Individuals with higher suicide risk showed more anger and disgust during rest.

Previous research showed that suicide risk was associated with the anger trait and the facial expression of anger when advising on life dilemmas. We investigated if suicide risk was associated with the facial expression of anger during rest, a state when individuals often reflect upon their lives. Participants took a 1-min rest before being assessed for suicide risk. We measured 147 participants' frontal-view facial expressions during their rest 1475-3694 times using automated facial expression analysis technology. Participants' suicide risk was significantly positively correlated with their anger and disgust during the rest, which may be related to psychological pain and death-related thoughts among individuals with suicide risk. Therefore, rest for clinical patients should not be seen simply as a "rest" for the mind. Rather, for counselors, rest may open a window to look into patients' inner thoughts that may be important to their lives.

Global, region and national trends and age-period-cohort effects in colorectal cancer burden from 1990 to 2019, with predictions to 2039.

Nowadays, colorectal cancer (CRC) is the second leading cause of cancer deaths and contributes to a gradually increasing disease burden. We aimed to estimate the secular trends of global CRC burden, the effect of age, period, and birth cohort, and project the global burden over time. Based on the epidemiological CRC data from 1990 to 2019 in 204 countries and territories from GBD 2019, the estimated annual percentage change (EAPC), was calculated from a linear model and joinpoint regression model. We utilized an age-period-cohort model to reckon age, period, and birth cohort effects on CRC age-standardized rate. The burden of CRC was projected by conducting the BAPC model. Globally, there was a slight decline in the age-standardized DALY rate, which was more apparent in females, with high SDI regions and in Australia and Western Europe areas. Meanwhile, our model predicts a weaker increase in morbidity (EAPC of 0.37) and a speedier reduction in mortality (EAPC of -0.66) by the next 20 years. The relative risk of period for high SDI regions decreased from 1.08 (95%UI: 1.06-1.1) in 1990-1994 to 0.85 (95%UI:0.83-0.88) in 2015-2019, but worsens in low and middle SDI regions. The local drifts were more than 1 in the 30-34 and 35-39 age groups, indicating the rising tide of early-onset CRC. Given the gender and region-specific CRC, targeted efforts to reduce the prevalence of risk factors, improve screening coverage rates, and strengthen foundational medical facilities are necessary.

Evaluation of performance of distributed delay model for chemotherapy-induced myelosuppression.

The distributed delay model has been introduced that replaces the transit compartments in the classic model of chemotherapy-induced myelosuppression with a convolution integral. The maturation of granulocyte precursors in the bone marrow is described by the gamma probability density function with the shape parameter (ν). If ν is a positive integer, the distributed delay model coincides with the classic model with ν transit compartments. The purpose of this work was to evaluate performance of the distributed delay model with particular focus on model deterministic identifiability in the presence of the shape parameter. The classic model served as a reference for comparison. Previously published white blood cell (WBC) count data in rats receiving bolus doses of 5-fluorouracil were fitted by both models. The negative two log-likelihood objective function (-2LL) and running times were used as major markers of performance. Local sensitivity analysis was done to evaluate the impact of ν on the pharmacodynamics response WBC. The ν estimate was 1.46 with 16.1% CV% compared to ν = 3 for the classic model. The difference of 6.78 in - 2LL between classic model and the distributed delay model implied that the latter performed significantly better than former according to the log-likelihood ratio test (P = 0.009), although the overall performance was modestly better. The running times were 1 s and 66.2 min, respectively. The long running time of the distributed delay model was attributed to computationally intensive evaluation of the convolution integral. The sensitivity analysis revealed that ν strongly influences the WBC response by controlling cell proliferation and elimination of WBCs from the circulation. In conclusion, the distributed delay model was deterministically identifiable from typical cytotoxic data. Its performance was modestly better than the classic model with significantly longer running time.

In vivo investigation of tissue-engineered periosteum for the repair of allogeneic critical size bone defects in rabbits.

AIM: The aim of the study was to evaluate the efficacy of tissue-engineered periosteum (TEP) in repairing allogenic bone defects in the long term. MATERIALS & METHODS: TEP was biofabricated with osteoinduced rabbit bone marrow mesenchymal stem cells and porcine small intestinal submucosa (SIS). A total of 24 critical sized defects were created bilaterally in radii of 12 New Zealand White rabbits. TEP/SIS was implanted into the defect site. Bone defect repair was evaluated with radiographic and histological examination at 4, 8 and 12 weeks. RESULTS: Bone defects were structurally reconstructed in the TEP group with mature cortical bone and medullary canals, however this was not observed in the SIS group at 12 weeks. CONCLUSION: The TEP approach can effectively restore allogenic critical sized defects, and achieve maturity of long-bone structure in 12 weeks in rabbit models.

Modeling Immune Response to BK Virus Infection and Donor Kidney in Renal Transplant Recipients.

In this paper we develop and validate with bootstrapping techniques a mechanistic mathematical model of immune response to both BK virus infection and a donor kidney based on known and hypothesized mechanisms in the literature. The model presented does not capture all the details of the immune response but possesses key features that describe a very complex immunological process. We then estimate model parameters using a least squares approach with a typical set of available clinical data. Sensitivity analysis combined with asymptotic theory is used to determine the number of parameters that can be reliably estimated given the limited number of observations.

Rapid and sensitive liquid chromatography-tandem mass spectrometry method for determination of 1-ß-d-arabinofuranosyluracil in human plasma and application to therapeutic drug monitoring in patient with leukemia.

A specific and reliable HPLC-MS/MS method was developed and validated for the determination of ara-U in human plasma. The analyte was separated on a C18 column (50 mm × 2.1mm, 1.7 µm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was applied for detection. The plasma sample was prepared by a simple protein precipitation pretreatment and the recovery was about 80%. The calibration curves were linear over a concentration range of 1.0-7000.0 ng/mL for ara-U. The intra-day and inter-day precision was less than 15% and the relative error (RE) was all within ± 15%. It was successfully applied to assess the disposition characteristics of ara-U and support the therapeutic drug monitoring after the patients with leukemia were infused with ara-C.

Host immune responses that promote initial HIV spread.

The host inflammatory response to HIV invasion is a necessary component of the innate antiviral activity that vaccines and early interventions seek to exploit/enhance. However, the response is dependent on CD4+ T-helper cell 1 (Th1) recruitment and activation. It is this very recruitment of HIV-susceptible target cells that is associated with the initial viral proliferation. Hence, global enhancement of the inflammatory response by T-cells and dendritic cells will likely feed viral propagation. Mucosal entry sites contain inherent pathways, in the form of natural regulatory T-cells (nTreg), that globally dampen the inflammatory response. We created a model of this inflammatory response to virus as well as inherent nTreg-mediated regulation of Th1 recruitment and activation. With simulations using this model we sought to address the net effect of nTreg activation and its specific functions as well as identify mechanisms of the natural inflammatory response that are best targeted to inhibit viral spread without compromising initial antiviral activity. Simulation results provide multiple insights that are relevant to developing intervention strategies that seek to exploit natural immune processes: (i) induction of the regulatory response through nTreg activation expedites viral proliferation due to viral production by nTreg itself and not to reduced Natural Killer (NK) cell activity; (ii) at the same time, induction of the inflammation response through either DC activation or Th1 activation expedites viral proliferation; (iii) within the inflammatory pathway, the NK response is an effective controller of viral proliferation while DC-mediated stimulation of T-cells is a significant driver of viral proliferation; and (iv) nTreg-mediated DC deactivation plays a significant role in slowing viral proliferation by inhibiting T-cell stimulation, making this function an aide to the antiviral immune response.

A comparison of nonlinear filtering approaches in the context of an HIV model.

In this paper three different filtering methods, the Extended Kalman Filter (EKF), the Gauss-Hermite Filter (GHF), and the Unscented Kalman Filter (UKF), are compared for state-only and coupled state and parameter estimation when used with log state variables of a model of the immunologic response to the human immunodeficiency virus (HIV) in individuals. The filters are implemented to estimate model states as well as model parameters from simulated noisy data, and are compared in terms of estimation accuracy and computational time. Numerical experiments reveal that the GHF is the most computationally expensive algorithm, while the EKF is the least expensive one. In addition, computational experiments suggest that there is little difference in the estimation accuracy between the UKF and GHF. When measurements are taken as frequently as every week to two weeks, the EKF is the superior filter. When measurements are further apart, the UKF is the best choice in the problem under investigation.

Modelling HIV immune response and validation with clinical data.

A system of ordinary differential equations is formulated to describe the pathogenesis of HIV infection, wherein certain features that have been shown to be important by recent experimental research are incorporated in the model. These include the role of CD4+ memory cells that serve as a major reservoir of latently infected cells, a critical role for T-helper cells in the generation of CD8 memory cells capable of efficient recall response, and stimulation by antigens other than HIV. A stability analysis illustrates the capability of this model in admitting multiple locally asymptotically stable (locally a.s.) off-treatment equilibria.We show that this more biologically detailed model can exhibit the phenomenon of transient viremia experienced by some patients on therapy with viral load levels suppressed below the detection limit. We also show that the loss of CD4+ T-cell help in the generation of CD8+ memory cells leads to larger peak values for the viral load during transient viremia. Censored clinical data is used to obtain parameter estimates. We demonstrate that using a reduced set of 16 free parameters, obtained by fixing some parameters at their population averages, the model provides reasonable fits to the patient data and, moreover, that it exhibits good predictive capability. We further show that parameter values obtained for most clinical patients do not admit multiple locally a.s off-treatment equilibria. This suggests that treatment to move from a high viral load equilibrium state to an equilibrium state with a lower (or zero) viral load is not possible for these patients.