Neural signals-based respiratory motion tracking: a proof-of-concept study.

Objective.Respiratory motion tracking techniques can provide optimal treatment accuracy for thoracoabdominal radiotherapy and robotic surgery. However, conventional imaging-based respiratory motion tracking techniques are time-lagged owing to the system latency of medical linear accelerators and surgical robots. This study aims to investigate the precursor time of respiratory-related neural signals and analyze the potential of neural signals-based respiratory motion tracking.Approach.The neural signals and respiratory motion from eighteen healthy volunteers were acquired simultaneously using a 256-channel scalp electroencephalography (EEG) system. The neural signals were preprocessed using the MNE python package to extract respiratory-related EEG neural signals. Cross-correlation analysis was performed to assess the precursor time and cross-correlation coefficient between respiratory-related EEG neural signals and respiratory motion.Main results.Respiratory-related neural signals that precede the emergence of respiratory motion are detectable via non-invasive EEG. On average, the precursor time of respiratory-related EEG neural signals was 0.68 s. The representative cross-correlation coefficients between EEG neural signals and respiratory motion of the eighteen healthy subjects varied from 0.22 to 0.87.Significance.Our findings suggest that neural signals have the potential to compensate for the system latency of medical linear accelerators and surgical robots. This indicates that neural signals-based respiratory motion tracking is a potential promising solution to respiratory motion and could be useful in thoracoabdominal radiotherapy and robotic surgery.

Mining Candidate Genes Related to Heavy Metals in Mature Melon (Cucumis melo L.) Peel and Pulp Using WGCNA.

The content of metal ions in fruits is inseparable from plant intake of trace elements and health effects in the human body. To understand metal ion content in the fruit and pericarp of melon (Cucumis melo L.) and the candidate genes responsible for controlling this process, we analyzed the metal ion content in distinct parts of melon fruit and pericarp and performed RNA-seq. The results showed that the content of metal ions in melon fruit tissue was significantly higher than that in the pericarp. Based on transcriptome expression profiling, we found that the fruit and pericarp contained elevated levels of DEGs. GO functional annotations included cell surface receptor signaling, signal transduction, organic substance metabolism, carbohydrate derivative binding, and hormone-mediated signaling pathways. KEGG pathways included pectate lyase, pentose and glucuronate interconversions, H+-transporting ATPase, oxidative phosphorylation, plant hormone signal transduction, and MAPK signaling pathways. We also analyzed the expression patterns of genes and transcription factors involved in hormone biosynthesis and signal transduction. Using weighted gene co-expression network analysis (WGCNA), a co-expression network was constructed to identify a specific module that was significantly correlated with the content of metal ions in melon, after which the gene expression in the module was measured. Connectivity and qRT-PCR identified five candidate melon genes, LOC103501427, LOC103501539, LOC103503694, LOC103504124, and LOC107990281, associated with metal ion content. This study provides a theoretical basis for further understanding the molecular mechanism of heavy metal ion content in melon fruit and peel and provides new genetic resources for the study of heavy metal ion content in plant tissues.

Two-dimensional fruit quality factors and soil nutrients reveals more favorable topographic plantation of Xinjiang jujubes in China.

Jujubes (Ziziphus jujuba Mill.) are among the main agroeconomically important crops in Xinjiang, China, and those from this region have the highest production worldwide. However, the reason for the high quality of the jujubes in the region is unknown. In our current research, the total phosphorus (P), total nitrogen (N), organic matter (OM), available P, alkaline N and quick potassium (K) were quantitatively analyzed in soils collected from orchards in 11 geographical locations, counties or cities, in Xinjiang. Meanwhile, the P, total triterpenoids, soluble solids, polysaccharide and cyclic adenosine monophosphate (CAMP) contents were also used to indicate fruit quality. Based on the analyzed data, principal component analysis (PCA) and multiple regression analysis revealed a high correlation between soil nutrients and the quality of the Jun jujube, which was used as an example. Specifically, the total P and quick K contents significantly differed among the orchard soils. Moreover, they significantly affected fruit quality. Total P significantly affected the soluble solids and total triterpenoids contents and was negatively correlated with the former and positively correlated with the latter. In addition, the soluble solids and total triterpenoids contents were significantly affected by the quick K content; as the quick K content increased, the soluble solids content gradually increased, while the total triterpenoids content decreased. According to the response surface model, we suggest that when the total P and quick K contents in the soil in Xinjiang were 0.76 g/kg and 365.04 mg/kg, respectively, the optimal fruit quality was obtained. Therefore, two-dimensional analysis of fruit quality and soil nutrients showed that it is necessary to increase the total P and quick K contents in the soil used to grow jujubes in Xinjiang.

Two-Year Safety and Effectiveness of Peficitinib in Moderate-To-Severe Rheumatoid Arthritis: A Phase IIb, Open-Label Extension Study.

INTRODUCTION: Peficitinib is a novel orally bioavailable, once-daily Janus kinase (JAK) inhibitor approved in Japan for the treatment of rheumatoid arthritis (RA). This 2-year extension study of two global phase IIb trials investigated the long-term safety and effectiveness of peficitinib. METHODS: All eligible patients with moderate-to-severe RA including patients in the placebo group who participated in one of two global phase IIb trials ('with methotrexate' or 'without methotrexate') were included in this 2-year open-label extension study and were converted to peficitinib 100 mg once daily. The primary objective was to evaluate an additional 2 years of safety by assessing treatment-emergent adverse events (AEs) and clinical laboratory evaluations for 105 weeks. Evaluation of an additional 2 years of effectiveness using American College of Rheumatology (ACR) 20/50/70 responses was the exploratory objective. RESULTS: Overall, 611 patients were enrolled in the extension study: 319 (52.2%) patients completed the study and 292 (48%) discontinued treatment, including for withdrawal of patient consent (n = 96), failure to achieve low disease activity (n = 62), and AE not including death (n = 41). AEs were reported in 463 (76%) patients. The most common AEs (per 100 patient-years) were upper respiratory tract infections (9.9) and urinary tract infections (7.2). Serious AEs were reported in 80 (13%) patients, with incidences per 100 patient-years of serious infections 2.7, herpes zoster 1.5 (including one herpes zoster ophthalmic), and malignancies 0.6 (most frequently basal cell carcinoma). At week 105, 269 (44%) patients demonstrated an ACR20 response relative to their respective phase IIb trial baselines. CONCLUSION: Among 319 patients who completed this 2-year extension of two global phase IIb studies, peficitinib 100 mg once daily demonstrated a stable safety profile and sustained effectiveness in patients with moderate-to-severe RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01711814. Registered 19 October 2012. FUNDING: Astellas Pharma Global Development, Inc.

Acaricidal Activity and Synergistic Effect of Thyme Oil Constituents against Carmine Spider Mite (Tetranychus Cinnabarinus (Boisduval)).

Studies examining the use of essential oils as replacements for synthetic insecticides require an understanding of the contribution of each constituent present, interactions among these components, and how they relate to overall toxicity. In the present study, the chemical composition of commercial thyme oil was identified by gas chromatography-mass spectrometry. Thyme oil and blends of its major constituents were tested for their acaricidal activitities against carmine spider mites (Tetranychus cinnabarinus (Boisduval)) using a slide-dip bioassay. Natural thyme oil showed greater toxicity than any single constituent or blend of constituents. Thymol was the most abundant component (34.4%), and also possessed the strongest acaricidal activity compared with other single constituents. When tested individually, four constituents (linalool, terpinene, p-cymene and carvacrol) also had activity, while α-pinene, benzoic acid and ethyl gallate had almost no activity. The toxicity of blends of selected constituents indicated a synergistic effect among the putatively active and inactive constituents, with the presence of all constituents necessary to reach the highest toxicity. The results indicated that thyme oil and some of its major constituents have the potential to be developed into botanical acaricides.

A randomized, double-blind, solifenacin succinate versus placebo control, phase 4, multicenter study evaluating urinary continence after robotic assisted radical prostatectomy.

PURPOSE: Bladder dysfunction influences recovery of urinary continence after radical prostatectomy. We performed a multicenter, randomized, double-blind study evaluating solifenacin vs placebo on return to continence in patients who were still incontinent 7 to 21 days after catheter removal after robot-assisted radical prostatectomy. MATERIALS AND METHODS: A wireless personal digital assistant was given to patients the day of catheter removal. Encrypted answers were transmitted daily to dedicated servers. After a 7 to 21-day treatment-free washout period, patients requiring 2 to 10 pads per day for 7 consecutive days were randomized (1:1) to 5 mg solifenacin daily or placebo. The primary end point was time from first dose to continence defined as 0 pads per day or a dry security pad for 3 consecutive days. Secondary end points included proportion of patients continent at end of study, average change in pads per day number and quality of life assessments. RESULTS: A total of 1,086 screened patients recorded personal digital assistant information. Overall 640 patients were randomized to solifenacin vs placebo and 17 failed to take medication. There was no difference in time to continence (p=0.17). Continence was achieved by study end in 91 of 313 (29%) vs 66 of 309 (21%), respectively (p=0.04). Pads per day change from baseline was -3.2 and -2.9, respectively (p=0.03). Dry mouth was the only common adverse event seen in 6.1% and 0.6%, respectively. Constipation rates were similar. The overall rate of continence in the entire population from screening to end of study was 73%. CONCLUSIONS: There was no effect on primary outcome but some secondary end points benefited the solifenacin arm. The study provides level 1B clinical evidence for continence outcomes after robot-assisted radical prostatectomy.

Solifenacin plus tamsulosin combination treatment in men with lower urinary tract symptoms and bladder outlet obstruction: a randomized controlled trial.

BACKGROUND: Alpha blockers are prescribed to manage lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Antimuscarinics are prescribed to treat overactive bladder (OAB). OBJECTIVE: To investigate the safety of a combination of solifenacin (SOLI) and tamsulosin oral controlled absorption system (TOCAS) in men with LUTS and bladder outlet obstruction (BOO). DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, parallel-group, placebo-controlled study in men aged >45 yr with LUTS and BOO for ≥3 mo, total International Prostate Symptom Score (IPSS) ≥8, BOO index ≥20, maximum urinary flow rate (Q(max)) ≤12 ml/s, and voided volume ≥120 ml. INTERVENTIONS: Once-daily coadministration of TOCAS 0.4 mg plus SOLI 6 mg, TOCAS 0.4 mg plus SOLI 9 mg, or placebo for 12 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary (safety) measurements: Q(max) and detrusor pressure at Q(max) (P(det)Q(max)). Other safety assessments included postvoid residual (PVR) volume. Secondary end points included bladder contractile index (BCI) score and percent bladder voiding efficiency (BVE). An analysis of covariance model compared each TOCAS plus SOLI combination with placebo. RESULTS AND LIMITATIONS: Both active treatment groups were noninferior to placebo at end of treatment (EOT) for P(det)Q(max) and Q(max). Mean change from baseline PVR was significantly higher at all time points for TOCAS 0.4 mg plus SOLI 6 mg, and at weeks 2, 12, and EOT for TOCAS 0.4 mg plus SOLI 9 mg versus placebo. Both treatment groups were similar to placebo for BCI and BVE. Urinary retention was seen in only one patient receiving TOCAS 0.4 mg plus SOLI 6 mg. Limitations of the study were that prostate size and prostate-specific antigen level were not measured. CONCLUSIONS: TOCAS 0.4 mg plus SOLI 6 mg or 9 mg was noninferior to placebo at EOT for P(det)Q(max) and Q(max) in men with LUTS and BOO, and there was no clinical or statistical evidence of increased risk of urinary retention.

Efficacy of Solifenacin on Overactive Bladder Symptoms, Symptom Bother, and Other Patient-Reported Outcomes in Subjects With or Without Incontinence: A Post Hoc Analysis of Data From VIBRANT.

OBJECTIVE: : To evaluate the efficacy of solifenacin versus placebo by baseline continence status using post hoc analysis. METHODS: : Patients with overactive bladder (OAB) were randomized to solifenacin or placebo for 12 weeks; patient-reported outcome (PRO) measures and bladder diaries were completed at prespecified time points. VESIcare Investigation of Bother and Quality of Life in Subjects with OAB (VIBRANT) was not designed to show treatment differences within continence status subgroups. RESULTS: : In the full analysis set (n = 750), 73% of patients were incontinent (n = 545) at baseline. After 12 weeks, incontinent patients receiving solifenacin showed significant improvements versus placebo on PRO measures and most diary-based end points; continent patients (n = 205) showed smaller but similar treatment-related changes. Tolerability was similar in both subgroups and by treatment; most frequent adverse events were dry mouth and constipation. CONCLUSIONS: : In the VIBRANT study, solifenacin significantly improved OAB symptom bother, health-related quality of life, and most symptoms versus placebo in incontinent patients. Continent patients showed smaller but similar trends. Solifenacin was well tolerated in both subgroups.

A clinicopathological study of resected non-small cell lung cancers 2 cm or less in diameter: a prognostic assessment.

The detection and diagnosis of small-sized (2 cm or less) non-small cell lung cancer (NSCLC) has increased with the development of computed tomography (CT). Over 80% of 5-year survival rate has been reported in surgically treated peripheral lung cancer. There are systematic mediastinal and hilar lymph node involvement pleural invasion and intrapulmonary metastasis even with tumor diameter less than 2 cm. The appropriate surgical procedure for such kinds of lung cancer is lobectomy with mediastinal lymph node dissection. To evaluate the prognostic factors and establish the optimal surgical strategy, we analyzed the clinicopathologic features and survival benefit in different tumor size of peripheral small-sized NSCLC. Among the resected lung cancer cases between January 1999 and July 2001, 185 patients were retrospectively analyzed in surgical methods, lymph node involvement, CT scan findings and survival rates. Survival was analyzed by Kaplan-Meier method and log-rank test. Lymph node involvement was recognized in 26(14.05%) patients. There was no statistically significant difference in the incidence of lymph node involvement between tumors 1.6-2.0 cm (17.82%) in diameter than in those 1.0-1.5 cm (11.94%). There was no lymph node metastasis in tumors less than 1.0 cm in diameter. The 5-year survival rates with or without lymph node involvement were 89.98 and 46.15%, respectively, showing significant difference (P=0.000). The overall 5-year survival rate was 83.78%. The 5-year survival rate in tumors 1.6-2.0 cm, 1.0-1.5 cm and less than 1.0 cm in diameter was 80.20, 85.07 and 100%, respectively, and showing significant difference (P=0.035). The 5-year survival rate of 19 patients showing ground-glass opacity (GGO) on CT scan was 94.74% without any metastasis and recurrence after operation. There are systematic mediastinal and hilar lymph node involvement even with tumor diameter less than 2 cm. The results of the present study suggested that systematic lymph node dissection is necessary even for cases with tumor diameter less than 2 cm. However, if the tumor is within 1.0 cm in diameter with obvious GGO showing on chest CT scan, these are good candidates for partial resection without mediastinal lymph node dissection.

Efficacy of Solifenacin on Symptom Bother and Health-Related Quality of Life in Patients With Acute, Early Chronic, and Late Chronic Overactive Bladder: Secondary Analysis of Data From the VOLT Study.

OBJECTIVES: : In many clinical trials of pharmacotherapy for overactive bladder (OAB), the duration of symptoms is reported as a baseline characteristic; none has investigated this as a prognostic variable. We evaluated the efficacy of solifenacin by patient-reported OAB duration. METHODS: : In this post hoc analysis, patients from a 12-week, open-label study of solifenacin were grouped into 3 OAB duration categories: 3 months to 1 year, 1 to 5 years, and more than 5 years. Changes from baseline to end point on the Patient Perception of Bladder Condition (PPBC), Overactive Bladder Questionnaire (OAB-q), and visual analog scale (VAS) are summarized for each duration cohort. In addition, analysis of covariance was used to compare baseline characteristics and treatment-related changes from baseline among the 3 duration cohorts. RESULTS: : After 12 weeks, all 3 duration cohorts showed numeric improvements in the PPBC, VAS, and OAB-q. Approximately 75% of patients in each group showed improvement on the PPBC. All 3 cohorts showed a 36- to 45-point improvement in the level of bother on the symptom-specific VAS. The magnitude of score improvements (14-31 points) on the OAB-q exceeded the minimally important within group difference of 10 points in all 3 groups. Although results from the analysis of covariance model indicated statistically significant differences between the 3 cohorts for some end points, these differences were numerically small and may not be clinically relevant. Tolerability was similar among the cohorts and compared with the safety population. The most frequently reported adverse events were dry mouth, constipation, headache, and blurred vision. CONCLUSIONS: : These findings showed that irrespective of OAB symptom duration, patients who received 12 weeks of solifenacin perceived meaningful improvements in symptom-specific bother, health-related quality of life, and their overall bladder condition.

[Prognostic Analysis of ERCC1, RRM1 and p53 Expressions in Postoperative Stage I-II Lung Cancer.].

BACKGROUND: Cisplatin is an important drug in lung cancer chemotherapy. It has been proven that ERCC1, RRM1, p53 expressions were related to resistance to platinum and prognosis of the patcents with lung cancer. The aim of this study is to analyze the association of the expression of ERCC1, RRM1, p53 with postoperative survival in patients with stage I-II non-small-cell lung cancer (NSCLC), and to explore the relationship between the expression of ERCC1, RRM1, p53 and resistance to cisplatin. METHODS: A total of 75 patients with stage I-II NSCLC receiving radical resection from Feb. 1992 to Jan. 1994 were followed up. Postoperative patients with stage I were randomized two groups (chemo and non-chemo groups). All patients with stage II received adjuvant cisplatinbased chemotherapy. Immunohistochemical staining was used to detect the expression of ERCC1, RRM1, p53 in paraffinembedded specimens. RESULTS: In stage I NSCLC, the prognosis of the patients with high expression of ERCC1 (High-ERCC1) was better than those with low expression of ERCC1 (Low-ERCC1). 1, 3, 5-year survival rate in the patients with high expression of ERCC1 was 100.00%, 91.30%, 86.74% and in those with Low-ERCC1 was 96.43%, 60.71%, 57.14%, respectively (P =0.0058). The patients with High- ERCC1 had a better survival rate than those with Low-ERCC1 in stage I NSCLC without chemotherapy. MST in high and low expression of ERCC1 was 72.00(+) months and 64.67 months, respectively (P =0.0327). In contrary to stage I NSCLC, the patients with had a better survival rate than those with in stage II. MST was 60.00(+) months in stage II patients with low expression of ERCC1, but MST was only 25.50 months with (P =0.0442). The postoperative survival of NSCLC patients was not any statistical different between with high expression and low expression of RRM1 and p53. CONCLUSIONS: High expression of ERCC1 is a better independent prognostic factor in stage I NSCLC patients. Cisplatin-base chemotherapy prolongs survival in stage II NSCLC patients with. Adjuvant chemotherapy regimen is determined according to ERCC1 expression levels in resected NSCLC.

Synergistic inhibitory activity of zoledronate and paclitaxel on bone metastasis in nude mice.

Zoledronic acid (Zometa, ZOL) and cytotoxic chemotherapy agents have been reported to have synergistic antitumor activities. However, there is limited data on the effects of combination therapies on the development of bone metastasis in animal models of lung cancer. The purpose of this study was to establish a human lung adenocarcinoma cell line with high bone metastatic potential in an immunodeficient mouse model and to evaluate the synergistic inhibitory activity of zoledronate and paclitaxel (P) on bone metastasis in nude mice. A human lung adenocarcinoma cell line with high bone metastatic potential (SPC-A1-BM) was established by 10 rounds of in vivo selection. Cells were inoculated into the cardiac ventricle of NIH-BNX mice, which were treated 8 days later with: ZOL (0.2 mg/kg s.c. twice weekly) alone, P (6.0 mg/kg every week, i.p.) alone, P + ZOL, or vehicle (10 mice per group). Tumor growth was evaluated with bone scans, X-rays and in situ immunohistochemistry. Serum n-telopeptide of type I collagen (NTX) was measured by ELISA. Survival was assessed using the Kaplan-Meier method. Bone scan, radiographic and histological assessments revealed fewer bone metastases in all treatment groups vs. vehicle, with P + ZOL significantly reducing the incidence of bone metastases detected by bone scans (P=0.020) and X-rays (P=0.036). A histological analysis revealed marginal differences in the number of bone metastases between P + ZOL and vehicle (P=0.058). There was a trend towards differences in survival between the groups (P=0.1511) and survival was significantly longer for the P + ZOL group vs. vehicle (P=0.022). Compared with vehicle and ZOL alone, cancerous cells in the bone of mice treated with P + ZOL expressed higher levels of Bax and lower levels of Bcl-2 and Bcl-xl. ZOL produced a trend towards reduced NTX levels vs. vehicle and P + ZOL produced a profound reduction in NTX vs. vehicle (P=0.022). The results of this study indicated that zoledronate enhanced the efficacy of paclitaxel synergistically, by reducing the incidence of bone metastasis from lung cancer and prolonging survival in a mouse model of non-small cell lung cancer with a high potential for metastasis to bone.

Putative hAPN receptor binding sites in SARS_CoV spike protein.

AIM: To obtain the information of ligand-receptor binding between the S protein of SARS-CoV and CD13, identify the possible interacting domains or motifs related to binding sites, and provide clues for studying the functions of SARS proteins and designing anti-SARS drugs and vaccines. METHODS: On the basis of comparative genomics, the homology search, phylogenetic analyses, and multi-sequence alignment were used to predict CD13 related interacting domains and binding sites in the S protein of SARS-CoV. Molecular modeling and docking simulation methods were employed to address the interaction feature between CD13 and S protein of SARS-CoV in validating the bioinformatics predictions. RESULTS: Possible binding sites in the SARS-CoV S protein to CD13 have been mapped out by using bioinformatics analysis tools. The binding for one protein-protein interaction pair (D757-R761 motif of the SARS-CoV S protein to P585-A653 domain of CD13) has been simulated by molecular modeling and docking simulation methods. CONCLUSION: CD13 may be a possible receptor of the SARS-CoV S protein, which may be associated with the SARS infection. This study also provides a possible strategy for mapping the possible binding receptors of the proteins in a genome.