Impression Effect vs. Click-through Effect: Mechanism Design of Online Advertising

Search advertising and display advertising are two major online advertising formats. Search advertising emphasizes ads’ click-through effect. Advertisers only pay when users click the link of their ads. Traditional display advertising emphasizes ads’ impression effect. Most display ads are charged based on the number of views on the ads. Considering that most online ads increase brand awareness (impression effect) and directly promote sales (click-through effect), the not-emphasized effect in search advertising or display advertising actually has a significant impact on the market outcome. However, these impacts have been largely ignored. In this paper, we examine various mechanisms in search and display advertising by considering both ads’ impression effect and click-through effect. Interestingly, we show a seesaw relationship between ads’ two effects in search advertising. The advertiser whose advertisement has a strong click-through effect benefits relatively less from its impression effect. In display advertising, the real-time-bidding (RTB) mechanism considers both ads’ impression effect and click-through effect. It allows a publisher to gain more surplus than that through a static auction. However, we show that RTB is associated with a high risk of market failure

Long Noncoding RNA Expression Signatures of Metastatic Nasopharyngeal Carcinoma and Their Prognostic Value

Long noncoding RNAs (lncRNAs) have recently been found to play important roles in various cancer types. The elucidation of genome-wide lncRNA expression patterns in metastatic nasopharyngeal carcinoma (NPC) could reveal novel mechanisms underlying NPC carcinogenesis and progression. In this study, lncRNA expression profiling was performed on metastatic and primary NPC tumors, and the differentially expressed lncRNAs between these samples were identified. A total of 33,045 lncRNA probes were generated for our microarray based on authoritative data sources, including RefSeq, UCSC Knowngenes, Ensembl, and related literature. Using these probes, 8,088 lncRNAs were found to be significantly differentially expressed (2-fold). To identify the prognostic value of these differentially expressed lncRNAs, four lncRNAs (LOC84740, ENST00000498296, AL359062, and ENST00000438550) were selected; their expression levels were measured in an independent panel of 106 primary NPC samples via QPCR. Among these lncRNAs, ENST00000438550 expression was demonstrated to be significantly correlated with NPC disease progression. A survival analysis showed that a high expression level of ENST00000438550 was an independent indicator of disease progression in NPC patients (). In summary, this study may provide novel diagnostic and prognostic biomarkers for NPC, as well as a novel understanding of the mechanism underlying NPC metastasis and potential targets for future treatment

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Long Noncoding RNA Expression Signatures of Metastatic Nasopharyngeal Carcinoma and Their Prognostic Value

Long noncoding RNAs (lncRNAs) have recently been found to play important roles in various cancer types. The elucidation of genome-wide lncRNA expression patterns in metastatic nasopharyngeal carcinoma (NPC) could reveal novel mechanisms underlying NPC carcinogenesis and progression. In this study, lncRNA expression profiling was performed on metastatic and primary NPC tumors, and the differentially expressed lncRNAs between these samples were identified. A total of 33,045 lncRNA probes were generated for our microarray based on authoritative data sources, including RefSeq, UCSC Knowngenes, Ensembl, and related literature. Using these probes, 8,088 lncRNAs were found to be significantly differentially expressed (≥2-fold). To identify the prognostic value of these differentially expressed lncRNAs, four lncRNAs (LOC84740, ENST00000498296, AL359062, and ENST00000438550) were selected; their expression levels were measured in an independent panel of 106 primary NPC samples via QPCR. Among these lncRNAs, ENST00000438550 expression was demonstrated to be significantly correlated with NPC disease progression. A survival analysis showed that a high expression level of ENST00000438550 was an independent indicator of disease progression in NPC patients (P = 0.01). In summary, this study may provide novel diagnostic and prognostic biomarkers for NPC, as well as a novel understanding of the mechanism underlying NPC metastasis and potential targets for future treatment

Impact of follow-up interval on patients with hepatocellular carcinoma after curative ablation

Abstract Background The optimal follow-up strategy after curative thermal ablation of hepatocellular carcinoma (HCC) remains unclear. Methods We retrospectively analyzed a prospective series of 616 patients who underwent curative thermal ablation for HCC within the Milan criteria. Multivariate Cox model was used to identify independent predictive factors for recurrence; accordingly, patients were stratified into 2 groups with different relapse risks: a low-risk group (solitary tumor ≤3 cm) and a high-risk group (multiple tumors ≤3 cm or solitary tumor between 3 and 5 cm). Then, patients were classified into short- (< 4 months) or long-interval (4–6 months) surveillance groups according to follow-up intensity within the first 2 years after ablation. The overall survival (OS) of patients were compared between short- and long-interval groups in low- or high-risk groups, as well as the stage of recurrent tumors and the proportion of patients who received curative-intent retreatments. Results In the low-risk group, 54 (83.0%) and 18 (72.0%) of patients exhibited early relapse at the Barcelona Clinic Liver Cancer (BCLC) 0/A stage in the short- and long-interval groups, respectively (P = 0.172); accordingly, 44 (77.2%) and 18 (81.8%) of patients received curative-intent retreatment (P = 0.086) after recurrence. Hence, 5-year OS was similar between short- and long-interval groups (80.4% vs. 77.5%, P = 0.400) in low-risk patients. However, in the high-risk group, patients with a short interval exhibited early relapse more frequently at the BCLC 0/A stage (83% vs. 72%, P = 0.028), with a trend showing that the corresponding proportion of patients who received curative-intent retreatment greater than that in the long-interval group (64.2% vs. 37.5%, P = 0.087). Moreover, the short-interval group showed better 5-year OS than the long-interval group in high-risk patients (69.9% vs. 42.7%, P = 0.020). Conclusions Compared to a short surveillance interval, a long surveillance interval does not reduce OS in low-risk patients; however, a long surveillance interval compromises OS in high-risk patients

Clinical features and outcome of multiple primary malignancies involving hepatocellular carcinoma: A long-term follow-up study

Abstract Background The prolonged survival of individuals diagnosed with cancer has led to an increase in the number of secondary primary malignancies. We undertook to perform a definitive study to characterize and predict prognosis of multiple primary malignancies (MPM) involving hepatocellular carcinoma (HCC), due to the scarcity of such reports. Methods Clinicopathological data were analyzed for 68 MPM patients involving HCC, with 35 (target group) underwent curative liver resection. Additional 140 HCC-alone patients with hepatectomy were selected randomly during the same period as the control group. Results Of the 68 patients with extrahepatic primary malignancies (EHPM), 22 were diagnosed synchronously with HCC, and 46 metachronously. The most frequent EHPM was nasophargeal carcinoma, followed by colorectal and lung cancer. Univariate analysis demonstrated that synchronous (P = 0.008) and non-radical treatment for EHPM (P P = 0.607, P = 0.131, respectively). Conclusions Curative treatment is an independent predictive factor for OS and HCC-specific OS, and should been taken into account both for synchronous and metachronous patients. MPM patients involving HCC should not be excluded from radical resection for HCC.</p

Long- versus short-interval follow-up after resection of hepatocellular carcinoma: a retrospective cohort study

Abstract Background Average postoperative follow-up intervals vary in patients undergoing hepatocellular carcinoma (HCC) resection because of limited evidence regarding the optimal interval. We aimed to compare the associations of long-versus short-interval follow-up with survival and recurrence in risk-stratified HCC patients. Methods We performed a retrospective cohort study between 2007 and 2014. In total, 1227 patients treated by curative resection of Barcelona Clinic Liver Cancer stage A or B HCC were stratified as having a low (n = 865) or high (n = 362) risk of early recurrence (within the first 2 years after resection) based on prognostic factors identified by the least absolute shrinkage and selection operation algorithm. Patients were further classified into long-interval (every 4–6 months) and short-interval (every 2–4 months) follow-up subgroups based on follow-up within 2 years after resection (low risk, long vs. short: n = 390 vs. n = 475; high-risk, long vs. short: n = 149 vs. n = 213). Results The short-interval follow-up did not prolong overall survival in either the low-risk (hazard ratio [HR] = 1.152; 95% confidence interval [CI] 0.720–1.843) or high-risk (HR = 1.213; 95% CI 0.702–2.094) patients. Early recurrence occurred in 401 patients. For high-risk patients, the short-interval follow-up subgroup exhibited smaller intrahepatic recurrence than did the long-interval group (2.6 vs. 3.5 cm, respectively, P = 0.045). However, no significant difference in the rate of Barcelona Clinic Liver Cancer stage 0/A recurrence was found between the long- and short-interval follow-up groups in either low- or high-risk patients (63.1% vs. 68.2%, respectively, P = 0.580; 31.3% vs. 41.5%, respectively, P = 0.280). The rate of curative intent treatment for recurrence (34.5% vs. 39.7%, respectively, P = 0.430; 14.6% vs. 20.3%, respectively, P = 0.388) was also similar between the follow-up groups for low- and high-risk patients. Conclusions Shortening the postoperative follow-up interval from every 4–6 months to every 2–4 months within the first 2 years after resection did not increase the rate of curative intent treatment or prolong the overall survival of patients with Barcelona Clinic Liver Cancer stage A or B HCC

Controllable Formation of Monodisperse Polymer Microbubbles as Ultrasound Contrast Agents

Microbubbles have been widely used as ultrasound contrast agents in clinical diagnosis and hold great potential for ultrasound-mediated therapy. However, polydispersed population and short half-life time (<10 min) of the microbubbles still limit their applications in imaging and therapy. To tackle these problems, we develop a microfluidic flow-focusing approach to produce monodisperse microbubbles stabilized by Poly­(lactic-co-glycolic acid) (PLGA) as the polymer shell. The size of PLGA microbubbles can be tightly controlled from ∼600 nm to ∼7 μm with a coefficient of variation less than 4% in size distribution for ensuring highly homogeneous echogenic behavior of PLGA polymer microbubbles in ultrasound fields. Both in vitro and in vivo experiments showed that the monodisperse PLGA microbubbles had excellent echogenicity and elongated sonographic duration time (>3 times) for ultrasound imaging in comparison with the commercial lipid microbubbles