ABSTRACT Hot dust-obscured galaxies (hot DOGs), selected from Wide-Field Infrared Survey Explorer's all-sky infrared survey, host some of the most powerful active galactic nuclei known and may ...represent an important stage in the evolution of galaxies. Most known hot DOGs are located at , due in part to a strong bias against identifying them at lower redshift related to the selection criteria. We present a new selection method that identifies 153 hot DOG candidates at , where they are significantly brighter and easier to study. We validate this approach by measuring a redshift z = 1.009 and finding a spectral energy distribution similar to that of higher-redshift hot DOGs for one of these objects, WISE J1036+0449 ( ). We find evidence of a broadened component in Mg ii, which would imply a black hole mass of and an Eddington ratio of . WISE J1036+0449 is the first hot DOG detected by the Nuclear Spectroscopic Telescope Array, and observations show that the source is heavily obscured, with a column density of . The source has an intrinsic 2-10 keV luminosity of , a value significantly lower than that expected from the mid-infrared/X-ray correlation. We also find that other hot DOGs observed by X-ray facilities show a similar deficiency of X-ray flux. We discuss the origin of the X-ray weakness and the absorption properties of hot DOGs. Hot DOGs at could be excellent laboratories to probe the characteristics of the accretion flow and of the X-ray emitting plasma at extreme values of the Eddington ratio.
Gastric cancer is one of the most common malignant cancers, with poor prognosis and high mortality rates worldwide. Therefore, development of an effective therapeutic method without side effects is ...an urgent need. It has been reported that cationic antimicrobial peptides can selectively bind to negatively charged prokaryotic and cancer cell membranes and exert cytotoxicity without causing severe drug resistance. In the current study, we prepared a series of peptide fragments derived from bovine lactoferrin and evaluated their anticancer potency toward the gastric cancer cell line AGS. Cell viability assay revealed that a 25-AA peptide fragment, lactoferricin B25 (LFcinB25), exhibited the most potent anticancer capability against AGS cells. Lactoferricin B25 selectively inhibited AGS cell growth in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) value of 64μM. Flow cytometry showed a notable increment of the sub-G1 populations of the cell cycle, indicating the induction of apoptosis by LFcinB25. Western blot analysis further revealed that upon LFcinB25 treatment for 2 to 6h, apoptosis-related caspases-3, 7, 8, 9, and poly(ADP-ribose) polymerase (PARP) were cleaved and activated, whereas autophagy-related LC3-II and beclin-1 were concomitantly increased. Thus, both apoptosis and autophagy are involved in the early stage of LFcinB25-induced cell death of AGS cells. However, upon treatment with LFcinB25 for 12 to 24h, LC3-II began to decrease, whereas cleaved beclin-1 increased in a time-dependent manner, suggesting that consecutive activation of caspases cleaved beclin-1 to inhibit autophagy, thus enhancing apoptosis at the final stage. These findings provide support for future application of LFcinB25 as a potential therapeutic agent for gastric cancer.
Background
Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed‐type hypersensitivity reactions (DHR) induced by PPI, such as ...Stevens‐Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI‐related DHR, followed up their tolerability to alternative anti‐ulcer agents, and investigated the T‐cell reactivity to PPI in PPI‐related DHR patients.
Methods
We retrospectively analyzed patients with PPI‐related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross‐hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon‐γ to confirm the causalities.
Results
There were 69 cases of PPI‐related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI‐related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross‐hypersensitivity reactions, whereas three patients developed cross‐hypersensitivity reactions to alternative structurally similar PPI. The cross‐reactivity to structurally similar PPI was also observed in LAT assay.
Conclusions
PPIs have the potential to induce life‐threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.
CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor ...(EGFR).
Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m2) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data.
From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40–0.75, P < 0.001 as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38–0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49–1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43–2.08, P = 0.877).
CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients.
NCT00891579.
Summary
Background Alopecia areata (AA) may be related to stress and has been reported to be associated with psychiatric disorders. Nevertheless, a nationwide study of the relationship between AA ...and comorbid psychiatric diseases has not been conducted, and the effect of onset age has rarely been reported.
Objectives To analyse the associations between AA and various psychiatric disorders using a nationwide database in Taiwan.
Methods Data were obtained from the National Health Insurance Research Database of Taiwan from 2000 to 2009. In total, 5117 patients with AA and 20 468 age‐ and gender‐matched controls were enrolled.
Results Patients with AA tended to have more coexisting anxiety and less comorbid schizophrenia. Differences in ages of onset revealed differences in comorbidities. An increased risk of depression odds ratio (OR) 2·23; 95% confidence interval (CI) 1·09–4·54 was found in patients with AA aged < 20 years. An increased rate of anxiety (OR 1·43; CI 1·15–1·77) was observed with AA onset between the ages of 20 and 39 years. The highest odds of obsessive–compulsive disorder (OR 3·00; CI 1·11–8·12) and anxiety (OR 2·05; CI 1·56–2·68) were observed in patients with AA aged 40–59 years. Moreover, about 50% of psychiatric disorders occurred earlier than AA.
Conclusions AA is related to various psychiatric disorders. Onset age of AA is an important factor in the association with different comorbid psychiatric diseases. In addition to cosmetic impact, which may bring about anxiety or depression, stress neuroendocrine immunology may play an important role in the pathogenesis of both AA and psychiatric disorders.
This study investigated seasonal variations in the mass concentration and chemical composition of ambient aerosols observed at three stations (coastal, mountainous, and downtown sites) in northern ...Taiwan from March 2009 to February 2012. The results show that the major aerosol components include ammonium, sulfate, nitrate, sea salt, dust, organic carbon, and elemental carbon, whereas the mass fraction of each species depends on the sampling location and season. A significant correlation (r = 0.7–0.8) was observed in aerosol concentrations measured at the respective stations, indicating that aerosol concentrations were dominated by regional‐scale factors. Ammonium, sulfate, and nitrate consistently reached respective peak values in the spring in conjunction with dust particle levels. This shows that the transport of dust and particulate air pollutants from the Asian continent has affected the atmospheric environment in this area. Distinct seasonality was observed for sea salt and secondary organic carbon (SOC): sea salt levels peaked in the autumn, whereas SOC levels peaked in the summer, implying that their sources were regulated by independent seasonal factors. Correlation between sea salt concentration and surface wind speed was derived from coastal measurements and showed a high value for the wind speed sensitivity parameter of around 0.37 for our location. In addition, it was revealed that the SOC concentration in aerosols was positively correlated with oxidant photolysis index (Ox × UVB), suggesting that the SOC seasonality was dominated by hydroxyl radical production.
Key Points
Inorganic particulate pollutants and dust consistently peaked in the spring due to Asian outflow effects
Ambient concentrations of sea salt particles were exponentially correlated with surface wind speeds
The production of secondary organic aerosols was dominated by the photolysis of total oxidants
End-stage renal disease (ESRD) patients are vulnerable to Mycobacterium tuberculosis (MTB) infection, but the magnitude of the risk is uncertain. In addition, there is no reliable information on the ...MTB infection rate of patients undergoing different types of renal replacement therapy (RRT). We used the Taiwan National Health Insurance Research Database to conduct a 9-year nationwide longitudinal study. Among 49 983 ESRD patients who received three renal replacement modalities, there were 562 cases of MTB infection, corresponding to an incidence rate of 3.0 per 1000 patient-years. The risk of MTB infection relative to the general population was 4.5. Multivariate Cox regression analysis indicated that the independent risk factors for MTB infection in ESRD patients are old age (hazard ratio (HR) 1.17 per 10 years, p <0.001), male gender (HR 1.37, p <0.001), silicosis (HR 5.82, p <0.001), and chronic obstructive pulmonary disease (HR 1.68, p 0.012). Hyperlipidaemia (HR 0.71, p <0.001) and hypertension (HR 0.81, p 0.05) are associated with a lower infection rate. There was no effect of RRT modality on MTB infection rate.
The Asteroid Terrestrial impact Last Alert System (ATLAS) system consists of two 0.5 m Schmidt telescopes with cameras covering 29 square degrees at plate scale of 1.86 arcsec per pixel. Working in ...tandem, the telescopes routinely survey the whole sky visible from Hawaii (above δ > − 50 ° ) every two nights, exposing four times per night, typically reaching o < 19 magnitude per exposure when the moon is illuminated and c < 19.5 magnitude per exposure in dark skies. Construction is underway of two further units to be sited in Chile and South Africa which will result in an all-sky daily cadence from 2021. Initially designed for detecting potentially hazardous near earth objects, the ATLAS data enable a range of astrophysical time domain science. To extract transients from the data stream requires a computing system to process the data, assimilate detections in time and space and associate them with known astrophysical sources. Here we describe the hardware and software infrastructure to produce a stream of clean, real, astrophysical transients in real time. This involves machine learning and boosted decision tree algorithms to identify extragalactic and Galactic transients. Typically we detect 10-15 supernova candidates per night which we immediately announce publicly. The ATLAS discoveries not only enable rapid follow-up of interesting sources but will provide complete statistical samples within the local volume of 100 Mpc. A simple comparison of the detected supernova rate within 100 Mpc, with no corrections for completeness, is already significantly higher (factor 1.5 to 2) than the current accepted rates.
We describe a novel surgical technique in 31 women with histopathologically confirmed placenta accreta spectrum (PAS) disorders managed by a multidisciplinary team using a prophylactic infrarenal ...abdominal aortic cross‐clamping technique during caesarean hysterectomy. We conclude that this new surgical procedure is a relatively safe technique to potentially control operative blood loss. Our work may stimulate others to develop protocols assessing this innovative technique to improve the surgical outcome of PAS disorders.
The associations between long-term risk of hepatocellular carcinoma (HCC) and spontaneous seroclearance of HBV e antigen (HBeAg), HBV DNA and HBV surface antigen (HBsAg) have never been examined by a ...prospective study using serially measured seromarkers. This study aimed to assess the importance of spontaneous HBeAg, HBV DNA and HBsAg seroclearance in the prediction of HCC risk.
This study included 2946 HBsAg seropositive individuals who were seronegative for antibodies against HCV and free of liver cirrhosis. Serial serum samples collected at study entry and follow-up health examinations were tested for HBeAg, HBV DNA and HBsAg. Cox proportional hazards models were used to calculate the HRs of developing HCC after seroclearance of HBV markers.
The HR (95% CI) of developing HCC after seroclearance of HBeAg, HBV DNA and HBsAg during follow-up was 0.63 (0.38 to 1.05), 0.24 (0.11 to 0.57) and 0.18 (0.09 to 0.38), respectively, after adjustment for age, gender and serum level of alanine aminotransferase at study entry. High HBV DNA levels at the seroclearance of HBeAg (mean±SD, 4.35±1.64 log10 IU/mL) may explain the non-significant association between HBeAg seroclearance and HCC risk. Among HBeAg seronegative participants with detectable serum HBV DNA at study entry, the lifetime (30-75-years-old) cumulative incidence of HCC was 4.0%, 6.6% and 14.2%, respectively, for those with seroclearance of both HBV DNA and HBsAg, seroclearance of HBV DNA only, and seroclearance of neither.
Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk.
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