Background
Human papillomavirus (HPV) persistence is the pivotal event in cervical carcinogenesis. We followed a large-scale community-based cohort for 16 years to investigate the role of ...genotype-specific HPV persistence in predicting cervical cancer including invasive and in situ carcinoma.
Methods
At the baseline examination in 1991-1992, 11 923 participants (aged 30-65 years) consented to HPV testing and cytology; 6923 participants were reexamined in 1993-1995. For HPV testing, we used a polymerase chain reaction-based assay that detected 39 HPV types. Women who developed cervical cancer were identified from cancer and death registries. Cumulative risks for developing cervical cancer among infected and persistently infected women were calculated by the Kaplan-Meier method.
Results
Of 10 123 women who were initially cytologically normal, 68 developed cervical cancer. The 16-year cumulative risks of subsequent cervical cancer for women with HPV16, HPV58 (without HPV16), or other carcinogenic HPV types (without HPV16 or HPV58) were 13.5%, 10.3%, and 4.0%, respectively, compared with 0.26% for HPV-negative women. Women with type-specific persistence of any carcinogenic HPV had greatly increased risk compared with women who were HPV-negative at both visits (hazard ratio = 75.4, 95% confidence interval = 31.8 to 178.9). The cumulative cervical cancer risks following persistent carcinogenic HPV infections increased with age: The risks were 5.5%, 14.4%, and 18.1% for women aged 30-44 years, 45-54 years, and 55 years and older, respectively. However, newly acquired infections were associated with a low risk of cervical cancer regardless of age.
Conclusions
HPV negativity was associated with a very low long-term risk of cervical cancer. Persistent detection of HPV among cytologically normal women greatly increased risk. Thus, it is useful to perform repeated HPV testing following an initial positive test.
Pain is associated with anxiety in a dental setting. It has remained unclear how cognitive-affective factors modulate pain and anxiety in a stressful context, such as receiving dental procedures. We ...hypothesized that both the situational factor (unpredictability about painful stimuli) and the trait factor (pain catastrophizing, i.e., the tendency to interpret pain in negative orientation) account for dental pain. Fifteen healthy participants were recruited to perform an associative learning task. They were asked to learn the pairing between visual cues and the intensity of incoming painful stimuli delivered at the right upper central incisor. Brain activation associated with pain was recorded by functional magnetic resonance imaging (fMRI). The participants reported increased anxiety and pain in the stressful context, where stimuli intensity was not predicted by the preceding cue. The score of the Pain Catastrophizing Scale was positively correlated with the increased pain modulated by unpredictability. Brain activation at the right posterior hippocampus, a region critically related to associative learning of aversive stimuli and context, was correlated with the individual catastrophizing level. Our findings suggest that both the situational factor (unpredictability) and the trait factor (catastrophizing) influence dental pain, highlighting the role of cognitive-affective factors in pain control of dental patients.
To understand the status of oropharyngeal yeast colonization in human immunodeficiency virus (HIV) -infected outpatients in the era of highly active antiretroviral therapy (HAART), we conducted a ...prospective, cross-sectional study from October 2009 to January 2010 at a medical centre in southern Taiwan. Fungal cultures of the oropharyngeal swabs were performed on 327 enrolled patients. At enrolment, 258 (79%) patients had been receiving HAART, and 42 (12.8%), 73 (22.3%) and 212 (64.8%) patients had CD4 cell counts ≤200, 201–350, and >350 cells/mm3, respectively. Oral yeast colonization was detected in 193 (59%) patients, among whom 157 (81.3%), 25 (13.0%), and 11 (5.7%) were colonized by a single, two and more than two species, respectively. Multivariate analysis showed that receipt of efavirenz-containing regiments and CD4 cell counts >200 cells/mm3 were associated with lower risks of oral yeast colonization, while intravenous drug users were at a higher risk. Among the 241 isolates recovered, Candida albicans accounted for 69.7%, followed by C. dubliniensis (9.5%), C. glabrata (8.3%), C. tropicalis (3.3%), C. intermedia (2.1%), C. parapsilosis (1.7%), and 11 other species (5.4%). Overall, 230 (95.4%), 236 (97.9%) and 240 (99.6%) isolates were susceptible to fluconazole, voriconazole and amphotericin B, respectively. In conclusion, colonization by C. dubliniensis has emerged in recent years. In addition to a CD4 cell count ≤200 cells/mm3, which is a known risk factor for oropharyngeal yeast colonization in HIV-infected patients that was identified in our previous studies, two risk factors, non-receipt of efavirenz-based combinations and intravenous drug use, were first identified in the present study. Fluconazole remained effective in vitro against the yeasts colonizing the oropharynx in this population.
Lightweight Ti65(AlCrNb)35 medium-entropy alloy (Ti-65) ingots were produced through arc melting and drop casting in a water-cooled copper mold. These alloy ingots were then treated through a ...sequence of homogenization, hot rolling, cold rolling, and recrystallization. The effect of this thermomechanical treatment (TMT) on their microstructures and mechanical properties was investigated through X-ray diffraction (XRD), electron backscatter diffraction analysis through scanning electron microscopy, and mechanical testing. The XRD results demonstrated that the Ti-65 alloy maintained a body-centered cubic structure after 50% hot rolling, 70% cold rolling, and recrystallization at 900 °C, 1000 °C, and 1100 °C, respectively. The fully recrystallized sample had an 80% smaller grain size than the as-cast sample. The cold-rolled Ti-65 alloy specimen exhibited a high tensile strength of 1620 MPa. In comparison with the tensile strength of the as-cast Ti-65 sample (1100 MPa), that of the Ti-65 alloy following annealing and subsequent partial recrystallization was significantly increased (1380 MPa). This tensile strength enhancement is attributable to its heterostructure composition of deformed bands and smaller recrystallized grains. This study demonstrated that an effective strength–ductility synergy of the Ti-65 alloy can be achieved through various TMTs.
•Thermomechanical treatment was employed to improve mechanical properties of novel lightweight Ti-65 medium-entropy alloys.•The recrystallized Ti-65 medium-entropy alloys composed of fine grains can be obtained via the rapid annealing treatment.•The partial-recrystallized medium-entropy alloy by rapid annealing treatment presents high strength with excellent ductility.
Due to the demand for reduced energy consumption by transportation vehicles, lighter weight high-entropy alloys (with density comparable to that of commercial Ti alloys around 4.5–5 g/cm3) are ...attracting more attention in terms of alloy design and application as structural materials. In this study, a nonequiatomic quaternary alloy system, Tix(AlCrNb)100-x, was designed through the calculation of phase diagrams. Simulation results reveal that a single body-centered cubic (BCC) phase can be formed and can be stable at temperatures above 950 °C. Accordingly, a series of Tix(AlCrNb)100-x (x = 45–80) alloys containing a BCC structure were prepared through vacuum arc melting and rapid cooling. The designed alloys can exhibit desirable mechanical properties with high compression yield strength about 1500 MPa, high compression fracture strength about 1800 MPa and high compression plasticity more than 30% at room temperature. Moreover, the Ti65 alloy can demonstrate a tensile strength of 1200 MPa with a tensile elongation of 32%, after a homogenization treatment for 24 h. The specific compression and tensile strength can reach 0.36 and 0.24 GPa cm3/g.
•Novel alloys designing of light weight high entropy alloys by calculation of phase diagrams.•High strength with high ductility medium-entropy alloys (MEAs).•Both of the as-cast and homogenized samples possess BCC structures and perform superior tensile strength as well plasticity.
Close coordination between chaperones is essential for protein biosynthesis, including the delivery of tail-anchored (TA) proteins containing a single C-terminal transmembrane domain to the ...endoplasmic reticulum (ER) by the conserved GET pathway. For successful targeting, nascent TA proteins must be promptly chaperoned and loaded onto the cytosolic ATPase Get3 through a transfer reaction involving the chaperone SGTA and bridging factors Get4, Ubl4a and Bag6. Here, we report cryo-electron microscopy structures of metazoan pretargeting GET complexes at 3.3-3.6 Å. The structures reveal that Get3 helix 8 and the Get4 C terminus form a composite lid over the Get3 substrate-binding chamber that is opened by SGTA. Another interaction with Get4 prevents formation of Get3 helix 4, which links the substrate chamber and ATPase domain. Both interactions facilitate TA protein transfer from SGTA to Get3. Our findings show how the pretargeting complex primes Get3 for coordinated client loading and ER targeting.
The scope of this review will be limited to highlighting the actions of 1 alpha ,25-dihydroxyvitamin D sub(3) (1,25(OH) sub(2)D sub(3)) mediated by nuclear vitamin D receptor (VDR) and discussing new ...developments in the structure/function analysis of the receptor, including the phenotype of VDR knockout mice and the biochemical classification of patients with point mutations in the receptor. These new advances, along with other recent research, will be interpreted to update our understanding of the molecular role of VDR, ranging from characterization of its natural gene and clinically significant polymorphisms, through its DNA contact sites and protein partners, to novel ligand analogs that hold the promise of influencing VDR conformation in a therapeutically beneficial fashion.
The quantitative relationship between serum albumin level and surgical outcomes has not been clearly established. This study included 3732 patients with colon cancer who underwent a potentially ...curative colectomy. Post‐operative mortality and morbidity were analysed according to the patients' demographic data, pre‐operative comorbidities, and tumour‐related factors. Age, asthma, renal impairment, and albumin level were significantly associated with post‐operative morbidity and mortality in the multivariate analyses. Logistic regression analysis revealed linear relationships of post‐operative morbidity and mortality with albumin level. The morbidity and mortality rates decreased by 7.3% and 15.6%, respectively, for each 0.1 g/dL increase in albumin level. This finding remained significant in the hypoalbuminaemia subgroup but not in the normoalbuminaemia subgroup. That is, the morbidity and mortality rates significantly decreased by 8.7% and 17.7%, respectively (both P < 0.001), in the former group and decreased by 2.7% (P = 0.112) and 11.6% (P = 0.092), respectively, in the latter group. This study demonstrated that serum albumin level linearly predicted the post‐operative morbidity and mortality among the colorectal cancer patients. Pre‐operative serum albumin level may therefore be used as a continuous rather than a categorical marker of disease severity, especially among patients with hypoalbuminaemia.
When two different oxides films stacked together, if the absorption (upper) layer has both its conduction and valence bands more negatively lower than that of the layer underneath, then the ...photo-excited electrons can be forwarded to the underneath layer to become an effect of energy storage. Recent studies discovered that the double-layers of Cu2O/TiO2 films possess such capacity. In order to investigate this specific phenomenon, we use a DC magnetron reactive sputtering to deposit a double-layer of Ag2O/TiO2 films on glass substrate. The film thicknesses of the double-layer are 300nm and 200nm respectively. X-Ray diffraction (XRD), scanning electron microscope (SEM) and UV–VIS–NIR photospectrometer and photoluminance tests were used to study the structure, morphology, optical absorption and band gaps of the stacked films. From XRD and SEM, we can confirm the microstructures of each layer. The UV–VIS–NIR spectrum revealed that the optical absorption of Ag2O/TiO2 fell in between the single film of Ag2O and TiO2. Further, two band gaps were estimated for Ag2O/TiO2 films based on the Beer-Lambert law and Tauc plot. Photoluminance and photoelectrochemical tests indicated that delayed emission by electron-hole recombination and photoelectrical current was effectively support the mechanism of electrons transfer from Ag2O to TiO2 at Ag2O/TiO2 interface in the double-layer films.
•A double-layer of Ag2O/TiO2 films was deposited on glass substrate by sputtering.•XRD confirms the nanocrystalline structures of the stack deposited films.•UV–VIS–NIR spectroscopy shows the enhanced of optical absorption in Ag2O/TiO2.•Photoluminance and photoelectrochemical tests show electron-hole separation effect.
Using the CALPHAD method, lightweight nonequiatomic Ti60(Al)x(VCrNb)40-x (x = 6, 8, 10, 12, and 18 at.%) medium-entropy alloys (MEAs) were designed and produced using vacuum arc melting and drop ...casting. The density of these cast alloys decreased with an increase in Al concentration from 5.45 to 4.79 g cm−3. All of these cast alloys exhibited a body-centered cubic (BCC) microstructure. However, a nanosized ordered B2 phase was identified in the cast alloys with higher Al concentrations (Al-12 and Al-18). The prediction of BCC phase formation using CALPHAD was consistent with the experimental results. These BCC-structured alloys can withstand over 50% strain at room temperature, which demonstrates excellent compressive ductility. Moreover, the results demonstrate that the as-cast Al-6 and Al-8 samples had superior plasticity under tensile testing, with a tensile strength of 1120 MPa and approximately 30% plastic strain. Furthermore, with an increase in Al concentration, the alloys exhibited a notable trend in yield strength and a decreasing trend in plastic strain. The change in mechanical properties of these MEAs caused by the formation of B2 nanoparticles was also investigated.
•Novel alloys designing of lightweight medium-entropy alloys by calculation of phase diagrams.•High strength with excellent ductility cast medium-entropy alloys.•Fracture and strengthening mechanism was investigated in detailed.