Markov modeling and performance analysis of infectious diseases with asymptomatic patients.

After over three years of COVID-19, it has become clear that infectious diseases are difficult to eradicate, and humans remain vulnerable under their influence in a long period. The presence of presymptomatic and asymptomatic patients is a significant obstacle to preventing and eliminating infectious diseases. However, the long-term transmission of infectious diseases involving asymptomatic patients still remains unclear. To address this issue, this paper develops a novel Markov process for infectious diseases with asymptomatic patients by means of a continuous-time level-dependent quasi-birth-and-death (QBD) process. The model accurately captures the transmission of infectious diseases by specifying several key parameters (or factors). To analyze the role of asymptomatic and symptomatic patients in the infectious disease transmission process, a simple sufficient condition for the stability of the Markov process of infectious diseases is derived using the mean drift technique. Then, the stationary probability vector of the QBD process is obtained by using RG-factorizations. A method of using the stationary probability vector is provided to obtain important performance measures of the model. Finally, some numerical experiments are presented to demonstrate the model's feasibility through analyzing COVID-19 as an example. The impact of key parameters on the system performance evaluation and the infectious disease transmission process are analyzed. The methodology and results of this paper can provide theoretical and technical support for the scientific control of the long-term transmission of infectious diseases, and we believe that they can serve as a foundation for developing more general models of infectious disease transmission.

Risk assessment and environmental determinants of urinary phthalate metabolites in pregnant women in Southwest China.

Pregnant women are widely exposed to phthalic acid esters (PAEs) that are commonly used in most aspects of modern life. However, few studies have examined the cumulative exposure of pregnant women to a variety of PAEs derived from the living environmental conditions in China. Therefore, this study aimed to determine the urinary concentrations of nine PAE metabolites in pregnant women, examine the relationship between urinary concentrations and residential characteristics, and conduct a risk assessment analysis. We included 1,888 women who were in their third trimester of pregnancy, and we determined their urinary concentrations of nine PAE metabolites using high-performance gas chromatography-mass spectrometry. The risk assessment of exposure to PAEs was calculated based on the estimated daily intake. A linear regression model was used to analyze the relationship between creatinine-adjusted PAE metabolite concentrations and residential characteristics. The detection rate of five PAE metabolites in the study population was > 90%. Among the PAE metabolites adjusted by creatinine, the urinary metabolite concentration of monobutyl phthalate was found to be the highest. Residential factors, such as housing type, proximity to streets, recent decorations, lack of ventilation in the kitchen, less than equal to three rooms, and the use of coal/kerosene/wood/wheat straw fuels, were all significantly associated with high PAE metabolite concentrations. Due to PAE exposure, ~ 42% (n = 793) of the participants faced potential health risks, particularly attributed to dibutyl phthalate, diisobutyl phthalate, and di(2-ethyl)hexyl phthalate exposure. Living in buildings and using coal/kerosene/wood/wheat straw as domestic fuel can further increase the risks.

Diagnostic performance of CT-derived resting distal to aortic pressure ratio (resting Pd/Pa) vs. CT-derived fractional flow reserve (CT-FFR) in coronary lesion severity assessment.

BACKGROUND: Computed tomography-derived fractional flow reserve (CT-FFR) has emerged as a promising non-invasive substitute for fractional flow reserve (FFR) measurement. Normally, CT-FFR providing functional significance of coronary artery disease (CAD) by using a simplified total coronary resistance index (TCRI) model. Yet the error or discrepancy caused by this simplified model remains unclear. METHODS: A total of 20 consecutive patients with suspected CAD who underwent CTA and invasive FFR measurement were retrospectively analyzed. CT-FFR and CT-(Pd/Pa)rest values derived from the coronary CTA images. The diagnostic performance of CT-FFR and CT-(Pd/Pa)rest were evaluated on a per-vessel level using C statistics with invasive FFR<0.80 as the reference standard. RESULTS: Of the 25 vessels eventually analyzed, the prevalence of functionally significant CAD were 64%. The Youden index of the ROC curve indicated that the best cutoff value of invasive resting Pd/Pa was 0.945 for identifying functionally significant lesions. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were 85%, 91%, 92%, 83% and 88% for CT-(Pd/Pa)rest and 85%, 58% 69%, 78% and 72% for CT-FFR. Area under the receiver-operating characteristic curve (AUC) to detect functionally significant stenoses of CT-(Pd/Pa)rest and CT-FFR were 0.87 and 0.90. CONCLUSIONS: In this study, the results suggest CT-derived resting Pd/Pa has a potential advantage over CT-FFR in triaging patients for revascularization.

Clinical Application of a New Assessment Tool for Myelopathy Hand Using Virtual Reality.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: To assess the effectiveness of a new assessment tool, myelopathy-hand functional evaluation system (MFES), in evaluating the hand dysfunction of patients with cervical myelopathy in the 10-second grip-and-release test (10 second G-R test). SUMMARY OF BACKGROUND DATA: Clumsy fingers movement is a common symptom of myelopathy patients. Evaluating the impaired hand function can provide a strong basis in assessing the severity of myelopathy. Currently, no objective and effective evaluation method is widely accepted in clinical practice. METHODS: MFES mainly consists of a pair of wise-gloves and a computer with software. One hundred and ninety-eight consecutive participants were asked to wear the wise-gloves and then perform 10 seconds G-R test. The movements of each finger were recorded by MFES and converted into waveforms. Relevant waveform parameters were measured and analyzed. The Japanese Orthopedics Association (JOA) scores of each patient were marked and the maximum spinal cord compression (MSCC) was measured on midsagittal T2-weighted magnetic resonance imaging (MRI). RESULTS: Myelopathy patients had a lower number of G-R cycles and a longer time per cycle than healthy subjects. There were significant differences in adduction and abduction time in patients with JOA scores greater than 6, but not in healthy subjects and patients with JOA scores less than 6. The waveforms of ulnar three fingers in myelopathy patients were lower and wider than those in healthy individuals. The average ratio value of wave height to wave width (a/b) could quantitatively reflect such differences of waveforms. According to receiver operating characteristic (ROC) curve analysis, the optimal threshold value of the normal average ratio was more than 1.92. The average a/b value was correlated with the JOA scores of the motor function in the upper extremities (r = 0.842). CONCLUSION: MFES appears to be an objective and quantitative assessment tool for patients with cervical myelopathy. LEVEL OF EVIDENCE: 3.

[Profile Characteristics of VOCs from Wood and Economic Crop Burning].

Wood and economic crops are still widely used in rural areas of China. Although their combustion is an important source of volatile organic compounds (VOCs), study on their emission characteristics is relatively weak. In this study, three kinds of wood (poplar, cedarwood, and citrus branches) and six economic crop straws (soybean stalk, sesame stalk, corn cob, cotton stalk, peanut stalk, and corn stalk) were selected and their burning was simulated in the laboratory. A dilution tunnel system was used to dilute the smoke, and then Tedlar bags were used to collect the smoke. The compositions of 102 VOCs were analyzed by Agilent 7820A/5977E gas chromatography/mass spectrometry. The ozone formation potential (OFP) of VOCs for different types of biomass burning was analyzed. The results indicated that there are differences in the VOC compositions of different types of biomass burning emissions. Ethane (11.1%), trans-2-pentene (15.4%), ethylene (8.3%), and dichloromethane (11.9%) are the main VOCs emitted from poplar and cedarwood burning. Toluene (49.8%) is the most abundant species of VOC emitted from burning of citrus branches. Ethylene (11.8%-17.5%) and acetone (9.2%-14.7%) are the main VOCs components of straw burning. Corn stalks, peanut stalks, and citrus branches have similar VOC source profiles, with the coefficient of divergence less than 0.1. The benzene/toluene ratio for biomass burning emissions obtained in this study and in the literature is in the range of 0.030-6.48. It is arguable that a value higher than 1 indicated the impact of biomass burning. The contributions of alkenens, oxygenated VOCs, and aromatic hydrocarbons to the OFP of biomass burning were 30.6%-80.3%, 6.5%-21.0%, and 3.8%-56.5%, respectively. The components contributing more than 10.0% to the OFP are ethylene, propylene, trans-2-pentene, cis-2-pentene, toluene, and propionaldehyde.

Ultralow-Friction and Ultralow-Wear TiN-Ag Solid Solution Coating in Base Oil.

Lubrication plays a pivotal role in reducing energy consumption and machinery wear, profoundly impacting technological and economic development and the environment. A recent study (Erdemir, A., et al. Nature 2016, 536, 67) reported the effective extraction of carbon-based tribofilms from lubricating oil by catalytic activation of the coating material, opening new possibilities for innovative lubrication material research and development. Here, we showcase a solute-atom-strengthened and catalytically functionalized coating design and demonstrate its implementation in a TiN-Ag solid solution film that exhibits concurrent ultralow friction and ultralow wear. Indentation tests and Raman and X-ray photoelectron spectroscopy combined with quantum mechanical simulations uncover the rare superhard nature of the TiN-Ag film along with a solute-Ag-atom-induced self-oxidation mechanism for its outstanding catalytic capacity. These findings identify an outstanding type of mechanically strong and catalytically active coating material with simultaneous superior protective and lubricating functionality, holding great promise for applications ranging from microdevices to large-scale industrial equipment.

CD4-binding obstacles in conformational transitions and allosteric communications of HIV gp120.

As the only exposed viral protein at the membrane surface of HIV, envelope glycoprotein gp120 is responsible for recognizing host cells and mediating virus-cell membrane fusion. Available structures of gp120 indicate that it exhibits two distinct conformational states, called closed and open states. Although experimental data demonstrates that CD4 binding stabilizes open state of gp120, detailed structural dynamics and kinetics of gp120 during this process remain elusive. Here, two open-state gp120 simulation systems, one without any ligands (ligand-free) and the other complexed with CD4 (CD4-bound), were subjected to microsecond-scale molecular dynamics simulations following the conformational transitions and allosteric pathways of gp120 evaluated by using the Markov state model and a network-based method, respectively. Our results provide an atomic-resolution description of gp120 conformational transitions, suggesting that gp120 is intrinsically dynamic from the open state to closed state, whereas CD4 binding blocks these transitions. Consistent with experimental structures, five metastable conformations with different orientations of the V1/V2 region and V3 loop have been extracted. The binding of CD4 significantly enhances allosteric communications from the CD4-binding site to V3 loop and ß20-21 hairpin, resulting in high-affinity interactions with coreceptors and activation of the conformational transitions switcher, respectively. This study will facilitate the structural understanding of the CD4-binding effects on conformational transitions and allosteric pathways of gp120.

Hyperactivated PI3Kδ promotes self and commensal reactivity at the expense of optimal humoral immunity.

Gain-of-function mutations in the gene encoding the phosphatidylinositol-3-OH kinase catalytic subunit p110δ (PI3Kδ) result in a human primary immunodeficiency characterized by lymphoproliferation, respiratory infections and inefficient responses to vaccines. However, what promotes these immunological disturbances at the cellular and molecular level remains unknown. We generated a mouse model that recapitulated major features of this disease and used this model and patient samples to probe how hyperactive PI3Kδ fosters aberrant humoral immunity. We found that mutant PI3Kδ led to co-stimulatory receptor ICOS-independent increases in the abundance of follicular helper T cells (TFH cells) and germinal-center (GC) B cells, disorganized GCs and poor class-switched antigen-specific responses to immunization, associated with altered regulation of the transcription factor FOXO1 and pro-apoptotic and anti-apoptotic members of the BCL-2 family. Notably, aberrant responses were accompanied by increased reactivity to gut bacteria and a broad increase in autoantibodies that were dependent on stimulation by commensal microbes. Our findings suggest that proper regulation of PI3Kδ is critical for ensuring optimal host-protective humoral immunity despite tonic stimulation from the commensal microbiome.

Is it reasonable to administer pegfilgrastim on day 1 of a myelosuppressive chemotherapy regimen? A cost-utility analysis.

BACKGROUND: There is recent evidence supporting the safety and efficacy of same-day dosing of pegfilgrastim in patients undergoing chemotherapy. OBJECTIVE: To determine the cost-effectiveness of pegfilgrastim on day 1 (D1) versus day 2 (D2) for primary prevention of neutropenia in women receiving chemotherapy. MATERIALS AND METHODS: A cost-utility model was designed comparing standard D2 versus D1 administration of pegfilgrastim to ovarian cancer patients receiving chemotherapy with an intermediate risk (10-15%) of febrile neutropenia (FN). Rates of FN despite prophylaxis were modeled as 10% for D1 and 5% for D2. Societal costs associated with D2 injection ($175.71) were incorporated. Quality of life (QOL) was modeled from published data; we assumed a small decrement in QOL on treatment days. Sensitivity analyses were performed. RESULTS: D1 administration was less costly ($17,195 versus $17,681) and resulted in higher QOL (0.2298 quality adjusted life years (QALYs) versus 0.2288 QALYs) than D2. Results were sensitive to the risk of FN. D1 remained dominant or cost-effective (ICER less than $50,000/QALY) compared to D2 if the FN rate with D1 was assumed less than 14.5% (baseline estimate 10%). If the FN rate with D1 was assumed greater than or equal to 15%, D1 was not cost-effective compared to D2, with an ICER greater than $100,000/QALY. Findings are insensitive to variations in the modeled cost of treating FN, the additional cost of D2 injection, and the reduced QOL associated with treatment visits. CONCLUSION: Administration of D1 pegfilgrastim is cost-effective in women with ovarian cancer who are treated with intermediate risk chemotherapy.

Preparation and Assessment of an Individualized Navigation Template for Lower Cervical Anterior Transpedicular Screw Insertion Using a Three-Dimensional Printing Technique.

STUDY DESIGN: Prospective trial. OBJECTIVE: To establish an individualized navigation template for safe and accurate insertion of lower cervical anterior transpedicular screw (ATPS) based on a three-dimensional (3D) printing technique. SUMMARY OF BACKGROUND DATA: Conventional screw insertion manually under fluoroscopy easily leading to deviation of ATPS screw channel, cervical instrumentation procedures demand the need for a precise technique for screw placement. METHODS: Twenty adult cervical spine specimens (10 men and 10 women, with a mean age of 50.29 ±â€Š6.98) were selected for computed tomography pre- and postoperatively. A 3D lower cervical spine model was reconstructed using Mimics software to measure the screw-related parameters and generate a reverse template with optimal screw channel as well as a prototype using 3D printing. Assisted by the navigation template, bilateral ATPS were inserted into the cadavers. RESULTS: The mean outer width and height of pedicle were 5.31 ±â€Š1.23 and 6.78 ±â€Š1.10 mm, respectively. The average length, sagittal, and axial angles of the optimal screw channel obtained through the optimal entry point were 36.34 ±â€Š4.39 mm, 40.67°â€Š±â€Š5.10°, and 93.7°â€Š±â€Š7.96°, respectively. The adjustable safe ranges of sagittal and axial angles were 3.89°â€Š±â€Š1.13° and 5.64°â€Š±â€Š0.97°, respectively. The axial and sagittal accuracies of the 200 screws were 99.5% and 97%, respectively. The average deviations of the actual entry point and the preset opening in the X, Y, and Z axes were 0.39 ±â€Š0.43, 0.21 ±â€Š0.41, and 0.29 ±â€Š0.14 mm, respectively (P > 0.05). CONCLUSION: An individualized ATPS navigation template was developed using Mimics software and 3D printing prototyping, based on computed tomography, for highly accurate screw insertion. LEVEL OF EVIDENCE: 4.

Inequality in the hepatitis B awareness level in rural residents from 7 provinces in China.

The hepatitis B (HB) awareness level is an important factor affecting the rates of HB virus vaccination. To better understand income-related inequalities in the HB awareness level, it is imperative to identify the sources of inequalities and assess the contribution rates of these influential factors. This study analyzed the unequal distribution of the HB awareness level and the contributions of various influential factors. We performed a cross-sectional household survey with questionnaire-based, face-to-face interviews in 7 Chinese provinces. Responses from 7271 respondents were used in this analysis. Multinomial logistic regression was used for the analysis of contributing factors, and the concentration index was used as a measure of HB awareness inequalities. The HB awareness level varied across participants with different characteristics. Multinomial logistic regression of the explanatory factors of the HB awareness level showed that several estimated coefficients and relative risk ratios were statistically significant for middle- and high-level awareness, except for sex, occupation, and household income. The concentration index of the HB knowledge score was 0.140, indicating inequality gradients disadvantageous to the poor. The contribution rate of socioeconomic factors was the largest (60.8%), followed by demographic characteristics (29.0%) and geographic factors (4.3%). Demographic, socioeconomic, and geographic factors are associated with the HB awareness inequality. Therefore, to reduce inequality, HB-related health education targeting individuals with low socioeconomic status should be performed. Less-developed provinces, especially with high proportions of poor residents, warrant particular attention. Our findings may be beneficial to improve the HB virus vaccination rate for individuals with low socioeconomic status.

Glycated albumin is superior to glycated hemoglobin for glycemic control assessment at an early stage of diabetes treatment: A multicenter, prospective study.

AIMS: This study was to determine whether serum glycated albumin (GA) was a better indicator of glycemic control than hemoglobin A1c (HbA1c) when starting a new treatment regimen for type 2 diabetes. METHODS: Newly diagnosed type 2 diabetes patients, or patients who had poor glycemic control with oral hypoglycemic agents, were enrolled at 10 hospitals in Beijing. Serum GA, HbA1c, fasting blood glucose (FBG), and C-peptide were assayed on Days 0, 14, 28, and 91 after treatment. RESULTS: Four hundred ninety-nine patients were enrolled. Mean FBG, GA and HbA1c decreased significantly in patients at Days 14, 28, and 91. In patients with improved glycemic control, the reduction of GA and HbA1c levels was 10.5±13.3% vs. 5.1±5.4% on Day 14, 16.0±13.4% vs. 9.0±7.0% on Day 28, and 18.0±16.7% vs. 18.3±9.4% on Day 91, respectively, compared with baseline values. Changes in GA on Day 14, 28 and 91 were all closely correlated with changes in HbA1c on Day 91. Change in GA on Day 14 was correlated with treatment effectiveness evaluated by HbA1c on Day 91. CONCLUSIONS: GA may be a useful marker for assessing glycemic control at an early stage of new diabetes treatment and assist in guiding adjustments to treatment and therapy.

Rapid assessment of knowledge, attitudes, practices, and risk perception related to the prevention and control of Ebola virus disease in three communities of Sierra Leone.

BACKGROUND: The recent outbreak of the Ebola virus disease (EVD) in Sierra Leone has been characterized by the World Health Organization as one of the most challenging EVD outbreaks to date. The first confirmed case in Sierra Leone was a young woman who was admitted to a government hospital in Kenema following a miscarriage on 24 May 2014. On 5 January 2015, intensified training for an EVD response project was initiated at the medical university of Sierra Leone in Jui. To understand the knowledge, attitudes, practices, and perceived risk of EVD among the public, especially after this training, a rapid assessment was conducted from 10 to 16 March 2015. METHODS: Interviews were conducted with 466 participants based on questionnaires that were distributed from 10 to 16 March 2015 by cluster sampling in three adjacent communities, namely Jui, Grafton, and Kossoh Town, in the Western Area Rural District of Sierra Leone. RESULTS: It was found that knowledge about EVD was comprehensive and high. Positive attitude towards prevention was found to be satisfactory. Nearly all participants knew the reporting phone number 117 and had reported some change in behavior since learning about Ebola. More than half (62 %) of the participants had a history of travelling to urban areas, which increases the risk of infection. The multivariable logistic regression analysis showed that community and occupation were variables associated with perceived risk of EVD. CONCLUSIONS: Our study showed that community level social mobilization and community engagement were an effective strategy in the special context.

[Vulnerability assessment on the coastal wetlands in the Yangtze Estuary under sea-level rise].

To study the response of coastal wetlands to climate change, assess the impacts of climate change on the coastal wetlands and formulate feasible and practical mitigation strategies are the important prerequisite for securing coastal ecosystems. In this paper, the possible impacts of sea level rise caused by climate change on the coastal wetlands in the Yangtze Estuary were analyzed by the Source-Pathway-Receptor-Consequence (SPRC) model and IPCC definition on the vulnerability. An indicator system for vulnerability assessment was established, in which sea-level rise rate, subsidence rate, habitat elevation, inundation threshold of habitat and sedimentation rate were selected as the key indicators. A quantitatively spatial assessment method based on the GIS platform was established by quantifying each indicator, calculating the vulnerability index and grading the vulnerability index for the assessment of coastal wetlands in the Yangtze Estuary under the scenarios of sea-level rise. The vulnerability assessments on the coastal wetlands in the Yangtze Estuary in 2030 and 2050 were performed under two sea-level rise scenarios (the present sea-level rise trend over recent 30 years and IPCC A1F1 scenario). The results showed that with the projection in 2030 under the present trend of sea-level rise (0.26 cm x a(-1)), 6.6% and 0.1% of the coastal wetlands were in the low and moderate vulnerabilities, respectively; and in 2050, 9.8% and 0.2% of the coastal wetlands were in low and moderate vulnerabilities, respectively. With the projection in 2030 under the A1F1 scenario (0.59 cm x a(-1)), 9.0% and 0.1% of the coastal wetlands were in the low and moderate vulnerabilities, respectively; and in 2050, 9.5%, 1.0% and 0.3% of the coastal wetlands were in the low, moderate and high vulnerabilities, respectively.

Cytompatibility assessment of the surface of titanium after phosphorylation.

In this study, orthophosphoric acid (H3PO4) in the treatment of porous titanium (Ti) is investigated and the ability of rat bone marrow stromal cells (BMSCs) is assessed to proliferate and differentiate on these modified surfaces in vitro. To improve the cytocompatibility of Ti surfaces, pure Ti was activated commercially by simple chemical pretreatment in H3PO4 with different densities. Next, the phosphorylated specimens were soaked in simulated body fluid (SBF) to study the effect of biomineralization. The3-[4,5-dimethylthiazol-2-y1]-2, 5-diphenytetrazolium bromide (MTT) assay and the measurement of alkaline phosphatase (ALP) activity utilized to assess proliferation and differentiation of BMSCs on exposure to modified Ti surfaces. Scanning electron microscopic (SEM) images showed that the surfaces of the pre-treated samples were characterized by a complex structure which consisted of a mesh-like morphological matrix and an uniform surface with different morphic crystals of titanium dihydrogen orthophosphate (Ti(H2PO4)3). These crystals contained hydroxyl with phosphate residues that resulted in biomineralization of cells. Therefore, BMSCs reveales a well-dispersed morphology on these modified and functionalized Ti surfaces. The viability and ALP activity of BMSCs on these altered biomimetic surfaces are found to be greater than those of the controls. It is concluded that the treatment of Ti by acid etching in orthophosphoric acid is a suitable method to enhance the in vitro proliferation and differentiation of BMSCs.

[Long-term assessment of relapse and associated risk factors in chronic hepatitis C patients treated with interferon and ribavirin].

OBJECTIVE: To investigate viral relapse and the associated risk factors during a long-term follow-up study of chronic hepatitis C (CHC) patients who achieved end-of-treatment response (ETR) after interferon and ribavirin therapy. METHODS: This retrospective study was conducted on 146 CHC patients treated with a combination of ribavirin and pegylated (PEG) interferon-alpha (IFNa) (n=126) or conventional IFNa (n=20) for 24 (hepatitis C virus (HCV) non-genotype 1b) or 48 (HCV genotype 1b) weeks. The main outcome measure was serum HCV RNA load. The risk factors analyzed included age, sex, HCV genotype, baseline HCV RNA load, and IFN type. RESULTS: The mean follow-up time for all patients was 33.45+/-16.41 months (range: 12-85 months). The cumulative relapse rate during follow-up was 14.80%. The relapse rate within six months (8.90%) was significantly higher than other periods during two years of follow-up, and no relapse occurred after 30 months. Of all relapsers (n=20), 65% occurred within six months, followed by 35% within 7-24 months after antiviral therapy. The relapse rates in patients with HCV genotype 1b and non-1b were not significantly different (20.37% vs. 12.12%, X2 =1.517, P=0.315). The mean baseline HCV RNA load was significantly higher in the relapsers than that in the non-relapsers (t=0.915, P=0.362). Relapse rates were similar in patients treated with PEG-IFNa-2b, PEG-IFNa-2a and IFNa (12.12% vs. 13.97% vs. 15.00%, respectively; X2=0.104, p=0.949). The mean age of relapsers was significantly higher than that of non-relapsers (P less than 0.005). CONCLUSION: The maximum probability of relapse for CHC patients exists within six months from when ETR is achieved by interferon and ribavirin therapy. A lower risk for relapse persists past this period. Thus, ETR CHC patients, especially older patients, should be carefully monitored during the two years after cessation of antiviral therapy. Standard antiviral therapy based on HCV genotype eliminates the influence of viral factors on treatment-response.

Ancestry informative marker set for han chinese population.

The population of Han Chinese is ∼1.226 billion people. Genetic heterogeneity between northern Han Chinese (N-Han) and southern Han Chinese (S-Han) has been demonstrated by recent genome-wide studies. As an initial step toward health disparities and personalized medicine in Chinese population, this study developed a set of ancestry informative markers (AIM) for Han Chinese population.

[Construction and biological assessment of tissue engineering intervertebral disc].

OBJECTIVE: To investigate the value of bone marrow-mesenchymal stem cells (BM-MSCs) transformed by nucleus pulposus (NPs) for construction of tissue engineering disc. METHODS: BM-MSCs and fetal NPs were cultured in vitro, planted on polylactic acid-polyglycolic acid copolymer (PLGA), and observed with inverted microscope and scanning electronic microscope. PLGA scaffolds with adherent BM-MSCs and NPs, as well as BM-MSCs and NPs suspension were implanted into intervertebral discs of New Zealand white rabbits, respectively. Intervertebral signal intensity was evaluated by Thompson grading 12 weeks later. Proteoglycan and type IIcollagen were determined by spectrophotometric method and immunohistochemistry, respectively. RESULTS: Spindle or multi-angular BM-MSCs turned into fibro-like phenotype coculture of BM-MSCs and NPs, which grew well with normal morphology when they attached on PLGA scaffolds. There was statistical difference in intervertebral signal intensity, and the expression of proteoglycan and type IIcollagen between PLGA scaffolds group and control group (P < 0.05), the content of proteoglycan was (3.93 ± 0.31) mg/100 mg in the PLGA scaffolds group whereas (3.52 ± 0.26) mg/100 mg in the control group. CONCLUSIONS: BM-MSCs can be induced into NPs by cocultivation, and PLGA scaffolds can provide good growing conditions, and maintain high mechanical properties and spacial structure which meet the requirement of tissue engineering disc to prevent degeneration.

Fragment-based local statistical potentials derived by combining an alphabet of protein local structures with secondary structures and solvent accessibilities.

General and transferable statistical potentials to quantify the compatibility between local structures and local sequences of peptide fragments in proteins were derived. In the derivation, structure clusters of fragments are obtained by clustering five-residue fragments in native proteins based on their conformations represented by a local structure alphabet (de Brevern et al., Proteins 2000;41:271-287), secondary structure states, and solvent accessibilities. On the basis of the native sequences of the structurally clustered fragments, the probabilities of different amino acid sequences were estimated for each structure cluster. From the sequence probabilities, statistical energies as a function of sequence for a given structure were directly derived. The same sequence probabilities were employed in a database-matching approach to derive statistical energies as a function of local structure for a given sequence. Compared with prior models of local statistical potentials, we provided an integrated approach in which local conformations and local environments are treated jointly, structures are treated in units of fragments instead of individual residues so that coupling between the conformations of adjacent residues is included, and strong interdependences between the conformations of overlapping or neighboring fragment units are also considered. In tests including fragment threading, pseudosequence design, and local structure predictions, the potentials performed at least comparably and, in most cases, better than a number of existing models applicable to the same contexts indicating the advantages of such an integrated approach for deriving local potentials and suggesting applicability of the statistical potentials derived here in sequence designs and structure predictions.