Improved automated spot counting and modeling with bias correction.

A complete workflow was presented for estimating the concentration of microorganisms in biological samples by automatically counting spots that represent viral plaque forming units (PFU) bacterial colony forming units (CFU), or spot forming units (SFU) in images, and modeling the counts. The workflow was designed for processing images from dilution series but can also be applied to stand-alone images. The accuracy of the methods was greatly improved by adding a newly developed bias correction method. When the spots in images are densely populated, the probability of spot overlapping increases, leading to systematic undercounting. In this paper, this undercount issue was addressed in an empirical way. The proposed empirical bias correction method utilized synthetic images with known spot sizes and counts as a training set, enabling the development of an effective bias correction function using a thin-plate spline model. Its application focused on the bias correction for the automated spot counting algorithm LoST proposed by Lin et al. Simulation results demonstrated that the empirical bias correction significantly improved spot counts, reducing bias for both fixed and random spot sizes and counts.

Automated Spot Counting in Microbiology.

Biological samples are routinely analyzed for microbe concentration. The samples are diluted, loaded onto established host cell cultures, and incubated. If infectious agents are present in the samples, they form circular spots that do not contain the host cells. Each spot is assumed to be originated from a single microbial unit such as a bacterial colony forming unit or viral plaque forming unit. The undiluted sample concentration is estimated by counting the spots and back-calculating. Counting the number of spots by trained technicians is currently the gold standard but it is laborious, subjective, and hard to scale. This paper presents a new automated algorithm for spot counting, Localized and Sequential Thresholding (LoST). Validation studies showed that LoST performance was comparable with manual counting and outperformed several existing tools on images with overlapping spots. The LoST algorithm employs sequential thresholding through a two-stage segmentation and borrows information across all images from the same dilution series to fine-tune the count and identify right censoring. The algorithm increases the efficiency of the spot counting and the quality of the downstream analysis, especially when coupled with an appropriate statistical serial dilution model to enhance the undiluted sample concentration estimation procedure.

Impact of early phase COVID-19 precautionary behaviors on seasonal influenza in Hong Kong: A time-series modeling approach.

Background: Before major non-pharmaceutical interventions were implemented, seasonal incidence of influenza in Hong Kong showed a rapid and unexpected reduction immediately following the early spread of COVID-19 in mainland China in January 2020. This decline was presumably associated with precautionary behavioral changes (e.g., wearing face masks and avoiding crowded places). Knowing their effectiveness on the transmissibility of seasonal influenza can inform future influenza prevention strategies. Methods: We estimated the effective reproduction number (R t ) of seasonal influenza in 2019/20 winter using a time-series susceptible-infectious-recovered (TS-SIR) model with a Bayesian inference by integrated nested Laplace approximation (INLA). After taking account of changes in underreporting and herd immunity, the individual effects of the behavioral changes were quantified. Findings: The model-estimated mean R t reduced from 1.29 (95%CI, 1.27-1.32) to 0.73 (95%CI, 0.73-0.74) after the COVID-19 community spread began. Wearing face masks protected 17.4% of people (95%CI, 16.3-18.3%) from infections, having about half of the effect as avoiding crowded places (44.1%, 95%CI, 43.5-44.7%). Within the current model, if more than 85% of people had adopted both behaviors, the initial R t could have been less than 1. Conclusion: Our model results indicate that wearing face masks and avoiding crowded places could have potentially significant suppressive impacts on influenza.

Associations of Chinese Herbal Medicine Use with the Risks of Acute Exacerbation and Mortality in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Retrospective Cohort Study.

Objectives: This study aimed to assess the correlation of exacerbation and the mortality rate in patients with chronic obstructive pulmonary disease (COPD) between biomedical treatments with or without Chinese herbal medicine (CHM) as an adjunct. Design: A total of 81,261 COPD patients were identified from the National Health Insurance Research Database in Taiwan between 2001 and 2012. After screening and matching, 3176 COPD patients were included in the study. Statistical analyses were performed to assess the differences in the baseline characteristics. The authors used the Cox proportional hazard regression analysis to calculate the risks of mortality and hospitalization due to acute exacerbation of COPD within 1 year between a CHM user cohort and non-CHM user cohort. The cumulative incidence of mortality in COPD patients with or without CHM treatment was calculated by the Kaplan-Meier method. Results: COPD patients in the CHM user cohort demonstrated a significantly lower risk of mortality (p < 0.001) and acute exacerbation (p < 0.05), compared with the non-CHM user cohort. In addition, the CHM users exhibited a reduced cumulative incidence of mortality compared with the non-CHM user cohort (p < 0.001). Xiao Qing Long Tang and Fritillariae thunbergii were the most common Chinese herbal formula and single Chinese herb prescribed for COPD patients. Conclusion: Combining CHM with biomedical treatment might reduce the risk of acute exacerbation and incidence of mortality in patients with COPD.

Prediction of stroke using an algorithm to estimate arterial stiffness.

BACKGROUND: Arterial stiffness is important because it is associated with adverse cardiovascular events including stroke. Methods that are based on pulse wave velocity have significant limitations in estimating arterial stiffness. The purpose of this paper is to present a novel easy to apply non-invasive method to estimate arterial stiffness that is based on pulse pressure. METHODS: Two indices to estimate arterial stiffness, (1) arterial stiffness 1 (AS1) and (2) arterial stiffness 2 (AS2) were developed and applied in two National Institutes of Health funded clinical trials, the Systolic Hypertension in the Elderly Program and the Systolic Blood Pressure Intervention Trial. These indices were developed by fitting individual survival models for selected predictor variables to the response, i.e. time to stroke, by selecting the coefficients that were statistically significant at the 0.05 α level after adjusting the variable weights. The indices were derived as the weighted linear combination of the coefficients. RESULTS: AS1 and AS2 performed well in two goodness of fit criteria i.e. overall model p-value and concordance correlation. Comparison of Cox models using indices AS1 and AS2 and chronological age indicated that AS1 and AS2 independently predicted the occurrence of stroke at five years better than chronological age. Nearly identical effects were observed when the analyses were limited to Black participants in SPRINT with a concordance correlation of 0.80 and log rank test p-value of 0.007. CONCLUSION: These indices that are derived from pulse pressure predict the occurrence of stroke better than either pulse pressure or chronological age alone and may be used in designing new randomized clinical trials, and possibly incorporated in hypertension and stroke guidelines.

Prognostics for lithium-ion batteries using a two-phase gamma degradation process model.

To address the degradation of rechargeable batteries, this paper presents a two-phase gamma process model with a fixed change-point for modeling the voltage-discharge curves of battery cycle aging under a constant current. The model can be applied to estimate the state of charge (SOC) and the remaining useful discharge time (RUT) in a cycle with consideration of the effect of cycle aging, and can also be applied to estimate the state of life (SOL) and the remaining useful life (RUL) across cycles. The applications of the proposed model are demonstrated using the experimental cycle aging data of a lithium iron phosphate battery. A comparison shows that the proposed model generates a more accurate prediction than the conventional two-term exponential model with capacity data under a particle filter framework, and this reveals the superiority of modeling with voltage over modeling with capacity. The analytical expression of mean useful discharge time in a cycle (or mean time to failure) is developed with approximation by a Taylor expansion and the Birnbaum-Saunders distribution, and the result is shown to be in good agreement with the true mean of a gamma process.

Successful intervention with Chinese herbal medicine for hyperthyroidism: Two case reports and a literature review.

BACKGROUND: Hyperthyroidism, the excessive production of thyroid hormones, is most commonly attributed to autoimmune dysfunction such as Graves' disease. Western medical treatment of hyperthyroidism includes antithyroid medications, radioiodine, and thyroidectomy, all of which are associated with side effects. We describe the successful treatment of two patients with Graves' disease who used Chinese herbal medicine (CHM) with or without Western medicine. CASE PRESENTATION: Both cases (a 50-year-old female [case 1] and a 56-year-old male [case 2]) received the Chinese herbal formula Jia Wei Xiao Yao San (JWXYS) as well as Prunella vulgaris, Fritillaria thunbergii, and Crassostrea gigas. Elevated thyroid hormone levels were restored to normal after 10 months of treatment in case 1 and 8 months in case 2. Neither patient experienced any complications or side effects during CHM treatment. Notably, symptoms and thyroid hormone levels have remained well controlled in both patients over 1 year of follow-up until the time of this report. To explore the possible mechanisms involved in CHM treatment of hyperthyroidism, we searched biomedical literature databases and reviewed the literature up to June 2020. CONCLUSIONS: As for the hyperthyroidism almost was controlled by Western medicine instead of CHM, we report that JWXYS as well as Prunella vulgaris, Fritillaria thunbergii, and Crassostrea gigas was a safe and effective formula and we propose that CHM may be considered as either a first choice or combination therapy to control hyperthyroidism.

Use of advanced statistical techniques to predict all-cause mortality in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) was conducted in patients with hypertension and additional risk for cardiovascular disease who were randomized to the intensive blood pressure group targeting systolic blood pressure (SBP) less than 120 mm Hg and to the standard group where the target was less than 140 mm Hg. Analyses were done in the matched group of participants with the same gender, same age (±2 years) and same SBP (±3 mm Hg) at three months of treatment regardless of initial randomization to intensive or standard group (shaded area in Figure 1). METHODS AND RESULTS: During 3.26 years of follow-up, intensive group participants had 14.8 mm Hg lower SBP and received on average one more (2.8 vs. 1.8) blood pressure lowering medications. This was associated with lower all-cause mortality in the intensive treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90, p = 0.003). The effect on SBP was achieved at 3 months and remained unchanged thereafter. This paper addresses two questions with respect to all-cause mortality in SPRINT in the matched set. 1) What is the effect of receiving more than one drug on all-cause mortality. Conditional logistic regression for all-cause mortality with respect to number of drugs indicated that during the 3.26 years of follow-up persons who received more than one drug were more likely to die (coefficient = 0.5039, OR = 1.6552, p = 0.0322) than patients who received one drug. 2) Was there a U curve relationship between on treatment SBP and all-cause mortality? A U curve fitting a quadratic equation (parabola) of SBP and all-cause death was observed. This was seen in the patients randomized to the standard target group in unadjusted analyses as well as in analyses adjusted for demographics or all covariates (p < 0.001 for all). The U curves in the combined group and the intensive treatment group were less pronounced. CONCLUSION: SPRINT participants who were matched for gender, age, and SBP at 3 months, and received more than one drug had higher all-cause mortality during the 3.26 years of follow-up. Those who were randomized to standard treatment target had a U curve relationship between SBP at three months and all-cause mortality. The U curves in the combined group and the intensive treatment group were less pronounced.

Automated tongue diagnosis on the smartphone and its applications.

Tongue features are important objective basis for clinical diagnosis and treatment in both western medicine and Chinese medicine. The need for continuous monitoring of health conditions inspires us to develop an automatic tongue diagnosis system based on built-in sensors of smartphones. However, tongue images taken by smartphone are quite different in color due to various lighting conditions, and it consequently affects the diagnosis especially when we use the appearance of tongue fur to infer health conditions. In this paper, we captured paired tongue images with and without flash, and the color difference between the paired images is used to estimate the lighting condition based on the Support Vector Machine (SVM). The color correction matrices for three kinds of common lights (i.e., fluorescent, halogen and incandescent) are pre-trained by using a ColorChecker-based method, and the corresponding pre-trained matrix for the estimated lighting is then applied to eliminate the effect of color distortion. We further use tongue fur detection as an example to discuss the effect of different model parameters and ColorCheckers for training the tongue color correction matrix under different lighting conditions. Finally, in order to demonstrate the potential use of our proposed system, we recruited 246 patients over a period of 2.5 years from a local hospital in Taiwan and examined the correlations between the captured tongue features and alanine aminotransferase (ALT)/aspartate aminotransferase (AST), which are important bio-markers for liver diseases. We found that some tongue features have strong correlation with AST or ALT, which suggests the possible use of these tongue features captured on a smartphone to provide an early warning of liver diseases.

The involvement of serotonin receptors in suanzaorentang-induced sleep alteration.

Sedative-hypnotic medications, including benzodiazepines and non-benzodiazepines, are usually prescribed for the insomniac patients; however, the addiction, dependence and adverse effects of those medications have drawn much attention. In contrast, suanzaorentang, a traditional Chinese herb remedy, has been efficiently used for insomnia relief in China, although its mechanism remains unclear. This study was designed to further elucidate the underlying mechanism of suanzaorentang on sleep regulation. One ingredient of suanzaorentang, zizyphi spinosi semen, exhibits binding affinity for serotonin (5-hydroxytryptamine, 5-HT) receptors, 5-HT(1A) and 5-HT(2), and for GABA receptors. Our previous results have implicated that GABA(A) receptors, but not GABA(B), mediate suanzaorentang-induced sleep alteration. In current study we further elucidated the involvement of serotonin. We found that high dose of suanzaorentang (4 g/kg/2 ml) significantly increased non-rapid eye movement sleep (NREMS) when comparing to that obtained after administering starch placebo, although placebo at dose of 4 g/kg also enhanced NREMS comparing with that obtained from baseline recording. Rapid eye movement sleep (REMS) was not altered. Administration of either 5-HT(1A) antagonist (NAN-190), 5-HT(2) antagonist (ketanserin) or 5-HT(3 )antagonist (3-(4-Allylpiperazin-1-yl)-2-quinoxalinecarbonitrile) blocked suanzaorentang-induced NREMS increase. These results implicate the hypnotic effect of suanzaorentang and its effects may be mediated through serotonergic activation, in addition to GABAergic system.