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1.
Cell Calcium ; 84: 102104, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706065

RESUMO

CaV3.2 calcium channels play important roles in both neural excitability and aldosterone secretion. Recent clinical studies found four germline mutations (S196 L, M1549I, V1951E and P2083 L) in CaV3.2 channels. All four mutations caused primary aldosteronism (PA), while only the M1549I mutation resulted in obvious neural malfunctions besides PA. In human, there are two major CaV3.2 channel gene (CACNA1H) splice variants, either with or without exon 26. In this study, we tested the expression of the two CACNA1H splice variants in zona glomerulosa (ZG) cells of human adrenal cortex and the possibility that CaV3.2 (-26) and CaV3.2 (+26) channels have different functional responses to the four PA mutations. We found that human ZG cells only express long form CaV3.2(+26) channels. The M1549I mutation slowed the inactivation of CaV3.2(+26) more than 5 fold, and CaV3.2(-26) more than 2 fold. The S196 L, V1951E and P2083 L mutations accelerated channel recovery from inactivation for CaV3.2(+26), but not CaV3.2(-26) channels. All four mutations resulted in gain of function of CaV3.2(+26) channels, leading to overproduction of aldosterone. In conclusion, the four PA mutations caused more profound changes on CaV3.2 (+26) currents than on CaV3.2 (-26) currents, and except the M1549I mutation, the S196 L, V1951E and P2083 L have little effect on the electrophysiological properties of CaV3.2(-26) currents, which may partially explain the limitation of the phenotype associated with the V1951E, S196 L and P2083 L germline mutations to PA.

2.
Ann Emerg Med ; 74(5): 633-678, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31668240
3.
Dalton Trans ; 48(40): 15160-15169, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31565716

RESUMO

Three peroxidovanadium(v) compounds with different ligands (L1-L3) {L1 = N-tris(hydroxymethyl)methylglycine; L2 = ethylenediamine-N,N'-diacetic acid; L3 = 2,2-[(2-amino-2-oxoethyl)imino]diacetic acid} were first synthesized, characterized and further investigated for their anticancer activities under the mediation of transition metal cations. Encouragingly, all compounds showed preferentially enhanced cytotoxicity toward cancer cells (MCF-7 and A549) compared to normal cells (BEAS-2B) under the mediation of transition metal cations (Mn2+ or Fe2+), especially for Mn2+. It was noted that cell death was triggered by the transition metal cation-mediated peroxidovanadium(v) compounds through the induction of early apoptosis, inhibition of cell cycles, and boosting the generation of intracellular reactive oxygen species (ROS). Mechanistic studies further elucidated the vital roles of an acidic environment and transition metal cations for the anticancer activity of peroxidovanadium(v) compounds. Therefore, this study will offer precious insight into the development of the transition metal cation-mediated peroxidovanadium(v) compounds for further clinical translation.

4.
Cell Cycle ; 18(23): 3337-3350, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31599189

RESUMO

Gallbladder cancer (GBC) is the common malignancy of the bile tract system with extremely poor clinical outcomes, owing to its metastatic property and intrinsic resistance to the first-line drugs. Although it is well-established that cholesterol abnormity contributes to gallstone formation, a leading risk factor for GBC, the link of cholesterol homeostasis with GBC has not been investigated. The present study systematically examined the genes implicated in cholesterol homeostasis, and revealed altered gene expressions of de novo cholesterol biosynthesis and sterol sulfonation (SULT2B1), reduced bile acid synthesis (CYP7B1 and CYP39A1) and impaired sterol efflux (ABCA1, ABCG5, LCAT, and CETP) in GBC tissues. Suppression of cholesterol biosynthesis by lovastatin inhibited GBC cell proliferation possibly through attenuating the DNA repair process. Further investigation revealed lovastatin sensitized GBC cells to cisplatin-induced apoptosis and suppressed the activation of CHK1, CHK2, and H2AX during DNA damage response. By using chemically distinct statins, HMGCR depletion or supplementing mevalonate, the product of HMGCR, we showed the inhibitory effects on DNA repair process of lovastatin were due to the blockage of the mevalonate pathway. Subcutaneous xenograft mice model suggested lovastatin promoted the therapeutic efficacy of cisplatin, and significantly prolonged the survival times of tumor-bearing mice. Moreover, HMGCR ablation repressed tumor growth in vivo, which can be rescued partially by restored expression of HMGCR, suggesting the on-target effects of lovastatin. Therefore, our study provides the clinical relevance of cholesterol homeostasis with GBC progression, and highlights a novel intervention of combined use of lovastatin and cisplatin for GBC.

5.
J Chem Phys ; 151(12): 124307, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575165

RESUMO

Ce atom reactions with ethylene, 2-butene, and isobutene are carried out in a pulsed laser vaporization molecule beam source. Ce-containing species are observed with time-of-flight mass spectrometry, and Ce(C4H6) is characterized with mass-analyzed threshold ionization (MATI) spectroscopy and relativistic quantum chemical calculations. Two structural isomers are identified for Ce(C4H6): one is the tetrahedronlike Ce[C(CH2)3] in C3v symmetry and the other is the five-membered metallocyclic Ce(CH2CHCHCH2) in Cs. The MATI spectrum of the C3v isomer exhibits two vibronic band systems separated by 88 cm-1, while that of the Cs isomer displays three split by 60 and 101 cm-1. The multiple band systems are attributed to spin-orbit splitting and vibronic transitions involving metal-hydrocarbon and hydrocarbon-based vibrations. The splitting in the C3v isomer arises from interactions of two triplet and two singlet states at the lowest energies, while each splitting in the Cs isomer involves two triplets and a singlet. Although the Ce atom has ground electron configuration 4f15d16s2, Ce valence electron configurations in both isomers are 4f16s1 in the neutral ground state and 4f1 in the ion. The remaining Ce 5d electrons in the isolated atom are spin paired in molecular orbitals that are a bonding combination between Ce 5dπ and hydrocarbon π* orbitals.

6.
ACS Appl Mater Interfaces ; 11(41): 38347-38352, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31550122

RESUMO

Based on arrays of Au seeds fabricated with atomic force microscopy (AFM) nanoxerography, the seeded growth of gold nanoparticles (Au NPs) on surface is achieved. The size evolution of Au NPs in each spot is tracked by in situ AFM and SEM images because each spot can be easily localized in the array system. The extinction microspectra extracted in real time with enhanced signals and red-shift can further monitor the increasing size of Au NPs. As a powerful platform, AFM nanoxerography makes it easy to tune the spot size and the intervals among spots in the Au NP arrays without preparing a template. It also allows for fabricating arbitrary patterns including various symbols and graphs. More interestingly, the in situ growth of Au NPs offers an approach to decreasing the interparticle distance, and thus forming closely interconnected Au nanowire assembly, exhibiting immense potential in the nanoelectronic system.

7.
Extremophiles ; 23(6): 747-757, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31489482

RESUMO

16S rRNA gene profiling is a powerful method for characterizing microbial communities; however, no universal primer pair can target all bacteria and archaea, resulting in different primer pairs which may impact the diversity profile obtained. Here, we evaluated three pairs of high-throughput sequencing primers for characterizing archaeal communities from deep-sea sediments and permafrost soils. The results show that primer pair Arch519/Arch915 (V4-V5 regions) produced the highest alpha diversity estimates, followed by Arch349f/Arch806r (V3-V4 regions) and A751f/AU1204r (V5-V7 regions) in both sample types. The archaeal taxonomic compositions and the relative abundance estimates of archaeal communities are influenced by the primer pairs. Beta diversity of the archaeal community detected by the three primer pairs reveals that primer pairs Arch349f/Arch806r and Arch519f/Arch915r are biased toward detection of Halobacteriales, Methanobacteriales and MBG-E/Hydrothermarchaeota, whereas the primer pairs Arch519f/Arch915r and A751f/UA1204r are biased to detect MBG-B/Lokiarchaeota, and the primers pairs Arch349f/Arch806r and A751f/UA1204r are biased to detect Methanomicrobiales and Methanosarcinales. The data suggest that the alpha and beta diversities of archaeal communities as well as the community compositions are influenced by the primer pair choice. This finding provides researchers with valuable experimental insight for selection of appropriate archaeal primer pairs to characterize archaeal communities.

8.
Chem Commun (Camb) ; 55(78): 11774-11777, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31515552

RESUMO

A copper-catalyzed 1,4-addition reaction of sulfonyl iodides with 1,3-enynes affording various allenyl halides in high yields under mild conditions has been developed. Mechanistic studies showed that the reaction proceeds through a radical mechanism.

9.
Org Lett ; 21(19): 7897-7901, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31525932

RESUMO

Highly enantioselective [4 + 2] cyclizations of azadienes with in situ generated ketenes were developed through sequential visible-light photoactivation/isothiourea catalysis, which offers a novel approach for the creation of all-carbon quaternary stereocenters through disubstituted C1-ammonium enolates. The visible-light-induced sustained release of reactive ketene species through Wolff rearrangement of α-diazoketones is crucial for achieving high levels of chemical efficiency and stereoinduction.

10.
Jpn J Radiol ; 37(10): 701-709, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401722

RESUMO

OBJECTIVES: To evaluate quantitative three-dimensional (3D) dynamic contrast-enhanced ultrasound (DCE-US) in the assessment of tumor angiogenesis using an orthotropic liver tumor model. METHODS: Nine New Zealand white rabbits with liver orthotropic VX2 tumors were established and imaged by two-dimensional (2D) and 3D DCE-US after SonoVue® bolus injections. The intraclass correlation coefficients of perfusion parameters, including peak intensity (PI), mean transit time, time to peak, and area under the curve, were calculated based on time-intensity curve. The percentage area of microvascular (PAMV) and the expression of vascular endothelial growth factor (VEGF) were both evaluated by immunohistochemical analysis and weighted by the tumor activity area ratio. Correlations between quantitative and histologic parameters were analyzed. RESULTS: The reproducibility of 3D DCE-US quantitative parameters was excellent (ICC 0.91-0.99); but only PI showed high reproducibility (ICC 0.97) in 2D. None of the parameters of quantitative 2D DCE-US were significantly correlated with weighted PAMV or VEGF. For 3D DCE-US, there was a positive correlation between PI and weighted PAMV (r = 0.74, P = 0.04) as well as VEGF (r = 0.79, P = 0.02). CONCLUSION: Quantitative parameters of 3D DCE-US show feasibility, higher reproducibility and accuracy for the assessment of tumor angiogenesis using an orthotropic liver tumor model compared with 2D DCE-US.

11.
Biochem Pharmacol ; 168: 384-391, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31381872

RESUMO

Drug uptake transporters are membrane proteins responsible for the trans-membrane transport of endo- and xenobiotics, including numerous drugs. They are important for the uptake of drugs into target tissues or into organs for metabolism and excretion. Many drug uptake transporters have a broad spectrum of structural-independent substrates, which make them vulnerable to drug-drug interactions. Recent studies have shown more and more complex pharmacokinetics involving transporters, and regulatory agencies now require studies to be performed to measure the involvement of transporters in drug development. A better understanding of the factors affecting the expression of transporters is needed. Despite many efforts devoted to the functional characterization of different drug uptake transporters, transporter in vitro to in vivo extrapolations are far from predicting the behavior under physiological conditions. There is an increasing number of uptake transporters demonstrated to form protein-protein interactions or to oligomerize. This raises the possibility that these interactions between or among transporters could help explaining the gap between in vitro and in vivo measurement of drug transporters. In this review, we summarized protein-protein interactions of drug uptake transporters that are important for pharmacokinetics, especially those in the liver and the kidneys.

12.
Angew Chem Int Ed Engl ; 58(42): 15104-15110, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31441203

RESUMO

A new strategy for enantioselective synthesis of axially chiral naphthyl-indoles has been established through catalytic asymmetric addition reactions of racemic naphthyl-indoles with bulky electrophiles. Under chiral phosphoric acid catalysis, azodicarboxylates and o-hydroxybenzyl alcohols served as bulky but reactive electrophiles that were attacked by C2-unsubstituted naphthyl-indoles, which underwent a dynamic kinetic resolution to afford two series of axially chiral naphthyl-indoles in good yields (up to 98 %) and high enantioselectivities (up to 98:2 er).

13.
Mol Nutr Food Res ; 63(20): e1801380, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31378007

RESUMO

SCOPE: The anti-neuroinflammatory effect of a novel quinolyl-substituted analogue of resveratrol (RV01) on lipopolysaccharide (LPS)-induced microglial activation is investigated, as well as the possible underlying mechanisms. METHODS AND RESULTS: Cell viability is measured using an MTT assay. Nitric oxide (NO) release is determined by nitrite assay. The interaction between RV01 and inducible nitric oxide synthase (iNOS) is studied using molecular docking. Free radical scavenging activity and reactive oxygen species (ROS) production are determined by DPPH reduction assay and DCFH-DA assay. Pretreatment with RV01 (1-30 µm) prior to LPS (1 µg mL-1 ) stimulation decreased NO release and iNOS expression without observable cytotoxicity. RV01 reduced the mRNA levels and secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). RV01 also inhibited LPS-induced ROS production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. Furthermore, RV01 decreases the protein expression of toll-like receptor 4 (TLR4) and inhibits the LPS-induced activation of the mitogen-activated protein kinase (MAPK) and nuclear transcription factor-κB (NF-κB) signaling pathways. Additionally, conditioned medium from microglia co-treated with LPS and RV01 alleviates the death of SH-SY5Y cells induced by conditioned medium from activated N9 microglial cells. Lastly, a mouse neuroinflammation model is further used to confirm the effect of RV01 in vivo. CONCLUSION: These results show that RV01 suppresses microglia-mediated neuroinflammation and protects neurons from inflammatory damage, which indicates that RV01 has great potential as a nutritional preventive strategy for neuroinflammation-related diseases.

14.
Int J Biol Macromol ; 135: 898-906, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31170495

RESUMO

Porous chitosan microspheres were successfully developed by the simple procedure of freezing chitosan hydrogel beads and subsequently lyophilizing the frozen structure in present study. The characterization of porous chitosan microspheres was subjected to detailed analysis of scanning electron microscopy (SEM), porosity and Fourier transform infrared spectra (FTIR), and their adsorption performance for hexavalent chromium (Cr(VI)) was investigated. Results showed that when the chitosan solution concentration ranged from 2.5% to 3.5% (w/v), porous spherical structures with uniform size distribution and good sphericity formed, and the pore size and porosity could decrease significantly by increasing the concentration of chitosan solution or reducing the freezing temperature. The porous chitosan microsphere prepared with 3% chitosan solution at -40 °C for 200 min experienced the highest Cr(VI) adsorption due to its higher porosity. FTIR result suggested that porous chitosan microspheres provided adsorption sites of the amino and hydroxyl groups for the removal of Cr(VI).

15.
Mar Drugs ; 17(6)2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31226756

RESUMO

Local administration of platelet-derived growth factor-BB (PGDF-BB) and bone morphogenetic protein-2 (BMP-2) in a sequential release manner could substantially promote bone healing. To achieve this goal, a delivery system that could sustain the release of PGDF-BB and BMP-2 by way of temporal separation was developed. One type of PGDF-BB-encapsulated alginate microsphere and another type of BMP-2-encapsulated microsphere with a core-shell structure were respectively produced using emulsification methods. These two types of microspheres were then embedded into chitosan/glycerophosphate hydrogel for constructing composite gels. Some of them were found to be injectable at ambient temperature and had thermo-sensitive features near physiological temperature and pH. The optimally formulated composite gels showed the ability to control the release of PGDF-BB and BMP-2 in a sequential fashion in which PDGF-BB was released earlier than BMP-2. In vitro release patterns indicated that the release rates could be significantly regulated by varying the embedded amount of the factor-encapsulated microspheres, which can in turn mediate the temporal separation release interval between PGDF-BB and BMP-2. The released PDGF-BB and BMP-2 were detected to be bioactive based on their respective effects on Balb/c 3T3 and C2C12 cells. These results suggest that the presently developed composite gels have the potential for bone repair by synergistically utilizing the early chemotactic effect of PDGF-BB and the subsequent osteogenic and angiogenic functions of PDGF-BB and BMP-2.

16.
BMJ Open ; 9(5): e023729, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31129571

RESUMO

OBJECTIVE: To summarise the effects of herbal medications for the prevention of anxiety, depression, pain, and postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic, obstetrical/gynaecological or cardiovascular surgical procedures. METHODS: Searches of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and LILACS up until January 2018 were performed to identify randomised controlled trials (RCTs). We included RCTs or quasi-RCTs evaluating any herbal medication among adults undergoing laparoscopic, obstetrical/gynaecological or cardiovascular surgeries. The primary outcomes were anxiety, depression, pain and PONV. We used the Grading of Recommendations Assessment, Development and Evaluation approach to rate overall certainty of the evidence for each outcome. RESULTS: Eleven trials including 693 patients were eligible. Results from three RCTs suggested a statistically significant reduction in vomiting (relative risk/risk ratio (RR) 0.57; 95% CI 0.38 to 0.86) and nausea (RR 0.69; 95% CI 0.50 to 0.96) with the use of Zingiber officinale (ginger) compared with placebo in both laparoscopic and obstetrical/gynaecological surgeries. Results suggested a non-statistically significantly reduction in the need for rescue medication for pain (RR 0.52; 95% CI 0.13 to 2.13) with Rosa damascena (damask rose) and ginger compared with placebo in laparoscopic and obstetrical/gynaecological surgery. None of the included studies reported on adverse events (AEs). CONCLUSIONS: There is very low-certainty evidence regarding the efficacy of both Zingiber officinale and Rosa damascena in reducing vomiting (200 fewer cases per 1000; 288 fewer to 205 fewer), nausea (207 fewer cases per 1000; 333 fewer to 27 fewer) and the need for rescue medication for pain (666 fewer cases per 1000; 580 fewer to 752 more) in patients undergoing either laparoscopic or obstetrical/gynaecological surgeries. Among our eligible studies, there was no reported evidence on AEs. PROSPERO REGISTRATION NUMBER: CRD42016042838.

17.
Theranostics ; 9(6): 1651-1665, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037129

RESUMO

Rationale: Brain-derived neurotrophic factor (BDNF) is a key mediator in the development of chronic pain. Sortilin is known to interact with proBDNF and regulate its activity-dependent secretion in cortical neurons. In a rat model of inflammatory pain with intraplantar injection of complete Freund's adjuvant (CFA), we examined the functional role of proBDNF-sortilin interaction in dorsal root ganglia (DRG). Methods: Expression and co-localization of BDNF and sortilin were determined by immunofluorescence. ProBDNF-sortilin interaction interface was mapped using co-immunoprecipitation and bimolecular fluorescence complementation assay. The analgesic effect of intrathecal injection of a synthetic peptide interfering with proBDNF-sortilin interaction was measured in the CFA model. Results: BDNF and sortilin were co-localized and their expression was significantly increased in ipsilateral L4/5 DRG upon hind paw CFA injection. In vivo adeno-associated virus-mediated knockdown of sortilin-1 in L5 DRG alleviated pain-like responses. Mapping by serial deletions in the BDNF prodomain indicated that amino acid residues 71-100 supported the proBDNF-sortilin interaction. A synthetic peptide identical to amino acid residues 89-98 of proBDNF, as compared with scrambled peptide, was found to interfere with proBDNF-sortilin interaction, inhibit activity-dependent release of BDNF in vitro and reduce CFA-induced mechanical allodynia and heat hyperalgesia in vivo. The synthetic peptide also interfered with capsaicin-induced phosphorylation of extracellular signal-regulated kinases in ipsilateral spinal cord of CFA-injected rats. Conclusions: Sortilin-mediated secretion of BDNF from DRG neurons contributes to CFA-induced inflammatory pain. Interfering with proBDNF-sortilin interaction reduced activity-dependent release of BDNF and might serve as a therapeutic approach for chronic inflammatory pain.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31030046

RESUMO

Thermally activated delayed fluorescence (TADF) emitter is applied to obtain high triplet exciton utilization through reverse intersystem crossing process. However, for efficient TADF emitter, the contradiction between high efficiency and utilization need to be carefully balanced. In this work, we provide a theoretical design strategy to realize high exciton utilization and high luminescence efficiency simultaneously by taking the TADF molecules as host and efficient fluorescent luminescence molecules as guest to form TADF-host:fluorescence-guest system. Through investigating the photophysical properties by optimal Hartree-Fock (OHF) method, different TADF-host and various fluorescence-guest schemes are arranged. Moreover, large overlap between the emission spectra of TADF-host and the absorption spectra of fluorescence-guest indicates efficient Förster energy transfer process. Thus, five systems with blue to red emission are obtained. Furthermore, the charge transfer properties are studied by Marcus equation, efficient charge mobility and balanced charge transfer can be expected for studied systems which are important in constructing organic light emitting diodes (OLEDs). This work could provide promising emitting layer architecture for OLEDs with ultimate performance.

19.
Arch Oral Biol ; 102: 93-100, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981077

RESUMO

OBJECTIVES: To investigate the role of microRNA-23a (miR-23a) in the osteogenesis of periodontal mesenchymal stem cells (PDLSCs) in periodontitis. MATERIALS AND METHODS: Gingival crevicular fluid samples were collected from 21 control subjects and 29 patients with chronic periodontitis. MiR-23a was determined by quantitative real-time PCR. PDLSCs were transfected with miR-23a overexpressing lentiviruses. Subsequently, PDLSCs were induced with osteogenic differentiation media. Osteogenic differentiation of PDLSCs was assessed by alkaline phosphatase activity assay, Alizarin red staining, and qRT-PCT detection of osteogenic gene expression. Western blot was performed to detect the protein levels of the SMAD family member 1/5/9 (Smad1/5/9) and their phosphorylation level. TargetScan was used to predict the target gene of miR-23a. Cotransfections of bone morphogenetic protein receptor type 1B (BMPR1B) and miR-23a applied to explore the relationship between BMPR1B and miR-23a. RESULTS: MiR-23a was significantly increased in PDLSCs and gingival crevicular fluid of periodontitis patients. Patients with gingival crevicular fluid miR-23a levels above a threshold showed more clinical indicators of periodontitis. After periodontal therapy, miR-23a levels significantly decreased. Overexpression miR-23a inhibited osteogenesis of PDLSCs, which was evidenced by reduced Alizarin Red S and osteogenic gene expressions. In addition, miR-23a inhibited the phosphorylation of Smad1/5/9. TargetScan predicted that BMPR1B is a target gene of miR-23a. Overexpression of BMPR1B abolished the effects caused by overexpression of miR-23a. CONCLUSION: Our study provides novel evidence that miR-23a acts as a negative regulator of osteogenesis in periodontitis patients'PDLSCs and that miR-23a may serve as a biomarker and potential target of periodontitis.

20.
Sci Rep ; 9(1): 6009, 2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-30979926

RESUMO

109 pathologically proven subsolid nodules (SSN) were segmented by 2 readers on non-thin section chest CT with a lung nodule analysis software followed by extraction of CT attenuation histogram and geometric features. Functional data analysis of histograms provided data driven features (FPC1,2,3) used in further model building. Nodules were classified as pre-invasive (P1, atypical adenomatous hyperplasia and adenocarcinoma in situ), minimally invasive (P2) and invasive adenocarcinomas (P3). P1 and P2 were grouped together (T1) versus P3 (T2). Various combinations of features were compared in predictive models for binary nodule classification (T1/T2), using multiple logistic regression and non-linear classifiers. Area under ROC curve (AUC) was used as diagnostic performance criteria. Inter-reader variability was assessed using Cohen's Kappa and intra-class coefficient (ICC). Three models predicting invasiveness of SSN were selected based on AUC. First model included 87.5 percentile of CT lesion attenuation (Q.875), interquartile range (IQR), volume and maximum/minimum diameter ratio (AUC:0.89, 95%CI:[0.75 1]). Second model included FPC1, volume and diameter ratio (AUC:0.91, 95%CI:[0.77 1]). Third model included FPC1, FPC2 and volume (AUC:0.89, 95%CI:[0.73 1]). Inter-reader variability was excellent (Kappa:0.95, ICC:0.98). Parsimonious models using histogram and geometric features differentiated invasive from minimally invasive/pre-invasive SSN with good predictive performance in non-thin section CT.

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