Features of the TCR repertoire associate with patients' clinical and molecular characteristics in acute myeloid leukemia.

Background: Allogeneic hematopoietic stem cell transplant remains the most effective strategy for patients with high-risk acute myeloid leukemia (AML). Leukemia-specific neoantigens presented by the major histocompatibility complexes (MHCs) are recognized by the T cell receptors (TCR) triggering the graft-versus-leukemia effect. A unique TCR signature is generated by a complex V(D)J rearrangement process to form TCR capable of binding to the peptide-MHC. The generated TCR repertoire undergoes dynamic changes with disease progression and treatment. Method: Here we applied two different computational tools (TRUST4 and MIXCR) to extract the TCR sequences from RNA-seq data from The Cancer Genome Atlas (TCGA) and examine the association between features of the TCR repertoire in adult patients with AML and their clinical and molecular characteristics. Results: We found that only ~30% of identified TCR CDR3s were shared by the two computational tools. Yet, patterns of TCR associations with patients' clinical and molecular characteristics based on data obtained from either tool were similar. The numbers of unique TCR clones were highly correlated with patients' white blood cell counts, bone marrow blast percentage, and peripheral blood blast percentage. Multivariable regressions of TCRA and TCRB median normalized number of unique clones with mutational status of AML patients using TRUST4 showed significant association of TCRA or TCRB with WT1 mutations, WBC count, %BM blast, and sex (adjusted in TCRB model). We observed a correlation between TCRA/B number of unique clones and the expression of T cells inhibitory signal genes (TIGIT, LAG3, CTLA-4) and foxp3, but not IL2RA, CD69 and TNFRSF9 suggestive of exhausted T cell phenotypes in AML. Conclusion: Benchmarking of computational tools is needed to increase the accuracy of the identified clones. The utilization of RNA-seq data enables identification of highly abundant TCRs and correlating these clones with patients' clinical and molecular characteristics. This study further supports the value of high-resolution TCR-Seq analyses to characterize the TCR repertoire in patients.

Validating METCAM/MUC18 as a Novel Biomarker to Predict the Malignant Potential of Prostate Cancer at an Early Stage by Using a Modified Gold Nanoparticles-Based Lateral Flow Immunoassay.

(1) Background: To further validate METCAM/MUC18 as a diagnostic biomarker for prostate cancer, a modified Lateral Flow Immune Assay (LFIA) with increased sensitivity and specificity was designed by taking advantage of the extremely high affinity between biotin and streptavidin and used. (2) Methods: The combination of a commercial biotinylated rabbit antibody (EPP11278), or the home-made biotinylated chicken antibody, and the nano-gold conjugated home-made chicken antibody or a commercial rabbit antibody (EPP11278), had the higher sensitivity and specificity in this modified LFIA to establish calibration curves from the two recombinant METCAM/MUC18 proteins and were used for determining METCAM/MUC18 concentrations in serum specimens from normal individuals, benign prostatic hyperplasia (BPH) patients, prostatic intraepithelial neoplasia (PIN) patients, prostate cancer patients with various Gleason scores, and treated patients. (3) Results: Data obtained by this modified LFIA were statistically better than traditional LFIA and prostate-specific antigen (PSA) test. Interestingly, serum METCAM/MUC18 concentrations were higher in pre-malignant PIN patients than prostate cancer patients and both were higher than normal individuals, BPH patients, and treated patients. Serum METCAM/MUC18 concentrations were directly proportional to most serum PSA. (4) Conclusions: Elevated serum METCAM/MUC18 concentrations may be used for predicting the malignant potential of prostate cancer at an early premalignant (PIN) stage, which is not achievable by the current PSA test.

Effects of a Community Care Station Program With Structured Exercise Intervention on Physical Performance and Balance in Community-Dwelling Older Adults: A Prospective 2-Year Observational Study.

The Taiwanese government has developed community care stations (CCSs) for community-based older adult care. We investigated the effects of a structured exercise intervention, applied at CCS for 6 months, on physical performance and balance in community-dwelling older adults, including a 2-year reassessment. Fifty-eight participants (aged 76.9 ± 6.3 years) participated in the study. The Elderly Mobility Scale, Short Physical Performance Battery (SPPB), Timed Up and Go (TUG), gait speed, functional reach, one-leg-stance (OLS), and flexibility were evaluated at baseline, 6 months, and 2 years. Compared with baseline, the participants improved significantly in the SPPB (0.93 points), TUG (1.94 s), gait speed (0.13 m/s), and right and left OLS (2.56 and 3.12 s) at 6 months. Furthermore, these significant effects, except for OLS, were maintained at the 2-year reassessment according to repeated-measures ANOVA (p < .01). Our preliminary data suggest that adding a structured exercise program can benefit older adults participating in Taiwanese CCSs.

Stereotactic Comparison Study of (18)F-Alfatide and (18)F-FDG PET Imaging in an LLC Tumor-Bearing C57BL/6 Mouse Model.

This study aimed to stereotactically compare the PET imaging performance of (18)F-Alfatide ((18)F-ALF-NOTA-PRGD2, denoted as (18)F-Alfatide) and (18)F-fluorodeoxyglucose (FDG) and immunohistochemistry (IHC) staining in Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mouse model. (18)F-FDG standard uptake values (SUVs) were higher than (18)F-Alfatide SUVs in tumors, most of the normal tissues and organs except for the bladder. Tumor-to-brain, tumor-to-lung, and tumor-to-heart ratios of (18)F-Alfatide PET were significantly higher than those of (18)F-FDG PET (P < 0.001). The spatial heterogeneity of the tumors was detected, and the tracer accumulation enhanced from the outer layer to the inner layer consistently using the two tracers. The parameters of the tumors were significantly correlated with each other between (18)F-FDG SUV and GLUT-1 (R = 0.895, P < 0.001), (18)F-Alfatide SUV and αvß3 (R = 0.595, P = 0.019), (18)F-FDG SUV and (18)F-Alfatide SUV (R = 0.917, P < 0.001), and GLUT-1 and αvß3 (R = 0.637, P = 0.011). Therefore, (18)F-Alfatide PET may be an effective tracer for tumor detection, spatial heterogeneity imaging and an alternative supplement to (18)F-FDG PET, particularly for patients with enhanced characteristics in the brain, chest tumors or diabetes, meriting further study.

Noninvasive Evaluation of Metabolic Tumor Volume in Lewis Lung Carcinoma Tumor-Bearing C57BL/6 Mice with Micro-PET and the Radiotracers 18F-Alfatide and 18F-FDG: A Comparative Analysis.

PURPOSE: To explore the value of a new simple lyophilized kit for labeling PRGD2 peptide (18F-ALF-NOTA-PRGD2, denoted as 18F-alfatide) in the determination of metabolic tumor volume (MTV) with micro-PET in lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice verified by pathologic examination and compared with those using 18F-fluorodeoxyglucose (FDG) PET. METHODS: All LLC tumor-bearing C57BL/6 mice underwent two attenuation-corrected whole-body micro-PET scans with the radiotracers 18F-alfatide and 18F-FDG within two days. 18F-alfatide metabolic tumor volume (VRGD) and 18F-FDG metabolic tumor volume (VFDG) were manually delineated slice by slice on PET images. Pathologic tumor volume (VPath) was measured in vitro after the xenografts were removed. RESULTS: A total of 37 mice with NSCLC xenografts were enrolled and 33 of them underwent 18F-alfatide PET, and 35 of them underwent 18F-FDG PET and all underwent pathological examination. The mean ± standard deviation of VPath, VRGD, and VFDG were 0.59±0.32 cm3 (range,0.13~1.64 cm3), 0.61±0.37 cm3 (range,0.15~1.86 cm3), and 1.24±0.53 cm3 (range,0.17~2.20 cm3), respectively. VPath vs. VRGD, VPath vs. VFDG, and VRGD vs. VFDG comparisons were t = -0.145, P = 0.885, t = -6.239, P<0.001, and t = -5.661, P<0.001, respectively. No significant difference was found between VPath and VRGD. VFDG was much larger than VRGD and VPath. VRGD seemed more approximate to the pathologic gross tumor volume. Furthermore, VPath was more strongly correlated with VRGD (R = 0.964,P<0.001) than with VFDG (R = 0.584,P<0.001). CONCLUSIONS: 18F-alfatide PET provided a better estimation of gross tumor volume than 18F-FDG PET in LLC tumor-bearing C57BL/6 mice.

[UV-Vis spectrum characteristics of phycocyanin in water from Taihu lake].

The present paper analyzed the UV-Vis spectrum characteristics of phycocyanin extracted from 75 water samples around Meiliang Bay of Taihu Lake, China in spring, summer and autumn, 2011, taking standard sample of phycocyanin, Micro-cystic aeruginosa and Anabaena cultured indoor as the reference, and discussed the difference and relation of spectrum among water samples, standard sample and single algae samples. According to the number of absorption peak in the wavelength range from 500 to 700 nm, phycocyanin spectrum of water sampling in Taihu Lake can be divided into three patterns: no peak, single peak and two peaks. In the first pattern, the absorbance changed smoothly and no absorption peak was observed around 620 nm. Depending on the absorption difference in the wavelength range from 300 to 450 nm, this pattern can be divided into type I and type II. Type I only had a absorption peak near 260 nm, with the similar spectrum of chromophoric dissolved organic matter (CDOM) in the wavelength range from 250 to 800 nm. Type II had absorption peak respectively near 260 and 330 nm. In single peak pattern and two peaks pattern, significant absorption peak of phycocyanin appeared around 620 nm. Compared to the other patterns, single peak pattern was more similar to that of standard sample and single algae samples, but different in their maximum absorption peaks position and relative absorption intensity in the wavelength range of 250 approximately 300, 300 approximately 450 and 500 approximately 700 nm, because of different algae species and purity after extraction. In the two peaks pattern, another absorption peak appeared at 670nm, with the absorption shoulder from 350 to 450 nm, and shared the absorption characteristics of phycocyanin and chlorophyll complex protein. The research can provide a basic support for the phycocyanin quantitation and blooms monitoring in Taihu Lake.

[Baseline correction of spectrum for the inversion of chlorophyll-a concentration in the turbidity water].

Suspended particle material is the main factor affecting remote sensing inversion of chlorophyll-a concentration (Chla) in turbidity water. According to the optical property of suspended material in water, the present paper proposed a linear baseline correction method to weaken the suspended particle contribution in the spectrum above turbidity water surface. The linear baseline was defined as the connecting line of reflectance from 450 to 750 nm, and baseline correction is that spectrum reflectance subtracts the baseline. Analysis result of field data in situ of Meiliangwan, Taihu Lake in April, 2011 and March, 2010 shows that spectrum linear baseline correction can improve the inversion precision of Chl a and produce the better model diagnoses. As the data in March, 2010, RMSE of band ratio model built by original spectrum is 4.11 mg x m(-3), and that built by spectrum baseline correction is 3.58 mg x m(-3). Meanwhile, residual distribution and homoscedasticity in the model built by baseline correction spectrum is improved obviously. The model RMSE of April, 2011 shows the similar result. The authors suggest that using linear baseline correction as the spectrum processing method to improve Chla inversion accuracy in turbidity water without algae bloom.

Effectiveness of thermal stimulation for the moderately to severely paretic leg after stroke: serial changes at one-year follow-up.

UNLABELLED: Liang C-C, Hsieh T-C, Lin C-H, Wei Y-C, Hsiao J, Chen J-C. Effectiveness of thermal stimulation for the moderately to severely paretic leg after stroke: serial changes at one-year follow-up. OBJECTIVE: To evaluate the serial changes of long-term effects of thermal stimulation (TS) on acute stroke patients. DESIGN: A prospective study with follow-up at 3, 6, and 12 months after TS to assess motor and balance function of the paretic leg of acute stroke patients. SETTING: A general hospital rehabilitation department. PARTICIPANTS: Poststroke patients (N=30) with moderate to severe impairment of leg function. INTERVENTIONS: In addition to receiving standard rehabilitation, eligible patients were randomly assigned to a TS group (5 thermal stimulations per week for 6wk) or a control group (3 consultations per week for 6wk). MAIN OUTCOME MEASURES: Fugl-Meyer lower extremity score, Medical Research Council Scale for the Lower Extremity, Berg Balance Scale, Modified Motor Assessment Scale, Functional Ambulation Classification, and Barthel Index were administered at baseline, after 4 and 6 weeks of treatment, and at the 3-, 6-, and 12-month follow-up. RESULTS: No significant differences were found between the 2 groups at baseline. After TS, the Fugl-Meyer lower extremity score, Medical Research Council Scale for the Lower Extremity, Modified Motor Assessment Scale, and Functional Ambulation Classification were significantly better in the TS group, and the effects persisted for 3 months (P<.05). Significant differences were found between the 2 groups for the Berg Balance Scale and Barthel Index only at the 3-month follow-up (P<.05). However, all the effects except for the Fugl-Meyer lower extremity score had disappeared at the 6-month follow-up (P>.05). CONCLUSIONS: The long-term benefits of TS for patients with acute stroke may be sustained for 3 months but disappear by the 6-month and 1-year follow-up.

Facilitation of motor and balance recovery by thermal intervention for the paretic lower limb of acute stroke: a single-blind randomized clinical trial.

OBJECTIVE: To evaluate the effectiveness of thermal stimulation accompanied by either active or passive movement added to standard rehabilitation in facilitating motor and balance function of the paretic leg of acute stroke. DESIGN: Pilot, observer-blinded, randomized clinical trial. SETTING: Department of rehabilitation medicine in a general hospital. SUBJECTS: Thirty-six patients were enrolled within four weeks of the onset of a stroke causing moderate to severe leg paresis (Brunnstrom stage ≤III). INTERVENTIONS: Patients were randomly assigned to thermal (standard rehabilitation plus approximately 30-40 minutes of thermal stimulation therapy daily for six weeks) and control (standard rehabilitation only) groups. MAIN MEASURES: Fugl-Meyer lower extremity score, Medical Research Council scale for lower extremity, Modified Motor Assessment Scale, Postural Assessment Scale for Stroke Patients Trunk Control, Berg Balance Scale, Functional Ambulation Classification and Modified Ashworth Scale. RESULTS: Patients in the thermal group experienced significantly better median scores for Fugl-Meyer lower extremity (14.0; interquartile range, 10.5-15.5), Medical Research Council scale for lower extremity (6.0; 4.0-7.0), Modified Motor Assessment Scale (16.0; 12.5-18.5), Berg Balance Scale (28.0; 20.5-33.5), and Functional Ambulation Classification (2.0; 2.0-2.0) (all P < 0.05). The thermal group also had more independent walkers (15/17; 88.2%) than the control group (9/16; 56.3%) after six weeks (P = 0.06). No adverse effect occurred. CONCLUSIONS: Thermal stimulation accompanied by either manual facilitation or encouragement for active participation of the paretic lower limb may be an effective promising supplementary treatment for the early-phase rehabilitation of moderate to severe stroke that warrants additional study.

[Individual identification and paternity testing of bulls using microsatellite].

The polymorphism distributions of 14 microsatellite loci were detected using the Bovine Paternity PCR Typing Kit (including 11 X-STR) and 3 selected Y-STR microsatellite DNA markers. The genetic diversity were evaluated, and the feasibility of the application to individual identification and paternity testing were discussed. The results showed that all the 14 microsatellite loci had genetic polymorphisms in bulls, and the polymorphism information content (PIC) in loci MCM158 was the biggest (0.888), while the ETH10 was the lowest (0.482). Power of discrimination (DP) value of the 14 STR loci ranged from 0.715 to 0.968. The Cumulate DP (CDP) was 99.99%, and the Cumulate PE (CPE) also reached 99.99%. These results indicate that the 14 microsatellites can be applied to the individual identification.

[Evaluating eutrophic state of Taihu Lake by in situ hyperspectra].

In situ experiments including water quality analyzing and spectra measuring were conducted on Jun., 2004 and Aug., 2004 in Taihu Lake for 21 samples. Then eutrophic state of Taihu Lake was evaluated by measured hyperspectra data, and the evaluating index was eutrophic state index (TSI). Firstly, the simulation model of water reflectance was built by analytic model using inherent optical properties (IOPs). Then Chlorophyll a content (Chl-a) was inversed by optimizing method by Matlab software; Secondly, TSI was calculated by inversed Chl-a, and the eutrophic state of Taihu Lake was evaluated by using ArcView' s interpolation function. The evaluation figures show that: there are notable differences between Jun., 2004 and Aug., 2004. The proportion of mesotropher state is as high as 61% in June, while the proportion of light eutrophic is as high as 52% in August. In totally, the most serious eutrophic state occurs in north of Taihu Lake. Eutrophlic state wears off from north to south. The lowest eutrophic region is in the east of Taihu Lake.

[Integrated fuzzy evaluation of water eutrophication based on GIS in the Taihu Lake].

Supported by geographic information system and geostatistics, the application of fuzzy mathematics and analytic hierarchy process for water eutrophication evaluation was discussed. Taking Taihu Lake as an example, the research selected total phosphorus, total nitrogen, chlorophyll a, COD, BOD5, DO and transparence as evaluation index. After geostatistical analysis of the datum of monitoring site, the values of evaluation indices were estimated in the whole research area. Given that, the different dependence functions were developed for these indices and the function values were calculated. Furthermore, according to the principle of analytic hierarchy process, the weight of every index was calculated, then integrated evaluation value was obtained for the whole research area and the evaluation map for water eutrophication was drawn. The result shows that the level of nutrition is the highest in the north and north-west of lake, which is hypertrophic, that is meso-eutrophic in the middle and that is the lowest in the south-east of lake, which is mesotrophic.