To evaluate the dose–response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables.
We analyzed data from 12 case–control studies within the ...International Pancreatic Cancer Case–Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models.
Compared with never smokers, the OR was 1.2 (95% confidence interval CI 1.0–1.3) for former smokers and 2.2 (95% CI 1.7–2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR = 3.4 for ≥35 cigarettes per day, P for trend <0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR = 2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years.
This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.
Effective targeted therapy for non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) mutations remains an unmet need. This study investigated the antitumor ...effect of an irreversible pan-HER receptor tyrosine kinase inhibitor, pyrotinib.
Using patient-derived organoids and xenografts established from an HER2-A775_G776YVMA-inserted advanced lung adenocarcinoma patient sample, we investigated the antitumor activity of pyrotinib. Preliminary safety and efficacy of pyrotinib in 15 HER2-mutant NSCLC patients in a phase II clinical trial are also presented.
Pyrotinib showed significant growth inhibition of organoids relative to afatinib in vitro (P = 0.0038). In the PDX model, pyrotinib showed a superior antitumor effect than afatinib (P = 0.0471) and T-DM1 (P = 0.0138). Mice treated with pyrotinib displayed significant tumor burden reduction (mean tumor volume, −52.2%). In contrast, afatinib (25.4%) and T-DM1 (10.9%) showed no obvious reduction. Moreover, pyrotinib showed a robust ability to inhibit pHER2, pERK and pAkt. In the phase II cohort of 15 patients with HER2-mutant NSCLC, pyrotinib 400 mg resulted in a objective response rate of 53.3% and a median progression-free survival of 6.4 months.
Pyrotinib showed activity against NSCLC with HER2 exon 20 mutations in both patient-derived organoids and a PDX model. In the clinical trial, pyrotinib showed promising efficacy.
NCT02535507.
Abstract
We report the discovery of Pegasus IV, an ultra-faint dwarf galaxy found in archival data from the Dark Energy Camera processed by the DECam Local Volume Exploration Survey. Pegasus IV is a ...compact, ultra-faint stellar system (
r
1
/
2
=
41
−
6
+
8
pc;
M
V
= −4.25 ± 0.2 mag) located at a heliocentric distance of
90
−
6
+
4
kpc
. Based on spectra of seven nonvariable member stars observed with Magellan/IMACS, we confidently resolve Pegasus IV’s velocity dispersion, measuring
σ
v
=
3.3
−
1.1
+
1.7
km s
−1
(after excluding three velocity outliers); this implies a mass-to-light ratio of
M
1
/
2
/
L
V
,
1
/
2
=
167
−
99
+
224
M
⊙
/
L
⊙
for the system. From the five stars with the highest signal-to-noise spectra, we also measure a systemic metallicity of Fe/H =
−
2.63
−
0.30
+
0.26
dex, making Pegasus IV one of the most metal-poor ultra-faint dwarfs. We tentatively resolve a nonzero metallicity dispersion for the system. These measurements provide strong evidence that Pegasus IV is a dark-matter-dominated dwarf galaxy, rather than a star cluster. We measure Pegasus IV’s proper motion using data from Gaia Early Data Release 3, finding (
μ
α
*
,
μ
δ
) = (0.33 ± 0.07, −0.21 ± 0.08) mas yr
−1
. When combined with our measured systemic velocity, this proper motion suggests that Pegasus IV is on an elliptical, retrograde orbit, and is currently near its orbital apocenter. Lastly, we identify three potential RR Lyrae variable stars within Pegasus IV, including one candidate member located more than 10 half-light radii away from the system’s centroid. The discovery of yet another ultra-faint dwarf galaxy strongly suggests that the census of Milky Way satellites is still incomplete, even within 100 kpc.
Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction.
A pooled analysis of a history ...of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case–control studies (5048 cases of ductal pancreatic adenocarcinoma and 10 947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4).
The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96–3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72–21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53–6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02–2.76; P value for interaction: 0.006).
Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612–2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.
Galaxy And Mass Assembly (GAMA): stellar mass estimates Taylor, Edward N.; Hopkins, Andrew M.; Baldry, Ivan K. ...
Monthly notices of the Royal Astronomical Society,
December 2011, Letnik:
418, Številka:
3
Journal Article
Recenzirano
Odprti dostop
This paper describes the first catalogue of photometrically derived stellar mass estimates for intermediate-redshift (z < 0.65; median z= 0.2) galaxies in the Galaxy And Mass Assembly (GAMA) ...spectroscopic redshift survey. These masses, as well as the full set of ancillary stellar population parameters, will be made public as part of GAMA data release 2. Although the GAMA database does include near-infrared (NIR) photometry, we show that the quality of our stellar population synthesis fits is significantly poorer when these NIR data are included. Further, for a large fraction of galaxies, the stellar population parameters inferred from the optical-plus-NIR photometry are formally inconsistent with those inferred from the optical data alone. This may indicate problems in our stellar population library, or NIR data issues, or both; these issues will be addressed for future versions of the catalogue. For now, we have chosen to base our stellar mass estimates on optical photometry only. In light of our decision to ignore the available NIR data, we examine how well stellar mass can be constrained based on optical data alone. We use generic properties of stellar population synthesis models to demonstrate that restframe colour alone is in principle a very good estimator of stellar mass-to-light ratio, M
*/Li
. Further, we use the observed relation between restframe (g−i) and M
*/Li
for real GAMA galaxies to argue that, modulo uncertainties in the stellar evolution models themselves, (g−i) colour can in practice be used to estimate M
*/Li
to an accuracy of ≲0.1 dex (1σ). This 'empirically calibrated' (g−i)-M
*/Li
relation offers a simple and transparent means for estimating galaxies' stellar masses based on minimal data, and so provides a solid basis for other surveys to compare their results to z≲0.4 measurements from GAMA.
Nanosize multiferroic YFeO3 powders have been synthesized via the low temperature solid-state reaction. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy ...(SEM), transmission electron microscopy (TEM) and Raman spectroscopy all indicated that the phase-pure orthorhombic YFeO3 powders were obtained at 800°C with a size below 150nm. X-ray photoelectron spectroscopy (XPS) showed the Fe3+ ions to be predominant. Magnetic hysteresis loops exhibited some ferromagnetic behaviour of the YFeO3 nanopowders at ambient temperature. The maximum and remnant magnetizations of the powders were about 2.49 and 0.88emu/g, respectively. Moreover, optical measurements demonstrated that the optical band gap of the nanopowders was around 2.4eV, proving that they can strongly absorb visible light. So an easy and efficient way to synthesize YFeO3 nanopowders with promising application in the magnetic and optical fields has been successfully developed.
The city as a refuge for insect pollinators Hall, Damon M.; Camilo, Gerardo R.; Tonietto, Rebecca K. ...
Conservation biology,
February 2017, Letnik:
31, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Research on urban insect pollinators is changing views on the biological value and ecological importance of cities. The abundance and diversity of native bee species in urban landscapes that are ...absent in nearby rural lands evidence the biological value and ecological importance of cities and have implications for biodiversity conservation. Lagging behind this revised image of the city are urban conservation programs that historically have invested in education and outreach rather than programs designed to achieve high-priority species conservation results. We synthesized research on urban bee species diversity and abundance to determine how urban conservation could be repositioned to better align with new views on the ecological importance of urban landscapes. Due to insect pollinators' relatively small functional requirements—habitat range, life cycle, and nesting behavior—relative to larger mammals, we argue that pollinators put high-priority and high-impact urban conservation within reach. In a rapidly urbanizing world, transforming how environmental managers view the city can improve citizen engagement and contribute to the development of more sustainable urbanization. Las investigaciones sobre los insectos polinizadores urbanos están cambiando las percepciones sobre el valor biológico y la importancia ecológica de las ciudades. La abundancia y la diversidad de las especies nativas de abejas en los paisajes urbanos, que además están ausentes en los terrenos rurales cercanos, evidencian el valor biológico y la importancia ecológica de las ciudades y tienen implicaciones para la conservación de la biodiversidad. A paso lento detrás de esta imagen revisada de las ciudades están los programas de conservación urbana que históricamente han invertido en la educación y el alcance en lugar de los programar diseñados para adquirir resultados de conservación para especies de prioridad alta. Sintetizamos las investigaciones sobre la diversidad de especies de abejas urbanas y la abundancia para determinar cómo la conservación urbana podría ser reposicionada para alinearse de mejor manera con las nuevas visiones sobre la importancia ecológica de los paisajes urbanos. Debido a los requerimientos funcionales relativamente pequeños de los insectos polinizadores - extensión del hábitat, ciclo de vida, comportamiento de anidamiento - en relación con los mamíferos más grandes, argumentamos que los polinizadores colocan a la conservación urbana de alta prioridad y alto impacto dentro de nuestro alcance. En un mundo rápidamente urbanizado, transformar la forma en que los administradores ambientales ven a las ciudades puede mejorar la participación ciudadana y contribuir al desarrollo de una urbanización más sustentable.
Adipogenesis can be spatially and temporally regulated by extracellular matrix (ECM). We hypothesized that the regulation of hyaluronic acid (HA), a component of the ECM, can affect adipogenesis in ...fat cells. The effects of HA on adipogenesis were investigated in vitro in 3T3-L1 cells and in vivo in high-fat diet-feeding C57BL/6J mice.
We investigated the effects of HA by degradation of pre-existing or synthesized HA and artificial inhibition of HA synthesis in adipogenesis.
In vitro adipogenesis in 3T3-L1 cells was inhibited by treating them with exogenous hyaluronidase (HYAL) and with 4-methylumbelliferone, which inhibited the synthesis of HA in a concentration-dependent manner. In vivo, abdominal fat accumulation in high-fat diet-feeding C57BL/6J mice was suppressed by exogenous HYAL 10(4) IU injections, which was associated with reduction of lipid accumulation in liver and increase of insulin sensitivity.
Changes in the ECM such as accumulation of high molecular weight of HA by HAS and degradation of HA by endogenous HYAL were essential for adipogenesis both in vitro and in vivo.
Abstract
The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are important nuclear receptors involved in the regulation of cellular responses from exposure to many xenobiotics ...and various physiological processes. Phenobarbital (PB) is a non-genotoxic indirect CAR activator, which induces cytochrome P450 (CYP) and other xenobiotic metabolizing enzymes and is known to produce liver foci/tumors in mice and rats. From literature data, a mode of action (MOA) for PB-induced rodent liver tumor formation was developed. A MOA for PXR activators was not established owing to a lack of suitable data. The key events in the PB-induced liver tumor MOA comprise activation of CAR followed by altered gene expression specific to CAR activation, increased cell proliferation, formation of altered hepatic foci and ultimately the development of liver tumors. Associative events in the MOA include altered epigenetic changes, induction of hepatic CYP2B enzymes, liver hypertrophy and decreased apoptosis; with inhibition of gap junctional intercellular communication being an associative event or modulating factor. The MOA was evaluated using the modified Bradford Hill criteria for causality and other possible MOAs were excluded. While PB produces liver tumors in rodents, important species differences were identified including a lack of cell proliferation in cultured human hepatocytes. The MOA for PB-induced rodent liver tumor formation was considered to be qualitatively not plausible for humans. This conclusion is supported by data from a number of epidemiological studies conducted in human populations chronically exposed to PB in which there is no clear evidence for increased liver tumor risk.
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