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Sequence polymorphisms in the coding region of Toll-like receptor 6 gene were investigated in Chinese Cantonese population. By amplifying and sequencing a 2787 bp segment containing the entire coding region of TLR6 gene of 191 individuals in Chinese Cantonese population, a total of seven single nucleotide polymorphisms (SNP) along with their frequencies were detected. Comparing these data with SNP published in dbSNP database of National Center for Biotechnology Information (NCBI), two SNP (+176T/C and +1408G/T) were firstly reported, and five SNP caused amino-acid substitution. Sixteen haplotypes and their distributions were reconstructed. Linkage disequilibrium analysis and neutrality test were also performed. Comparing with other ethnic populations, Chinese Cantonese displayed obvious differences in TLR6 polymorphism. It may in part reflect the ethnic diversity of pathogen susceptibility and facilitate to develop the disease-association studies as well as population genetics and evolutionary research. [ABSTRACT FROM AUTHOR]

Image watermarking has become a popular technique for authentication and copyright protection. However, many proposed image watermarking techniques are sensitive to affine transforms, such as rotation, scaling and translation. Here, a local affine transform invariant watermarking is designed and tested against attacks performed by Stirmark using the Krawtchouk moment invariants. Watermark is inserted into the perceptually significant Krawtchouk moment invariants of the original image, and watermarking based on Krawtchouk moment invariants are local, that is, the embedded watermark affects only a selected portion of the original image, the position of which can be decided by the user. This, in effect, permits the watermark to be embedded at the portion of the image which is most significant information-wise. This also means that the watermark is especially robust to cropping. Independent component analysis (ICA) is utilised by detector to extract the perfect watermark blindly. The computational aspects of the proposed watermarking are also discussed in detail. Experimental results have demonstrated that the proposed watermarking technique has a good robustness against other attacks performed by Stirmark including affine transform, cropping, filtering, image compression and random geometric distortions. It is indicated that the proposed watermarking has superior advantages over the existing ones in many aspects. [ABSTRACT FROM AUTHOR]

Background: Anemia significantly contributes to the global disease burden, with its incidence potentially influenced by the trace metal content within the body., Objective: This study aims to examine the associations between trace metals and anemia risk, with a particular focus on investigating the potential mediating roles of iron status and inflammation in these associations., Methods: Five trace metals (Ni, Co, Mn, Se, and Mo) were examined in 1274 US adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. The individual and combined effects of these metals on anemia were assessed using logistic regression, quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR). A sex-stratified analysis was conducted to discern any gender-specific susceptibilities. Additionally, mediation analysis was employed to explore the potential mediating roles of iron status and inflammation in the associations between these metals and anemia., Results: Increased risks of anemia were positively associated with Co and Ni levels but negatively correlated with Se and Mn levels (all with p < 0.05). The trace metal mixture was negatively associated with anemia, with the highest weights of Co and Se in different directions in both the QGC and BKMR models. In the sex-specific analysis, we observed less pronounced protective effects from trace metals in females. Moreover, the mediating proportion of the iron status and inflammation in these relationships ranged from 10.29% to 58.18%., Conclusion: Our findings suggest that the trace element mixture was associated with decreased anemia risk, among which Se was a protective factor while Co was a risk factor, and females were more susceptible. The effects of these trace metals on anemia may be mediated by the iron status and inflammation.

The cancer treatment landscape has changed dramatically since the turn of the century, resulting in substantial improvements in outcomes for patients. This Review summarizes trends in the approval of oncology therapeutic products by the United States Food and Drug Administration (FDA) from January 2000 to October 2022, based on a categorization of these products by their mechanism of action and primary target. Notably, the rate of oncology indication approvals has increased in this time, driven by approvals for targeted therapies, as has the rate of introduction of new therapeutic approaches. Kinase inhibitors are the dominant product class by number of approved products and indications, yet immune checkpoint inhibitors have the second most approvals despite not entering the market until 2011. Other trends include a slight increase in the share of approvals for biomarker-defined populations and the emergence of tumour-site-agnostic approvals. Finally, we consider the implications of the trends for the future of oncology therapeutic product development, including the impact of novel therapeutic approaches and technologies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: This study examined changes in product-related injury morbidity among under-20 Americans between 2001 and 2020., Method: Product-related injury morbidity data came from the National Electronic Injury Surveillance System (NEISS). Using age-standardized morbidity rates, the authors performed Joinpoint regression models to identify time periods with significant changes between 2001 and 2020 and quantified the annual magnitude of morbidity changes with annual percent changes (APCs) in rates and 95 % confidence intervals (CIs)., Results: Age-standardized product-related injury morbidity declined consistently among under-20 Americans from 2001 to 2020 (from 7449.3 to 4023.5 per 100,000 persons; APC = -1.5 %, 95 % CI: -2.3 %, -0.7 %), with the most striking morbidity drop in 2019-2020 (-1576.8 per 100,000 persons). Sports and recreation equipment and home were the most common product and location, respectively, for nonfatal pediatric product-related injuries. Large morbidity differences and varying spectrum by product and by occurring location existed across sex and age groups., Conclusions: Product-related injury morbidity declined significantly among under-20 Americans between 2001 and 2020, but large variations remained across sex and age groups., Practical Applications: Further research is recommended to understand causal factors contributing to the observed decrease in product-related injury morbidity over the past 20 years and to understand product-related injury morbidity disparities across sex and age groups. Understanding of causal factors could lead to implementation of additional interventions to reduce product-related injury among children and adolescents., (Published by Elsevier Ltd.)

Background: Age-related macular degeneration (AMD) has been the leading cause of irreversible blindness in industrialized countries. Emerging data suggest that serum vitamin D levels may be associated with AMD but show mixed results. National-level population data on the relationship between vitamin D and AMD severities are still lacking., Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2008. Retinal photographs were taken and graded for AMD stage. The odds ratio (OR) of AMD and its subtype was calculated after adjusting for confounding factors. Restricted cubic spline (RCS) analyses were used to explore potential non-linear relations., Results: A total of 5041 participants with a mean age of 59.6 years were included. After adjusting for covariates, participants with higher level of serum 25-hydroxyvitamin D [25(OH)D] had significantly greater odds of early AMD (OR, 1.65; 95% CI, 1.08-2.51) and decreased risk of late AMD (OR, 0.29; 95% CI, 0.09-0.88). When stratified by age, a positive association between the level of serum 25(OH)D and early AMD was present in the <60 years group (OR, 2.79; 95% CI, 1.08-7.29), whereas a negative relation between the level of serum 25(OH)D and late AMD was detected in the ≥60 years group (OR, 0.24; 95% CI, 0.08-0.76)., Conclusions: A higher level of serum 25(OH)D was related to increased risk of early AMD in those <60 years and decreased risk of late AMD in those ≥60 years.

Sarcopenia is age-related, pathophysiological muscle atrophy. Research regarding nutrition treatment of sarcopenia has developed rapidly, particularly as populations age. We evaluated the development of trends in this field using a bibliometric analysis. Articles up to July 2022 were searched in the Scopus database. Bibliographic information from the selected publications, such as countries, citations, world maps, institutions, authors, journals, and keywords, were converted and analyzed automatically using the "bibliometrix" package in R environment (version 4.2.0). We identified 368 Scopus articles from 1998-2021. According to citation analyses, 27 documents received more than 100 citations. Bibliometric analysis based on the literature included in this study revealed that South Korea (61 publications), United States (50), Japan (35), China (30), and Italy (20) contributed the most publications. Tehran University of Medical Science (19 records, 2.55% of articles) contributed the most publications. The most productive author was Landi, with eight articles (2.17% of articles). The publications were located in 196 journals, with Nutrients having the most publications (30, 8.15% of articles). The curves representing keywords "sarcopenia" and "aged" were the most apparent. Our analysis suggested that global nutrition and sarcopenia-related research increased rapidly from 2001 to 2021, demonstrating that this was a promising area of future research that could benefit from continued advances. Future research may focus on the effects of age and sex as well as intervention effectiveness, particularly exercise and nutrition supplementation.

Introduction: Osteonecrosis of the femoral head (ONFH) is a progressive and disabling disease with severe socioeconomic burdens. In the last 30 years, a growing number of publications have reported significant advances in understanding ONFH. However, only a few studies have clarified its global trends and current status. Thus, the purpose of our study was to summarize the global trends and current status in ONFH through bibliometrics., Materials and Methods: Publications related to ONFH from 1991 to 2020 were searched from the Web of Science (WOS) core collection database. The data were analyzed with bibliometric methods. Microsoft Excel was used for statistical analysis and to draw bar charts. SPSS was applied to perform linear regression analysis. VOSviewer was used to conduct bibliographic coupling analysis, co-authorship analysis, co-citation analysis and co-occurrence analysis., Results: A total of 5,523 publications were covered. The United States consistently ranked first in total publications, sum of times cited, average citations per item and H-index. Kyushu University was the main contributor to ONFH. Clinical Orthopaedics and Related Research was the major publishing channels for ONFH-related articles. Takuaki Yamamoto published the most ONFH-related articles. Studies regarding ONFH could be divided into five clusters: 1) mechanism study, 2) treatment study, 3) complication study, 4) radiological study and 5) etiological study. Mechanism study might become a hot spot in the future., Conclusions: The total number of publications in ONFH has generally increased over the last three decades. The United States was the leading country in ONFH research. Transplantation, engineering, cell and molecular biology, pharmacology and endocrinology have gradually increased and become hot topics in ONFH research. Mechanism study in ONFH including mesenchymal stem cells, apoptosis, oxidative stress, adipogenesis, osteogenic differentiation and endothelial progenitor cells, have attracted more attention and will become a hot spot in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wen, Li, Cai, Fan, Wang, Ding, Huang and Xiao.)

Drug labeling informs physicians and patients on the safe and effective use of medication. However, recent studies suggested discrepancies in labeling of the same drug between different regulatory agencies. Here, we evaluated the hepatic safety information in labeling for 549 medications approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Limited discrepancies were found regarding risk for hepatic adverse drug reactions (ADRs) (8.7% in hepatic ADR warnings and 21.3% in contraindication for liver disease), while caution should be exercised over drugs with inconsistencies in contraindications for liver disease and evidence for hepatotoxicity (4.9%). Most discrepancies were attributable to less-severe hepatic events and low-frequency hepatic ADR reports and had limited implication on clinical outcomes., Competing Interests: Competing interests The authors have no conflicts to disclose., (Published by Elsevier Ltd.)

Background: Over the past decades, lots of advance have occurred in the prevention, diagnosis, and treatment of head and neck cancer (HNC). However, the contemporaneous incidence and survival trends, on the basis of population-based registry, have not been reported., Methods: The HNC cancer cases were accessed from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence trend was analyzed by joinpoint analysis, with the survival trend being analyzed by period analysis of relative survival rate (RSR) and Kaplan-Meier analyses. Cox regression analysis was performed to identify the prognostic factors for overall survival., Results: The general incidence trend of HNC increases slightly, with an average annual percentage change of 0.6%, along with five fluctuating segments. The improvement of net survival over the past decades was showed by increasing 60-month RSR, from 54.1% to 56.0% to 60.9% to 66.8%, which was further confirmed by Kaplan-Meier analyses. Moreover, disparities in incidence and survival patterns can be observed in different subgroups., Conclusion: A fluctuating incidence pattern and an ever-improving survival were observed in HNC over time., Competing Interests: The authors declare no competing financial interests., (Copyright © 2021 Kangwen Guo et al.)

Brain tumors, a group of heterogeneous diseases, are the second most common cancer and the leading cause of cancer-related deaths in children. Insight into the prognosis of pediatric brain tumor survival has led to improved outcomes and could be further advanced through precision in prognosis. We analyzed the United States SEER population-based dataset of 15,723 pediatric brain tumor patients diagnosed and followed between 1975 and 2016 using a stratified Cox proportional hazards model. Mortality risk declined with increased age at diagnosis, the adjusted hazard ratio (aHR) (95 % confidence interval) was 0.60 (0.55, 0.67) and 0.47 (0.42, 0.52) for ages at diagnosis 1-10 years and 10-19 years, respectively, when compared with infants. Non-Hispanic Caucasian patients showed a lower risk of mortality than non-Hispanic African Americans (1.21 (1.11, 1.32)) and Hispanics (1.21 (1.11, 1.32)). Primary tumor sites, grades, and histology showed substantial heterogeneity in mortality risk. Brainstem (2.62 (2.41, 2.85)) and Cerebrum (1.63 (1.46, 1.81)) had an elevated risk of mortality than lobes. Similarly, Grade II (1.32 (1.07, 1.62)), Grade III (3.39 (2.74, 4.19)), and Grade IV (2.18 (1.80, 2.64)) showed an inflated risk of mortality than Grade I. Compared to low-grade glioma, high-grade glioma (7.92 (7.09, 8.85)), Primitive neuroectodermal tumors (4.72 (4.15, 5.37)), Medulloblastoma (3.11 (2.79, 3.47)), and Ependymal-tumors (2.20 (1.95, 2.48)) had increased risk of mortality. County-level poverty and geographic region showed substantial variation in survival. This large population-based comprehensive study confirmed identified prognostic factors of pediatric brain tumor survival and provided estimates as epidemiologic evidence with greater generalization., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Microbial infections have significantly increased over the last decades, and the mortality rates remain unacceptably high. The emergence of new resistance patterns and the spread of new viruses challenge the eradication of infectious diseases. The declining efficacy of antimicrobial drugs has become a global public health problem. Natural products derived from natural sources, such as plants, animals, and microorganisms, have significant efficacy for the treatment of infectious diseases accompanied by less adverse effects, synergy, and ability to overcome drug resistance. As the Chinese female scientist Youyou Tu received the Nobel Prize for the antimalarial drug artemisinin, antimicrobial drugs developed from Traditional Chinese Medicine are expected to receive increasing attention again. This review summarizes the antimicrobial agents derived from natural products approved for nearly 20 years and describes their efficacy and mode of action. The aim of this unit is to review the current status of antimicrobial drugs from natural products in order to increase the value of natural products as a source of novel drug candidates for infectious diseases., Competing Interests: Declaration of Competing Interest The authors declare that no conflict of interest exists., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Sudden cardiac arrest survivors are a special group of patients, often with unique and complex needs that are not adequately addressed by current treatments. In May 2020, the American Heart Association (AHA) developed a scientific statement on sudden cardiac arrest survivorship based on relevant research developments, which emphasized the importance of a unified patient-centered assessment and resources. This article attempts to interpret the key content of the scientific statement, hoping to provide reference and help for domestic medical staff to understand and apply it.

Objective: To explored the progress of intensive care unit (ICU) delirium between 2010 and 2020 based on knowledge visualization analysis., Methods: The literatures related to ICU delirium included in Web of Sciences (WOS) and China National Knowledge Infrastructure (CNKI) databases from 2010 to 2020 were collected. A bibliometric analysis was performed. The growth trend was showed by Excel 2019 software. The information about country, institution and author were extracted by VOSviewer 1.6.15 for generating cooperative network, to find the main research power and each cooperative relation. At the same time, Citespace 5.0.R1 was used to analyze those high frequency keywords and bursting keywords and build the map of co-citation reference, in order to explore the evolution of research in the field of ICU delirium and the hotspots about this field in recent 10 years., Results: A total of 1 102 Chinese journal articles and 2 422 English "Articles" or "Reviews" from 2010 to 2020 were collected preliminarily, and the number of published literatures increased steadily. In the respect of quality, the impact factors of most articles were concentrated between 2 and 3, and the literatures with impact factor over 5 accounted for 27.9% (337/1 209). According to the knowledge visualization analysis, the United States published most of the related articles (total 1 152) in this field, while the England and Canada ranked second and third respectively, totaling 220 and 204. In terms of the distribution of research institutions, the Vanderbilt University School of Medicine was not only far ahead in the number of publication (n = 149), but more importantly, top three high-impact authors located in this institution. The amount of domestic publications was lower than developed countries, however, the burst index, which reflected the sudden increase, ranked first (7.09), suggesting that the interest and investment of Chinese researchers was increasing recently. The most productive institution in China was Capital Medical University School of Nursing with totaling 23 articles. Wu Ying, who published most Chinese papers (n = 14), belongs to this institution. However, it was a pity that there was no large scientific community be constructed in China, and the cooperation between institutions was deficient. By generating the co-occuring keyword mapping, the research hotpots mainly focused on the prevention, treatment and prevention of delirium in mechanically ventilated patients, the effect of dexmedetomidine and exploring the risk factor of ICU delirium. Finally, the results of co-citation reference analysis showed that Cluster 4 (risk assessment) was still in the process of development, in hence it was the frontier in this domain., Conclusions: There was a big gap between China and leading countries in the field of ICU delirium research. The main research power was located in the United States, and the trending of future studies mainly focus on delirium-related risk assessment.

Objective: To investigate the people's cardiopulmonary resuscitation (CPR) ability in Hunan Province and whether there are differences in the skill level of CPR among respondents of different ages and education levels., Methods: A self-made questionnaire was conducted to survey people in Hunan Province by means of WeChat from May 2018 to April 2019. The questionnaire referred to 2016 National consensus on cardiopulmonary resuscitation in China issued by Cardiopulmonary Resuscitation Specialized Committee of Chinese Research Hospital Association and 2017 version of American Heart Association (AHA) CPR operational guide, and combined with the CPR assessment scale of Hunan Provincial People's Hospital. The contents of the survey included the basic information of the subjects, the common knowledge and skills of first aid, the willingness to learn CPR skills and implement CPR, and the operational requirements of high quality CPR, etc., Results: A total of 6 563 people received the on-site first aid knowledge questionnaire, and 4 355 people completed and submitted the questionnaire. The recovery rate was 66.36%, of which 3 602 valid questionnaires were from IP in Hunan Province, and the qualified rate was 82.71%. Among the subjects, 1 532 were men (42.53%) and 2 070 were women (57.47%). The majority aged group from 19 to 30 (59.41%) and from 31 to 50 (36.70%). 307 were rural (8.52%) and 3 295 were urban (91.48%); and the majority levels of education were senior or technical secondary school (38.26%) and undergraduate or junior college (44.50%). Of the 3 602 respondents, 39.09% indicated that they had been exposed to CPR knowledge and only 0.36% indicated that they did not wish to participate in CPR training. 69.93% of the respondents said they would actively to help if they wet cardic arrest, and 97.92% of those were willing to do so if the patients were relatives or friends. The survey results showed that only 8.91% of respondents chose relatively high-quality CPR options (chest compressions were performed first, the pressing point was located in the sternum of the midpoint of bilateral nipple line, the pressing frequency was 100-120 times/min, pressing depth was 5-6 cm, the ratio of chest compression to artificial ventilation was 30:2). Among these people, the correct rate was higher in the ages of 31-50 years old and ≤ 18, 19-30 than those ≥ 51 years old (12.71% vs. 0%, 6.87%, 8.70%, χ 2 = 41.420, P < 0.01). The correct rate of education at graduate level and above was higher than those in junior middle school and below, high school or technical secondary school, undergraduate or junior college (19.57% vs. 2.07%, 3.41%, 13.72%, χ 2 = 152.262, P < 0.01)., Conclusions: The public in Hunan Province have a strong sense of first aid, and some of the theoretical knowledge of CPR. People between 31 years old and 50 years old of age and with graduate education and above know more about CPR, but the overall mastery of CPR skills is poor. It is necessary to further improve the ability of the public as the first witness by teaching various skills of CPR in various forms.

Background: The incidence of oropharynx cancers has increased substantially in the United States. However, risk stratification tools for the identification of high-risk individuals do not exist. In this study, an individualized risk prediction model was developed and validated for oropharynx cancers in the US population., Methods: A synthetic, US population-based case-control study was conducted. Oropharynx cancer cases diagnosed at Ohio State University (n = 241) were propensity-weighted to represent oropharynx cancers occurring annually in the United States during 2009-2014 (n = 12,656). Controls (n = 9327) included participants in the National Health and Nutrition Examination Survey (2009-2014) and represented the annual US population aged 30 to 69 years (n = 154,532,508). The individualized 1-year absolute risk of oropharynx cancer was estimated with weighted logistic regression., Results: The risk prediction model included age, sex, race, smoking, alcohol use, lifetime sexual partners, and oral oncogenic human papillomavirus (HPV) status. The model had good discrimination and calibration in split-sample validation (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.92-0.97; observed/expected [O/E], 1.01; 95% CI, 0.70-1.32) and external validation (AUC, 0.87; 95% CI, 0.84-0.90; O/E, 1.08; 95% CI, 0.77-1.39). In the US population, 1-year predicted risks of oropharynx cancer were highest for older individuals (21.1/100,000 for 65- to 69-year-olds), men (13.9/100,000), whites (10.4/100,000), smokers (18.0/100,000 for >20 pack-years), heavy alcohol users (18.4/100,000), and those with prevalent oral oncogenic HPV (140.4/100,000). The risk prediction model provided substantial risk stratification, with approximately 77% of all oropharynx cancers and approximately 99% of HPV-positive oropharynx cancers occurring in the 10% of the US population with the highest model-predicted risk., Conclusions: This risk prediction model will enable the efficient design of studies to address the outstanding questions pertaining to the natural history, screening, and secondary prevention of oropharynx cancers., (© 2019 American Cancer Society.)

The treatment regimens for acute promyelocytic leukemia (APL) dramatically changed over time. However, its survival trend, based on a large sample size has not been reported. Patients diagnosed with APL were accessed from the Surveillance, Epidemiology, and End Results database. Their incidence and survival trend were evaluated in overall and subgroup levels. The overall incidence of APL increased with an annual percentage change of 5.5% from 1992 to 2006 and remained stable thereafter. In addition, the 5-year relative survival rates of APL improved significantly, from 12.3 to 32.2% to 59.5 to 72.1% over past four decades ( p  < .0001), sharing similar trend with different subgroups. Importantly, survival disparities exist among races and different socioeconomic status groups, with superior survival in whites and patients in low-poverty regions. Increasing incidence urges for increased awareness of clinicians over diagnosis of APL. In addition, a wider insurance coverage may help balance survival gap.

Purpose The incidence of human papilloma virus (HPV)-positive oropharyngeal cancers has risen rapidly in recent decades among men in the United States. We investigated the US population-level effect of prophylactic HPV vaccination on the burden of oral HPV infection, the principal cause of HPV-positive oropharyngeal cancers. Methods We conducted a cross-sectional study of men and women 18 to 33 years of age (N = 2,627) within the National Health and Nutrition Examination Survey 2011 to 2014, a representative sample of the US population. Oral HPV infection with vaccine types 16, 18, 6, or 11 was compared by HPV vaccination status, as measured by self-reported receipt of at least one dose of the HPV vaccine. Analyses accounted for the complex sampling design and were adjusted for age, sex, and race. Statistical significance was assessed using a quasi-score test. Results Between 2011 and 2014, 18.3% of the US population 18 to 33 years of age reported receipt of at least one dose of the HPV vaccine before the age of 26 years (29.2% in women and 6.9% in men; P < .001). The prevalence of oral HPV16/18/6/11 infections was significantly reduced in vaccinated versus unvaccinated individuals (0.11% v 1.61%; P adj = .008), corresponding to an estimated 88.2% (95% CI, 5.7% to 98.5%) reduction in prevalence after model adjustment for age, sex, and race. Notably, the prevalence of oral HPV16/18/6/11 infections was significantly reduced in vaccinated versus unvaccinated men (0.0% v 2.13%; P adj = .007). Accounting for vaccine uptake, the population-level effect of HPV vaccination on the burden of oral HPV16/18/6/11 infections was 17.0% overall, 25.0% in women, and 6.9% in men. Conclusion HPV vaccination was associated with reduction in vaccine-type oral HPV prevalence among young US adults. However, because of low vaccine uptake, the population-level effect was modest overall and particularly low in men.

Background: Human papillomavirus (HPV) causes most oropharyngeal cancers in the United States. Oral HPV prevalence is associated with immunosuppression, and drug use can be immunosuppressive, but the epidemiology of oral HPV among people who use drugs is not well described., Methods: We enrolled men and women with a current or prior history of injection drug use in this cross-sectional sub-study within the AIDS Linked to the Intravenous Experience (ALIVE) cohort. We tested oral rinse samples for 37 types of HPV DNA and collected self-reported risk factor information. We compared oral HPV prevalence across categories using chi-squared statistics and multivariable logistic regression., Results: Among 199 subjects, 32% were HIV-positive (median CD4 count 384 cells/μL), 90% were Black, 56% had less than a high school education, 17% had recently used injection drugs, and the median age was 54 years. Most had performed oral sex (82%) but had fewer than 5 lifetime partners (58%). The prevalence of any oral HPV was 29%, and of any oncogenic oral HPV was 13%. Oral HPV prevalence was high among both heterosexual men (30%) and women (20%). After adjustment, odds of oral HPV were increased among HIV-positive individuals with a low CD4 count (<350 cells/μl, aOR = 2.7, 95%CI = 1.2-6.4, vs. HIV-negative individuals), but not among HIV-positive individuals with a higher CD4 cell count. Odds were also elevated for those who had recently performed oral sex on a woman (aOR = 2.2, 95%CI = 1.01-4.6) and, even after this adjustment, among bisexual/lesbian females (aOR = 5.6, 95%CI = 1.4-23, vs. heterosexual females). Oral HPV prevalence was not associated with vaginal sex, performing oral sex on a man, or recent drug use., Conclusions: Recent drug use was not associated with oral HPV prevalence in our study. However, despite modest numbers of sexual partners, the prevalence of oral HPV among this largely Black population with lower socioeconomic status was high.

Importance: Human papillomavirus-related oropharyngeal carcinoma (HPV-OPC) is increasing in incidence in the United States. Although HPV-OPC has favorable prognosis, 10% to 25% of HPV-OPCs recur. Detection of human papillomavirus (HPV) DNA in oral rinses is associated with HPV-OPC, but its potential as a prognostic biomarker is unclear., Objective: To determine whether HPV DNA detection in oral rinses after treatment for HPV-OPC is associated with recurrence and survival., Design, Setting, and Participants: Prospective cohort study of patients with incident HPV-OPC diagnosed from 2009 to 2013 at 4 academic tertiary referral cancer centers in the United States. Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis), and evaluated for HPV DNA. Among an initial cohort of 157 participants with incident HPV-OPC treated with curative intent, 124 had 1 or more posttreatment oral rinses available and were included in this study., Main Outcomes and Measures: Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the association of HPV DNA detection in oral rinses with survival was evaluated using Cox regression analysis., Results: Oral HPV type 16 (HPV16) DNA was common at diagnosis (67 of 124 participants [54%]). In contrast, oral HPV16 DNA was detected in only 6 participants after treatment (5%), including 5 with HPV16 DNA also detected at diagnosis (persistent oral HPV16 DNA). Two-year DFS and OS were 92% (95% CI, 94%-100%) and 98% (95% CI, 93%-99%). Persistent oral HPV16 DNA was associated with worse DFS (hazard ratio, 29.7 [95% CI, 9.0-98.2]) and OS (hazard ratio, 23.5 [95% CI, 4.7-116.9]). All 5 participants with persistent oral HPV16 DNA developed recurrent disease, 3 with local disease involvement. In contrast, just 9 of 119 participants (8%) without persistent oral HPV16 DNA developed recurrent disease, only 1 (11%) with local disease involvement. Median (range) time from earliest posttreatment oral HPV16 DNA detection to recurrence was 7.0 (3.7-10.9) months., Conclusions and Relevance: Human papillomavirus type 16 DNA in oral rinses is common at diagnosis but rare after treatment for HPV-OPC. Our data suggest that, although infrequent, persistent HPV16 DNA in posttreatment oral rinses is associated with poor prognosis and is a potential tool for long-term tumor surveillance, perhaps more so for local recurrence.

The incidence of human papillomavirus (HPV)-positive oropharyngeal cancers is higher and increasing more rapidly among men than women in the United States for unknown reasons. We compared the epidemiology of oral oncogenic HPV infection between men and women ages 14 to 69 years (N = 9,480) within the U.S. National Health and Nutritional Examination Surveys (NHANES) 2009-2012. HPV presence was detected in oral DNA by PCR. Analyses were stratified by gender and used NHANES sample weights. Oral oncogenic HPV prevalence was higher among men than women (6.6% vs. 1.5%, P < 0.001), corresponding to 7.07 million men versus 1.54 million women with prevalent infection at any point in time during 2009-2012. Prevalence increased significantly with age, current smoking, and lifetime number of sexual partners for both genders (adjusted Ptrend < 0.02). However, men had more partners than women (mean = 18 vs. 7, P < 0.001). Although oncogenic HPV prevalence was similar for men and women with 0 to 1 lifetime partners, the male-female difference in prevalence significantly increased with number of lifetime partners (adjusted prevalence differences for none, 1, 2-5, 6-10, 11-20, and 20+ partners = 1.0%, 0.5%, 3.0%, 5.7%, 4.6%, and 9.3%, respectively). Importantly, the per-sexual partner increase in prevalence was significantly stronger among men than among women (adjusted synergy index = 3.3; 95% confidence interval, 1.1-9.7), and this increase plateaued at 25 lifetime partners among men versus 10 partners among women. Our data suggest that the higher burden of oral oncogenic HPV infections and HPV-positive oropharyngeal cancers among men than women arises in part from higher number of lifetime sexual partners and stronger associations with sexual behaviors among men., (©2015 American Association for Cancer Research.)

We investigated the association of demographic and behavioral factors with oral human papillomavirus (HPV) load for 18 high-risk types among 211 individuals with prevalent high-risk HPV within the National Health and Nutrition Examination Survey 2009-2010. Factors independently associated with HPV load above the median included older age (odds ratio, 1.04 per year increase [95% confidence interval, 1.01-1.07]; P = .004) and intensity of current smoking (P for trend <.001). A marginally greater percentage of men than women had an HPV load above the median (55.7% vs 32.8%; P = .069), and HPV load increased marginally with increasing alcohol use (P for trend = .062). In conclusion, older age and current smoking are associated with a high oral load of high-risk HPV types among individuals with a prevalent infection., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The primary objective of this study was to clarify the influence of crop plants on atmospheric methane (CH4) in an agriculture-dominated landscape in the Upper Midwest of the United States. Measurements were carried out at two contrasting scales. At the plant scale, CH4 fluxes from soybean and corn plants were measured with a laser-based plant chamber system. At the landscape scale, the land surface flux was estimated with a modified Bowen ratio technique using measurements made on a tall tower. The chamber data revealed a diurnal pattern for the plant CH4 flux: it was positive (an emission rate of 0.4±0.1 nmol m(-2) s(-1), average of soybean and corn, in reference to the unit ground area) during the day, and negative (an uptake rate of -0.8±0.8 nmol m(-2) s(-1)) during the night. At the landscape scale, the flux was estimated to be 14.8 nmol m(-2) s(-1) at night and highly uncertain during the day, but the available references and the flux estimates from the equilibrium methods suggested that the CH4 flux during the entire observation period was similar to the estimated nighttime flux. Thus, soybean and corn plants have a negligible role in the landscape-scale CH4 budget.

Objective: To determine and compare outcomes with accepted benchmarks in burn care at 6 academic burn centers., Background: Since the 1960s, US morbidity and mortality rates have declined tremendously for burn patients, likely related to improvements in surgical and critical care treatment. We describe the baseline patient characteristics and well-defined outcomes for major burn injuries., Methods: We followed 300 adults and 241 children from 2003 to 2009 through hospitalization, using standard operating procedures developed at study onset. We created an extensive database on patient and injury characteristics, anatomic and physiological derangement, clinical treatment, and outcomes. These data were compared with existing benchmarks in burn care., Results: Study patients were critically injured, as demonstrated by mean % total body surface area (TBSA) (41.2 ± 18.3 for adults and 57.8 ± 18.2 for children) and presence of inhalation injury in 38% of the adults and 54.8% of the children. Mortality in adults was 14.1% for those younger than 55 years and 38.5% for those aged 55 years and older. Mortality in patients younger than 17 years was 7.9%. Overall, the multiple organ failure rate was 27%. When controlling for age and % TBSA, presence of inhalation injury continues to be significant., Conclusions: This study provides the current benchmark for major burn patients. Mortality rates, notwithstanding significant % TBSA and presence of inhalation injury, have significantly declined compared with previous benchmarks. Modern day surgical and medically intensive management has markedly improved to the point where we can expect patients younger than 55 years with severe burn injuries and inhalation injury to survive these devastating conditions.

Tumor human papillomavirus (HPV) status is a prognostic factor for oropharyngeal cancer, but classification methods are not standardized. Here we validate the HPV classification methods used in US cooperative group trials. Tumor DNA and RNA purified from 240 paraffin-embedded oropharyngeal cancers diagnosed from 2000 to 2009 were scored as evaluable if positive for DNA and mRNA controls by quantitative polymerase chain reaction (PCR). Eighteen high-risk (HR) HPV types were detected in tumors by consensus PCR, followed by HR-HPV E6/7 oncogene expression analysis by quantitative reverse transcriptase PCR. The sensitivity (S), specificity (SP), and positive (PPV) and negative predictive values (NPV) of p16 expression detected by immunohistochemistry (IHC) and HPV16 detected by in situ hybridization (ISH) were evaluated in comparison with HR-HPV E6/7 oncogene expression. Interrater agreement among 3 pathologists was evaluated by κ statistics. Of 235 evaluable tumors, 158 (67%; 95% confidence interval, 61.2-73.3) were positive for HR-HPV E6/7 oncogene expression [HPV type 16 (92%), 18 (3%), 33 (3%), 35 (1%), or 58 (1%)]. p16 IHC had high sensitivity (S 96.8%, SP 83.8%, PPV 92.7%, and NPV 92.5%), whereas HPV16 ISH had high specificity (S 88.0%, SP 94.7%, PPV 97.2%, and NPV 78.9%) for HR-HPV oncogene expression. Interrater agreement was excellent for p16 (κ=0.95 to 0.98) and HPV16 ISH (κ=0.83 to 0.91). Receiver operating curve analysis determined the cross-product of p16 intensity score and percentage of tumor staining to optimally discriminate HR-HPV E6/7-positive and HR-HPV E6/7-negative tumors. p16 IHC and HPV16 ISH assays show excellent performance, with high sensitivity and specificity, respectively. A new validated H-score for p16 IHC assessment is proposed. Appropriate assay choice depends on clinical implications of a false-positive or false-negative test.

Context: Human papillomavirus (HPV) infection is the principal cause of a distinct form of oropharyngeal squamous cell carcinoma that is increasing in incidence among men in the United States. However, little is known about the epidemiology of oral HPV infection., Objective: To determine the prevalence of oral HPV infection in the United States., Design, Setting, and Participants: A cross-sectional study was conducted as part of the National Health and Nutrition Examination Survey (NHANES) 2009-2010, a statistically representative sample of the civilian noninstitutionalized US population. Men and women aged 14 to 69 years examined at mobile examination centers were eligible. Participants (N = 5579) provided a 30-second oral rinse and gargle with mouthwash. For detection of HPV types, DNA purified from oral exfoliated cells was evaluated by polymerase chain reaction and type-specific hybridization. Demographic and behavioral data were obtained by standardized interview. Statistical analyses used NHANES sample weights to provide weighted prevalence estimates for the US population., Main Outcome Measures: Prevalence of oral HPV infection., Results: The prevalence of oral HPV infection among men and women aged 14 to 69 years was 6.9% (95% CI, 5.7%-8.3%) and of HPV type 16 was 1.0% (95% CI, 0.7%-1.3%). Oral HPV infection followed a bimodal pattern with respect to age, with peak prevalence among individuals aged 30 to 34 years (7.3%; 95% CI, 4.6%-11.4%) and 60 to 64 years (11.4%; 95% CI, 8.5%-15.1%). Men had a significantly higher prevalence than women for any oral HPV infection (10.1% [95% CI, 8.3%-12.3%] vs 3.6% [95% CI, 2.6%-5.0%], P < .001; unadjusted prevalence ratio [PR], 2.80 [95% CI, 2.02-3.88]). Infection was less common among those without vs those with a history of any type of sexual contact (0.9% [95% CI, 0.4%-1.8%] vs 7.5% [95% CI, 6.1%-9.1%], P < .001; PR, 8.69 [95% CI, 3.91-19.31]) and increased with number of sexual partners (P < .001 for trend) and cigarettes smoked per day (P < .001 for trend). Associations with age, sex, number of sexual partners, and current number of cigarettes smoked per day were independently associated with oral HPV infection in multivariable models., Conclusion: Among men and women aged 14 to 69 years in the United States, the overall prevalence of oral HPV infection was 6.9%, and the prevalence was higher among men than among women.

Purpose: Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking., Patients and Methods: HPV status was determined for all 271 oropharyngeal cancers (1984-2004) collected by the three population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression. Trends in HPV prevalence across four calendar periods were estimated by using logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonrandom selection and to calculate incidence trends. Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses., Results: HPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay (P trend < .05). For example, HPV prevalence by Inno-LiPA increased from 16.3% during 1984 to 1989 to 71.7% during 2000 to 2004. Median survival was significantly longer for HPV-positive than for HPV-negative patients (131 v 20 months; log-rank P < .001; adjusted hazard ratio, 0.31; 95% CI, 0.21 to 0.46). Survival significantly increased across calendar periods for HPV-positive (P = .003) but not for HPV-negative patients (P = .18). Population-level incidence of HPV-positive oropharyngeal cancers increased by 225% (95% CI, 208% to 242%) from 1988 to 2004 (from 0.8 per 100,000 to 2.6 per 100,000), and incidence for HPV-negative cancers declined by 50% (95% CI, 47% to 53%; from 2.0 per 100,000 to 1.0 per 100,000). If recent incidence trends continue, the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020., Conclusion: Increases in the population-level incidence and survival of oropharyngeal cancers in the United States since 1984 are caused by HPV infection.