Structurally divergent and recurrently mutated regions of primate genomes.

We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, and marmoset. We identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. We estimate that 819.47 Mbp or ∼27% of the genome has been affected by SVs across primate evolution. We identify 1,607 structurally divergent regions wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (e.g., CARD, C4, and OLAH gene families) and additional lineage-specific genes are generated (e.g., CKAP2, VPS36, ACBD7, and NEK5 paralogs), becoming targets of rapid chromosomal diversification and positive selection (e.g., RGPD gene family). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species.

Exosomes derived from induced cardiopulmonary progenitor cells alleviate acute lung injury in mice.

Cardiopulmonary progenitor cells (CPPs) constitute a minor subpopulation of cells that are commonly associated with heart and lung morphogenesis during embryonic development but completely subside after birth. This fact offers the possibility for the treatment of pulmonary heart disease (PHD), in which the lung and heart are both damaged. A reliable source of CPPs is urgently needed. In this study, we reprogrammed human cardiac fibroblasts (HCFs) into CPP-like cells (or induced CPPs, iCPPs) and evaluated the therapeutic potential of iCPP-derived exosomes for acute lung injury (ALI). iCPPs were created in passage 3 primary HCFs by overexpressing GLI1, WNT2, ISL1 and TBX5 (GWIT). Exosomes were isolated from the culture medium of passage 6-8 GWIT-iCPPs. A mouse ALI model was established by intratracheal instillation of LPS. Four hours after LPS instillation, ALI mice were treated with GWIT-iCPP-derived exosomes (5 × 109, 5 × 1010 particles/mL) via intratracheal instillation. We showed that GWIT-iCPPs could differentiate into cell lineages, such as cardiomyocyte-like cells, endothelial cells, smooth muscle cells and alveolar epithelial cells, in vitro. Transcription analysis revealed that GWIT-iCPPs have potential for heart and lung development. Intratracheal instillation of iCPP-derived exosomes dose-dependently alleviated LPS-induced ALI in mice by attenuating lung inflammation, promoting endothelial function and restoring capillary endothelial cells and the epithelial cells barrier. This study provides a potential new method for the prevention and treatment of cardiopulmonary injury, especially lung injury, and provides a new cell model for drug screening.

Association of cardiometabolic and triglyceride-glucose index with left ventricular diastolic function in asymptomatic individuals.

BACKGROUND AND AIMS: Obesity and insulin resistance are associated with left ventricular diastolic dysfunction (LVDD) and increased risk of heart failure. Cardiometabolic index (CMI) and triglyceride glucose (TyG) are new indexes to assess visceral obesity and insulin resistance, respectively. The study aimed to investigate the clinical usefulness of these indexes for identifying LVDD individuals. METHODS AND RESULTS: Overall, 1898 asymptomatic individuals were included in this cross-sectional study. Participants underwent anthropometrics, serum biochemical evaluation, and echocardiography. Multiple linear regression analysis revealed that both indexes were independent determinants of diastolic parameters among females; while for males, CMI and TyG were not associated with A velocity. In the multivariate logistic analysis, the proportion of LVDD in the third and fourth quartiles of CMI remained significantly greater than that in the lowest quartile in females (Q3 vs. Q1: odds ratio (OR) = 2.032, 95% confidence interval (CI): 1.181-3.496; Q4 vs. Q1: OR = 2.393, 95% CI: 1.347-4.249); while in males, the incidence of LVDD was significantly greater only in the fourth quartile. For TyG, the presence of LVDD in the fourth quartile was significantly greater in both genders. The discriminant values between the CMI (AUC: 0.704, 95% CI: 0.668-0.739) and TyG (AUC: 0.717, 95% CI: 0.682-0.752) were similar in females. Both indexes performed better in females than in males to identify LVDD. CONCLUSION: The CMI and TyG might both serve as effective tools to identify LVDD in routine health check-ups in primary care, mainly in females. With simpler parameters, the CMI could be utilized in medically resource-limited areas.

Meta-Analysis on the Recovery Effect of Acupuncture Combined With Rehabilitation Therapy in Spinal Cord Injury Patients.

Objective: To explore the recovery effect of acupuncture combined with rehabilitation therapy on muscle spasms in patients with spinal cord injury through a systematic review of meta-analysis methods. Methods: Use "acupuncture," "electronic-acupuncture," "spinal cord," "spasm," and "paraplegia" as keywords, CNKI, Google, Wanfang, VIP, sci-hub, Web of Science, PubMed, and other Chinese or English databases were searched. To collect the domestic and foreign research on acupuncture combined with rehabilitation for muscle spasms in patients with spinal cord injury. Preliminary screening was conducted, and data extraction and quality evaluation were carried out on the included literature, including publication time, sample size, treatment methods, recovery effects, etc. According to the literature, the influence of acupuncture combined with rehabilitation therapy on muscle spasms in patients with spinal cord injury and related indices was analyzed. The search period was from January 2018 to June 2023, and the selected research results were tested by RevMan5.3 software and data consolidation for consistency. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Results: A preliminary literature search yielded 172 papers. 53 papers from sci-hub, 71 papers from HowNet, 36 papers from Wanfang, and 12 papers from VIP. Finally, 10 articles that met the criteria were included, including 594 patients. According to different treatment methods, the literature about acupuncture combined with rehabilitation therapy for muscle spasms in patients with spinal cord injury was analyzed for consistency, and data were merged. It was concluded that acupuncture combined with rehabilitation The clinical curative effect of the experimental group of patients is higher than that of the control group MD=5.31, 95%CI (2.94, 7.81), Z=5.64, P < .001; the clinical effective rate of the experimental group is higher than that of the control group. The improvement of the clinical spasticity index (CSI) score index of the patients in the experimental group was better than that of the control group MD = -3.09, 95%CI (-4.51, -1.67), Z =4.28, P < .001; the MAS score of the patients in the experimental group The improvement was better than that of the control group MD =-0.76, 95%CI (-1.16, -0.38), Z=8.13, P < .001; the improvement of Barthel index (BI) in the experimental group was better than that of the control group MD=9.81, 95%CI (7.84,11.71), Z=12.71, P < .001; no adverse events were reported in the experimental group and the control group. Conclusion: This study shows that acupuncture and rehabilitation are more effective than other therapeutic methods in the treatment of muscle spasms after spinal cord injury, and more randomized controlled trials are needed to verify this in the future.

Is there a bidirectional relationship between workplace bullying and the risk of sickness absence? Systematic review and meta-analysis of prospective studies.

Exposure to workplace bullying increases the risk of sickness absence. However, the extent and direction of this relationship for different follow-up lengths are not well established. To provide evidence regarding the direction and extent of the relationship between workplace bullying and different durations of sickness absence. We searched nine databases from their inception to 29 November 2022. Multiple independent observers screened the literature, extracted the data and used the Risk Of Bias In Non-randomised Studies of Exposure to assess the methodological quality. The overall effect sizes of odds ratio, relative risk, hazard ratio and 95% confidence intervals were calculated. Our meta-analysis demonstrated a 26% increased risk of sick leave among workers exposed to workplace bullying for all follow-up lengths (95% CI 1.18 to 1.35), even after adjusting for confounding factors. Moreover, we found a significant association between long-term sickness absence and a higher likelihood of subsequent exposure to workplace bullying, with a pooled OR of 1.63 (95% CI 1.21 to 2.04). Our study established a bidirectional relationship between workplace bullying and long-term sickness absence, highlighting that it increases the risk of sickness absence at different follow-up lengths among employees who have been bullied. Hence, organisations should be mindful of workers who resume work after prolonged absences due to illness and adopt appropriate management strategies to prevent workplace bullying.

Pyrite coupled with biochar alleviating the toxicity of silver nanoparticles on pollutants removal in constructed wetlands.

Silver nanoparticles (AgNPs) has been widely detected in the substrates of constructed wetlands (CWs), posing threaten to pollutants removal efficiency of CWs. However, the way to alleviate the toxicity of AgNPs on CWs is unclear. In this study, the gravel (GR), biochar (BC), pyrite (PY) and pyrite coupled with biochar matrix (PYBC) were selected as substrates to restore the pollutants removal efficiency of CWs under the exposure to the environment (0.2 mg/L) and accumulation (10 mg/L) concentration of AgNPs. Results showed that the BC and PY showed limited mitigation effects, while the PYBC alleviated the toxicity significantly. Especially in the exposure to the accumulation concentration of AgNPs, the removal of NH4+-N, TN, COD and TP in the PYBC were 10.2%, 8.3%, 9.4% and 10.7% higher than that in the GR, respectively. Mechanism analysis verified that AgNPs were transformed into Ag-Fe-S core shell aggregates (size >200 nm) decreasing bioavailability and the damage to cytomembrane. The PYBC restored the nitrogen removal efficiency by increasing the abundance of Nitrospira and Geothrix, which these bacteria were defined as nitrifiers and Feammox bacteria. This study provides a promising strategy to mitigate AgNPs' toxicity on the pollutant removal efficiency in CWs.

Assessment of MRI image distortion based on 6 consecutive years of annual QAs and measurements on 14 MRI scanners used for radiation therapy.

PURPOSE: To determine the magnitude of MRI image distortion based on 6 consecutive years of annual quality assurances/measurements on 14 MRI scanners used for radiation therapy and to provide evidence for the inclusion of additional margin for treatment planning. METHODS AND MATERIALS: We used commercial MRI image phantoms to quantitatively study the MRI image distortion over period of 6 years for up to 14 1.5 and 3 T MRI scanners that could potentially be used to provide MRI images for treatment planning. With the phantom images collected from 2016 to 2022, we investigated the MRI image distortion, the dependence of distortion on the distance from the imaging isocenter, and the possible causes of large distortion discovered. RESULTS: MRI image distortion increases with the distance from the imaging isocenter. For a region of interest (ROI) with a radius of 100 mm centered at the isocenter, the mean magnitude of distortion for all MRI scanners is 0.44 ± 0.18 mm $0.44 \pm 0.18\;{\rm{mm}}$ , and the maximum distortion varies from 0.52 to 1.31 mm $0.52\;{\rm{to}}\;1.31\;{\rm{mm}}$ depending on MRI scanners. For an ROI with a radius of 200 mm centered at the isocenter, the mean magnitude of distortion increases to 0.84 ± 0.45 mm $0.84 \pm 0.45\;{\rm{mm}}$ , and the range of the maximum distortion increases to 1.92 - 5.03 mm $1.92 - 5.03\;{\rm{mm}}$ depending on MRI scanners. The distortion could reach 2 mm at 150 mm from the isocenter. CONCLUSION: An additional margin to accommodate image distortion should be considered for treatment planning. Imaging with proper patient alignment to the isocenter is vital to reducing image distortion. We recommend performing image distortion checks annually and after major upgrade on MRI scanners.

Acute stress promotes brain oscillations and hippocampal-cortical dialog in emotional processing.

Hippocampal-cortical circuit oscillations in local field potential (LFP) represent network-level signals which promotes behavior. Investigating these signals promote our understanding on how the brain process cognition and emotion, and provide further perspectives into electroencephalogram endophenotypes, especially under the pathological state. The physiological adaptive stress responses to threatening stimuli are critical for individuals. The disturbance of stress response may lead to psychiatric disorders such as major depressive disorder (MDD). To quantitatively examine the effects of acute stress on hippocampal-cortical circuit, we recorded LFPs in the hippocampus (HC) and the medial prefrontal cortex (mPFC). We analyzed three major LFP oscillations with their temporal coupling. Consistent with our hypothesis that strengthened communication of hippocampal-cortical circuit may occur in stress adaption, we found that intensive acute stress induced enhanced ripple-delta-spindle coupling. The LFP coupling may facilitate the recruitment of relevant structures in hippocampal-cortical circuit, in response to acute stress, and play a role in emotional encoding migration.

[Neural oscillation and its application in mechanistic study of neuropsychiatric disorders].

Neural oscillations reflect synchronized activities of neuronal ensembles in central nervous system. In the hippocampus, thalamus, neocortex and other brain subregions, neural oscillation can be detected and plays a crucial role in many complicated cognitive processes. Decoupling and damaging of neural oscillation play a key role in the induction of severe cognition deficits in many psychiatric disorders. In this review, we summarize research advances in the underlying mechanisms and physiological functions of neural oscillations. We also discuss the abnormal changes of sharp wave-ripple, gamma oscillation and sleep spindle oscillation in major depressive disorder, schizophrenia and Alzheimer's disease, etc. Finally, the application potential of neural oscillations as clinical diagnosis and treatment targets is evaluated and prospected.

C/EBPß is a key transcription factor of ox-LDL inducing THP-1 cells to release multiple pro-inflammatory cytokines.

OBJECTIVE: CCAAT/enhancer binding protein ß (C/EBPß) plays an important role during atherogenesis. However, how C/EBPß functions remains unclear. In this study, we explore the relationship between C/EBPß and oxidized LDL-induced multiple pro-inflammatory cytokines released in monocytes. MATERIALS AND METHODS: THP-1 cells (human monocyte cell line) were stimulated by ox-LDL, ChIP was used to detect the binding function of C/EBPß to target genes, small interfering RNA was used to knock down the expression of C/EBPß, Western Blot was used to detect protein expression, and ChIP-seq was used to detect different groups of C/EBPß bound gene fragments. The integrative genomics viewer (IGV), model-based analysis of ChIP-seq (MACS) were used to visualize the results of ChIP-seq. GO (gene ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes) and Reactome data bases enrichment analysis were performed by the ClusterProfiler software. Ingenuity pathway analysis (IPA) was used to analyze the results of ChIP-seq and to summarize the data within the database. RESULTS: We identified C/EBPß as a key protein that regulated IL-1ß, IL-6 through database. Then our results confirmed that C/EBPß could bind directly to the gene of IL-18 and C/EBPß plays a role in the increased expression and secretion of IL-18 protein after ox-LDL stimulation of THP-1. Using ChIP-seq, we found that the enhanced transcriptional function of C/EBPß after ox-LDL treatment triggered changes in C/EBPß-regulated downstream pathways. In the ChIP-seq results, we extracted inflammatory cytokines with significant expression differences, and by comparing them with the database of inflammatory cytokines that C/EBPß directly regulated, we screened five inflammatory cytokines, CXCL8, IL17B, TNFSF11, CSF3, and CCL2, and the results showed that knockdown of C/EBPß expression inhibited ox-LDL-induced secretion of CXCL8, TNFSF11, CSF3, and CCL2 by THP-1. CONCLUSION: Our results suggest that ox-LDL stimulation enhances C/EBPß-regulated transcription in THP-1 and C/EBPß upregulate the release of multiple pro-inflammatory cytokines including IL-18, IL-1ß, and IL-6 through direct binding to genes.

MiR-135b promotes HCC tumorigenesis through a positive-feedback loop.

Hippo pathway plays critical roles in cell proliferation and apoptosis and its dysregulation leads to various types of cancers, including hepatocellular carcinoma (HCC). However, the mechanism maintaining Hippo pathway homeostasis still remains unclear. In this study, we discovered that the expression of miR-135b is apparently upregulated in HCC tissues and HCC cell lines. The level of miR-135b was positively correlated with HCC stages and negatively correlated with the survival of HCC patients, suggesting an oncogenic role of miR-135b in HCC progression. Similarly, miR-135b mimic promoted HCC cell proliferation and migration, whereas its inhibitor played an opposite role. Mechanistically, we identified a seed sequence of miR-135b in the MST1 3'-UTR region. MiR-135b inhibited the Hippo pathway by silencing MST1 expression. Additionally, we revealed that miR-135b was a transcriptional target of the Hippo pathway. Based on these data, we propose that a positive-feedback axis of MST1-YAP-miR-135b exists for HCC aggravation. Our study not only deepens the insight into the Hippo pathway homeostasis, but also suggests miR-135b as a potential prognosis biomarker and therapeutic target for HCC.

Nanoplastics Disturb Nitrogen Removal in Constructed Wetlands: Responses of Microbes and Macrophytes.

Nanosized plastics (nanoplastics) releasing into the wastewater may pose a potential threat to biological nitrogen removal. Constructed wetland (CW), a wastewater treatment or shore buffer system, is an important sink of nanoplastics, while it is unclear how nitrogen removal in CWs occurs in response to nanoplastics. Here, we investigated the effects of polystyrene (PS) nanoplastics (0, 10, and 1000 µg/L) on nitrogen removal for 180 days in CWs. The results revealed that total nitrogen removal efficiency decreased by 29.5-40.6%. We found that PS penetrated the cell membrane and destroyed both membrane integrity and reactive oxygen species balance. Furthermore, PS inhibited microbial activity in vivo, including enzyme (ammonia monooxygenase, nitrate reductase, and nitrite reductase) activities and electron transport system activity (ETSA). These adverse effects, accompanied by a decline in the relative abundance of nitrifiers (e.g., Nitrosomonas and Nitrospira) and denitrifiers (e.g., Thauera and Zoogloea), directly accounted for the strong deterioration observed in nitrogen removal. The decline in leaf and root activities decreased nitrogen uptake by plants, which is an important factor of deterioration in nitrogen removal. Overall, our results imply that the presence of nanoplastics in the aquatic environment is a hidden danger to the global nitrogen cycle and should receive more attention.

Improvement in MR quality control workflow and outcomes with a web-based database.

PURPOSE: To describe a custom-built, web-based MR Quality Control (QC) database, and to assess its impact on the QC workflow and outcomes in a large U.S. academic medical center. METHODS: The MR QC database was built with Microsoft Access 2010 and published on a Microsoft Sharepoint website owned and maintained by the authors' institution. Authorized users can access the database remotely with mainstream web browsers on any institutional computers. QC technologists were granted access to add, review, and print daily and weekly QC records. Qualified medical physicists (QMPs) were granted additional access to edit, review, and approve existing QC records and to change tolerance limits. A macro was utilized to conduct an automatic weekly review of QC status and to email the results to a QMP. This web-based QC database was implemented on 17 clinical MRIs at the authors' institution. Weekly ACR QC findings within one year before and after implementation were compared. RESULTS: We analyzed 158 QC issues detected by the web-based database and 127 QC issues identified in conventional paper records before we implemented the database. The web-based database significantly reduced the number of QC issues due to technologist error (before/after: 59/24 cases, P < 0.0001) but did not affect the number of QC issues related to scanner performance (before/after: 49/46 cases, P = 1). Further analysis revealed that the web-based database significantly reduced the average time for the QMPs to identify a QC issue (before/after: 177 ± 110/2 ± 2 days, P < 0.0001) and time to correction (before/after: 81 ± 102/7 ± 8 days, P < 0.0001). The correction rate also significantly increased (before/after: 22%/99%, P < 0.0001). CONCLUSION: The web-based QC database provides a positive impact on our MR QC workflow and outcomes. It simplifies QC workflow, enables early detection of quality issues, and facilitates quick resolution of problems that may affect the quality of clinical MRI studies.

Circ_0005075 promotes hepatocellular carcinoma progression by suppression of microRNA-335.

Accumulating evidence suggests that noncoding RNAs play a vital role in cancer biology. Circular RNAs (circRNAs), a newly defined class of endogenously widespread noncoding RNAs, have been intensively reported to influence cell function and development, and even cancer prognosis by sponging microRNAs in various types of cancer. Nevertheless, the circRNAs research in hepatocellular carcinoma (HCC) still remains far insufficient. Herein, we investigated the role of a newly defined circRNAs, circ_0005075, in HCC development. We found circ_0005075 was upregulated in HCC tissues. HCC progression was suppressed by downregulation of circ_0005075 in vitro and in vivo, and the suppression was partially reversed by inhibition of microRNA-335 (miR-335) expression. Further, we found the expression of mitogen-activated protein kinase 1 (MAPK1) was substantially regulated by circ_0005075 and miR-335. Mechanically, it was demonstrated that circ_0005075 could directly bind to miR-335 and miR-335 could bind to MAPK1. Our data provide evidence that circ_0005705 promotes the HCC progression by sponging miR-335 and further regulating MAPK1 expression.

Assessment of chicken breast meat quality after freeze/thaw abuse using magnetic resonance imaging techniques.

BACKGROUND: Freezing/thawing meat can result in quality losses as a result of the formation, melting and reformation of ice. These changes in water state can result in alterations in texture, water holding and other key quality attributes. It was hypothesized that magnetic resonance imaging (MRI) could quantify changes in mobility and localization of water as a function of freezing/thawing, which could be correlated with quality measurements. RESULTS: Drip loss increased significantly for unbrined samples by over 100% after each freeze/thaw cycle (1.5% to 3.3% to 5.3% drip loss). Brine uptake decreased 50% after 2 cycles (from 53% to 28% mass uptake). Drip loss for brined samples increased after 2 cycles; other attributes were not significantly affected. MRI showed brined samples had less change in both proton density and T2 distributions. High-field nuclear magnetic resonance (NMR) imaging showed greater change in T2 distributions. CONCLUSION: As freeze/thaw damage increased, meat quality was reduced in both brined and unbrined chicken breasts, with more prominent changes in unbrined meat. These decreases in quality correlated with changes, albeit small, in water mobility and localization as measured by MRI. High-field NMR micro-imaging showed more dramatic changes in T2 distributions in unbrined samples. These MRI techniques are shown to be useful in the assessment of meat quality after freeze/thaw abuse. © 2018 Society of Chemical Industry.

Association of change in waist circumference and dyslipidaemia risk: The rural Chinese cohort study.

OBJECTIVE: To investigate the association of change in waist circumference (WC) and incidence of dyslipidaemia in a cohort study of a rural Chinese population. METHODS: Change in WC (ΔWC) was defined as the value at follow-up minus the corresponding value at baseline. Risk of dyslipidaemia associated with ΔWC was assessed by odds ratios and 95% confidence intervals in a logistic regression model, and the odds ratios were transformed to relative risks (RRs). RESULTS: Among 7691 participants without dyslipidaemia at baseline, 3213 (41.78%) showed dyslipidaemia at 6 year follow-up. Risk of dyslipidaemia was decreased for participants with the first quartile of ΔWC and normal baseline WC (adjusted RR [aRR] = 0.79 [95% confidence interval: 0.64-0.98]) and was increased with the fourth quartile of ΔWC and male gender, age 18 to 30 years, age 31 to 50 years, or normal baseline WC (aRR = 1.55 [1.19-2.03], 2.40 [1.16-4.95], 1.32 [1.06-1.64], and 1.66 [1.35-2.04], respectively). The risk of dyslipidaemia increased with change in WC from normal at baseline to abnormal at follow-up for both genders (aRR = 1.88 [1.39-2.55] for men and 1.60 [1.30-1.97] for women) and decreased with abnormal baseline WC changed to normal WC for women (aRR = 0.61 [0.45-0.83]). CONCLUSIONS: Dynamic change in waist circumference was closely related to the incidence of dyslipidaemia in a rural Chinese population. Waist circumference reduction could decrease dyslipidaemia risk, whereas WC increase may increase the risk. Interventions to control or reduce WC to within the normal range are important for early prevention of dyslipidaemia.

Preclinical evaluation of an 18F-trifluoroborate methionine derivative for glioma imaging.

PURPOSE: 11C-methionine (MET) is one of the most commonly used amino acid tracers for PET imaging of brain tumors. In this study, we report an 18F-labeled boron-derived methionine analogue, denoted as 18F-B-MET, as a potential substitute of 11C-MET for glioma PET imaging. METHODS: 19F-B-MET was synthesized from readily available chemicals according to our previous publication. For kit development, 19F-B-MET was aliquoted in quantities of 10 nmol for on-demand one-step labeling. The 18F-labeling was performed by 18F-19F isotope exchange, and quality control was performed by both HPLC and radio-TLC. Uptake of the tracer was determined in GL26, C6 and U87 tumor cells. PET imaging and the biodistribution assay were performed on mice bearing subcutaneous or orthotopic C6 and U87 tumor xenografts. RESULTS: Starting with 740-1110 MBq 18F-fluoride, >370 MBq of 18F-B-MET was obtained in 25 min (n = 5) with >99% purity and high specific activity (>37 GBq/µmol). 18F-B-MET demonstrated excellent in vitro stability with <1% decomposition after incubation with plasma for 2 h. In vitro cell uptake assay showed that 18F-B-MET accumulated in tumor cells in a time dependent manner and could be competitively inhibited by natural methionine and other L-type transporter transported amino acids. In vivo biodistribution and imaging studies showed high tumor accumulation (2.99 ± 0.23 %ID/g, n = 6) compared with low uptake of brain (0.262 ± 0.05 %ID/g, n = 6) at 60 min after injection in a subcutaneous C6 tumor model. Orthotropic C6 and U87 tumors were clearly visualized with high tumor to brain ratios at 60 min post-injection, corroborating with tumor L-type amino acid transporter 1 (LAT-1) expression levels. CONCLUSION: 18F-B-MET was radiolabeled with high yield in a one-step labeling process, showed excellent pharmacokinetic properties in vivo, with high tumor-to-brain contrast.

Development and validation of a questionnaire to evaluate the factors influencing training transfer among nursing professionals.

BACKGROUND: Most organizations invest in people for training to improve human capital and maximize profitability. Yet it is reported in industry and nursing as well that training effectiveness is constrained because of inadequate transfer of training and the underlying reasons for the transfer problem remain unknown. And there is lack of tool to measure transfer problem. METHODS: The purpose of this study was to develop and validate a questionnaire to evaluate the scores of factors influencing training transfer (FITT) among nursing professionals. The questionnaire was developed by item generation through interview with nurses and literature review. The FITT was validated in terms of content validity through expert reviews. Psychometric properties of the final instrument were assessed in a sample of 960 nurses with training experiences. RESULTS: The content validity of the instrument were as follows: the IR was 0.8095. 51 items on the 63-item scale had I-CVIs of 1.0 and the remaining 12 items had I-CVIs of 0.88. The S-CVI/UA was 0.976 and the S-CVI/Ave was 0.977. For the exploratory step, principal axis factoring (PAF) was selected for this study. Parallel analysis was used to decide the number of factors to extract and oblimin rotation method was used. Exploratory factor analysis identified a five-factor solution including 53 items, accounting for 68.23% of the total variance. The confirmatory factor analysis showed some support for this five-factor model. The findings demonstrate high internal consistency (Cronbach's alpha = .965). CONCLUSIONS: This study indicates that the FITT is a valid and reliable instrument for assessing the factors influencing training transfer among nursing professionals. The FITT can be used to assess individual perceptions of catalysts and barriers to the transfer of training among nursing professionals, which can help promote training transfer and training effectiveness in the workplace.

Factors influencing training transfer in nursing profession: a qualitative study.

BACKGROUND: There is a growing recognition that training is not translated into performance and the 'transfer problem' exists in organization training today. Although factors contributing to training transfer have been identified in business and industry, the factors influencing training transfer in nursing profession remain less clear. METHODS: A qualitative descriptive study was undertaken in two tertiary referral hospitals in China from February 2013 to September 2013. Purposeful sampling of 24 nursing staffs were interviewed about the factors influencing training transfer. RESULTS: Seven themes evolved from the analysis, categorized in 4 main domains, which described the factors influencing training transfer in nursing profession in trainee characteristics, training design, work environment and profession domain. The trainee characteristics domain included attitude and ability. The training design domain included training content and instruction method. The work environment domain included supports as facilitators and opposition as hindrance. The theme pertaining to the profession domain was professional development. CONCLUSIONS: Health care managers need to understand the factors influencing training transfer for maximizing the benefits of training. The right beliefs and values about training, the rigorous employee selection for training, the relevance of training content, training instructions facilitating learning and transfer, supports from peer, supervisors and the organization, organizational culture such as change, sharing, learning and support, and professional development are key to successful training transfer. Furthermore, managers should be aware of the opposition from co-workers and find ways to prevent it.

Combinatorial Screening of DNA Aptamers for Molecular Imaging of HER2 in Cancer.

HER2, a cell membrane protein overexpressed in many types of cancers, is correlated with poor diagnosis, suboptimal treatment outcome, and low survival rate. Multiple HER2-targeted drugs have been developed for the treatment of HER2-overexpressing tumor, which can in turn down-regulate HER2 expression. It is thus significant to profile HER2 expression for cancer prognosis, patient stratification, and monitoring therapy response. Aptamers, a class of single-stranded DNA/RNA (ssDNA/ssRNA) ligands, are promising for molecular biomarker imaging. Aptamers typically have strong binding affinity, high selectivity, batch-to-batch reproducibility, and low toxicity, and systemically injected aptamers often have high tumor-to-background ratio within a short time. However, current aptamers have been mostly screened in vitro, and these aptamers may lose binding ability in vivo due to conformational change under physiological environments. Here, a DNA library was combinatorially screened in vitro and in vivo, to select HER2-targeting DNA aptamers, termed Heraptamers, and labeled with 18F for positron emission tomography (PET) imaging of HER2 in ovarian cancer. Specifically, using systematic evolution of ligands by exponential enrichment (SELEX), Heraptamer candidates were first selected and validated in vitro using HER2 extracellular domain (ECD) and HER2-positive SKOV3 cancer cells; then, aptamer candidates were modified with alkyne, radiolabeled with 18F using azide-functionalized precursors by click chemistry, and screened in SKOV3-tumor-bearing mice using PET. Two aptamers, Heraptamer1 and Heraptamer2, reached high tumor uptake ratios within as short as 1 h. At 1.5 h post injection, the tumor uptake ratio of these two aptamers was up to 0.5%ID/g (injection dose/gram tissue), with tumor-to-muscle ratio of 4.55 ± 1.63 in SKOV3 tumor. In contrast, these aptamers have low uptake ratios in control MDA-MB-231 tumors. These preclinical studies showed that Heraptamers are promising for specific HER2 imaging.