination forecast through an analysis of linear and nonlinear characteristics by applying an SVM nonlinear regression model. A comparative assessment with the existing atmospheric contamination forecast algorithm was conducted as well. The assessment results show that the forecast accuracy of the proposed algorithm improved by 20.81% for fine dust, and by 43.77% for ozone, compared to the performance of the existing models.

Activated carbon nanofibers were prepared with polymer blends that consisted of polyacrylonitrile (PAN) and cellulose acetate (CA), by electrospinning and subsequent thermal treatment. The average fiber diameter of samples was about 200 nm, ranging from 150 to 400 nm. The specific surface area, total pore volume, and micropore volume increased with increasing CA content. As the CA content was increased up to 20%, the pore characteristics for the adsorption performance were enhanced. However, excess CA content (over 30%) was harmful to volatile organic compounds (VOCs) adsorption ability due to changing morphology of the activated carbon nanofibers. The O/C ratio was increased with increasing CA content. However, the O/C ratios of all activated carbon nanofibers prepared with blends represent small values revealing non-polarity of the surface. The adsorption capacities of PC10, PC09, PC08 and PC07 were 65 g/100 g, 66 g/100 g, 72 g/100 g and 67 g/100 g. The blends of the PAN with CA showed better characteristics than those of PAN alone, but apparently there is an appropriate blending ratio (20%) for high-performance of activated carbonaceous materials.