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Foodborne diseases are a global public health issue, with their causes often originating from lapses in food production or transportation leading to food contamination. Therefore, food packaging plays a crucial role in preserving the safety and quality of food. In pursuit of sustainable development, this study aims to utilize agricultural waste-derived functional mesoporous silica nanoparticles in combination with biodegradable molecules to create food packaging films. Through recycling and the use of environmentally friendly green films, the goal is to achieve sustainability and the objectives of green chemistry. The study anticipates the production of biodegradable films and the testing of their antibacterial capabilities, antioxidant properties, biocompatibility, and film stress coefficients. This research will provide robust support for advancing green packaging technology to address the challenges of global food safety and environmental sustainability. The experiment is divided into two parts. The first part involves the synthesis of multifunctional mesoporous silica nanoparticles with antibacterial properties derived from rice husk (Rice husk mesoporous silica nanoparticles, rMSN) as nano-fillers. These nanoparticles are surface modified with a biodegradable polymer, chitosan (Chi), that interacts with the material. Natural extract curcumin (Cur), known for its antioxidant capabilities, is loaded into the pores, and the material's inherent antibacterial properties are utilized. The second part involves blending the material with the natural polymer sodium alginate (SA) to form a film (rMSN-Chi@Cur/Alg film). The film's thickness, stress strength, antibacterial, and antioxidant capabilities are tested to ensure the material possesses antibacterial and antioxidant properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Motor competence (MC) is a key component reflecting one's ability to execute motor tasks and is an important predictor of physical fitness. For adolescents, understanding the factors affecting MC is pertinent to their development of more sophisticated sporting skills. Previous studies considered the influence of poor proprioceptive ability on MC, however, the relationship between lower limb joint position sense, kinematic control, and MC is not well understood. Therefore, the aim of this study was to determine the relation between joint position sense and kinematic control with MC in adolescents during a lower limb movement reproduction task., Methods: This study was a cross-sectional design. Young people (n = 427, 196 girls and 231 boys) aged 13 to 14 years were recruited. A movement reproduction task was used to assess joint position sense and kinematic control, while the Movement Assessment Battery for Children (mABC-2) was used to assess MC. In this study, participants were categorized into the Typically Developed (TD, n = 231) and Probable Developmental Coordination Disorder (DCD, n = 80) groups for further analysis of joint position sense, kinematic control, and MC between groups., Results: Kinematic data, specifically normalized jerk, showed a significant correlation with MC. There was no correlation between knee joint position sense and MC, and no group differences between DCD and TD were found., Conclusions: Joint position sense should not be used as a measure to distinguish TD and DCD. Rather than joint position sense, control of kinematic movement has a greater influence on the coordination of the lower limbs in adolescents. Movement control training should be implemented in the clinical setting to target kinematic control, rather than focus on joint position sense practice, to improve motor competency., Trial Registration Identifier: NCT03150784. Registered 12 May 2017, https://clinicaltrials.gov/study/NCT03150784 ., (© 2024. The Author(s).)

Background: Repeated transcranial magnetic stimulation (rTMS) could induce alterations in cortical excitability and promote neuroplasticity. To precisely quantify these effects, functional near-infrared spectroscopy (fNIRS), an optical neuroimaging modality adept at detecting changes in cortical hemodynamic responses, has been employed concurrently alongside rTMS to measure and tailor the impact of diverse rTMS protocols on the brain cortex., Objective: This systematic review and meta-analysis aimed to elucidate the effects of rTMS on cortical hemodynamic responses over the primary motor cortex (M1) as detected by fNIRS., Methods: Original articles that utilized rTMS to stimulate the M1 cortex in combination with fNIRS for the assessment of cortical activity were systematically searched across the PubMed, Embase, and Scopus databases. The search encompassed records from the inception of these databases up until April, 2024. The assessment for risk of bias was also conducted. A meta-analysis was also conducted in studies with extractable raw data., Results: Among 312 studies, 14 articles were eligible for qualitative review. 7 studies were eligible for meta-analysis. A variety of rTMS protocols was employed on M1 cortex. In inhibitory rTMS, multiple studies observed a reduction in the concentration of oxygenated hemoglobin [HbO] at the ipsilateral M1, contrasted by an elevation at the contralateral M1. Meta-analysis also corroborated this consistent trend. Nevertheless, certain investigations unveiled diminished [HbO] in bilateral M1. Several studies also depicted intricate inhibitory or excitatory interplay among distinct cortical regions., Conclusion: Diverse rTMS protocols led to varied patterns of cortical activity detected by fNIRS. Meta-analysis revealed a trend of increasing [HbO] in the contralateral cortices and decreasing [HbO] in the ipsilateral cortices following low frequency inhibitory rTMS. However, due to the heterogeneity between studies, further research is necessary to comprehensively understand rTMS-induced alterations in brain activity., (© 2024. The Author(s).)

Combination therapy merges chemical photodynamic therapy (CPDT) to improve cancer treatment. It synergizes chemotherapy with photodynamic therapy (PDT), using photosensitizers to produce reactive oxygen species (ROS) when exposed to light, effectively killing drug-resistant cancer cells. It is not affected by drug resistance, making it an attractive option for combination with chemotherapy. In this study, the focus was on the design of a combination therapy of chemotherapy and PDT. They synthesized diatomaceous earth mesoporous silica nanoparticles (dMSN) containing lanthanide metal ions in a PDT composition. These nanoparticles can generate ROS under near-infrared light irradiation and have MRI and fluorescence imaging capabilities, confirming their phototherapeutic effect on HCT116 cancer cells at a 200 μg/mL concentration. Fucoidan, derived from brown algae, was used as the chemotherapy component. The fucoidan extracted from Sargassum oligocystum in Pingtung Haikou showed the highest anticancer activity, with cell viability of 57.4 % at 200 μg/mL on HCT116 cancer cells. For combination therapy, fucoidan was loaded into nanoparticles (dMSN-EuGd@fucoidan). Cell viability experiments revealed that at 200 μg/mL, the cell survival rate of dMSN-EuGd@Fucoidan on HCT116 cancer cells was 47.7 %. Combination therapy demonstrated superior anticancer efficacy compared to PDT or chemotherapy alone, successfully synthesizing nanoparticles for combined chemotherapy and photodynamic therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this study, we introduced dual-targeting folic acid (FA) and hyaluronic acid (HA) modified on the surface of rice husk mesoporous silica nanoparticles (rMSNs). The rMSNs were employed as a drug delivery system loaded with camptothecin (CPT) as a model drug, Eu 3+ ions as a photosensitizer for photodynamic therapy (PDT), bismuth (Bi) for photothermal therapy (PTT), and Gd 3+ ions for magnetic resonance imaging (MRI) to develop novel nanoparticles, rMSN-EuGd-Bi@CPT-HA-FA, with dual-targeted function and triple therapy for cancer treatment. The results of the cell cytotoxicity experiment showed that the A549 cancer cells had a survival rate of approximately 35% when treated with 200 μg mL -1 of rMSN-EuGd-Bi@CPT-HA-FA under 808 nm irradiation for 15 min. The dual-targeted function and synergistic treatment of CPT, PTT, and PDT were also responsible for the 20% survival rate of the A549 cancer cells treated with 200 μg mL -1 of rMSN-EuGd-Bi@CPT-HA-FA under 808 nm irradiation for 30 min. The results showed that rMSN-EuGd-Bi@CPT-HA-FA can effectively combine chemotherapy (through CPT), PDT, and PTT for cancer treatment., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Understanding local public attitudes toward receiving vaccines is vital to successful vaccine campaigns. Social media platforms may help uncover vaccine sentiments during infectious disease outbreaks at the local level, and whether offline local events support vaccine-promotion efforts. Communication Infrastructure Theory (CIT) served as a guiding framework for this case study of the San Diego region examining local public sentiment toward vaccines expressed on Twitter during the COVID-19 pandemic. We performed a sentiment analysis (including positivity and subjectivity) of 187,349 tweets gathered from May 2020 to March 2021, and examined how sentiment corresponded with local vaccine deployment. The months of November and December (52.9%) 2020 saw a majority of tweets expressing positive sentiment and coincided with announcements of offline local events signaling San Diego's imminent deployment of COVID-19 vaccines. Across all months, tweets remained mostly objective (never falling below 63%). In terms of CIT, considering multiple levels of the Story Telling Network in online spaces, and examining sentiment about vaccines on Twitter may help scholars to explore the Communication Action Context, as well as cultivate positive community attitudes to improve the Field of Health Action regarding vaccines. Real-time analysis of local tweets during development and deployment of new vaccines may help monitor local public responses and guide promotion of immunizations in communities.

Fucoidan derived from brown algae has been shown to exhibit antitumor and antioxidant effects, so research on sulfated polysaccharides is increasing. The purpose of this study was to evaluate the characteristics and biological activity of fucoidan that was extracted at two temperatures (65 and 80 °C) from Sargassum ilicifolium (Turner) C. Agardh from five regions of Taiwan. The data show that there are significant differences in the yield, sulfate and total sugar content of Sargassum ilicifolium (Turner) C. Agardh grown in different locations in the same sea area. HPLC was used to determine the monosaccharide compositions of the fucoidan, which contains fucose, mannose, mannose, glucose and galactose and have a low molecular weight of less than 5 kDa, and then we will select the algae collected in Fugang, Taitung, for further biological activity research. The sampled Sargassum ilicifolium (Turner) C. Agardh at all five locations has a good polyphenol content, and it shows great DPPH radical scavenging activity, ABTS radical scavenging activity, Ferrous ion-chelating activity and Reducing power. The Sargassum ilicifolium (Turner) C. Agardh that was collected from Taitung Fugang is not toxic to L929 normal cells, but for A549 cancer cells and HCT116 cancer cells, it is known from the results that it has good cytotoxicity for A549 cancer cells. Thus, this study found that the Sargassum ilicifolium (Turner) C. Agardh that was collected from Taitung Fugang has significant antioxidant and anticancer properties., (© 2022. The Author(s).)

Introduction: During the COVID-19 pandemic, health and social inequities placed racial and ethnic minority groups at increased risk of severe illness. Our objective was to investigate this health disparity by analyzing the relationship between potential social determinants of health (SDOH), COVID-19, and chronic disease in the spatial context of San Diego County, California., Methods: We identified potential SDOH from a Pearson correlation analysis between socioeconomic variables and COVID-19 case rates during 5 pandemic stages, from March 31, 2020, to April 3, 2021. We used ridge regression to model chronic disease hospitalization and death rates by using the selected socioeconomic variables. Through the lens of COVID-19 and chronic disease, we identified vulnerable communities by using spatial methods, including Global Moran I spatial autocorrelation, local bivariate relationship analysis, and geographically weighted regression., Results: In the Pearson correlation analysis, we identified 26 socioeconomic variables as potential SDOH because of their significance (P ≤ .05) in relation to COVID-19 case rates. Of the analyzed chronic disease rates, ridge regression most accurately modeled rates of diabetes age-adjusted death (R 2 = 0.903) and age-adjusted hospitalization for hypertensive disease (hypertension, hypertensive heart disease, hypertensive chronic kidney disease, and hypertensive encephalopathy) (R 2 = 0.952). COVID-19 and chronic disease rates exhibited positive spatial autocorrelation (0.304≤I≤0.561, 3.092≤Z≤6.548, 0.001≤P≤ .002), thereby justifying spatial models to highlight communities that are vulnerable to COVID-19., Conclusion: Novel spatial analysis methods reveal relationships between SDOH, COVID-19, and chronic disease that are intuitive and easily communicated to public health decision makers and practitioners. Observable disparity patterns between urban and rural areas and between affluent and low-income communities establish the need for spatially differentiated COVID-19 response approaches to achieve health equity.

The pandemic spread rapidly across Italy, putting the region's health system on the brink of collapse, and generating concern regarding the government's capacity to respond to the needs of patients considering isolation measures. This study developed a sentiment analysis using millions of Twitter data during the first wave of the COVID-19 pandemic in 10 metropolitan cities in Italy's (1) north: Milan, Venice, Turin, Bologna; (2) central: Florence, Rome; (3) south: Naples, Bari; and (4) islands: Palermo, Cagliari. Questions addressed are as follows: (1) How did tweet-related sentiments change over the course of the COVID-19 pandemic, and (2) How did sentiments change when lagged with policy shifts and/or specific events? Findings show an assortment of differences and connections across Twitter sentiments (fear, anger, and joy) based on policy measures and geographies during the COVID-19 pandemic. Results can be used by policy makers to quantify the satisfactory level of positive/negative acceptance of decision makers and identify important topics related to COVID-19 policy measures, which can be useful for imposing geographically varying lockdowns and protective measures using historical data.

In this study, we used the nanoparticle delivery system to reduce the side effect of conventional cancer treatment- radiation therapy and chemotherapy. We used rice husk silicon source mesoporous silica nanoparticle doped in Eu 3+ and Gd 3+ as the carrier in the delivery system and to enable fluorescence and MRI dual-imaging functions for follow-up therapy. In addition, we choose a popular seaweed extract-fucoidan was extracted from the same brown algae-Sargassum aquifolium collected from Taiwan-Pingtung-Kenting-Chuanfan Rock. In this research, we used acid hydrolysis to prepared two different molecular weight fucoidan, the small molecular fucoidan (Fus) as drug, and the molecular weight approximately 1 kDa fucoidan (Ful) as the nanoparticle gatekeeper, and as targeting molecule for overexpressed P-selectin on the surface of the metastatic tumors. The results of the cell cytotoxicity experiment showed that HCT116 cancer cells have a survival rate of approximately 58.12% when treated with 200 μg/mL fucoidan. Dual-imaging rice husk mesoporous silica nanoparticles (rMSN-EuGd) were modified with 1 kDa fucoidan (Ful) as the gatekeeper and target, and the small molecule fucoidan (Fus) was loaded into nanoparticles (Ful-Fus@rMSN-EuGd) at a concentration of 200 μg/mL. The HCT116 cancer cells had a survival rate of approximately 55.56%. The cell cytotoxicity experiment results show that Ful-Fus@rMSN-EuGd can improve the anticancer effect of fucoidan, and the nanoparticle drug delivery system using fucoidan as a drug, target, and gatekeeper was successfully synthesized., (© 2022. The Author(s).)

Traditional treatment of cancers such as chemotherapy still causes many side effects after the treatment even nowadays, therefore combination therapies by using drug delivery systems are valued by more and more scientists. However, loading multiple drugs in the nanoparticles for drug delivery system may cause insufficient drugs or functional groups, which might let the nanomaterial have fewer functions. Therefore, making the mesoporous silica nanoparticles (MSNs) have photodynamic therapy function by "doping " lanthanide ions into the material structure, can evade this problem. Moreover, with the doping of lanthanide metals, the MSNs can have not only dual imaging functions of both magnetic resonance imaging and fluorescence, but also achieve photodynamic function. To feature the material with more function, chemotherapeutic drug-doxorubicin was loaded into the pores of MSNs and then bonded hyaluronic acid which is the active target and a gatekeeper, on the surface of MSNs. Finally, an all-in-one drug delivery system" Hyaluronidase and pH-responsive mesoporous silica nanoparticles with dual-imaging activity for chemo-photodynamic therapy" is synthesized. The first part in this experiment was to confirm the physical properties of the lanthanides dopped MSN and its photodynamic treatment effect. The second part was to confirm that each organic molecule had been successfully bonded to the surface of the MSN and achieve pH and Hyaluronidase response drug release effect, The last part was to prove that the drug delivery system had a significant anticancer effect through cell experiments., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Tobacco products cause about 1 in 5 deaths premature deaths each year. With increased retailing of both tobacco and electronic nicotine delivery systems (ENDS) products, cancer centers such as City of Hope are prioritizing tobacco and ENDS control. Therefore, we conducted formative geospatial analyses of dedicated smoke and vape shops linked to neighborhood demographic characteristics. The objective of the study was to analyze local data on smoke and vaping shop locations by age, socio-economic status, and racial/ethnic group. Our geospatial analysis used aggregate data from the U.S. Census, Google Maps, and Yelp. Geospatial maps were created using ArcGIS Pro with American Community Survey and U.S. Census 2010. The distributions of exclusive tobacco and vaping shop locations data were overlaid with data from the U.S. Census 2010 to generate maps of the relative geographic distributions of shops across varying area demographic characteristics. Results showed that a higher concentration of exclusive smoke and vaping shops were in areas with a higher concentration of ethnic minorities and lower income and lower status neighborhoods. These findings suggest that laws and licensing should be evaluated to regulate the placement of these shops to reduce and even prevent targeting of minorities and other vulnerable populations., Competing Interests: Conflicts of interest: The authors declare that there is no conflict of interest.

Fucoidan is a sulfated polysaccharide that is mainly extracted from brown algae. In this study, a simple and efficient method of hot water extraction, which is commonly used in industry, was used to obtain crude polysaccharides. Furthermore, agricultural waste was our source of biogenic silica, and it was then synthesized into drug carrier-nanoparticles. In combination with a popular drug delivery system, the carrier was doped with a dual imaging lanthanide metal and loaded with the drug. Fucoidan has decent bioactivities, such as anticancer activity. The extracted fucoidan is expensive, but we can exploit the nanocarrier to reduce the necessary dose of fucoidan. The experimental section is divided into three parts. The first part analyzed the chemical properties and antioxidant activity of the extracted fucoidan. The second part endowed the material with fluorescent and magnetic dual-imaging properties by incorporating Eu 3+ and Gd 3+ during the synthesis of rice husk mesoporous silica nanoparticles (rMSNs). The third part tested the anti-cancer ability of rMSN-EuGd@Fucoidan. The drug delivery system rMSN-EuGd@Fucoidan, which was synthesized in this research, showed cytotoxicity against A549 cancer cells. The results of the cell viability tests for fucoidan and rMSN-EuGd@Fucoidan were 58% and 47%, respectively. After inverse calculation from the TGA data yielded a value of 54.5%, we determined that the amount of fucoidan loaded in rMSN-EuGd@Fucoidan was 109 μg. Our results showed that rMSN-EuGd@Fucoidan needs less fucoidan to be effective, and its toxicity against A549 cells is higher than that of fucoidan., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Colorectal cancer is curable if diagnosed early and treated properly. Black and Hispanic patients with colorectal cancer are more likely to experience treatment delays and/or receive lower standards of care. Socioeconomic deprivation may contribute to these disparities, but this has not been extensively quantified. We studied the interrelationship between patient race/ethnicity and neighborhood socioeconomic status (nSES) on receipt of timely appropriate treatment among patients with colorectal cancer in California., Methods: White, Black, and Hispanic patients (26,870) diagnosed with stage I-III colorectal cancer (2009-2013) in the California Cancer Registry were included. Logistic regression models were used to examine the association of race/ethnicity and nSES with three outcomes: undertreatment, >60-day treatment delay, and >90-day treatment delay. Joint effect models and mediation analysis were used to explore the interrelationships between race/ethnicity and nSES., Results: Hispanics and Blacks were at increased risk for undertreatment [Black OR = 1.39; 95% confidence interval (CI) = 1.23-1.57; Hispanic OR = 1.17; 95% CI = 1.08-1.27] and treatment delay (Black/60-day OR = 1.78; 95% CI = 1.57-2.02; Hispanic/60-day OR = 1.50; 95% CI = 1.38-1.64) compared with Whites. Of the total effect (OR = 1.15; 95% CI = 1.07-1.24) of non-white race on undertreatment, 45.71% was explained by nSES., Conclusions: Lower nSES patients of any race were at substantially higher risk for undertreatment and treatment delay, and racial/ethnic disparities are reduced or eliminated among non-white patients living in the highest SES neighborhoods. Racial and ethnic disparities persisted after accounting for neighborhood socioeconomic status, and between the two, race/ethnicity explained a larger portion of the total effects., Impact: This research improves our understanding of how socioeconomic deprivation contributes to racial/ethnic disparities in colorectal cancer., (©2021 American Association for Cancer Research.)

Objectives. To examine how and what information is communicated via social media during an infectious disease outbreak. Methods. In the context of the 2016 through 2018 hepatitis A outbreak in San Diego County, California, we used a grounded theory-based thematic analysis that employed qualitative and quantitative approaches to uncover themes in a sample of public tweets (n = 744) from Twitter, a primary platform used by key stakeholders to communicate to the public during the outbreak. Results. Tweets contained both general and hepatitis A-specific information related to the outbreak, restatements of policy and comments critical of government responses to the outbreak, information with the potential to shape risk perceptions, and expressions of concern regarding individuals experiencing homelessness and their role in spreading hepatitis A. We also identified misinformation and common channels of content driving themes that emerged in our sample. Conclusions. Public health professionals may identify real-time public risk perceptions and concerns via social media during an outbreak and target responses that fulfill the informational needs of those who seek direction and reassurance during times of uncertainty.

Several studies have recently applied sentiment-based lexicons to Twitter to gauge local sentiment to understand health behaviors and outcomes for local areas. While this research has demonstrated the vast potential of this approach, lingering questions remain regarding the validity of Twitter mining and surveillance in local health research. First, how well does this approach predict health outcomes at very local scales, such as neighborhoods? Second, how robust are the findings garnered from sentiment signals when accounting for spatial effects? To evaluate these questions, we link 2,076,025 tweets from 66,219 distinct users in the city of San Diego over the period of 2014-12-06 to 2017-05-24 to the 500 Cities Project data and 2010-2014 American Community Survey data. We determine how well sentiment predicts self-rated mental health, sleep quality, and heart disease at a census tract level, controlling for neighborhood characteristics and spatial autocorrelation. We find that sentiment is related to some outcomes on its own, but these relationships are not present when controlling for other neighborhood factors. Evaluating our encoding strategy more closely, we discuss the limitations of existing measures of neighborhood sentiment, calling for more attention to how race/ethnicity and socio-economic status play into inferences drawn from such measures., Competing Interests: The authors have declared that no competing interests exist.

Taking ecological perspectives to overweight and obesity, the current study applies data mining approach to examine the association between information and social environments and regional prevalence of overweight and obesity. In particular, we focus on online search and social media data since the increasing popularity of location-based geo-targeting could be an influential source of regional differences in health information and social environment. In Study 1, we calculated the correlation between regional overweight and obesity rates with regional Google searches for a time period of 12 years (2004 to 2016). The findings showed that in regions with high overweight and obesity rates, people were looking for and obtaining information on weight-loss and diet;, but in regions with low overweight and obesity rates, people were looking for and obtaining information on fitness services and facilities. In Study 2, we analyzed and compared 4010 tweets from Houston, a city with a high overweight and obesity rate, and 3281 tweets from San Diego, a city with a low overweight and obesity rate. The tweets were collected from August 2015 to August of 2016. We analyzed the textual content of tweets by word frequency analysis and topic modeling. The findings suggest that San Diego has a social environment that focuses on fitness and combining exercising with dieting. In contrast, Houston's social environment emphasizes dieting. The implication of these findings is that health practitioners should push a paradigm shift to a stronger focus on "healthy life" (combining exercising and dieting) in regions with high overweight and obesity rates.

The current study examined conversations on Twitter related to use and perceptions of e-cigarettes in the United States. We employed the Social Media Analytic and Research Testbed (SMART) dashboard, which was used to identify and download (via a public API) e-cigarette-related geocoded tweets. E-cigarette-related tweets were collected continuously using customized geo-targeted Twitter APIs. A total of 193,051 tweets were collected between October 2015 and February 2016. Of these tweets, a random sample of 973 geocoded tweets were selected and manually coded for information regarding source, context, and message characteristics. Our findings reveal that although over half of tweets were positive, a sizeable portion was negative or neutral. We also found that, among those tweets mentioning a stigma of e-cigarettes, most confirmed that a stigma does exist. Conversely, among tweets mentioning the harmfulness of e-cigarettes, most denied that e-cigarettes were a health hazard. These results suggest that current efforts have left the public with ambiguity regarding the potential dangers of e-cigarettes. Consequently, it is critical to communicate the public health stance on this issue to inform the public and provide counterarguments to the positive sentiments presently dominating conversations about e-cigarettes on social media. The lack of awareness and need to voice a public health position on e-cigarettes represents a vital opportunity to continue winning gains for tobacco control and prevention efforts through health communication interventions targeting e-cigarettes.

We retrospectively investigated 59 surgically resected primary intestinal diffuse large B-cell lymphomas (PI-DLBCL) including 31 males and 28 females with a median age of 66. Eleven (19%) tumors were perforated at presentation; 8 (14%) were multicentric. Ileum (n=24; 43%) and ileocecum (n=17; 30%) were most frequently involved. Twenty-one (36%) patients did not receive chemotherapy or radiotherapy including 6 with perforation and died in 0.2 to 7 months. The 1-, 2-, and 5-year overall survival rates were 68.4%, 56.5%, and 50.0%, respectively. Seven (12%) of 59 cases were positive for Epstein-Barr virus (EBV) by in situ hybridization. IGH, BCL2, BCL6, and MYC foci were rearranged in 22%, 3%, 17%, and 7% cases, respectively, with 14% exhibiting gain/amplification at the MYC locus. Perforation (P=0.009), high ECOG PS (≥2) (P=0.018), and no adjuvant chemotherapy (P<0.001) were poor prognostic factors but not immunophenotype including co-expression of bcl-2 and myc, EBV status, or chromosomal aberrations. Perforation and chemotherapy remained significant by multivariate analysis. PI-DLBCL in Taiwan carried a relatively higher rate of perforation, lower frequency of germinal center B-cell phenotype, and higher EBV association as compared with studies from other geographic areas. Furthermore, perforation was a poor prognostic factor.

Traditional methods for monitoring influenza are haphazard and lack fine-grained details regarding the spatial and temporal dynamics of outbreaks. Twitter gives researchers and public health officials an opportunity to examine the spread of influenza in real-time and at multiple geographical scales. In this paper, we introduce an improved framework for monitoring influenza outbreaks using the social media platform Twitter. Relying upon techniques from geographic information science (GIS) and data mining, Twitter messages were collected, filtered, and analyzed for the thirty most populated cities in the United States during the 2013-2014 flu season. The results of this procedure are compared with national, regional, and local flu outbreak reports, revealing a statistically significant correlation between the two data sources. The main contribution of this paper is to introduce a comprehensive data mining process that enhances previous attempts to accurately identify tweets related to influenza. Additionally, geographical information systems allow us to target, filter, and normalize Twitter messages.

Background: Early insights into the timing of the start, peak, and intensity of the influenza season could be useful in planning influenza prevention and control activities. To encourage development and innovation in influenza forecasting, the Centers for Disease Control and Prevention (CDC) organized a challenge to predict the 2013-14 Unites States influenza season., Methods: Challenge contestants were asked to forecast the start, peak, and intensity of the 2013-2014 influenza season at the national level and at any or all Health and Human Services (HHS) region level(s). The challenge ran from December 1, 2013-March 27, 2014; contestants were required to submit 9 biweekly forecasts at the national level to be eligible. The selection of the winner was based on expert evaluation of the methodology used to make the prediction and the accuracy of the prediction as judged against the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet)., Results: Nine teams submitted 13 forecasts for all required milestones. The first forecast was due on December 2, 2013; 3/13 forecasts received correctly predicted the start of the influenza season within one week, 1/13 predicted the peak within 1 week, 3/13 predicted the peak ILINet percentage within 1 %, and 4/13 predicted the season duration within 1 week. For the prediction due on December 19, 2013, the number of forecasts that correctly forecasted the peak week increased to 2/13, the peak percentage to 6/13, and the duration of the season to 6/13. As the season progressed, the forecasts became more stable and were closer to the season milestones., Conclusion: Forecasting has become technically feasible, but further efforts are needed to improve forecast accuracy so that policy makers can reliably use these predictions. CDC and challenge contestants plan to build upon the methods developed during this contest to improve the accuracy of influenza forecasts.

In an effort to identify the functional alleles associated with hepatocellular carcinoma (HCC), we investigated 152 genes found in the 4q21-25 region that exhibited loss of heterozygosity (LOH). A total of 2,293 pairs of primers were designed for 1,449 exonic and upstream promoter regions to amplify and sequence 76.8-114 Mb on human chromosome 4. Based on the results from analyzing 12 HCC patients and 12 healthy human controls, we discovered 1,574 sequence variations. Among the 99 variants associated with HCC (p < 0.05), four are from the Dickkopf 2 (DKK2) gene: three in the promoter region (g.-967A>T, g.-923C>A, and g.-441T>G) and one in the 5'UTR (c.550T>C). To verify the results, we expanded the subject cohort to 47 HCC cases and 88 healthy controls for conducting haplotype analysis. Eight haplotypes were detected in the non-tumor liver tissue samples, but one major haplotype (TAGC) was found in the tumor tissue samples. Using a reporter assay, this HCC-associated allele registered the lowest level of promoter activity among all the tested haplotype sequences. Retention of this allele in LOH was associated with reduced DKK2 transcription in the HCC tumor tissues. In HuH-7 cells, DKK2 functioned in the Wnt/β-catenin signaling pathway, as an antagonist of Wnt3a, in a dose-dependent manner that inhibited Wnt3a-induced cell proliferation. Taken together, the genotyping and functional findings are consistent with the hypothesis that DKK2 is a tumor suppressor; by selectively retaining a transcriptionally inactive DKK2 allele, the reduction of DKK2 function results in unchecked Wnt/β-catenin signaling, contributing to HCC oncogenesis. Thus our study reveals a new mechanism through which a tumor suppressor gene in a LOH region loses its function by allelic selection.

We previously identified 34 genes of interest (GOI) in 2006 to aid the oncologists to determine whether post-mastectomy radiotherapy (PMRT) is indicated for certain patients with breast cancer. At this time, an independent cohort of 135 patients having DNA microarray study available from the primary tumor tissue samples was chosen. Inclusion criteria were 1) mastectomy as the first treatment, 2) pathology stages I-III, 3) any locoregional recurrence (LRR) and 4) no PMRT. After inter-platform data integration of Affymetrix U95 and U133 Plus 2.0 arrays and quantile normalization, in this paper we used 18 of 34 GOI to divide the mastectomy patients into high and low risk groups. The 5-year rate of freedom from LRR in the high-risk group was 30%. In contrast, in the low-risk group it was 99% (p < 0.0001). Multivariate analysis revealed that the 18-gene classifier independently predicts rates of LRR regardless of nodal status or cancer subtype.

Outdoor air pollution is a serious problem in many developing countries today. This study focuses on monitoring the dynamic changes of air quality effectively in large cities by analyzing the spatiotemporal trends in geo-targeted social media messages with comprehensive big data filtering procedures. We introduce a new social media analytic framework to (1) investigate the relationship between air pollution topics posted in Sina Weibo (Chinese Twitter) and the daily Air Quality Index (AQI) published by China's Ministry of Environmental Protection; and (2) monitor the dynamics of air quality index by using social media messages. Correlation analysis was used to compare the connections between discussion trends in social media messages and the temporal changes in the AQI during 2012. We categorized relevant messages into three types, retweets, mobile app messages, and original individual messages finding that original individual messages had the highest correlation to the Air Quality Index. Based on this correlation analysis, individual messages were used to monitor the AQI in 2013. Our study indicates that the filtered social media messages are strongly correlated to the AQI and can be used to monitor the air quality dynamics to some extent.

Dynamic social media content, such as Twitter messages, can be used to examine individuals' beliefs and perceptions. By analyzing Twitter messages, this study examines how Twitter users exchanged and recognized toponyms (city names) for different cities in the United States. The frequency and variety of city names found in their online conversations were used to identify the unique spatiotemporal patterns of "geographical awareness" for Twitter users. A new analytic method, Knowledge Discovery in Cyberspace for Geographical Awareness (KDCGA), is introduced to help identify the dynamic spatiotemporal patterns of geographic awareness among social media conversations. Twitter data were collected across 50 U.S. cities. Thousands of city names around the world were extracted from a large volume of Twitter messages (over 5 million tweets) by using the Twitter Application Programming Interface (APIs) and Python language computer programs. The percentages of distant city names (cities located in distant states or other countries far away from the locations of Twitter users) were used to estimate the level of global geographical awareness for Twitter users in each U.S. city. A Global awareness index (GAI) was developed to quantify the level of geographical awareness of Twitter users from within the same city. Our findings are that: (1) the level of geographical awareness varies depending on when and where Twitter messages are posted, yet Twitter users from big cities are more aware of the names of international cities or distant US cities than users from mid-size cities; (2) Twitter users have an increased awareness of other city names far away from their home city during holiday seasons; and (3) Twitter users are more aware of nearby city names than distant city names, and more aware of big city names rather than small city names.

Background: Existing influenza surveillance in the United States is focused on the collection of data from sentinel physicians and hospitals; however, the compilation and distribution of reports are usually delayed by up to 2 weeks. With the popularity of social media growing, the Internet is a source for syndromic surveillance due to the availability of large amounts of data. In this study, tweets, or posts of 140 characters or less, from the website Twitter were collected and analyzed for their potential as surveillance for seasonal influenza., Objective: There were three aims: (1) to improve the correlation of tweets to sentinel-provided influenza-like illness (ILI) rates by city through filtering and a machine-learning classifier, (2) to observe correlations of tweets for emergency department ILI rates by city, and (3) to explore correlations for tweets to laboratory-confirmed influenza cases in San Diego., Methods: Tweets containing the keyword "flu" were collected within a 17-mile radius from 11 US cities selected for population and availability of ILI data. At the end of the collection period, 159,802 tweets were used for correlation analyses with sentinel-provided ILI and emergency department ILI rates as reported by the corresponding city or county health department. Two separate methods were used to observe correlations between tweets and ILI rates: filtering the tweets by type (non-retweets, retweets, tweets with a URL, tweets without a URL), and the use of a machine-learning classifier that determined whether a tweet was "valid", or from a user who was likely ill with the flu., Results: Correlations varied by city but general trends were observed. Non-retweets and tweets without a URL had higher and more significant (P<.05) correlations than retweets and tweets with a URL. Correlations of tweets to emergency department ILI rates were higher than the correlations observed for sentinel-provided ILI for most of the cities. The machine-learning classifier yielded the highest correlations for many of the cities when using the sentinel-provided or emergency department ILI as well as the number of laboratory-confirmed influenza cases in San Diego. High correlation values (r=.93) with significance at P<.001 were observed for laboratory-confirmed influenza cases for most categories and tweets determined to be valid by the classifier., Conclusions: Compared to tweet analyses in the previous influenza season, this study demonstrated increased accuracy in using Twitter as a supplementary surveillance tool for influenza as better filtering and classification methods yielded higher correlations for the 2013-2014 influenza season than those found for tweets in the previous influenza season, where emergency department ILI rates were better correlated to tweets than sentinel-provided ILI rates. Further investigations in the field would require expansion with regard to the location that the tweets are collected from, as well as the availability of more ILI data.

Background: Renal cell carcinoma, a common malignant tumor arising from the kidney, occurs in 3.62 and 1.95 cases per one hundred thousand people among men and women, respectively, in Taiwan each year. Approximately 80% of cases are classified as clear-cell renal cell carcinoma. Inactivation of the von Hippel-Lindau tumor suppressor gene has been implicated in the tumorigenic pathway of renal cell carcinoma. Two single nucleotide polymorphisms, rs779805 and rs1642742, located in the promoter and 3' untranslated regions of the von Hippel-Lindau gene are informative and implicated in the occurrence of renal cell carcinoma worldwide. The aim of this study is to clarify whether these polymorphisms are associated with renal cell carcinoma in Taiwanese. Genomic DNA was isolated from normal and tumor tissues of 19 renal cell carcinoma patients. The samples were screened for allelic polymorphisms by restriction fragment length polymorphism with BsaJ I and Acc I digestion. Reconfirmation was carried out by direct sequencing., Results: Consistent with Knudson's two-hit theory, AA to AG somatic mutations were observed in rs779805. In addition, loss of heterozygosity in both rs779805 and rs1642742 was demonstrated in 10 out of 15 RCC patients aged 50 or over. The G allele or AG heterozygote frequencies at these two loci were much higher in patient germline DNA when compared with the control group. After adjusting for age, the frequency of the G allele in both loci was much higher for late onset renal cell carcinoma in the Taiwanese population., Conclusions: Our current results confirmed that the existence of G allele in both rs779805 and rs1642742 in the von Hippel-Lindau tumor suppressor gene is of importance in renal cell carcinoma tumorigenesis. However, more comprehensive and detailed research is needed to address the clinical relevance. Larger sample size is required to determine the exact power of correlation between these two genetic polymorphisms and renal cell carcinoma.

Background: Surveillance plays a vital role in disease detection, but traditional methods of collecting patient data, reporting to health officials, and compiling reports are costly and time consuming. In recent years, syndromic surveillance tools have expanded and researchers are able to exploit the vast amount of data available in real time on the Internet at minimal cost. Many data sources for infoveillance exist, but this study focuses on status updates (tweets) from the Twitter microblogging website., Objective: The aim of this study was to explore the interaction between cyberspace message activity, measured by keyword-specific tweets, and real world occurrences of influenza and pertussis. Tweets were aggregated by week and compared to weekly influenza-like illness (ILI) and weekly pertussis incidence. The potential effect of tweet type was analyzed by categorizing tweets into 4 categories: nonretweets, retweets, tweets with a URL Web address, and tweets without a URL Web address., Methods: Tweets were collected within a 17-mile radius of 11 US cities chosen on the basis of population size and the availability of disease data. Influenza analysis involved all 11 cities. Pertussis analysis was based on the 2 cities nearest to the Washington State pertussis outbreak (Seattle, WA and Portland, OR). Tweet collection resulted in 161,821 flu, 6174 influenza, 160 pertussis, and 1167 whooping cough tweets. The correlation coefficients between tweets or subgroups of tweets and disease occurrence were calculated and trends were presented graphically., Results: Correlations between weekly aggregated tweets and disease occurrence varied greatly, but were relatively strong in some areas. In general, correlation coefficients were stronger in the flu analysis compared to the pertussis analysis. Within each analysis, flu tweets were more strongly correlated with ILI rates than influenza tweets, and whooping cough tweets correlated more strongly with pertussis incidence than pertussis tweets. Nonretweets correlated more with disease occurrence than retweets, and tweets without a URL Web address correlated better with actual incidence than those with a URL Web address primarily for the flu tweets., Conclusions: This study demonstrates that not only does keyword choice play an important role in how well tweets correlate with disease occurrence, but that the subgroup of tweets used for analysis is also important. This exploratory work shows potential in the use of tweets for infoveillance, but continued efforts are needed to further refine research methods in this field.

Purpose: This study is designed to validate a previously developed locoregional recurrence risk (LRR) scoring system and further define which groups of patients with breast cancer would benefit from postmastectomy radiation therapy (PMRT)., Methods and Materials: An LRR risk scoring system was developed previously at our institution using breast cancer patients initially treated with modified radical mastectomy between 1990 and 2001. The LRR score comprised 4 factors: patient age, lymphovascular invasion, estrogen receptor negativity, and number of involved lymph nodes. We sought to validate the original study by examining a new dataset of 1545 patients treated between 2002 and 2007., Results: The 1545 patients were scored according to the previously developed criteria: 920 (59.6%) were low risk (score 0-1), 493 (31.9%) intermediate risk (score 2-3), and 132 (8.5%) were high risk (score ≥4). The 5-year locoregional control rates with and without PMRT in low-risk, intermediate-risk, and high-risk groups were 98% versus 97% (P=.41), 97% versus 91% (P=.0005), and 89% versus 50% (P=.0002) respectively., Conclusions: This analysis of an additional 1545 patients treated between 2002 and 2007 validates our previously reported LRR scoring system and suggests appropriate patients for whom PMRT will be beneficial. Independent validation of this scoring system by other institutions is recommended., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Infectious granulomatous prostatitis is uncommon, and most cases of granulomatous prostatitis are classified as nonspecific granulomatous prostatitis. From 2007 to 2009, 5 patients experienced poor wound healing after radical prostatectomy for prostate cancer at a specialist cancer center. Mycobacterium abscessus was cultured from the debridement specimens, and acid-fast-positive bacilli were identified histologically within the prostates. All 180 radical prostatectomy specimens from May 2007 to June 2009 were reviewed, and 7 additional cases with morphologies suspicious of M. abscessus granulomatous prostatitis (MAGP) were identified. The characteristic morphologic feature of MAGP was suppurative necrotizing granulomatous inflammation extensively (10% to 80% of the gland; mean, 39%) involving the prostate. The centers of MAGP were large areas of neutrophilic abscess and necrotic debris, which were surrounded by histiocytes, lymphocytes, plasma cells, scattered multinucleated giant cells, and eosinophils. In the adjacent areas, there was a lobular extension of mixed inflammatory infiltrates into dilated and ruptured ducts. Involvement of extraprostatic soft tissue and seminal vesicles/vas deferens was found in 9 and 4 cases, respectively. Acid-fast-positive bacilli were identified in 5 radical prostatectomies. Eleven patients had fresh tissue specimens stored at -150°C, and M. abscessus was cultured from 8 prostates. Random amplified polymorphic DNA-polymerase chain reaction showed the same clone for all isolates. After prostatectomy, 8 patients experienced prolonged wound healing, with urethrorectal fistula formation in 1 patient and a pelvic abscess in another. It is critical for pathologists to recognize MAGP and to distinguish it from the more common nonspecific granulomatous prostatitis and other granulomatous lesions within the prostate.

Most primary intestinal natural killer (NK)-cell and T-cell lymphomas (PINKTL) in the Northern Europe are enteropathy-associated T-cell lymphomas, a complication of celiac disease, which is rare in the East. Primary intestinal NK-cell lymphoma is extremely rare and is poorly characterized. We investigated 30 cases of PINKTL from Taiwan with male: female at 2:1, median age at 55.5, 80% with jejunal/ileal involvement, 77% with perforation, 27% with multicentric tumors, and 67% at stage IE. All 7 cases tested for serum IgA anti-tissue transglutaminase were negative. Only 3 (10%) tumors showed enteropathy. Six (20%) were NK-cell lymphoma and 24 (80%) were T-cell lymphoma. The tumor cells in 21/30 (70%) cases were small to medium sized, which correlated with the coexpression of both CD8 and CD56. All tumors expressed at least 1 cytotoxic marker. All 6 NK-cell lymphomas were negative for betaF1, diffusely positive for Epstein-Barr virus-encoded mRNA (EBER), and polyclonal for T-cell receptor gene rearrangement. Five (22%) of the 24 T-cell tumors expressed betaF1, 8 (35%) of the 23 tumors were positive for EBER, and 20 (95%) of the 21 tumors were clonal for T-cell receptor. The overall 1-year survival was 36%. Univariate regression analysis showed that NK-cell lineage, multicentricity, and perforation were associated with poor prognosis. NK-cell lineage (P=0.037) was a poor prognostic factor by multivariate Cox proportional hazard regression analysis. PINKTL in Taiwan is predominantly not enteropathic with a high frequency of perforation, small to medium tumor cell size and cytotoxic phenotype. Primary intestinal NK-cell lymphoma carries a very poor prognosis, and is probably a distinct entity.

Purpose: To examine the diagnostic effect of immediate on-site cytopathologic evaluation of tissue core touch preparations in computed tomographic (CT)-guided coaxial needle biopsy., Materials and Methods: The authors reviewed the records of 430 patients and included 413 patients with 432 biopsies (210 in the lungs, 222 in other locations). Each time the guiding needle was moved to a new location in the lesion for tissue core procurement with the cutting needle, it represented a new session. Core specimen touch preparations were obtained and immediately evaluated on-site for specimen adequacy and preliminary diagnosis. New sessions were considered and/or executed in the case of inconclusive cytopathologic readings. Each final diagnosis was reached according to the pathology report showing "positive for malignancy," "negative but with a specific diagnosis," or "unclear" for further surgical resection specimen or radiologic follow-up., Results: The accuracy of on-site cytopathologic examination of touch preparations was 80.6% for the first session and increased to 85.9% and 86.3%, respectively, for the second and third sessions. The corresponding accuracies for biopsy were 88.2%, 93.8%, and 94.9%. The overall accuracy was 97.1% for lesions in the lungs and 92.8% for lesions at other sites. More biopsy sessions were deemed necessary in lesions measuring 2 cm or smaller (P = .0045). During CT-guided lung biopsy, 10 patients (4.8%) had major complications that necessitated chest tube insertion., Conclusions: The diagnostic accuracy of CT-guided needle biopsy can be increased through repeated sessions with immediate on-site cytologic evaluation, especially for lesions of 2 cm or smaller and those from nonpulmonary sites.

Objectives: To report the pathologic features of prostate cancer and its clinical outcome in the Chinese population in Taiwan., Methods: A total of 139 radical prostatectomy specimens removed at Koo Foundation Sun Yat-Sen Cancer Center from 1993 to 2001 were reviewed., Results: The median patient age was 69 years. The histologic type was acinar adenocarcinoma in 137, mucinous adenocarcinoma in 1, and ductal adenocarcinoma in 1. The median tumor number in each prostate gland was 2. The main tumor location was distributed in peripheral zone (76.3%), followed by the transitional zone (15.1%). The Gleason score of the largest tumor was 2 to 4 in 1.5%, 5 to 6 in 7.9%, 7 in 48.9%, and 8 to 10 in 41.7%. Extraprostatic tumor extension, seminal vesicle invasion, and lymph node metastasis were found in 59.0%, 28.8%, and 13.7% of the patients, respectively. Of the 139 specimens, 56 (40.3%), 64 (46.1%), and 19 (13.7%) were pathologic Stage T2, T3, and T4, respectively. The clinical stage (P = 0.0059), serum prostate-specific antigen (PSA) level (greater than 20 ng/mL versus 10 ng/mL or less, P = 0.002), extraprostatic extension (P = 0.0012), seminal vesicle invasion (P <0.0001), and surgical margin status (P <0.0001) were all significant factors for disease progression on univariate analysis. On multivariate analysis, the serum PSA level (greater than 20 ng/mL versus 10 ng/mL or less, P = 0.03), seminal vesicle invasion (P = 0.02), and surgical margin status (P = 0.02) remained significant., Conclusions: The patients with prostate cancer cared for at the Koo Foundation Sun Yat-Sen Cancer Center were older and had greater PSA levels, a more advanced stage, higher grade tumors, and high positive surgical margin rates. Increased public awareness and implementing a PSA screening program in Taiwan are of crucial importance.

Cancer has been the leading cause of death in Taiwan over the past two decades and liver cancer is the leading cause of all cancer deaths in Taiwan with a trend of increase in incidence. Therapeutic options and efficacy for liver cancer have been limited and the 5-year survival rate is less than 7% in the Unite States. The study was conducted to establish a histoculture system of human hepatocellular carcinomas (HCC) for biological and pharmacological studies and to determine the efficacy of anticancer drugs with the established HCC histocultures. Patient HCC tissues freshly obtained after surgeries were prepared and histocultured. The histocultured HCC were treated with doxorubicin and paclitaxel of various concentrations for 96-h. Upon drug treatments, the activity of tumor cell proliferation and extent of cell death induction were measured and changes of the alpha-fetoprotein levels in the culture medium were determined. We demonstrated that human HCC can be successfully cultured in a 3-dimensional histoculture system and used for pharmacological studies. Doxorubicin and paclitaxel showed concentration-dependent activities in anti-proliferation and cell death induction against the human HCC. Inhibitory effects of both drugs on alpha-fetoprotein production of the cultured HCC were in agreement with their anti-proliferative effects. Exposure time-dependent antitumoral effects of paclitaxel treatments at 3-, 24-, and 96-h against the histocultured HCC PLC/PRF/5 xenograft tumors were also observed. In conclusion, we have demonstrated a histoculture system for patient HCC and it can be utilized in selection of active drugs prior to treatments in patients and in evaluation of new agents against HCC, for which therapeutic agents are in desperate needs worldwide.

Purpose: This study established a prognostic scoring system for nasopharyngeal carcinoma (NPC), which estimates the probability of locoregional (LR) control following definitive conformal radiotherapy., Methods and Materials: Patients with nondisseminated NPC at initial presentation (n = 630) were enrolled in this study. All patients had magnetic resonance imaging of the head and neck and were treated with conformal radiotherapy. Among them, 93% had concurrent chemotherapy, and 76% had postradiation chemotherapy. The extent of the primary tumor, age at diagnosis, primary tumor size, tumor and nodal classification, histology, and serum lactate dehydrogenase (LDH) level before treatment were included in the analysis for building a prognostic scoring system. The end point for this study was LR control., Results: The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Four factors had similarly independent prognostic effects (hazard ratio, 2.0-2.6): age >40 years, histologic WHO type I-II, serum LDH level > or =410 U/L, and involvement of two or more sites of the following anatomic structures, i.e., sphenoid floor, clivus marrow, clivus cortex, prevertebral muscles, and petrous bone. The score predicted the 5-year probability of LR control as follows: 0 (15% of the patients), 100%; 1 (42% of the patients), 93%; 2 (29% of the patients), 83%; 3 or higher (13% of the patients), 71%., Conclusion: This scoring system is useful in the decision-making for individual patients and the design of clinical trials to improve LR control for advanced-stage NPC.

Purpose: This study aims to explore gene expression profiles that are associated with locoregional (LR) recurrence in breast cancer after mastectomy., Patients and Methods: A total of 94 breast cancer patients who underwent mastectomy between 1990 and 2001 and had DNA microarray study on the primary tumor tissues were chosen for this study. Eligible patient should have no evidence of LR recurrence without postmastectomy radiotherapy (PMRT) after a minimum of 3-year follow-up (n = 67) and any LR recurrence (n = 27). They were randomly split into training and validation sets. Statistical classification tree analysis and proportional hazards models were developed to identify and validate gene expression profiles that relate to LR recurrence., Results: Our study demonstrates two sets of gene expression profiles (one with 258 genes and the other 34 genes) to be of predictive value with respect to LR recurrence. The overall accuracy of the prediction tree model in validation sets is estimated 75% to 78%. Of patients in validation data set, the 3-year LR control rate with predictive index more than 0.8 derived from 34-gene prediction models is 91%, and predictive index 0.8 or less is 40% (P = .008). Multivariate analysis of all patients reveals that estrogen receptor and genomic predictive index are independent prognostic factors that affect LR control., Conclusion: Using gene expression profiles to develop prediction tree models effectively identifies breast cancer patients who are at higher risk for LR recurrence. This gene expression-based predictive index can be used to select patients for PMRT.

Purpose: To develop clinical prediction models for local regional recurrence (LRR) of breast carcinoma after mastectomy that will be superior to the conventional measures of tumor size and nodal status., Methods and Materials: Clinical information from 1,010 invasive breast cancer patients who had primary modified radical mastectomy formed the database of the training and testing of clinical prognostic and prediction models of LRR. Cox proportional hazards analysis and Bayesian tree analysis were the core methodologies from which these models were built. To generate a prognostic index model, 15 clinical variables were examined for their impact on LRR. Patients were stratified by lymph node involvement (<4 vs. >or =4) and local regional status (recurrent vs. control) and then, within strata, randomly split into training and test data sets of equal size. To establish prediction tree models, 255 patients were selected by the criteria of having had LRR (53 patients) or no evidence of LRR without postmastectomy radiotherapy (PMRT) (202 patients)., Results: With these models, patients can be divided into low-, intermediate-, and high-risk groups on the basis of axillary nodal status, estrogen receptor status, lymphovascular invasion, and age at diagnosis. In the low-risk group, there is no influence of PMRT on either LRR or survival. For intermediate-risk patients, PMRT improves LR control but not metastases-free or overall survival. For the high-risk patients, however, PMRT improves both LR control and metastasis-free and overall survival., Conclusion: The prognostic score and predictive index are useful methods to estimate the risk of LRR in breast cancer patients after mastectomy and for estimating the potential benefits of PMRT. These models provide additional information criteria for selection of patients for PMRT, compared with the traditional selection criteria of nodal status and tumor size.

Only 7 cases of pancreatic tumor with hepatocytic differentiation have been reported in the literature, including 6 cases of hepatoid carcinoma and one case of hepatoid adenoma. Diagnosis of hepatoid carcinoma depends on recognition of characteristic histological features, supported by other evidence linked to hepatic lineage including alpha-fetoprotein production, positive immunoreactivity to liver synthesized proteins, and in situ hybridization detection of albumin mRNA. In addition, a synchronous focus of carcinoma arising in pancreatic ducts, islet cells, or acinar cells is essential. We report a unique case of pancreatic tumor with exclusive hepatocytic differentiation. In this tumor, we were unable to find a synchronous focus of carcinoma arising in pancreatic ducts, islet cells, or acinar cells, ruling out the possibility of its being hepatoid carcinoma. Long term follow-up can help to determine whether this tumor is benign or malignant. The patterns of reticulin staining and immunohistochemical staining are suggestive of malignancy, but mitotic activity is low and nuclear pleomorphism is minimal.

Patients with nasopharyngeal carcinoma (NPC) are common in Taiwan. To provide efficient management to patients, the surgeons often perform cytological imprints immediately after biopsies of lesions suspicious for NPC. The results of cytological assessment of imprints usually are reported within 30 min after biopsies. The patients with positive cytological results can then be arranged for further examinations during the same visit. We reviewed 191 imprints and corresponding biopsies from 187 patients during 1997-2004 at Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The cytological diagnoses were categorized into four groups: negative (62 cases), suspicious (8 cases), positive (116 cases), and inadequate specimen (5 cases). There were 18 false-negative and 1 false-positive diagnoses. All suspicious cases were positive histologically. Our results showed a sensitivity of 87.2% and a specificity of 97.8%. The accuracy was 89.8%. Therefore, nasopharyngeal imprint cytology is a sensitive and specific method for rapid diagnosis of nasopharyngeal cancer at an outpatient setting., (2006 Wiley-Liss, Inc.)

Xanthogranulomatous inflammation is an uncommon, though well-recognized entity that has been described in various organs but mostly commonly in the kidney and gallbladder. There have been few reports of its occurrence in the appendix. We report a 39-year-old man who presented with fever, right lower quadrant abdominal pain and mass. Abdominal computed tomography (CT) revealed diffuse wall thickening over the terminal ileum and cecum with involvement of the mesentery. CT-guided biopsy showed colitis with infiltration of lymphocytes, neutrophils and eosinophils. The patient's illness responded to intravenous antibiotics, but relapsed after switching to oral antibiotics. After the second course of intravenous antibiotics was given without resolution of symptoms, exploratory laparotomy was performed. Although operative findings favored colitis of the cecum, cancer of the cecum could not be completely ruled out. Right hemicolectomy was done and pathology confirmed the diagnosis of xanthogranulomatous appendicitis. This case illustrates that xanthogranulomatous appendicitis may mimic a locally advanced cancer, has a benign course, and can be cured by surgical resection.

Objectives: The clinicopathological characteristics of malignant lymphomas vary according to geography, especially for the T-cell lymphoma (TCL). The aim of this study is to demonstrate the incidence and clinicopathological characteristics of TCL in Taiwan according to WHO classification., Methods: Archival tissue from 600 malignant lymphomas during the period of 1995-2002 was retrieved, there were 74 cases diagnosed with TCL. Hematoxylin and eosin slides stained and other special studies were reviewed. All cases were reclassified according to the WHO classification. Clinical data, including age, gender, clinical staging, and follow-up, were scrutinized., Results: There were 52 males and 22 females with male predilectation. The incidence of TCL in malignant lymphoma was 12.3%. The most prevalent histologic subtype was peripheral T-cell lymphoma (PTCL), followed by nasal T-cell/Natural killer- (T-/NK-) cell lymphoma, T-lymphoblastic lymphoma (LBL), anaplastic large cell lymphoma, and enteropathy-type intestinal lymphoma (ETCL). Clinically, 39 cases (49%) had higher clinical stage (III/IV). Overall 2-year and 5-year survival rate was 51.4% and 34.7%, respectively. It was noteworthy that ETCL had high incidence rate (8.1%) and high mortality. There was significant difference in survival rates in respect of clinical stages and histological subtypes., Conclusions: TCL is relatively less frequent in Taiwan, compared to other countries in Asian and western countries. The most common histological subtypes are PTCL, unspecified and T-/NK-cell lymphoma. Five-year survival rate is 34.7%. ETCL has higher incidence rate in Taiwan. The clinical stage and histological subtypes are prognostic parameters in determining the survival rates., (Copyright Blackwell Munksgaard 2005.)

Objective: The purpose of this prospective study was to investigate the toxicity and efficacy of integrating extended-field para-aortic and pelvic external radiation, high-dose-rate intracavity brachytherapy, and concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer., Method: A phase I/II study was performed from 1998 to 2003 including sixty-three patients with both clinical FIGO and MRI/CT-based TNM stage IIB-IVA cervical cancer. Patients were treated with extended-field external radiation to the para-aortic and pelvic regions with 45 Gy in 25 fractions, and an additional boost to the gross nodes to 50.4 Gy and the parametrium to 59.4 Gy. Patients also received a high-dose-rate (HDR) intracavity brachytherapy with doses of 22-31 Gy to point A in 4-6 fractions. Concurrently, two cycles of cisplatin (50-80 mg/m(2)) were administered in weeks 1 and 5 during radiotherapy, as well as two cycles of cisplatin (60-80 mg/m(2)) for 1 day and 5-fluorouracil (600-800 mg/m(2)) for 4 days at 1 and 2 months after completion of radiotherapy. The treatment-related acute and late side effects were evaluated using RTOG criteria, and the disease control and survival rate were calculated using the Kaplan-Meier method. The median follow-up interval was 36 months., Results: All sixty-three patients completed the planned extended-field radiotherapy and high-dose-rate brachytherapy with 2 concurrent cycles of cisplatin. Fifty-eight (92%) patients received 2 cycles of the post-radiation adjuvant chemotherapy of cisplatin and 5-fluorouracil. RTOG grade III acute toxicity was gastrointestinal (2%) and hematological (10%). No patient had grade IV acute toxicity. Late grades III-IV morbidity actuarial risk of 6% at 6.5 years primarily involved the injuries to the bowels requiring surgical intervention for intestinal obstruction or fistula formation. Initial sites of recurrence were locoregional failure alone (pelvic and para-aortic regions within the radiation field), 3%; distant metastases only, 8%; and locoregional failure plus distant metastases, 8%. The observed rates at 3-year and 5-year of locoregional control, freedom from distant metastasis, and overall survival were 86% and 86%, 81% and 81%, and 81% and 77%, respectively., Conclusion: Incorporating HDR brachytherapy into a regimen including concurrent chemotherapy and extended radiation appears safe and effective.

Purpose: Neoadjuvant concomitant chemoradiotherapy has been used in cases of locally advanced rectal cancer to preserve sphincter function, decrease local recurrence, and improve survival. Preoperative staging is essential for planning and providing optimal therapy. The purpose of this study is to determine the accuracy of staging with magnetic resonance imaging and to define any factors that interfere in interpretation of images obtained after preoperative chemoradiation therapy., Methods: Thirty-six patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative concomitant 5-fluorouracil-based chemotherapy and radiation, followed six to eight weeks later by radical surgery. Preoperative magnetic resonance images were reinterpreted by one radiologist and the results compared with histopathologic staging., Results: T-level downstaging occurred in 10 of 36 patients (28 percent), and N-level downstaging occurred in 29 of 36 patients (80 percent) after completion of chemoradiation therapy. Pathologic complete remission after chemoradiotherapy occurred in five patients (12 percent). Of the 36 patients, 17 (47 percent) were overstaged and 2 (6 percent) were understaged in T-level, whereas 10 patients (28 percent) were overstaged and 3 patients (8 percent) were understaged in N-level. The accuracy of magnetic resonance imaging for determining depth of wall invasion was 47 percent, with 64 percent accuracy for nodal staging., Conclusions: Magnetic resonance imaging is commonly used in staging of pelvic malignancies because of its fine resolution, but chemoradiotherapy may decrease its accuracy. Thickening of the rectal wall after radiation by marked fibrosis, and peritumoral infiltration of inflammatory cells and vascular proliferation may contribute to overestimation of stage. By contrast, pathologic residual cancer beneath normal mural structure after chemoradiation therapy may result in understaging of rectal cancer.

We describe a comprehensive modeling approach to combining genomic and clinical data for personalized prediction in disease outcome studies. This integrated clinicogenomic modeling framework is based on statistical classification tree models that evaluate the contributions of multiple forms of data, both clinical and genomic, to define interactions of multiple risk factors that associate with the clinical outcome and derive predictions customized to the individual patient level. Gene expression data from DNA microarrays is represented by multiple, summary measures that we term metagenes; each metagene characterizes the dominant common expression pattern within a cluster of genes. A case study of primary breast cancer recurrence demonstrates that models using multiple metagenes combined with traditional clinical risk factors improve prediction accuracy at the individual patient level, delivering predictions more accurate than those made by using a single genomic predictor or clinical data alone. The analysis also highlights issues of communicating uncertainty in prediction and identifies combinations of clinical and genomic risk factors playing predictive roles. Implicated metagenes identify gene subsets with the potential to aid biological interpretation. This framework will extend to incorporate any form of data, including emerging forms of genomic data, and provides a platform for development of models for personalized prognosis.

The endoscopic findings of mucosa-associated lymphoid tissue (MALT) lymphoma were classified into exophytic and infiltrative types by Palmer and Seifert. Normal-appearing gastric MALT lymphoma is quite uncommon, and only one case had been reported in the literature. Here we report the case of a 49-year-old woman who underwent esophagogastroduodenoscopy for health screening. Endoscopy revealed indistinct follicular gastritis mucosal change and a duodenal ulcer scar, and random biopsy was taken from her stomach to check for the presence of Helicobacter pylori (H. pylori). Biopsy revealed chronic gastritis with H. pylori, and atypical lymphoid infiltration highly suggestive of MALT lymphoma. Polymerase chain reaction study using primers specific for immunoglobulin heavy chain gene showed a clonal B cell lymphoproliferation consistent with MALT lymphoma. Treatment with amoxicillin, clarithromycin, and omeprazole for H. pylori rendered complete resolution of the disease. In conclusion, follicular gastritis may be a high-risk condition that gives rise to MALT lymphoma, and further investigation is indicated.

Nearly 30% of the breast cancer patients in the Taiwanese community have their diseases diagnosed before the age of 40. Their 5-year survival rate is poorer than that of their late-onset breast cancer counterparts. Genomic abnormalities between these two breast cancer age groups were compared using comparative genomic hybridization (CGH) analyses. The sample set was made up of 44 early-onset (<35 years old) and 54 late-onset cases (>63 years old). Frequent CGH changes were noted, such as gains on 8q, 1q, and 17q and losses on 16q, 17p, and 8p. These were very similar for the two age groups, as well as for Taiwanese women and other ethnic populations. In contrast, several less common lesions, such as gains on 16p and 8p and losses on 11q and 9p, were significantly different between the early- and late-onset breast tumors. In addition, more profound chromosomal changes were consistently associated with the more advanced-stage tumors, and less expression of the estrogen and the progesterone receptors, and of HER-2/neu. About 19% of the breast cancers examined carried a TP53 mutation in exons 4-9. Of these, 88% (15/17) were missense point mutations and these were distributed randomly along the tested gene fragments without apparent clustering, as has been shown in certain other ethnic or regional studies. On average, patients carrying these TP53 mutations had 9.5 CGH lesions per case, compared to only 2.8 changes in samples that had no TP53 mutation. Our results indicate that certain genomic lesions, especially 11q loss, may play a role in early-onset breast tumor formation, and that combined use of genomic patterns and molecular targets may provide a useful tool for diagnostic, therapeutic, and prognostic purposes.

We describe a 46-year-old man with a mass in the lower lobe of the right lung. The tumor was initially suspected to be a poorly differentiated adenocarcinoma after endobronchial biopsy. Subsequently, a right lower lobectomy was performed, and a paraganglioma was diagnosed histologically. Using whole-body CT scan and metaiodobenzylguanidine (MIBG) scintigraphy, we excluded the involvement of other organs. No evidence of recurrence or metastasis was found during the follow-up period of 3 years. Primary pulmonary paragangliomas are very uncommon tumors. Literature relevant to this disease entity is discussed.

Purpose: When the primary tumor of nasopharyngeal carcinoma (NPC) is treated at the base of skull and intracranium with conventional radiotherapy, the result is generally poor. In this report, we investigated whether hyperfractionated radiotherapy (HFRT) and concomitant chemotherapy (CCT) could achieve better local control and survival in NPC patients with T3 and T4 lesions., Patients and Methods: Forty-eight patients (11 T3 and 37 T4 NPC) were treated with HFRT and CCT. HFRT was administered at 1.2 Gy per fraction, two fractions per day, Monday-Friday for 62 fractions for a total dose of 74.4 Gy. Concomitant chemotherapy consisting of cis-diamino-dichloroplatinum (CDDP) alone or CDDP and 5-fluorouracil was delivered simultaneously with radiotherapy during Weeks 1 and 6. Adjuvant chemotherapy consisted of CDDP and 5-fluorouracil for 2 to 3 cycles and was given monthly beginning 1 month after completion of radiation., Results: With a median follow-up of 57 months (range: 28-94 months), the 3-year locoregional control rate was 93%, the disease-free survival rate was 71%, and the overall survival rate was 72%. For T4 patients, the 3-year locoregional control rate was 91%, disease-free survival was 62%, and overall survival was 63%. The major acute toxicity was Grade 3 mucositis in 73% and Grade 2 weight loss in 31% of patients. Fifty percent of patients were tube fed. Most patients tolerated the combined modality treatments relatively well; 88% of patients completed their radiation treatment within 8 weeks., Conclusion: HFRT and CCT for T3 and T4 NPC were associated with excellent local control and improved survival. The treatment-related toxicity was acceptable and reversible. We would recommend using HFRT with CCT for advanced T-stage NPC if the three-dimensional conformal radiation planning shows a significant portion of the brainstem to be inside the treatment field.