Radiomics-based distinction of small (≤2 cm) hepatocellular carcinoma and precancerous lesions based on unenhanced MRI.

AIM: To assess the feasibility of a radiomics model based on unenhanced magnetic resonance imaging (MRI) to differentiate small hepatocellular carcinoma (S-HCC) (≤2 cm) and pre-hepatocellular carcinoma (Pre-HCC). MATERIALS AND METHODS: One hundred and fourteen histopathologically confirmed 114 hepatic nodules were analysed retrospectively. All patients had undergone MRI before surgery using a 3 T MRI system. Each nodule was segmented on unenhanced MRI sequences (T1-weighted imaging [T1] and T2WI with fat-suppression [FS-T2]). Radiomics features were extracted and the optimal features were selected using the least absolute shrinkage and selection operator (LASSO). The support vector machine (SVM) was used to establish the radiomics model. One abdominal radiologist performed the conventional qualitative analysis for classification of S-HCC and Pre-HCC. The diagnostic performances of the radiomics and radiologist models were evaluated using receiver operating characteristic (ROC) analysis. RESULT: Radiomics features (n=1,223) were extracted from each sequence and the optimal features were selected from T1, FS-T2, and T1+FS-T2 to construct the radiomics models. The radiomics model based on T1+FS-T2 showed the best performance among the three models, with areas under the ROC curves (AUCs) of 0.95 (95 % confidence interval [CI], 0.875-0.986) and 0.942 (95 % CI, 0.775-0.985), accuracies of 86 % and 88.5 %, sensitivities of 94.12 % and 100 %, and specificities of 85.48 % and 85.19 %, respectively. The radiomics model on FS-T2 showed better performance on a single sequence than that of the T1-based model. The diagnostic performance for the radiomic model was significantly higher than that for the radiologist (AUC = 0.518, p<0.05). CONCLUSION: This study suggested that a radiomics model based on unenhanced MRI may serve as a feasible and non-invasive tool to classify S-HCC and Pre-HCC.

Measurement of the ν_{e}-Nucleus Charged-Current Double-Differential Cross Section at ⟨E_{ν}⟩=2.4 GeV Using NOvA.

The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×10^{20} protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q^{2} (squared four-momentum transfer) and energy, in the range 1 GeV≤E_{ν}<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q^{2}.

Average and statistical properties of coherent radiation from steady-state microbunching.

A promising accelerator light source mechanism called steady-state microbunching (SSMB) is being actively studied. With the combination of strong coherent radiation from microbunching and high repetition rate of a storage ring, high-average-power narrow-band radiation can be anticipated from an SSMB storage ring, with wavelengths ranging from THz to soft X-ray. Such a novel light source could provide new opportunities for accelerator photon science like high-resolution angle-resolved photoemission spectroscopy and industrial applications like extreme ultraviolet (EUV) lithography. In this paper, a theoretical and numerical study of the average and statistical properties of coherent radiation from SSMB are presented. The results show that 1 kW average-power quasi-continuous-wave EUV radiation can be obtained from an SSMB ring provided that an average current of 1 A and a microbunch train with bunch length of 3 nm can be formed at the radiator which is assumed to be an undulator. Together with the narrow-band feature, the EUV photon flux can reach 6 × 1015 photons s-1 within a 0.1 meV energy bandwidth, which is three orders of magnitude higher than that in a conventional synchrotron source and is appealing for fundamental condensed matter physics and other research. In this theoretical investigation, we have generalized the definition and derivation of the transverse form factor of an electron beam which can quantify the impact of its transverse size on coherent radiation. In particular, it has been shown that the narrow-band feature of SSMB radiation is strongly correlated with the finite transverse electron beam size. Considering the pointlike nature of electrons and quantum nature of radiation, the coherent radiation fluctuates from microbunch to microbunch, or for a single microbunch from turn to turn. Some important results concerning the statistical properties of SSMB radiation are presented, with a brief discussion on its potential applications, for example the beam diagnostics. The presented work is of value for the development of SSMB to better serve potential synchrotron radiation users. In addition, this also sheds light on understanding the radiation characteristics of free-electron lasers, coherent harmonic generation, etc.

Search for Active-Sterile Antineutrino Mixing Using Neutral-Current Interactions with the NOvA Experiment.

This Letter reports results from the first long-baseline search for sterile antineutrinos mixing in an accelerator-based antineutrino-dominated beam. The rate of neutral-current interactions in the two NOvA detectors, at distances of 1 and 810 km from the beam source, is analyzed using an exposure of 12.51×10^{20} protons-on-target from the NuMI beam at Fermilab running in antineutrino mode. A total of 121 of neutral-current candidates are observed at the far detector, compared to a prediction of 122±11(stat.)±15(syst.) assuming mixing only between three active flavors. No evidence for ν[over ¯]_{µ}→ν[over ¯]_{s} oscillation is observed. Interpreting this result within a 3+1 model, constraints are placed on the mixing angles θ_{24}<25° and θ_{34}<32° at the 90% C.L. for 0.05 eV^{2}≤Δm_{41}^{2}≤0.5 eV^{2}, the range of mass splittings that produces no significant oscillations at the near detector. These are the first 3+1 confidence limits set using long-baseline accelerator antineutrinos.

Neoadjuvant weekly paclitaxel and carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer: a Brown University Oncology Research Group (BrUOG) study.

PURPOSE: In HER2-positive breast cancer (HER2+ BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC. METHODS: Patients with clinical stage II-III HER2+ BC received weekly paclitaxel 80 mg/m2 and carboplatin AUC2 with every 3-week trastuzumab and pertuzumab (wPCbTP), with the option of splitting the pertuzumab loading dose. After 12 weeks, responding patients continued wPCbTP for another 6 weeks, while non-responders switched to AC. Dose modifications and post-op therapy were at investigator discretion. RESULTS: In 30 evaluable patients, the pCR rate was 77% (95% CI 58-90%); 12/14 (86%) in ER-negative and 11/16 (69%) in ER-positive. Only two patients transitioned to AC for non-response, of which one achieved pCR. There were no episodes of febrile neutropenia or grade ≥ 3 peripheral neuropathy, though several patients who continued wPCbTP stopped before week 18. Split-dose pertuzumab was associated with less grade ≥ 2 diarrhea (40%) than the standard loading dose (60%). CONCLUSION: pCR rates with our regimen were as high as reported with TCHP with fewer grade ≥ 3 toxicities, though diarrhea remains a concern. Too few patients had a suboptimal response to adequately test switching to AC. The wPCbTP regimen should be considered an alternative to TCHP as neoadjuvant therapy for HER2+ BC. TRAIL REGISTRATION: ClinicalTrials.gov identifier: NCT02789657.

[Application of aldosterone/direct renin ratio before drug washout in the screening of primary aldosteronism].

Objective: To explore the cut-off point of aldosterone/direct renin ratio (ADRR) before drug washout in the screening for primary aldosteronism (PA) in the Chinese population and reduce the potential risk caused by drug washout during PA screening. Methods: Hospitalized hypertensive patients in the Hypertension Ward of Fuwai Hospital, Chinese Academy of Medical Sciences from January 2017 to October 2019 were enrolled. PA was diagnosed according to the criterion of 2016 American Guideline and 2016 Chinese Consensus for PA. The plasma aldosterone concentration (PAC), direct renin concentration (DRC) and ADRR before and after drug washout were measured. The receiver operating characteristic (ROC) curve of ADRR was drawn and the maximal Youden index was used to determine the best cut-off value. Results: A total of 542 hypertensive patients were included, with 467 patients diagnosed with essential hypertension (EHT) (297 males and 170 females), and 75 patients diagnosed with PA (51 males and 24 females). Patients with PA had higher PAC and ADRR before and after drug washout than those with EHT(150.0 (130.0, 210.0) vs 120.0 (80.0, 170.0) ng/L, 170.0 (120.0, 260.0) vs 130.0 (90.0, 180.0) ng/L; 28.9 (15.9, 63.5) vs 4.3 (1.9, 11.8) (ng/L) / (mU/L) , 55.6 (39.0, 109.0) vs 9.8 (4.5, 21.3) (ng/L) /(mU/L), all P<0.001). However, DRC of PA patients before and after washout were lower than those with EHT (4.0 (2.0, 10.0) vs 27.0 (10.0, 64.0) mU/L, 3.0 (2.0, 4.0) vs 12.2 (5.0, 27.0) mU/L, P<0.001). In EHT and PA groups, PAC and ADRR significantly increased (P=0.001, P<0.001) , but DRC significantly decreased after drug washout (all P<0.001) . The area under the ROC curve of ADRR before drug washout was 0.868 (95%CI 0.836-0.895) with the best cut-off value of 7.8 (ng/L) / (mU/L) for the screening of PA .The sensitivity and specificity was 94.7% and 66.8%, respectively, with the maximal Youden index of 0.615. Conclusion: ADRR before drug washout > 7.8 (ng/L) / (mU/L) can be used as an alternative cut-off point to screen PA when drug washout is not available.

Significant Day-time Ionospheric Perturbation by Thunderstorms along the West African and Congo Sector of Equatorial Region.

The equatorial Congo has been recognized as the most active lightning chimney region in the Globe. Although the perturbation of tropospheric thunderstorms on the lower ionosphere has been noticed in the middle latitudes through their transient lightning electric fields or convective gravity waves, the effects on equatorial ionosphere and the horizontal extent of this perturbation remains a mystery because of the difficulties in extracting the effects due to the sporadic nature of the equatorial ionosphere. Here we present observational results showing solid evidence of deviations in ionospheric total electron content (TEC) and its direction of propagation associated with thunderstorms using the method of polynomial filtering, by utilizing the TEC measured from equatorial Global Positioning System (GPS) Receiver stations along the West African region-Congo Basin. The TEC deviations due to the thunderstorms were found to be mostly propagated in a specific direction from the point of the event, with the highest absolute peak TEC at ~±1.5 TECUs. The internal dynamics of the equatorial ionosphere have been found to be suppressed by large thunderstorm effects during the daytime, with negligible impact at night.

First measurement of neutrino oscillation parameters using neutrinos and antineutrinos by NOvA.

The NOvA experiment has seen a 4.4σ signal of ν[over ¯]_{e} appearance in a 2 GeV ν[over ¯]_{µ} beam at a distance of 810 km. Using 12.33×10^{20} protons on target delivered to the Fermilab NuMI neutrino beamline, the experiment recorded 27 ν[over ¯]_{µ}→ν[over ¯]_{e} candidates with a background of 10.3 and 102 ν[over ¯]_{µ}→ν[over ¯]_{µ} candidates. This new antineutrino data are combined with neutrino data to measure the parameters |Δm_{32}^{2}|=2.48_{-0.06}^{+0.11}×10^{-3} eV^{2}/c^{4} and sin^{2}θ_{23} in the ranges from (0.53-0.60) and (0.45-0.48) in the normal neutrino mass hierarchy. The data exclude most values near δ_{CP}=π/2 for the inverted mass hierarchy by more than 3σ and favor the normal neutrino mass hierarchy by 1.9σ and θ_{23} values in the upper octant by 1.6σ.

miRNA-217 inhibits proliferation of hepatocellular carcinoma cells by regulating KLF5.

OBJECTIVE: The aim of this study was to figure out the effect of microRNA-217 on the proliferation of hepatocellular carcinoma (HCC) cells, and to explore its influence on KLF5 expression and the underlying regulatory mechanisms. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of microRNA-217 in tumor tissues and paracancerous tissues of 60 patients with HCC. Meanwhile, the relationship between microRNA-217 expression and HCC pathological parameters was analyzed. In HCC cell lines, including HepG2 and Bel-7402, negative control group (NC) and microRNA-217 overexpression group were set up, and qRT-PCR was performed to further verify their transfection efficiency. In addition, Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay were performed to analyze the effect of microRNA-217 on the biological function of HCC cells. Finally, the potential mechanism of KLF5, the downstream gene of microRNA-217, was explored using bioinformatics analysis and cell recovery experiments. RESULTS: QRT-PCR results showed that microRNA-217 level in tumor tissues of HCC patients was conspicuously lower than that in adjacent tissues, and the difference was statistically significant. Compared with patients with high expression of microRNA-217, the pathological stage was higher and the overall survival rate was lower in patients with low expression. Compared with the NC group, the cell proliferation ability of the microRNA-217 mimics group was conspicuously decreased. Subsequently, in the HCC cell line and tissue verification, the expression of KLF5 was found remarkably increased, and microRNA-217 exhibited a negative correlation with KLF5 level. In addition, the overexpression of microRNA-217 conspicuously reduced the protein expression of CD31, Ki-67, c-Myc, MMP-2, and MMP-9. In cell recovery experiment, it was found that the overexpression of KLF5 could counteract the effect of microRNA-217 mimics on the cell proliferation of HCC, thereby inhibiting the malignant progression of this disease. CONCLUSIONS: The above studies demonstrated that microRNA-217 was markedly associated with the pathological stage and poor prognosis of HCC, and could inhibit the malignant progression of this disease. In addition, our investigation has showed that microRNA-217 might be capable of inhibiting cell proliferation of HCC via regulating KLF5.

First Measurement of the Total Neutron Cross Section on Argon between 100 and 800 MeV.

We report the first measurement of the neutron cross section on argon in the energy range of 100-800 MeV. The measurement was obtained with a 4.3-h exposure of the Mini-CAPTAIN detector to the WNR/LANSCE beam at LANL. The total cross section is measured from the attenuation coefficient of the neutron flux as it traverses the liquid argon volume. A set of 2631 candidate interactions is divided in bins of the neutron kinetic energy calculated from time-of-flight measurements. These interactions are reconstructed with custom-made algorithms specifically designed for the data in a time projection chamber the size of the Mini-CAPTAIN detector. The energy averaged cross section is 0.91±0.10(stat)±0.09(syst) b. A comparison of the measured cross section is made to the GEANT4 and FLUKA event generator packages, where the energy averaged cross sections in this range are 0.60 and 0.68 b, respectively.

Evidence of a Resonant Structure in the e

The cross section of the process e^{+}e^{-}→π^{+}D^{0}D^{*-} for center-of-mass energies from 4.05 to 4.60 GeV is measured precisely using data samples collected with the BESIII detector operating at the BEPCII storage ring. Two enhancements are clearly visible in the cross section around 4.23 and 4.40 GeV. Using several models to describe the dressed cross section yields stable parameters for the first enhancement, which has a mass of 4228.6±4.1±6.3 MeV/c^{2} and a width of 77.0±6.8±6.3 MeV, where the first uncertainties are statistical and the second ones are systematic. Our resonant mass is consistent with previous observations of the Y(4220) state and the theoretical prediction of a DD[over ¯]_{1}(2420) molecule. This result is the first observation of Y(4220) associated with an open-charm final state. Fits with three resonance functions with additional Y(4260), Y(4320), Y(4360), ψ(4415), or a new resonance do not show significant contributions from either of these resonances. The second enhancement is not from a single known resonance. It could contain contributions from ψ(4415) and other resonances, and a detailed amplitude analysis is required to better understand this enhancement.

Contribution of biomimetic collagen-ligand interaction to intrafibrillar mineralization.

Contemporary models of intrafibrillar mineralization mechanisms are established using collagen fibrils as templates without considering the contribution from collagen-bound apatite nucleation inhibitors. However, collagen matrices destined for mineralization in vertebrates contain bound matrix proteins for intrafibrillar mineralization. Negatively charged, high-molecular weight polycarboxylic acid is cross-linked to reconstituted collagen to create a model for examining the contribution of collagen-ligand interaction to intrafibrillar mineralization. Cryogenic electron microscopy and molecular dynamics simulation show that, after cross-linking to collagen, the bound polyelectrolyte caches prenucleation cluster singlets into chain-like aggregates along the fibrillar surface to increase the pool of mineralization precursors available for intrafibrillar mineralization. Higher-quality mineralized scaffolds with better biomechanical properties are achieved compared with mineralization of unmodified scaffolds in polyelectrolyte-stabilized mineralization solution. Collagen-ligand interaction provides insights on the genesis of heterogeneously mineralized tissues and the potential causes of ectopic calcification in nonmineralized body tissues.

Expressions of miR-525-3p and its target gene SEMG1 in the spermatozoa of patients with asthenozoospermia.

BACKGROUND: Semenogelin 1 (SEMG1) is an important secretory protein in spermatozoa involved in the formation of a gel matrix encasing ejaculated spermatozoa. Previous studies show that the SEMG1 gene is highly expressed in spermatozoa from patients with asthenozoospermia (AZS); however, the underlying molecular mechanisms are not yet clear. OBJECTIVES: To study the molecular mechanism of high expression of SEMG1 gene and its potential roles in AZS. MATERIALS AND METHODS: Western blot and real-time PCR were used to detect the expression levels of SEMG1 protein and mRNA in the ejaculated spermatozoa from normozoospermic males and AZS patients. Bioinformatics analysis was used to predict miRNAs targeting for SEMG1 3'-untranslated region detection of the expression levels of all the candidate miRNAs in ejaculatory spermatozoa in AZS patients or normozoospermic volunteers. Luciferase reporter assays were performed to confirm it can directly bind to SEMG1. Correlation of miR-525-3p and SEMG1 mRNA expression with clinical sperm parameters were also analyzed. Finally, we conducted a follow-up study of reproductive history about all the subjects. RESULTS: SEMG1 mRNA and protein level were significantly higher in AZS patients compared to that in normozoospermic volunteers (p < 0.001). Subsequently, microRNA-525-3p (miR-525-3p) which was predicted as a candidate regulator of SEMG1 was found lower expressed in ejaculatory spermatozoa in AZS patients (p = 0.0074). Luciferase experiment revealed that microRNA-525-3p could directly target SEMG1 3'-untranslated region and suppress its expression. Importantly, our retrospective follow-up study showed that both low miR-525-3p expression and high SEMG1 expression level was significantly associated with low progressive sperm motility, abnormal sperm morphology, and infertility. DISCUSSION AND CONCLUSION: The elevated expression of SEMG1 and reduced expression of miR-525-3p are associated with AZS and male infertility. Our study provides a potential therapeutic target for the treatment of male infertility or for male contraception.

Measurement of the Branching Fraction For the Semileptonic Decay D

Using a data sample corresponding to an integrated luminosity of 2.93 fb^{-1} taken at a center-of-mass energy of 3.773 GeV with the BESIII detector operated at the BEPCII collider, we perform an analysis of the semileptonic decays D^{0(+)}→π^{-(0)}µ^{+}ν_{µ}. The branching fractions of D^{0}→π^{-}µ^{+}ν_{µ} and D^{+}→π^{0}µ^{+}ν_{µ} are measured to be (0.272±0.008_{stat}±0.006_{syst})% and (0.350±0.011_{stat}±0.010_{syst})%, respectively, where the former is of much improved precision compared to previous results and the latter is determined for the first time. Using these results along with previous BESIII measurements of D^{0(+)}→π^{-(0)}e^{+}ν_{e}, we calculate the branching fraction ratios to be R^{0}≡B_{D^{0}→π^{-}µ^{+}ν_{µ}}/B_{D^{0}→π^{-}e^{+}ν_{e}}=0.922±0.030_{stat}±0.022_{syst} and R^{+}≡B_{D^{+}→π^{0}µ^{+}ν_{µ}}/B_{D^{+}→π^{0}e^{+}ν_{e}}=0.964±0.037_{stat}±0.026_{syst}, which are compatible with the theoretical expectation of lepton flavor universality within 1.7σ and 0.5σ, respectively. We also examine the branching fraction ratios in different four-momentum transfer square regions, and find no significant deviations from the standard model predictions.

[Expression of Fermintin family homologous protein 2 in non-small cell lung cancer and its clinical significance].

Objective: To investigate the expression of Fermintin family homologous protein 2 (FERMT2) in non-small cell lung cancer and its clinical significance. Methods: Seventy-two patients with non-small cell lung cancer were collected at Xinxiang Central Hospital, Henan Province, from January 2015 to January 2017.There were 48 male and 24 female patients, the age ranged from 37 to 78 years (mean 58 years). The expression of FERMT2 in tumor samples and para-cancerous tissues were detected by immunohistochemistry. Protein and mRNA expression of FERMT2 were detected by Western blot and real-time fluorescence quantitative PCR, respectively. Western blot method was also used to detect integrin-related protein expression, including integrin beta 1 (CD29), vascular cell adhesion molecule (VCAM1), and mobile related protein-1 (MRP1). Results: Immunohistochemistry showed that the positive rates of FERMT2 expression were 81.9%(59/72)in carcinoma tissue and 15.4%(11/72) in para-cancerous tissues, and the difference was statistically significant (P<0.01). Positive FERMT2 expression was different in tumors at different tumor stages: 11/17 at stage Ⅰ, 16/20(80.0%)at stage Ⅱ, 17/20(85.0%)at stage Ⅲ, and 15/15 at stage Ⅳ, and there was a significant difference between each stage (P<0.01). By real-time PCR and Western blot, the expression of FERMT2 in non-small cell lung cancer tissues was significantly higher than that of para-cancerous tissue (P<0.01). The expression levels of integrin related proteins (integrin ß1, VCAM1 and MRP1) in tumor tissues were significantly higher than those in para-cancerous tissues, and positively correlated with the expression of FERMT2 (r=0.531, P<0.01; r=0.483, P<0.01; r=0.612, P<0.01). Conclusions: FERMT2 is highly expressed in non-small cell lung carcinomas. Its expression is closely correlated with the tumor clinical stage. It is hypothesized that FERMT2 may promote tumor metastasis through interactions with integrin-like protein.