Individualization of cancer management requires prognostic markers and therapy-predictive markers. Prognostic markers assess risk of disease progression independent of therapy, whereas ...therapy-predictive markers identify patients whose disease is sensitive or resistant to treatment. We show that an experimentally derived IFN-related DNA damage resistance signature (IRDS) is associated with resistance to chemotherapy and/or radiation across different cancer cell lines. The IRDS genes STAT1, ISG15, and IFIT1 all mediate experimental resistance. Clinical analyses reveal that IRDS(+) and IRDS(-) states exist among common human cancers. In breast cancer, a seven-gene-pair classifier predicts for efficacy of adjuvant chemotherapy and for local-regional control after radiation. By providing information on treatment sensitivity or resistance, the IRDS improves outcome prediction when combined with standard markers, risk groups, or other genomic classifiers.
Fe3O4@C microcapsules were prepared using carbon-coated α-FeOOH nanorods as precursors, which were synthesized via two-step hydrothermal reactions. During the subsequent sintering procedure, α-FeOOH ...was reduced to Fe3O4 by carbon, accompanied by the formation of mesopores. In Fe3O4@C microcapsules, mesoporous Fe3O4 nanorods are coated with amorphorous carbon layers. The Fe3O4/C composites with such special structures demonstrate high specific capacity and good cyclic stability as anode materials in Li test cells.
Periodontal homeostasis is maintained by the dynamic equilibrium between cell death, differentiation and proliferation of resident cells in the periodontal microenvironment. Loss of resident ...periodontal ligament fibroblasts (PDLFs) has been a major challenge in the periodontal treatment. This study aimed to investigate the exact role of necroptotic cell death in periodontal diseases. Elevated levels of receptor-interacting protein serine-threonine kinases -1 (RIPK1), phosphorylated RIPK3, mixed lineage kinase domain-like protein (MLKL), phosphorylated MLKL and FLIP
were observed in gingival tissues collected from patients with untreated chronic periodontitis; whereas no difference in caspase 8 was observed between the periodontitis and healthy control group. In contrast to the high incidence of necroptotic cell death in monocytes during live P. gingivalis infection with a low multiplicity of infection (MOI), necroptosis was only observed in PDLFs with a high MOI. Priming PDLFs with frozen thawed monocytes enhanced proinflammatory responses to P. gingivalis infection; moreover, frozen thawed monocytes stimulation triggered RIPK1, RIPK3 and MLKL-mediated-necroptotic cell death in PDLFs. These results indicated that RIPK3 and MLKL-mediated-necroptotic cell death participated in the pathogenesis of periodontitis, and DAMPs released from monocytes after P. gingivalis stimulation by necroptosis triggered not only inflammatory responses, but also necroptosis of PDLFs.
We compared CALIPSO column aerosol optical depths at 0.532 μm to measurements at 147 AERONET sites, synchronized to within 30 min of satellite overpass times during a 3-yr period. We found 677 ...suitable overpasses, and a CALIPSO bias of −13% relative to AERONET for the entire data set; the corresponding absolute bias is −0.029, and the standard deviation of the mean (SDOM) is 0.014. Consequently, the null hypothesis is rejected at the 97% confidence level, indicating a statistically significant difference between the datasets. However, if we omit CALIPSO columns that contain dust from our analysis, the relative and absolute biases are reduced to −3% and −0.005 with a standard error of 0.016 for 449 overpasses, and the statistical confidence level for the null hypothesis rejection is reduced to 27%. We also analyzed the results according to the six CALIPSO aerosol subtypes and found relative and absolute biases of −29% and −0.1 for atmospheric columns that contain the dust subtype exclusively, but with a relatively high correlation coefficient of R = 0.58; this indicates the possibility that the assumed lidar ratio (40 sr) for the CALIPSO dust retrievals is too low. Hence, we used the AERONET size distributions, refractive indices, percent spheres, and forward optics code for spheres and spheroids to compute a lidar ratio climatology for AERONET sites located in the dust belt. The highest lidar ratios of our analysis occur in the non-Sahel regions of Northern Africa, where the median lidar ratio at 0.532 μm is 55.4 sr for 229 retrievals. Lidar ratios are somewhat lower in the African Sahel (49.7 sr for 929 retrievals), the Middle East (42.6 sr for 489 retrievals), and Kanpur, India (43.8 sr for 67 retrievals). We attribute this regional variability in the lidar ratio to the regional variability of the real refractive index of dust, as these two parameters are highly anti-correlated (correlation coefficients range from −0.51 to −0.85 for the various regions). The AERONET refractive index variability is consistent with the variability of illite concentration in dust across the dust belt.
The role of specificity protein 1 (Sp1) in controlling gene expression in lung tumor development and metastasis is not well understood. In this study, we showed that the Sp1 level was highly ...increased and required for lung tumor growth in transgenic mice bearing Kras-induced lung tumors under the control of doxycycline. Furthermore, the Sp1 level was highly upregulated in lung adenocarcinoma cells with low invasiveness and in patients with stage I lung cancer. We also demonstrated that Sp1 was downregulated in lung adenocarcinoma cells with high invasiveness and in patients with stage IV lung adenocarcinoma. Moreover, Sp1 inversely regulated migration, invasion and metastasis of lung adenocarcinoma cells in vivo. In addition, a decrease in the Sp1 level in highly invasive lung adenocarcinoma cells resulted from instability of the Sp1 protein. Furthermore, overexpression of Sp1 in highly invasive lung adenocarcinoma cells increased expression of E-cadherin, a suppressor of metastasis, and attenuated the translocation of β-catenin into the cellular nucleus that leads to tumor malignancy. Taken together, Sp1 level accumulated strongly in early stage and then declined in late stage, which is important for lung cancer cell proliferation and metastasis during tumorigenesis.
Abstract
PSR J1953+1844 (i.e., M71E) is a millisecond pulsar in a 53 minute binary orbit discovered by the Five-hundred-meter Aperture Spherical radio Telescope. The mass function from pulsar timing ...is 2.3 × 10
−7
M
⊙
. The possible redback origin of this system has been discussed by Pan et al. We discuss here an alternative evolution track for this binary system, namely that PSR J1953+1844 is a descendant of an ultracompact X-ray binary (UCXB), which has a hydrogen-poor donor accreting onto a neutron star (NS) with an orbital period of ≤1 hr. We noticed that some UCXB systems hold an accreting millisecond X-ray pulsar (AMXP) and a donor with a mass of about 0.01
M
⊙
. M71E has a very similar orbit to those of AMXPs, indicating that it might be evolved from a UCXB similar to PSR J1653–0158. The companion star of M71E should be significantly bloated and it most probably has a carbon and oxygen composition, otherwise a low inclination angle of the orbit is required for a helium companion. The discovery of this M71E binary system may shed light on when and how an NS in a UCXB turns into a radio pulsar.
There is no standard first-line chemotherapy for advanced urothelial carcinoma (aUC) in cisplatin-ineligible (cisplatin-unfit) patients. The study assessed the efficacy and tolerability profile of ...two vinflunine-based cytotoxic regimens in this setting.
Patients with aUC a creatinine clearance (CrCl) of <60 but ≥30 ml/min, performance status 0 or 1 and no prior chemotherapy for advanced disease were randomized (1: 1). They received vinflunine 250 or 280 mg/m2 (based on baseline CrCl) on day 1, plus either gemcitabine 750 mg/m2 escalated to 1000 mg/m2 in cycle 2 if no toxicity grade (G) ≥2 on days 1 and 8 (VG) or plus carboplatin area under the curve 4.5 day 1 (VC) every 21 days. To detect a 22% improvement in each arm compared with H0 (41%) in the primary end point, disease control rate (DCR = complete response + partial response + stable disease), 31 assessable patients per arm were required (α = 5%, β = 20%).
Sixty-nine patients were enrolled (34 VG, 35 VC). Less G3/4 haematological adverse events (AEs) were reported with VG: neutropaenia was seen in 38% (versus 68% with VC) and febrile neutropaenia in 3% (versus 14% with VC) of patients. No major differences were observed for non-haematological AEs. DCR was 77% in both groups; overall response rate (ORR) was 44.1% versus 28.6%, with a median progression-free survival of 5.9 versus 6.1 months and median OS of 14.0 versus 12.8 months with VG and VC, respectively.
Both vinflunine-based doublets offer a similar DCR, ORR and OS. The better haematological tolerance favours the VG combination, which warrants further study.
NCT 01599013.
Gender disparities in tuberculosis (TB) cases are reported worldwide, and socio-cultural factors have been proposed as possible causes. To date, gender differences in treatment outcomes of TB ...patients remain controversial. In this prospective observational study, newly diagnosed, culture-proven TB patients from six hospitals in Taiwan were enrolled for analysis. Gender differences in demographic characteristics and treatment outcomes, including sputum conversion and on-treatment mortality, were analysed accordingly. From January 2007 through to December 2009, a total of 1059 patients were enrolled, including 819 (77.3%) males and 240 (22.7%) females. The ratio of male gender was around 50~60% in TB patients below 35 years and >80% for those older than 65 years. When compared with the female patients, the male patients were older, more likely to have the habit of smoking, chronic obstructive pulmonary disorder, malignancy and liver cirrhosis, and more likely to present with haemoptysis, body weight loss and pleural effusion. Regarding treatment outcomes, male gender is associated with a lower 2-month sputum culture conversion rate (78.8% vs. 89.3%, p 0.002) and higher on-treatment mortality (21.1% vs. 12.1%, p 0.002). Kaplan-Meier survival analysis demonstrated significantly higher mortality in the men (p 0.005). In multivariate analysis, male gender was an independent risk factor for 2-month sputum culture un-conversion (OR, 1.96; 95% CI, 1.12–3.41). Our findings suggest that male gender is associated with older age, more co-morbidities and worse treatment outcomes. Gender-specific strategies, including active case finding in elderly women and smoking cessation in male patients, are warranted to optimize TB management.
Context. Quasi-periodic oscillations are usually detected as spatial displacements of coronal loops in imaging observations or as periodic shifts of line properties (i.e., Doppler velocity, line ...width and intensity) in spectroscopic observations. They are often applied for remote diagnostics of magnetic fields and plasma properties on the Sun. Aims. We combine the imaging and spectroscopic measurements of available space missions, and investigate the properties of non-damping oscillations at flaring loops. Methods. We used the Interface Region Imaging Spectrograph (IRIS) to measure the spectrum over a narrow slit. The double-component Gaussian fitting method was used to extract the line profile of Fe XXI 1354.08 Å at the “O I” spectral window. The quasi-periodicity of loop oscillations were identified in the Fourier and wavelet spectra. Results. A periodicity at about 40 s is detected in the line properties of Fe XXI 1354.08 Å, hard X-ray emissions in GOES 1−8 Å derivative, and Fermi 26−50 keV. The Doppler velocity and line width oscillate in phase, while a phase shift of about π/2 is detected between the Doppler velocity and peak intensity. The amplitudes of Doppler velocity and line width oscillation are about 2.2 km s−1 and 1.9 km s−1, respectively, while peak intensity oscillates with amplitude at about 3.6% of the background emission. Meanwhile, a quasi-period of about 155 s is identified in the Doppler velocity and peak intensity of the Fe XXI 1354.08 Å line emission, and AIA 131 Å intensity. Conclusions. The oscillations at about 40 s are not damped significantly during the observation; this might be linked to the global kink modes of flaring loops. The periodicity at about 155 s is most likely a signature of recurring downflows after chromospheric evaporation along flaring loops. The magnetic field strengths of the flaring loops are estimated to be about 120−170 G using the magnetohydrodynamic seismology diagnostics, which are consistent with the magnetic field modeling results using the flux rope insertion method.
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