Perturbation of periodic spot-generation balance leads to diversified pigmentation patterning of harlequin Phalaenopsis orchids: in silico prediction.

BACKGROUND: A retrotransposon HORT1 in the promoter of the anthocyanin activator gene PeMYB11, microRNA858 (miR858) that targets PeMYB11, and a repressor PeMYBx have been implicated in pigmentation patterning diversity of harlequin Phalaenopsis orchids. However, the interrelationship among them remains to be elucidated. RESULTS: To understand how these factors interact to generate anthocyanin spots in Phalaenopsis, we successfully developed a mathematical model based on the known reaction-diffusion system to simulate their interplay and refined the conceptual biological model. Intriguingly, the expression of both PeMYBx and PeMYB11 were in phase for purple spot formation, even though they showed adverse effects on anthocyanin accumulations. An increase in the self-activation rate of PeMYB11 resulted in the increased size of purple spots, but no effects on spot fusion. Decreased degradation rate of miR858 in the purple regions, led to disruption of the formation of spotted pigmentation patterning and a full-red pigmentation pattern. Significantly, the reduced miR858 level promotes the fusion of large dark purple dots induced by the solo-LTR of HORT1, eventually generating the purple patches. In addition, the spatially heterogeneous insertion of HORT1 caused by the remnant solo-LTR of HORT1 derived from random homologous unequal recombination of HORT1 in individual cells of floral organs could explain the diverse pigmentation patterning of harlequin Phalaenopsis. CONCLUSIONS: This devised model explains how HORT1 and miR858 regulate the formation of the pigmentation patterning and holds great promise for developing efficient and innovative approaches to breeding harlequin Phalaenopsis orchids.

Early changes in skin surface temperature predict body temperature increases in patients with fever: A pilot study.

OBJECTIVE: To investigate the correlation between body temperature and skin surface temperature in intensive care unit patients and to identify specific indicators of skin surface temperature for early fever detection. RESEARCH METHODOLOGY/DESIGN: This pilot study was a prospective, observational investigation conducted at National Cheng Kung University Hospital in Tainan, Taiwan. A total of 54 patients admitted to the Surgical Intensive Care Unit of a tertiary hospital between April and August 2020 were included. Patients utilized the wearable device HEARThremoTM to continuously monitor skin surface temperature and heart rate. Analysis of Variance was applied to identify the association of skin surface temperature with different body temperature groups. The comparison between skin surface temperature and fever over eight time intervals was studied using a generalized estimating equation. RESULTS: In 34 patients (63 %) with a fever (≥38 °C), skin surface temperature increased (P < 0.001) when body temperature increased. The maximum skin surface temperature was significantly associated with fever 180-210 min before the fever events occurred (OR: 2.22, 95 % CI: 1.30-3.80). The mean skin surface temperature was associated with fever 120-150 min before the fever events (OR: 8.70, 95 % CI: 2.08-36.36). CONCLUSIONS: Skin surface temperature can be an important early predictive sign before the onset of fever. Continuous temperature monitoring can detect fever early and initiate treatment in advance. This study serves as a preliminary exploration in this area, laying the groundwork for future comprehensive research. IMPLICATIONS FOR CLINICAL PRACTICE: Continuous monitoring of skin surface temperature empowers nurses to swiftly detect fever, transcending conventional methods. This proactive approach allows for the early identification of physiological abnormalities, facilitating the prompt initiation of further physical assessments and relevant examinations for early treatment commencement.

Improvement of Sensitivity of Pooling Strategies for COVID-19.

Group testing (or pool testing), for example, Dorfman's method or grid method, has been validated for COVID-19 RT-PCR tests and implemented widely by most laboratories in many countries. These methods take advantages since they reduce resources, time, and overall costs required for a large number of samples. However, these methods could have more false negative cases and lower sensitivity. In order to maintain both accuracy and efficiency for different prevalence, we provide a novel pooling strategy based on the grid method with an extra pool set and an optimized rule inspired by the idea of error-correcting codes. The mathematical analysis shows that (i) the proposed method has the best sensitivity among all the methods we compared, if the false negative rate (FNR) of an individual test is in the range [1%, 20%] and the FNR of a pool test is closed to that of an individual test, and (ii) the proposed method is efficient when the prevalence is below 10%. Numerical simulations are also performed to confirm the theoretical derivations. In summary, the proposed method is shown to be felicitous under the above conditions in the epidemic.

An Innovative Wearable Device For Monitoring Continuous Body Surface Temperature (HEARThermo): Instrument Validation Study.

BACKGROUND: Variations in body temperature are highly informative during an illness. To date, there are not many adequate studies that have investigated the feasibility of a wearable wrist device for the continuous monitoring of body surface temperatures in humans. OBJECTIVE: The objective of this study was to validate the performance of HEARThermo, an innovative wearable device, which was developed to continuously monitor the body surface temperature in humans. METHODS: We implemented a multi-method research design in this study, which included 2 validation studies-one in the laboratory and one with human subjects. In validation study I, we evaluated the test-retest reliability of HEARThermo in the laboratory to measure the temperature and to correct the values recorded by each HEARThermo by using linear regression models. We conducted validation study II on human subjects who wore HEARThermo for the measurement of their body surface temperatures. Additionally, we compared the HEARThermo temperature recordings with those recorded by the infrared skin thermometer simultaneously. We used intraclass correlation coefficients (ICCs) and Bland-Altman plots to analyze the criterion validity and agreement between the 2 measurement tools. RESULTS: A total of 66 participants (age range, 10-77 years) were recruited, and 152,881 completed data were analyzed in this study. The 2 validation studies in the laboratory and on human skin indicated that HEARThermo showed a good test-retest reliability (ICC 0.96-0.98) and adequate criterion validity with the infrared skin thermometer at room temperatures of 20°C-27.9°C (ICC 0.72, P<.001). The corrected measurement bias averaged -0.02°C, which was calibrated using a water bath ranging in temperature from 16°C to 40°C. The values of each HEARThermo improved by the regression models were not significantly different from the temperature of the water bath (P=.19). Bland-Altman plots showed no visualized systematic bias. HEARThermo had a bias of 1.51°C with a 95% limit of agreement between -1.34°C and 4.35°C. CONCLUSIONS: The findings of our study show the validation of HEARThermo for the continuous monitoring of body surface temperatures in humans.

Spatiotemporal Dynamics of Cerebral Vascular Permeability in Type 2 Diabetes-Related Cerebral Microangiopathy.

Aims: Diabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral vascular permeability (Ktrans) in the progression of type 2 diabetes mellitus (T2DM). Methods: Ktrans was cross-sectionally measured in T2DM and non-diabetes groups with or without CSVD using dynamic contrast-enhanced MRI (DCE-MRI). Results: In all patients with T2DM, the Ktrans of white matter (WM) was increased, whereas the Ktrans of gray matter (GM) was increased only in T2DM with CSVD. The involvement of WM was earlier than GM and was before the CSVD features could be visualized on MRI. Among the commonly available four CSVD items of MRI, microbleeds were the most sensitive, indicating the increased permeability in all patients. Increased Ktrans in T2DM was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces, in contrast to patients without diabetes. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs. Conclusions: This study highlights the early development of cerebral microangiopathy with increased BBB leakage in T2DM, before the CSVD features can be visualized on MRI. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.

Trajectories of hepatic and coagulation dysfunctions related to a rapidly fatal outcome among hospitalized patients with dengue fever in Tainan, 2015.

BACKGROUND: Hepatic dysfunction and coagulopathy are common in acute dengue illness. We analyzed the trajectories of the above parameters in the survivors and fatal patients in the outbreak in Tainan, 2015. METHODS: A retrospective study was conducted using data from a tertiary hospital between January and December 2015. Multilevel modeling (MLM) was used to identify the changes in aminotransferase (AST), alanine aminotransferase (ALT), activated partial thromboplastin time (aPTT), and platelet counts from Day 0 to Day 7 of the onset of dengue infection. The machine-learning algorithm was used by purity measure assumption to calculate the accuracy of serum transaminases and coagulation variables to discriminate between the fatal and survival groups. RESULTS: There were 4,069 dengue patients, of which 0.9% died in one week after illness onset (i.e., early mortality). Case fatality rate was the highest for those aged ≥70 years. Both AST and ALT values of the fatal group were significantly higher than those of the survivor group from Day 3 (AST median, 624 U/L vs. 60 U/L, p < 0.001; ALT median, 116 U/L vs. 29 U/L, p = 0.01) of illness onset and peaked on Day 6 (AST median, 9805 U/L vs. 90 U/L, p < 0.001; ALT median, 1504 U/L vs. 49 U/L, p < 0.001). AST ≥ 203 U/L, ALT ≥ 55 U/L, AST2/ALT criteria ≥337.35, or AST/platelet count ratio index (APRI) ≥ 19.18 on Day 3 of dengue infection had a high true positive rate, 90%, 78%, 100%, or 100%, respectively, of early mortality. The platelet counts of the fatal group declined significantly than those of the survivor group since Day 3 of illness onset (median, 19 x103/µl vs. 91 x103/µl, p < 0.01), and aPTT values of the fatal group significantly prolonged longer since Day 5 (median, 68.7 seconds vs. 40.1 seconds, p < 0.001). CONCLUSIONS: AST, ALT, and platelet counts should be monitored closely from Day 0 to Day 3 of dengue infection, and aPTT be followed up on Day 5 of infection to identify the individuals at risk for early mortality.

Symptoms associated with adverse dengue fever prognoses at the time of reporting in the 2015 dengue outbreak in Taiwan.

BACKGROUND: Tainan experienced the most severe dengue epidemic in Taiwan in 2015. This study investigates the association between the signs and symptoms at the time of reporting with the adverse dengue prognoses. METHODS: A descriptive study was conducted using secondary data from the Dengue Disease Reporting System in Tainan, Taiwan, between January 1 and December 31, 2015. A multivariate stepwise logistic regression was used to identify the risk factors for the adverse prognoses: ICU admissions and mortality. RESULTS: There were 22,777 laboratory-confirmed reported cases (mean age 45.6 ± 21.2 years), of which 3.7% were admitted to intensive care units (ICU), and 0.8% were fatal. The most common symptoms were fever (92.8%), myalgia (26.6%), and headache (22.4%). The prevalence of respiratory distress, altered consciousness, shock, bleeding, and thrombocytopenia increased with age. The multivariate analysis indicated that being in 65-89 years old age group [Adjusted Odds Ratio (aOR):4.95], or the 90 years old and above age group (aOR: 9.06), and presenting with shock (aOR: 8.90) and respiratory distress (aOR: 5.31) were significantly associated with the risk of ICU admission. While old age (aOR: 1.11), respiratory distress (aOR: 9.66), altered consciousness (aOR: 7.06), and thrombocytopenia (aOR: 2.55) were significantly associated with the risk of mortality. CONCLUSIONS: Dengue patients older than 65 and those with severe and non-specific signs and symptoms at the time of reporting were at a higher risk of ICU admission and mortality. First-line healthcare providers need to be aware of the varied presentations between the different age groups to allow early diagnosis and in-time management, which would prevent ICU admissions and fatalities in dengue patients.

High estimated prevalence of asymptomatic dengue viremia in blood donors during a dengue epidemic in southern Taiwan, 2015.

BACKGROUND: Southern Taiwan experienced a severe dengue epidemic in 2015. Adult asymptomatic cases would raise concerns on transfusion-transmitted dengue virus (DENV) infection. The aim of this study was to evaluate the magnitude of such a risk in Tainan City during this epidemic. STUDY DESIGN AND METHODS: The daily prevalence of asymptomatic dengue viremia in blood donors in Tainan City and in selected high-incidence districts during the 2015 dengue epidemic was estimated by an established mathematical model. Duration of viremia, duration of viremia before symptom onset, apparent-to-inapparent infection ratio, and reporting-to-underreporting ratio were four main parameters used in the model. RESULTS: The estimated maximal and mean daily prevalence of asymptomatic dengue viremia in blood donors in Tainan during this dengue epidemic was 74.4 (95% confidence interval [CI], 60.8-88.0) and 15.0 (95% CI, 12.3-17.7) per 10,000, respectively. In the district with the highest incidence, the maximal and mean daily prevalence of asymptomatic viremia was 328.8 (95% CI, 271.1-386.2) and 55.3 (95% CI, 43.4-63.3) per 10,000, respectively. Approximately 234 (95% CI, 191-276) blood components containing DENV were produced during the epidemic. CONCLUSION: Although dengue is currently not endemic in Taiwan, physicians need to be aware of the risk of transfusion-transmitted DENV infection. Our results suggest that screening measures to ensure blood safety should be evaluated and implemented during dengue epidemics even in nonendemic areas. Timely estimation of daily asymptomatic viremia prevalence by districts can help to select high-risk areas for such measures and to evaluate cost-effectiveness.

Effects of Estimators on Ultrasound Nakagami Imaging in Visualizing the Change in the Backscattered Statistics from a Rayleigh Distribution to a Pre-Rayleigh Distribution.

Ultrasound Nakagami imaging has recently attracted interest as an imaging technique for analyzing envelope statistics. Because the presence of structures has a strong effect on estimation of the Nakagami parameter, previous studies have indicated that Nakagami imaging should be used specifically for characterization of soft tissues with fewer structures, such as liver tissues. Typically, changes in the properties of the liver parenchyma cause the backscattered statistics to transform from a Rayleigh distribution to a pre-Rayleigh distribution, and this transformation can be visualized using a Nakagami imaging technique. However, different estimators result in different estimated values; thus, the performance of a Nakagami image may depend on the type of estimator used. This study explored the effects of various estimators on ultrasound Nakagami imaging to describe the backscattered statistics as they change from a Rayleigh distribution to a pre-Rayleigh distribution. Simulations and clinical measurements involving patients with liver fibrosis (n = 85) yielded image data that were used to construct B-mode and conventional Nakagami images based on the moment estimator (denoted as mINV images) and maximum-likelihood estimator (denoted as mML images). In addition, novel window-modulated compounding Nakagami images based on the moment estimator (denoted as mWMC images) were also obtained. The means and standard deviations of the Nakagami parameters were examined as a function of the backscattered statistics. The experimental results indicate that the mINV, mML and mWMC images enabled quantitative visualization of the change in backscattered statistics from a Rayleigh distribution to a pre-Rayleigh distribution. Importantly, the mWMC image is superior to both mINV and mML images because it simultaneously realizes sensitive detection of the backscattered statistics and a reduction of estimation variance for image smoothness improvement. We therefore recommend using mWMC image as a novel strategy in Nakagami imaging technique for liver tissue characterization.

Ultrasound temperature estimation based on probability variation of backscatter data.

PURPOSE: In recent years, ultrasound imaging has become an attractive modality for noninvasive temperature monitoring. Temperature variations that occur during tissue heating could induce changes in various acoustic parameters that may affect the echo interference so as to make ultrasound backscattering a random process. In this study, we assumed that the degree of variation in the probability distribution of the backscattered signals is temperature dependent. The feasibility of using the variation in the backscatter statistics for ultrasound temperature estimation was investigated in this study. METHODS: We tested this hypothesis by carrying out experiments on agar phantoms and tissue samples using a temperature-regulated water tank and a microwave ablation system. During heating, raw images of the backscattered-signal envelope of each phantom and tissue at temperatures ranging between 37 °C and 45 °C were acquired to construct the parametric matrix based on the ratio of the change in the Nakagami parameter (RCN), which was used as a quantitative measure of the backscatter statistics. The absolute value of the RCN (ARCN) matrix was obtained, to which a polynomial approximation was applied to obtain the ARCN(pa) image. RESULTS: The results showed that the RCN matrix locally increased or decreased with increasing temperature, indicating bidirectional changes in the backscatter statistics. We also found that the ARCN significantly increased with the temperature, demonstrating that the magnitude of the variation in the probability distribution of the backscattered-signal envelope is a monotonic function of temperature. Unlike the phantom, tissues tended to exhibit a nonlinear dependency of the ARCN on the temperature that may be attributable to tissue denaturation. Especially, the ARCN(pa) image is highly suitable for visualizing the contour of the temperature distribution during microwave ablation of tissue samples. CONCLUSIONS: This study has demonstrated that temperature changes are reflected in variations in the envelope statistics. This novel approach makes it possible to develop an ultrasound temperature imaging method for simultaneously estimating the thermal dose and the tissue properties.

Using ultrasound CBE imaging without echo shift compensation for temperature estimation.

Clinical trials have demonstrated that hyperthermia improves cancer treatments. Previous studies developed ultrasound temperature imaging methods, based on the changes in backscattered energy (CBE), to monitor temperature variations during hyperthermia. Echo shift, induced by increasing temperature, contaminates the CBE image, and its tracking and compensation should normally ensure that estimations of CBE at each pixel are correct. To obtain a simplified algorithm that would allow real-time computation of CBE images, this study evaluated the usefulness of CBE imaging without echo shift compensation in detecting distributions in temperature. Experiments on phantoms, using different scatterer concentrations, and porcine livers were conducted to acquire raw backscattered data at temperatures ranging from 37°C to 45°C. Tissue samples of pork tenderloin were ablated in vitro by microwave irradiation to evaluate the feasibility of using the CBE image without compensation to monitor tissue ablation. CBE image construction was based on a ratio map obtained from the envelope image divided by the reference envelope image at 37°C. The experimental results demonstrated that the CBE image obtained without echo shift compensation has the ability to estimate temperature variations induced during uniform heating or tissue ablation. The magnitude of the CBE as a function of temperature obtained without compensation is stronger than that with compensation, implying that the CBE image without compensation has a better sensitivity to detect temperature. These findings suggest that echo shift tracking and compensation may be unnecessary in practice, thus simplifying the algorithm required to implement real-time CBE imaging.

Using ultrasound Nakagami imaging to assess liver fibrosis in rats.

This study explored the feasibility of using the ultrasound Nakagami image to assess the degree of liver fibrosis in rats. The rat has been widely used as a model in investigations of liver fibrosis. Ultrasound grayscale imaging makes it possible to observe fibrotic rat livers in real time. Statistical analysis of the envelopes of signals backscattered from rat livers may provide useful clues about the degree of liver fibrosis. The Nakagami-model-based image has been shown to be useful for characterizing scatterers in tissues by reflecting the echo statistics, and hence the Nakagami image may serve as a functional imaging tool for quantifying rat liver fibrosis. To validate this idea, fibrosis was induced in each rat liver (n=21) by an intraperitoneal injection of 0.5% dimethylnitrosamine. Livers were excised from rats for in vitro ultrasound scanning using a single-element transducer. The backscattered-signal envelopes of the acquired raw ultrasound signals were used for Nakagami imaging. The Metavir score determined by a pathologist was used to histologically quantify the degree of liver fibrosis. It was found that the Nakagami image could be used to distinguish different degrees of liver fibrosis in rats, since the average Nakagami parameter increased from 0.55 to 0.83 as the fibrosis score increased from 0 (i.e., normal) to 4. This correlation may be due to liver fibrosis in rats involving an increase in the concentration of local scatterers and the appearance of the periodic structures or clustering of scatterers that would change the backscattering statistics. The current findings indicate that the ultrasound Nakagami image has great potential as a functional imaging tool to complement the use of the conventional B-scan in animal studies of liver fibrosis.