We present the case of a 79-year-old female with symptomatic cavernous haemangioma of the liver. The patient had experienced progressive right lateral abdominal pain for years despite increased painkiller use. Surgical resection or transarterial embolisation was not recommended because of the patient’s age, cardiovascular comorbidities and large tumour size. Therefore, the patient was treated with 3-dimensional conformal radiotherapy (RT) with a total dose of 30 Gy in 15 fractions. Following RT, the painkillers were tapered from the third month, and complete symptomatic remission was achieved after the ninth month. The measured tumour volume from serial images pre-RT and 3, 9 and 15 months post-RT was 400 ml, 372 ml, 185 ml and 140 ml, respectively. The most dramatic volumetric reduction was found between 3 and 9 months post-RT, whereas the change before or after this period was minimal. The time course of the radiological volumetric changes correlated with that of the clinical symptoms. In addition, the observed vascular changes on serial imaging studies were consistent with the assumed radiobiological effects after fractionated RT.

Rapamycin is an immunosuppressive agent routinely used in organ transplantation, but also paradoxically, exerts antiviral and anti-tumor activities. Pathogen-specific memory CD8+ T cell (TCD8) responses were recently found to be augmented by rapamycin. However, whether rapamycin influences the magnitude and quality of anticancer TCD8 responses is unknown. Importantly, how rapamycin may regulate simultaneous virus/tumor-specific and alloreactive TCD8 in the same host remains unexplored. To answer these questions, we primed wild-type mice with allogeneic cells concomitantly expressing simian virus 40 large tumor antigen (T Ag), a viral oncoprotein with well-defined epitopes. Rapamycin selectively enhanced the cross-priming of TCD8 specific for T Ag’s most immunodominant epitope called site IV but not TCD8 alloreactivity. Rapamycin-treated mice also had a high percentage of splenic CD127highKLRG1low TCD8 as well as an increased frequency of site IV-specific T cells long after the peak of their primary response. When site IV was presented as a cytosolic minigene encoded by a recombinant vaccinia virus, rapamycin failed to boost the site IV-specific response. Therefore, the nature and presentation mode of antigen determine the susceptibility to the adjuvant effect of rapamycin. Our findings reveal the unexpected benefit of rapamycin treatment in recipients of allografts co-expressing tumor/viral Ags.

SF-1 (Steroidogenic Factor 1, NR5A1) is a tissue-specific transcription factor critical for the growth, development and differentiation of steroidogenic and a few other endocrine tissues. But how SF-1 regulates cell growth is not entirely clear. Here we found that SF-1 was localized to the centrosome in addition to the nucleus, and SF-1 depletion by shRNA caused centrosome over-duplication, aberrant mitosis and genomic instability, leading to a reduction of cell number. Centrosome amplification defect was rescued by both wild-type SF-1 and transcription-defective SF-1-G35E, suggesting a non-genomic activity of SF-1 involved in centrosome homeostasis. In addition, we identified in SF-1 a centrosome localization signal, whose overexpression led to reduced localization of both SF-1 and γ-tubulin to the centrosome. Our results uncover a novel role of SF-1 in the control of centrosome homeostasis and genomic stability.

We recently identified Grainyhead-like 2 (GRHL2), a mammalian homolog of Grainyhead in Drosophila, to be a novel transcription factor that regulates hTERT gene expression and enhances proliferation of normal human epidermal keratinocytes (NHEK). In the current study, we show that GRHL2 impairs keratinocyte differentiation through transcriptional inhibition of the genes clustered at the epidermal differentiation complex (EDC), located at chromosome 1q21. Gene expression profiling and subsequent in vitro assays revealed consistent downregulation of EDC genes, for example, IVL, KRT1, FLG, LCEs, and SPRRs, in NHEK expressing exogenous GRHL2. In vivo binding assay by chromatin immunoprecipitation revealed GRHL2 association at the promoter regions of its target genes, many of which belong to EDC. Exogenous GRHL2 expression also inhibited recruitment of histone demethylase Jmjd3 to the EDC gene promoters and enhanced the level of histone 3 Lys 27 trimethylation enrichment at these promoters. Survey of GRHL2 expression in human skin tissues demonstrated enhanced protein and mRNA levels in chronic skin lesions with impaired keratinocyte differentiation, for example, atopic dermatitis and psoriasis, compared with normal epidermis. These data indicate that GRHL2 impairs epidermal differentiation by inhibiting EDC gene expression through epigenetic mechanisms and support its role in the hyperproliferative skin diseases.

Vortex domain patterns in low-dimensional ferroelectrics and multiferroics have been extensively studied with the aim of developing nanoscale functional devices. However, control of the vortex domain structure has not been investigated systematically. Taking into account effects of inhomogeneous electromechanical fields, ambient temperature, surface and size, we demonstrate significant influence of mechanical load on the vortex domain structure in ferroelectric nanoplatelets. Our analysis shows that the size and number of dipole vortices can be controlled by mechanical load, and yields rich temperature-stress (T-S) phase diagrams. Simulations also reveal that transformations between “vortex states” induced by the mechanical load are possible, which is totally different from the conventional way controlled on the vortex domain by the electric field. These results are relevant to application of vortex domain structures in ferroelectric nanodevices, and suggest a novel route to applications including memories, mechanical sensors and transducers.

Background:

This study investigated the stroke risk in patients with head and neck cancers (HNCs) using population-based data.

Methods:

From claims collected in the Taiwan National Health Insurance database, we identified 13 390 HNC patients with diagnosis made in 2000–2002. A reference cohort of 53 517 non-cancer individuals matched for age, gender, and stroke risk factors was used for assessing stroke risk in follow-up to 2008.

Results:

The overall stroke incidence was 1.44-fold higher in the HNC than in the reference cohort (11.4 vs 7.9 per 1000 person-years). Adjusted hazard ratios (HRs) were 1.54 (95% confidence interval (CI): 1.40–1.68) for ischaemic stroke and 1.36 (95% CI: 1.09–1.69) for haemorrhagic stroke. The cancer-to-reference stroke incidence rate ratio was age dependent and the highest in the age group younger than 40 years (5.45, 95% CI: 3.78–7.87) and decreased with aging. Comparing different therapeutic modalities, HNC patients receiving both radiotherapy (RT) and chemotherapy (CT) had the highest stroke risk (HR: 1.46, 95% CI: 1.22–1.74), followed in sequence by those who had CT alone, RT alone, and without therapy.

Conclusion:

Patients with HNC are at increased risk of developing stroke, especially in the young age group and in those who received both RT and CT.

Objectives:

The Vitamin Intervention for Stroke Prevention trial found an association between baseline poststroke homocysteine (Hcy) and recurrent stroke. We investigated genes for enzymes and cofactors in the Hcy metabolic pathway for association with Hcy and determined whether associated single nucleotide polymorphisms (SNPs) influenced recurrent stroke risk.

Methods:

Eighty-six SNPs in 9 candidate genes (BHMT1, BHMT2, CBS, CTH, MTHFR, MTR, MTRR, TCN1, and TCN2) were genotyped in 2,206 subjects (83% European American). Associations with Hcy measures were assessed using linear regression models assuming an additive genetic model, adjusting for age, sex, and race and additionally for baseline Hcy when postmethionine load change was assessed. Associations with recurrent stroke were evaluated using survival analyses.

Results:

Five SNPs in the transcobalamin 2 (TCN2) gene were associated with baseline Hcy (false discovery rate [FDR]–adjusted p = 0.049). TCN2 SNP rs731991 was associated with recurrent stroke risk in the low-dose arm of the trial under a recessive model (log-rank test p = 0.009, hazard ratio 0.34). Associations with change in postmethionine load Hcy levels were found with 5 SNPs in the cystathionine β-synthase (CBS) gene (FDR-adjusted p < 0.031).

Conclusions:

TCN2 variants contribute to poststroke Hcy levels, whereas variants in the CBS gene influence Hcy metabolism. Variation in the TCN2 gene also affects recurrent stroke risk in response to cofactor therapy.

Aims/hypothesis

Mutations in GLIS3, which encodes a Krüppel-like zinc finger transcription factor, were found to underlie sporadic neonatal diabetes. Inactivation of Glis3 by gene targeting in mice was previously shown to lead to neonatal diabetes, but the underlying mechanism remains largely unknown. We aimed to elucidate the mechanism of action of GLIS family zinc finger 3 (GLIS3) in Glis3−/− mice and to further decipher its action in in-vitro systems.

Methods

We created Glis3−/− mice and monitored the morphological and biochemical phenotype of their pancreatic islets at different stages of embryonic development. We combined these observations with experiments on Glis3 expressed in cultured cells, as well as in in vitro systems in the presence of other reconstituted components.

Results

In vivo and in vitro analyses placed Glis3 upstream of Neurog3, the endocrine pancreas lineage-defining transcription factor. We found that GLIS3 binds to specific GLIS3-response elements in the Neurog3 promoter, activating Neurog3 gene transcription both directly, and synergistically with hepatic nuclear factor 6 and forkhead box A2.

Conclusions/interpretation

These results indicate that GLIS3 controls fetal islet differentiation via direct transactivation of Neurog3, a perturbation that causes neonatal diabetes in mice.

Oxidative stress and nitrosative stress are both suggested to be involved in cardiac ischemia-reperfusion (I/R) injury. Using time-lapse confocal microscopy of cardiomyocytes and high-affinity O2−• and Zn2+ probes, this study is the first to show that I/R, reactive oxygen species (ROS), and reactive nitrogen species (RNS) all cause a marked increase in the [O2−•]i, resulting in cytosolic and mitochondrial Zn2+ release. Exposure to a cell-penetrating, high-affinity Zn2+i chelator, TPEN, largely abolished the Zn2+i release and markedly protected myocytes from I/R-, ROS-, RNS-, or Zn2+/K+ (Zn2+i supplementation)-induced myocyte apoptosis for at least 24 h after TPEN removal. Flavonoids and U0126 (a MEK1/2 inhibitor) largely inhibited the myocyte apoptosis and the TPEN-sensitive I/R- or Zn2+i supplement-induced persistent extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, dephosphorylation of p-Ser9 on glycogen synthase kinase 3β (GSK-3β), and the translocation into and accumulation of p-Tyr216 GSK-3β and p53 in, the nucleus. Silencing of GSK-3β or p53 expression was cardioprotective, indicating that activation of the ERK–GSK-3β–p53 signaling pathway is involved in Zn2+-sensitive myocyte death. Moreover, the ERK-dependent Noxa–myeloid cell leukemia-1 (Mcl-1) pathway is also involved, as silencing of Noxa expression was cardioprotective and U0126 abolished both the increase in Noxa expression and in Mcl-1 degradation. Thus, acute upstream Zn2+i chelation at the start of reperfusion and the use of natural products, that is, flavonoids, may be beneficial in the treatment of cardiac I/R injury.

The synchronisation of time and frequency between remote locations is crucial for many important applications. Conventional time and frequency dissemination often makes use of satellite links. Recently, the communication fibre network has become an attractive option for long-distance time and frequency dissemination. Here, we demonstrate accurate frequency transfer and time synchronisation via an 80 km fibre link between Tsinghua University (THU) and the National Institute of Metrology of China (NIM). Using a 9.1 GHz microwave modulation and a timing signal carried by two continuous-wave lasers and transferred across the same 80 km urban fibre link, frequency transfer stability at the level of 5×10−19/day was achieved. Time synchronisation at the 50 ps precision level was also demonstrated. The system is reliable and has operated continuously for several months. We further discuss the feasibility of using such frequency and time transfer over 1000 km and its applications to long-baseline radio astronomy.

The aim of this study was to evaluate the difference in pharmacokinetics and pharmacodynamics between extended-release (ER) fluvastatin tablet and its immediate-release (IR) capsule in Chinese healthy subjects. This was an open-label, single/multiple-dose, two-period, two-treatment, crossover, randomized trial with a minimum washout period of 7 days. Twenty healthy male adult subjects were given fluvastatin ER tablet 80 mg QD by oral administration or fluvastatin IR capsule 40 mg BID for seven days. Blood samples were collected up to 24 hours after dosing on day 1 and day 7. Serum concentrations of fluvastatin were determined by LC-MS/MS. For fluvastatin ER tablet 80 mg QD, Cmax was 61.0 ± 39.0 and 63.9 ± 29.7 ng/mL, and AUC0−24 h was 242 ± 156 and 253 ± 91.1 ng·h/mL on day 1 and 7, respectively. For fluvastatin IR capsule 40 mg BID, Cmax was 283 ± 271 and 382 ± 255 ng/mL, and AUC0−24 h was 720 ± 776 and 917 ± 994 ng·h/mL on day 1 and day 7, respectively. The relative bioavailability of fluvastatin ER tablet 80 mg QD to fluvastatin IR capsule 40 mg BID is (45.3 ± 23.9)% and (43.3 ± 24.1)% on day 1 and day 7, respectively. Tmax for fluvastatin ER tablet was 2.50 and 2.60 h and for capsule was 0.78 and 0.88 h on day 1 and day 7, respectively. In the first period, compared to baseline, cholesterol decreased 15.3% in fluvastatin ER tablet 80 mg QD and 16.9% in fluvastatin IR capsule 40 mg BID. Triglyceride decreased 3.7% in fluvastatin ER tablet 80 mg QD and 19.1% in fluvastatin IR capsule 40 mg BID. The difference has no statistical significance at P > 0.05 in reduction percent of cholesterol and triglyceride between the two groups. No adverse events were recorded. The results indicated that Cmax of fluvastatin ER tablet is reduced and Tmax is prolonged compared with IR capsule. There is no accumulation for ER formulation after multiple doses.

In the title compound, C20H20N2, the quinoxaline ring adopts a very distorted half-chair conformation [N=C—C=N = 22.7 (2)° for the nominally coplanar atoms] and the cyclo­hexane ring adopts a chair conformation. The quinoxaline and cyclo­hexane rings are cis-fused. The two phenyl rings form a dihedral angle of 63.88 (7)°.

Cardiac depression in sepsis is associated with the increased morbidity and mortality. Although myofilaments damage, autonomic dysfunction, and apoptosis play roles in sepsis-induced myocardial dysfunction, the underlying mechanism is not clear. All of these possible factors are related to NFκB signaling, which plays the main role in sepsis signaling. Thaliporphine was determined to possess anti-inflammatory and cardioprotective activity by suppressing NFκB signaling in rodents. The purpose of this study is to further prove this protective effect in larger septic animals, and try to find the underlying mechanisms. The systolic and diastolic functions were evaluated in vivo by pressure-volume analysis at different preloads. Both preload-dependent and -independent hemodynamic parameters were performed. Inflammatory factors of whole blood and serum samples were analyzed. Several sepsis-related signaling pathways were also determined at protein level. Changes detected by conductance catheter showed Thaliporphine could recover impaired left ventricular systolic function after 4 hours LPS injection. It could also reverse the LPS induced steeper EDPVR and gentler ESPVR, thus improve Ees, Ea, and PRSW. Thaliporphine may exert this protective effect by decreasing TNFα and caspase3 dependent cell apoptosis, which was consistent with the decreased serum cTnI and LDH concentration. Thaliporphine could protect sepsis-associated myocardial dysfunction in both preload-dependent and -independent ways. It may exert these protective effects by both increase of “good”-PI3K/Akt/mTOR and decrease of “bad”-p38/NFκB pathways, which followed by diminishing TNFα and caspase3 dependent cell apoptosis.

The ability of phages to specifically interact with and lyse their host bacteria makes them ideal antibacterial agents. The range of applications of bacteriophage can be extended by their immobilization on inert surfaces. A novel method for the oriented immobilization of bacteriophage has been developed. The method was based on charge differences between the bacteriophage head, which exhibits an overall net negative charge, and the tail fibers, which possess an overall net positive charge. Hence, the head would be more likely to attach to positively charged surfaces, leaving the tails free to capture and lyse bacteria. Cellulose membranes modified so that they had a positive surface charge were used as the support for phage immobilization. It was established that the number of infective phages immobilized on the positively charged cellulose membranes was significantly higher than that on unmodified membranes. Cocktails of phages active against Listeria or Escherichia coli immobilized on these membranes were shown to effectively control the growth of L. monocytogenes and E. coli O157:H7 in ready-to-eat and raw meat, respectively, under different storage temperatures and packaging conditions. The phage storage stability was investigated to further extend their industrial applications. It was shown that lyophilization can be used as a phage-drying method to maintain their infectivity on the newly developed bioactive materials. In conclusion, utilizing the charge difference between phage heads and tails provided a simple technique for oriented immobilization applicable to a wide range of phages and allowed the retention of infectivity.

Objectives.

Cultivating healthy workplaces is a critical aspect of comprehensive worksite health promotion. The influence of healthy workplace exposures on employee health outcomes warrants research attention. To date, it is unknown if nature contact in the workplace is related to employee stress and health. This study was designed to examine the effects of nature contact experienced at work on employee stress and health.

Methods.

Office staff at a southeastern university (n=503, 30% response rate) participated in the cross-sectional study. We used a 16-item workplace environment questionnaire, the Nature Contact Questionnaire, to comprehensively measure, for the first time, nature contact at work. The Perceived Stress Questionnaire and 13 established health and behavioral items assessed the dependent variables, general perceived stress, stress-related health behaviors, and stress-related health outcomes.

Results.

There was a significant, negative association between nature contact and stress and nature contact and general health complaints. The results indicate that as workday nature contact increased, perceived stress and generalized health complaints decreased.

Conclusions.

The findings suggest that nature contact is a healthy workplace exposure. Increasing nature contact at work may offer a simple population-based approach to enhance workplace health promotion efforts. Future researchers should test the efficacy of nature-contact workplace stress interventions.

The purpose of this study was to determine the percentage of signal intensity loss (PSIL) threshold for the characterisation of focal liver lesions among patients with chronic liver disease. 55 nodules in 49 patients with chronic liver disease who underwent ferucarbotran-enhanced MR studies were included. Among the 49 patients, 40 had liver cirrhosis and 9 had chronic hepatitis. 8 haemangiomas, 3 focal nodular hyperplasia, 9 dysplastic nodules and 12 well, 19 moderately and 4 poorly differentiated hepatocellular carcinomas (HCCs) were revealed. The PSIL, signal-to-noise ratio and contrast-to-noise ratio of each lesion type were calculated. The diagnostic performance of PSIL on ferucarbotran-enhanced T2 weighted images (PSILT2WI) and T2 weighted fat-suppression images (PSILFS-T2WI) that characterised hepatic tumours was compared with receiver operating characteristic (ROC) analysis. Using ROC analysis, the diagnostic performance of PSILFS-T2WI was superior to that of PSILT2WI (p = 0.01). The mean PSILFS-T2WI of the benign lesions was significantly higher than that of HCC (p<0.001), and the mean PSILFS-T2WI of well-differentiated HCC was significantly higher than that of moderately/poorly differentiated HCCs (p = 0.001). With a PSILFS-T2WI threshold of 40% in lesions characterising ferucarbotran-enhanced FS-T2WI, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 88.6%, 95%, 90.9%, 96.9% and 82.6%, respectively. In conclusion, with ferucarbotran-enhanced FS-T2WI, a PSILFS-T2WI threshold of 40% for characterising focal liver nodules among patients with chronic liver disease is recommended. It is useful for distinguishing HCC from benign nodules.

The stem cells (SCs) of the corneal epithelium located in the limbal basal layer are the ultimate source to maintain corneal epithelial homeostasis. Like other adult tissue-specfic SCs, self renewal and fate decision of limbal SCs are regulated by a specialized in vivo microenvironment, termed “niche”. Loss of limbal SCs or dysfunction of the limbal niche renders corneas with a unique clinical disease labeled limbal stem cell deficiency (LSCD). Besides transplantation of autologous or allogeneic limbal SCs or amniotic membrane, a new strategy of treating LSCD is to transplant a bio-engineered graft by expanding limbal SCs ex vivo. Herein, we conduct a critical appraisal of six protocols that have successfully been practiced in treating human patients with LSCD, and identify issues whether niche regulation has been disrupted or maintained during isolation and expansion. Consequently, we propose a future direction that may circumvent the potential pitfalls existing in these conventional protocols by preserving the interaction between limbal SCs and their native niche cells during isolation and expansion. Such an approach may one day help realize considerable promise held by adult SCs in treating a number of diseases.

Objective: To substantially improve the peptide identification sensitivity and accuracy from the Orbitrap ETD data with computational methods. Method: The algorithm takes full advantage of the characteristics of the Orbitrap ETD data, including: (1) high mass resolution of the precursor ions, and (2) the distributions of different fragment ion types in the MS/MS scans. For the first characteristic, a pre-search step is conducted to determine the precursor mass error distribution. This does not only make the precursor mass more accurate by a software recalibration, but also allows the use of the mass error as an important feature in the peptide-spectrum matching score function. For the second characteristic, the frequencies of different fragment ion types at different precursor charge states are statistically learned, and used in the score calculation. Moreover, the precursor-related ions in the MS/MS spectra are removed. Additionally, the score function makes use of the similarity between a database peptide and the de novo sequencing result. Result: PeaksDB was compared against three other search engines: MSGF-DB, Mascot, and ZCore. The same shuffled decoy database was appended to the target database and searched together to estimate the false discovery rate (FDR) of each individual engine. The same search parameters were used for all engines except that MSGFDB does not support variable PTMs. If no variable PTM is allowed, the numbers of identified peptides of different engines at 1% FDR are: PeaksDB (2356) > MSGF-DB (2147) > Mascot (1459) > ZCore (1030). If a few common PTMs are allowed, the numbers change to PeaksDB (3501) > Mascot (2677) > MSGF-DB (2147) > ZCore(1125). Conclusion: PeaksDB substantially improved the sensitivity and accuracy of peptide identifications on Orbitrap ETD data. At 1% false discovery rate, PeaksDB identified 1.3 to 1.6 times as many peptides as Mascot 2.3.

The Cornell University Life Sciences Core Laboratories Center (CLC) provides an array of genomics, proteomics, imaging and informatics shared research resources and services to the university community and to outside investigators. The CLC includes fee-for-service research, technology testing and development, and educational components. The Center has seven core facilities, including genomics (DNA sequencing, genotyping, and microarrays), epigenomics, proteomics and mass spectrometry, microscopy and imaging, bioinformatics, bio-IT, and advanced technology assessment. The CLC is part of a New York State designated Center for Advanced Technology in Life Science Enterprise. The mission of the CLC is to promote research in the life sciences with advanced technologies in a shared resource environment. Use of the CLC resources and services is steadily increasing due to the growth in the number and types of cores in the center, to the expansion of existing services and the implementation of new core technologies, and to the coordinated integration and synergy of services between the CLC cores. Multidisciplinary support for multi-functional instrument platforms is implemented by integrated operations of the CLC core facilities. Investigators are offered coordinated project consultations with the directors and staff of all relevant cores during the design, data production and analysis phases of their projects. The CLC is involved in establishing and supporting multidisciplinary research projects that involve both intercampus initiatives and multi-institutional collaborations. With a concentration of advanced instrumentation and expertise in their applications, the CLC is a key resource for life sciences research.

Humans are constantly confronted with environmental stimuli that conflict with task goals and can interfere with successful behavior. Prevailing theories propose the existence of cognitive control mechanisms that can suppress the processing of conflicting input and enhance that of the relevant input. However, the temporal cascade of brain processes invoked in response to conflicting stimuli remains poorly understood. By examining evoked electrical brain responses in a novel, hemifield-specific, visual-flanker task, we demonstrate that task-irrelevant conflicting stimulus input is quickly detected in higher-level executive regions while simultaneously inducing rapid, recurrent modulation of sensory processing in the visual cortex. Importantly, however, both of these effects are larger for individuals with greater incongruency-related reaction time slowing. The combination of neural activation patterns and behavioral interference effects suggest that this initial sensory modulation induced by conflicting stimulus inputs reflects performance-degrading attentional distraction due to their incompatibility, rather than any rapid task-enhancing cognitive control mechanisms. The present findings thus provide neural evidence for a model in which attentional distraction is the key initial trigger for the temporal cascade of processes by which the human brain responds to conflicting stimulus input in the environment.

The purpose of this study was to determine the usefulness of first-pass whole nodule perfusion imaging in the differentiation of benign and malignant solitary pulmonary nodules (SPNs). 77 patients with non-calcified SPNs (46 malignant, 22 benign and 9 active inflammatory) underwent first-pass perfusion imaging with a 64-detector row CT scanner. Perfusion, peak enhancement intensity (PEI), time to peak (TTP) and blood volume (BV) were measured and statistically compared among different groups. Mean perfusion, PEI and BV for benign SPNs were significantly lower than those for malignant nodules (p<0.05) and active infections (p<0.05), but the differences were not statistically significant between malignant tumours and active infections (p>0.05). Receiver operating characteristic (ROC) curve analysis showed that SPNs with perfusion greater than 30.6 ml min–1 ml–1, PEI higher than 23.3 HU or BV larger than 12.2 ml per 100 g were more likely to be malignant. In conclusion, first-pass perfusion imaging with 64-detector row CT is a feasible way of assessing whole nodule perfusion and helpful in differentiating benign from malignant SPNs.