Molecular insight into the specific enzymatic properties of TREX1 revealing the diverse functions in processing RNA and DNA/RNA hybrids.

In various autoimmune diseases, dysfunctional TREX1 (Three prime Repair Exonuclease 1) leads to accumulation of endogenous single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and DNA/RNA hybrids in the cytoplasm and triggers immune activation through the cGAS-STING pathway. Although inhibition of TREX1 could be a useful strategy for cancer immunotherapy, profiling cellular functions in terms of its potential substrates is a key step. Particularly important is the functionality of processing DNA/RNA hybrids and RNA substrates. The exonuclease activity measurements conducted here establish that TREX1 can digest both ssRNA and DNA/RNA hybrids but not dsRNA. The newly solved structures of TREX1-RNA product and TREX1-nucleotide complexes show that 2'-OH does not impose steric hindrance or specific interactions for the recognition of RNA. Through all-atom molecular dynamics simulations, we illustrate that the 2'-OH-mediated intra-chain hydrogen bonding in RNA would affect the binding with TREX1 and thereby reduce the exonuclease activity. This notion of higher conformational rigidity in RNA leading TREX1 to exhibit weaker catalytic cleavage is further validated by the binding affinity measurements with various synthetic DNA-RNA junctions. The results of this work thus provide new insights into the mechanism by which TREX1 processes RNA and DNA/RNA hybrids and contribute to the molecular-level understanding of the complex cellular functions of TREX1 as an exonuclease.

A predictive survival model for patients with stage IV oropharyngeal squamous cell carcinoma treated with chemoradiation.

PURPOSE: To evaluate the pre-treatment and post-treatment clinical factors associated with rate of survival at 1, 3, and 5 years in stage IV oropharyngeal cancer patients treated with concurrent chemoradiation with/without neoadjuvant chemotherapy. METHODS: This retrospective cohort study involved 128 Stage IV oropharyngeal cancer patients that were treated at our tertiary referral center between 2008 and 2020. The pre-treatment and post-treatment clinical parameters including nutritional status and inflammatory markers were retrospectively reviewed. RESULTS: The 5-year overall survival rate for all patients was 36.72%. The disease-specific survival (DSS) at 1-year and 3-year were 80% and 63%, whereas the disease-free survival (DFS) at 1-year and 3-year were 49% and 40%, respectively. In multivariate analyses, pretreatment hemoglobin (Hb) < 12 g/dL (hazard ratio [HR] 2.551, 95% confidence interval [CI] 1.366-4.762, p = 0.003), pretreatment systemic immune inflammation (SII) ≥ 1751 (HR 2.173, 95% CI 1.015-4.652, p = 0.046), and posttreatment systemic inflammation response index (SIRI) ≥ 261 (HR 2.074, 95% CI 1.045-4.115, p = 0.037) were independent indicators for worsened DSS. Pretreatment Hb < 12 g/dl (HR 1.692, 95% CI 1.019-2.809, p = 0.032), pretreatment SII ≥ 1751 (HR 1.968, 95% CI 1.061-3.650, p = 0.032), and posttreatment SII ≥ 1690 (HR 1.922, 95% CI 1.105-3.345, p = 0.021) were independent indicators for worsened DFS. A nomogram was developed using pretreatment Hb, pretreatment SII, and posttreatment SIRI to forecast DSS. CONCLUSIONS: The pretreatment Hb, pretreatment SII, posttreatment SII, and posttreatment SIRI are associated with survival in patients with stage IV oropharyngeal cancers. The developed nomogram aids in survival prediction and treatment adjustment.

Speech and Swallowing Rehabilitation Potentially Decreases Body Weight Loss and Improves Survival in Head and Neck Cancer Survivors.

This retrospective observational cohort study aims to assess the outcomes and associated factors in head and neck cancer (HNC) survivors with dysphagia, and to investigate the relationship between outcomes and speech and swallowing rehabilitation (SSR). We enrolled patients who were diagnosed with HNC between October 2016 and July 2018; we included 393 patients who developed dysphagia after definite treatment and were referred to speech-language pathologists (SLPs). We then classified patients into groups according to whether they received SSR. We used the clinical variables-including age, sex, site of malignancy, cancer stage, treatment modality, SSR, initial ECOG score, initial KPS, initial body weight (BW), and initial BMI-to evaluate the association between the percentage of BW change and overall survival (OS). There were 152 (39%) and 241 (61%) patients who received and did not receive SSR, respectively. In multivariate linear regression, SSR was significantly associated with percentage change in BW at 3 months post-treatment. Having SSR was positively associated with the percentage change in BW and decreased the BW loss [ß coefficient (95% CIs) = 2.53 (0.92 to 4.14)] compared to having no SSR. In the multivariate Cox regression, SSR was an independent factor for OS. Compared to no SSR, the hazard ratio (95% CIs) for patients who received SSR was 0.48 (0.31 to 0.74). SSR helps to avoid BW loss and increases overall survival. HNC patients who develop dysphagia after treatment should be encouraged to participate in SSR.

Postchemoradiotherapy systemic inflammation response index predicts treatment response and overall survival for patients with locally advanced nasopharyngeal cancer.

BACKGROUND/PURPOSE: To explore the clinical utility of the systemic inflammation response index (SIRI) in the prediction of patients with poor treatment response to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal cancer (NPC). METHODS: A total of 167 stage III-IVB (AJCC 7th edition) nasopharyngeal cancer patients who received CCRT were retrospectively collected. The SIRI was calculated using the following formula: SIRI = neutrophil count × monocyte count/lymphocyte count (109/L). The optimal cutoff values of the SIRI for noncomplete response were determined by receiver operating characteristic curve analysis. Logistic regression analyses were performed to identify factors predictive of treatment response. We used Cox proportional hazards models to identify predictors of survival. RESULTS: Multivariate logistic regression showed that only the posttreatment SIRI was independently associated with treatment response in locally advanced NPC. A posttreatment SIRI≥1.15 was a risk factor for developing an incomplete response after CCRT (odds ratio 3.10, 95% confidence interval (CI): 1.22-9.08, p = 0.025). A posttreatment SIRI≥1.15 was also an independent negative predictor of progression-free survival (hazard ratio 2.38, 95% CI: 1.35-4.20, p = 0.003) and overall survival (hazard ratio 2.13, 95% CI: 1.15-3.96, p = 0.017). CONCLUSION: The posttreatment SIRI could be used to predict the treatment response and prognosis of locally advanced NPC.

A predictive model for advanced oropharyngeal cancer patients treated with chemoradiation.

BACKGROUND: To analyze clinical characteristics in the prediction of death within 1 year in advanced oropharyngeal cancer patients treated with chemoradiation. METHODS: One hundred forty-seven advanced oropharyngeal cancer patients who underwent curative-intent chemoradiation treatment were retrospectively enrolled. The pre-treatment clinical parameters including inflammatory markers were reviewed. RESULTS: The 1-year death rate for all patients was 29% [95% confidence interval (CI): 23-37%]. In multivariate logistic regression analysis, hemoglobulin (Hb) < 13.5 g/dl was an independent indicator of death within 1-year [Odds ratio (OR) 5.85, 95% CI 2.17-15.75, p < 0.001]. Systemic immune inflammation (SII) ≥ 1820 was also a significant factor for prediction of death within 1 year (OR 4.78, 95% CI 1.44-15.85, p = 0.011). We further used gander, age, Hb and SII to develop a nomogram to predict death within 1 year. The c-index of the model was 0.75 (95%CI 0.66-0.83). For patients with low nomogram score (< 14) versus high nomogram score (≥ 14), the 1-year and 2-year OS rates were 91 and 71% versus 53 and 29%, respectively. (p < 0.001). A difference in the disease persistence or recurrence rate between patients with high and low nomogram score was significant (73 and 28%, respectively; p < 0.001). CONCLUSIONS: The pre-treatment Hb < 13.5 g/dl and SII ≥ 1820 are associated with higher risks of death within 1-year in patients with advanced oropharyngeal cancers. Nomogram can aid in patient counseling and treatment modality adjustment. The development of a more effective treatment protocol for patients with high nomogram score will be essential.

Nutritional status at diagnosis is prognostic for pharyngeal cancer patients: a retrospective study.

BACKGROUND: Malnutrition in head and neck cancer (HNC) patients is associated with increased morbidity and mortality. Several nutrition indicators have been reported to be related to the prognosis of HNC. However, the prognostic effect of these multiple nutrition factors in HNC is not well elucidated. The aim of this study was to evaluate the prognostic effect of these factors, including the novel hemoglobin, albumin, lymphocyte, and platelet (HALP) score, for pharyngeal cancers. MATERIAL AND METHODS: From 2008 to 2019, a total of 319 pharyngeal cancer patients were recruited. We collected adult patients with a diagnosis of nasopharyngeal carcinoma, oropharyngeal carcinoma and hypopharyngeal carcinoma. Patients who completed definite staging workup and treatment were selected for analysis. We traced nutritional and hematological parameters, including body mass index (BMI), albumin, and complete blood count, for survival analysis. RESULTS: We found that multiple nutritional markers, including BMI, hemoglobin, albumin, prognostic nutritional index (PNI), nutritional risk index (NRI) and HALP score, were important predictors for pharyngeal cancers in univariate Cox regression analysis. In multivariate analysis, we found that the HALP score was still an independent factor (HR: 1.62, 1.13-2.32 for overall survival [OS]) after adjusting of gender, age, cancer site, clinical stage, and BMI. The PNI was the most important independent factor for OS (HR: 3.12, 2.18-4.47) and cancer-specific survival (HR: 2.88, 1.88-4.41) in multivariate analysis. CONCLUSION: We found that multiple nutrition markers, including BMI, hemoglobin, albumin, PNI, NRI and HALP score, are important predictors for pharyngeal cancers. This is the first report confirming the prognostic effect of the HALP score for HNCs. Nutritional status at diagnosis should be given more attention in pharyngeal cancer patients.

Clinical-associated characteristics and microbiological features of bloodstream nontyphoidal salmonella infection in adult patients receiving allogeneic hematopoietic stem cell transplantation.

Bloodstream nontyphoidal salmonella (NTS) infection is rare, but its associated characteristics and microbiological features in immunocompromised patients are worth paying attention to, particularly for those receiving allogeneic hematopoietic stem cell transplantation (SCT). No studies so far have analyzed post-transplant bloodstream NTS infection. Therefore, we reviewed 423 adult patients undergoing allogeneic hematopoietic SCT from 2003 to 2014. Nine out of four hundred twenty-three patients (2.13%) developed post-transplant bloodstream NTS infection, including two patients who had subsequent or combined metastatic infections. The median age at SCT was 35 years (interquartile range, 29-46) among the nine patients with bloodstream NTS infection. Male patients were predominant (78%). The median onset of bloodstream NTS infection was at 315 days after SCT (range, 207-629). Multivariate analysis revealed that extensive chronic graft-versus-host disease (GVHD) (OR 8.054, p = 0.003) and nonmyeloablative transplant conditioning (OR 4.604, p = 0.037) were significant associated characteristics for NTS infection. Currently, there are no published data analyzing and exploring post-transplant bloodstream NTS infections in adult allogeneic hematopoietic SCT. Our study determined the associated characteristics and microbiological features for this infection.

Decision-tree algorithm for optimized hematopoietic progenitor cell-based predictions in peripheral blood stem cell mobilization.

BACKGROUND: Enumerating hematopoietic progenitor cells (HPCs) by using an automated hematology analyzer is a rapid, inexpensive, and simple method for predicting a successful harvest compared with enumerating circulating CD34+ cells. However, the optimal HPC cutoff count and the indicating factors to be considered for improved predicting have not yet been determined. STUDY DESIGN AND METHODS: Between 2007 and 2012, a total of 189 consecutive patients who proceeded to peripheral blood stem cell (PBSC) harvesting were retrospectively recruited. Baseline characteristics were analyzed to identify the risk factors for a failed harvest, which were defined as less than 2 × 10(6) CD34+ cells/kg. Variables identified by multivariate logistic regression and correlation analysis for predicting a successful harvest were subjected to classification and regression tree (CART) analysis. RESULTS: PBSCs were successfully harvested in 154 (81.5%) patients. An age of at least 60 years, a diagnosis of a solid tumor, at least five prior chemotherapy cycles, prior radiotherapy, and mobilization with granulocyte-colony-stimulating factor alone or high-dose cyclophosphamide were independent baseline predictors of poor mobilization. In CART analysis, patients with zero to two host risk factors and either higher HPC (≥28 × 10(6) /L) or mononuclear cell (MNC; ≥3.5 × 10(9) /L) counts were categorized as good mobilizers and their harvest success rate was 92.3%. By contrast, 30.3% of harvests were adequate in the patients with three to five host risk factors and lower HPC and MNC counts. CONCLUSION: A CART algorithm incorporating host predictors and HPC and MNC counts improves predictions in a successful harvest and might reduce the necessity of monitoring peripheral CD34+ cells.

Cubitanoids and Cembranoids from the Soft Coral Sinularia nanolobata.

Two new cubitanoids, nanoculones A and B (1 and 2), and three new cembranoids, nanolobols A-C (3-5), as well as six known compounds, calyculone I (6), sinulariuol A (7), sinulariols C, D, H, and J (8-11), were isolated from the soft coral Sinularia nanolobata, collected off the coast of the eastern region of Taiwan. Their structures were elucidated on the basis of extensive spectroscopic analysis. Cytotoxicity of compounds 1-11 was evaluated. The nitric oxide (NO) inhibitory activity of selected compounds was further measured by assay of lipopolysaccharide (LPS)-stimulated NO production in activated RAW264.7 cells. The results showed that none of 1-11 exhibited cytotoxicity against the tested cancer cell lines, whereas compound 8 was found to significantly reduce NO production.

Diminishing prognostic role of preexisting diabetes mellitus for patients with diffuse large B-cell lymphoma in the rituximab era.

Rituximab reforms the treatment of diffuse large B-cell lymphoma (DLBCL) and the prognostic significance of baseline patient features should be reevaluated. Few population-based studies have investigated the association of diabetes mellitus (DM) and outcomes of lymphoma; however, the results remain inconclusive. From January 1, 2000 to December 31, 2009, a total of 468 consecutive newly diagnosed DLBCL patients receiving first-line chemotherapy with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) or rituximab plus CHOP (R-CHOP) were enrolled. Pre-existing DM was defined according to medical history, use of antidiabetic medications, or any record of an abnormal hemoglobin A1c test. Progression-free survival (PFS) and overall survival (OS) were estimated and compared using the Kaplan-Meier method with a log-rank test. CHOP was administered in 194 patients, and 274 patients received R-CHOP. DM was identified in 16.2 % (76/468) of patients. Diabetic patients were older and more performance restricted, compared to the non-DM patients in both the CHOP and R-CHOP groups. In the CHOP group, 5-year PFS and OS were inferior in DM patients (PFS, 32.4 vs. 50.0 % (P = 0.039); OS, 38.2 vs. 62.5 % (P = 0.002)). However, outcomes were similar for both DM and non-DM patients in the context of R-CHOP treatment (PFS, 69.0 vs. 57.3 % (P = 0.179); OS, 76.2 vs. 69.8 % (P = 0.586)). The response rate of chemotherapy in DM patients was also improved to a level similar to non-DM patients with rituximab use. In conclusion, the prognostic significance of preexisting DM in DLBCL patients is changing in the rituximab era. The potentially additional benefit of rituximab in DM patients merits further investigation.

Screening and surveillance of esophageal cancer by magnifying endoscopy with narrow band imaging improves the survival of hypopharyngeal cancer patients.

Introduction: Patients with head and neck cancer may develop a second primary neoplasm (SPN) of the esophagus due to field cancerization. This study investigated the impacts of esophageal cancer screening using magnifying endoscopy with narrow-band imaging (ME-NBI) on the outcomes of hypopharyngeal cancer patients. Methods: Patients with hypopharyngeal cancer diagnosed from 2008 to 2021 in a tertiary hospital were reviewed retrospectively. Screening and surveillance using ME-NBI examination of the esophagus were divided into three patterns: (1) ME-NBI never performed or more than 6 months after diagnosis of index primary hypopharyngeal cancer, (2) ME-NBI within 6 months only, and (3) ME-NBI within 6 months and regular surveillance. Results: A total of 261 were reviewed and 21 (8%) patients were in stage I, 20 (8%) in stage II, 27 (10%) in stage III, 116 (44%) in stage IVA, 65 (25%) in stage IVB, and 12 (5%) in stage IVC. Sixty-seven (26%) patients had SPN (50 esophagus, 10 oral cavity, 3 oropharynx, 2 nasopharynx, 1 larynx and 1 lung). Among esophageal SPN, 35 (70%) and 15 (30%) patients developed synchronous and metachronous neoplasia, respectively. In multivariate Cox regression analysis, advanced stages III and IV (compared with stages I and II, HR: 1.86, 1.18-2.95, p=0.008), ME-NBI examination of the esophagus received within 6 months and regular surveillance (HR: 0.53, 0.36-0.78, p=0.001) were independent factors affecting the overall survival of patients with hypopharyngeal cancer. Discussion: Our findings demonstrated that screening and surveillance of esophageal SPN by ME-NBI improves the survival of patients with hypopharyngeal cancer.

Endoscopic Screening for Second Primary Tumors of the Esophagus Among Head and Neck Cancer Patients.

Malignancies of the head and neck (HN) region and esophagus are among the most common cancers worldwide. Due to exposure to common carcinogens and the theory of field cancerization, HN cancer patients have a high risk of developing second primary tumors (SPTs). In our review of 28 studies with 51,454 HN cancer patients, the prevalence of SPTs was 12%. The HN area is the most common site of SPTs, followed by the lungs and esophagus, and 13% of HN cancer patients have been reported to have esophageal high-grade dysplasia or invasive carcinoma. The prognosis of HN cancer patients with concomitant esophageal SPTs is poor, and therefore identifying esophageal SPTs as early as possible is of paramount importance for risk stratification and to guide the treatment strategy. Image-enhanced endoscopy, especially using narrow-band imaging endoscopy and Lugol's chromoendoscopy, has been shown to improve the diagnostic performance in detecting esophageal neoplasms at an early stage. Moreover, the early detection and minimally invasive endoscopic treatment of early esophageal neoplasm has been shown to improve the prognosis. Well-designed prospective studies are warranted to establish appropriate treatment and surveillance programs for HN cancer patients with esophageal SPTs.

Spotted Temporal Lobe Necrosis following Concurrent Chemoradiation Therapy Using Image-Guided Radiotherapy for Nasopharyngeal Carcinoma.

Background: To explore spotted temporal lobe necrosis (TLN) and changes in brain magnetic resonance imaging (MRI) after image-guided radiotherapy (IGRT) in a patient with nasopharyngeal carcinoma (NPC). Case presentation: a 57-year-old male was diagnosed with stage III NPC, cT1N2M0, in 2017. He underwent concurrent chemoradiation therapy (CCRT) with cisplatin (30 mg/m2) and 5- fluorouracil (5-FU, 500 mg/m2) plus IGRT with 70 Gy in 35 fractions for 7 weeks. The following MRI showed a complete response in the NPC. However, the patient suffered from fainting periodically when standing up approximately 3 years after CCRT. Neck sonography showed mild atherosclerosis (< 15%) of bilateral carotid bifurcations and bilateral small-diameter vertebral arteries, with reduced flow volume. The following MRI showed a 9 mm × 7 mm enhancing lesion in the right temporal lobe without locoregional recurrence, and TLN was diagnosed. The lesion was near the watershed area between the anterior temporal and temporo-occipital arteries. The volume of the necrotic lesion was 0.51 c.c., and the mean dose and Dmax of the lesion were 64.4 Gy and 73.7 Gy, respectively. Additionally, the mean dose, V45, D1 c.c. (dose to 1 ml of the temporal lobe volume), D0.5 c.c. and Dmax of the right and left temporal lobes were 11.1 Gy and 11.4 Gy, 8.5 c.c. and 6.7 c.c., 70.1 Gy and 67.1 Gy, 72.0 Gy and 68.8 Gy, and 74.2 Gy and 72.1 Gy, respectively. Conclusion: Spotted TLN in patients with NPC treated by IGRT may be difficult to diagnose due to a lack of clinical symptoms and radiological signs. Endothelial damage may occur in carotid and vertebral arteries within the irradiated area, affecting the small branches supplying the temporal lobe and inducing spotted TLN. Future research on the relationship between vessels and RT or CCRT and the development of TLN is warranted.

Advances in Image-Guided Radiotherapy in the Treatment of Oral Cavity Cancer.

Image-guided radiotherapy (IGRT) is an advanced auxiliary radiotherapy technique. During cancer treatment, patients with oral cavity cancer (OCC) experience not only disease but also adverse effects due to RT. IGRT provides the relevant advantages of RT by precisely delivering tumoricidal doses via real-time knowledge of the target volume location and achieves maximal tumor control with minimal complications as recommended for cancer treatment. Additionally, studies have shown that IGRT can improve clinical outcomes in terms of not only treatment side effects but also survival benefits for cancer patients. IGRT can be performed alongside various imaging methods, including computed tomography and magnetic resonance imaging, and at different times during the radiotherapy regimen. This article reviews the literature to discuss the effects and importance of IGRT for patients with OCC, examines the rationale underlying the advantages of IGRT, discusses the limitations of IGRT with respect to different techniques, and summarizes the strategies and future prospects of IGRT in the treatment of OCC.

Validation of the medical outcomes study HIV (MOS-HIV) health survey among HIV-infected patients in Taiwan.

OBJECTIVES: To examine both the reliability and the validity of the 'Medical Outcomes Study HIV' (MOS-HIV) health survey among HIV-infected patients in Taiwan. METHODS: Data were collected from 619 HIV-infected outpatients, with the reliability and the validity of the MOS-HIV survey subsequently being examined by multi-trait scaling techniques, internal consistency, convergent validity, known-group validity and factorial validity. RESULTS: The MOS-HIV health survey was found to have excellent success rates in the item-consistency and discriminant-validity tests, as well as good convergent validity and known-group validity. An acceptable fit was found for three of the four indices in the original two-factor model (non-normed fit index = 0.92, comparative fit index = 0.94 and standardized root mean squared residual = 0.056). CONCLUSIONS: The findings of the present study provide strong evidence in support of the reliability and validity of the MOS-HIV health survey for the assessment of quality of life among HIV-infected patients in Taiwan. We find that the original factor structure of the MOS-HIV survey remains valid for patients from Chinese cultural backgrounds. This study therefore contributes to the existing evidence within the extant literature on the cultural relevance of the MOS-HIV health survey (a measure originally developed within a Western culture) as a valid measure for cross-cultural comparative studies on health-related quality of life.

Impact of parent-child relationship and sex on trajectories of children internalizing symptoms.

INTRODUCTION: Parenting and parental-child relationship may lead children to develop behavior disorders that can affect many aspects of their later life. This study aimed to examine the impact of parent-child relationship and sex on the development of internalizing symptoms in children. METHODS: Childhood and Adolescent Behaviors in Long-term Evolution (CABLE) is a longitudinal healthy-lifestyle research for which 18 elementary schools were randomly selected respectively in Taipei and Hsinchu in Taiwan. Data on sex, parent-child relations, and internalizing symptoms from four waves of follow-up were analyzed: 2003 (9 year olds), 2006 (12 year olds), 2009 (15 year olds) and 2012 (18 year olds). A latent growth model was used to examine the impact of parental-child relationship and sex on the trajectory of children's internalizing symptoms. RESULTS: Results show that internalizing symptoms is more severe (ß = 0.21, p < 0.01) and their growth rate faster (ß = 0.15, p < 0.01) in girls than in boys. Results from latent growth model show that parent-child relationship is negatively related to the internalizing symptoms intercept (ß = -0.59, p < 0.01) and is positively related to the internalizing symptoms slope (ß = 0.18, p < 0.01). LIMITATIONS: Self-reported measures were used. Parent-child relationship was only provided at 2003. CONCLUSION: The findings suggest that girls are more susceptible to internalizing symptoms in puberty, and better parent-child relationship can have a protective influence although the protective impact reduced through time. Health professionals should be sensitive to sex, family functioning and provide positive parenting programs for children at risk for internalizing symptoms.

Therapeutic Zfra4-10 or WWOX7-21 Peptide Induces Complex Formation of WWOX with Selective Protein Targets in Organs that Leads to Cancer Suppression and Spleen Cytotoxic Memory Z Cell Activation In Vivo.

Synthetic Zfra4-10 and WWOX7-21 peptides strongly suppress cancer growth in vivo. Hypothetically, Zfra4-10 binds to the membrane Hyal-2 of spleen Z cells and activates the Hyal-2/WWOX/SMAD4 signaling for cytotoxic Z cell activation to kill cancer cells. Stimulation of membrane WWOX in the signaling complex by a WWOX epitope peptide, WWOX7-21, is likely to activate the signaling. Here, mice receiving Zfra4-10 or WWOX7-21 peptide alone exhibited an increased binding of endogenous tumor suppressor WWOX with ERK, C1qBP, NF-κB, Iba1, p21, CD133, JNK1, COX2, Oct4, and GFAP in the spleen, brain, and/or lung which led to cancer suppression. However, when in combination, Zfra4-10 and WWOX7-21 reduced the binding of WWOX with target proteins and allowed tumor growth in vivo. In addition to Zfra4-10 and WWOX7-21 peptides, stimulating the membrane Hyal-2/WWOX complex with Hyal-2 antibody and sonicated hyaluronan (HAson) induced Z cell activation for killing cancer cells in vivo and in vitro. Mechanistically, Zfra4-10 binds to membrane Hyal-2, induces dephosphorylation of WWOX at pY33 and pY61, and drives Z cell activation for the anticancer response. Thus, Zfra4-10 and WWOX7-21 peptides, HAson, and the Hyal-2 antibody are of therapeutic potential for cancer suppression.

Different prevalence rates of Parkinson's disease in urban and rural areas: a population-based study in Taiwan.

BACKGROUND: Rural living has long been debated as a risk factor for idiopathic Parkinson's disease (IPD). But few community-based studies compared this difference between urban and rural areas. METHODS: Population-based surveys by neurologists using a standardized diagnostic protocol were conducted in the urban areas of Keelung City and compared the prevalence rates of IPD with those we had previously determined in the rural area of Ilan County, Taiwan. Subjects were diagnosed with IPD when at least 2 of the 4 cardinal signs of parkinsonism were present and by exclusion of secondary parkinsonism. Gender-specific age-standardized prevalence rates of IPD by using the 1970 and 2000 US censuses were calculated for comparison. RESULTS: The participation rate was 84.9%. The crude prevalence rate of IPD in persons aged 40 years and over was 706 (95% CI: 551-864) per 100,000 population. The age-adjusted prevalence rates by using the 1970 US census were 633 (95% CI: 620-646) for people aged 40 and over and 230 (95% CI: 227-234) for all ages. Our results were similar to those obtained in Sicily, Rotterdam, and 3 communities in China. Moreover, the prevalence rates of IPD in Keelung, the urban area studied, were twice as high as those in Ilan, the rural area studied (p < 0.001). CONCLUSIONS: Our results suggest that urban living is more important as a risk factor for IPD development than rural living in Taiwan.

Enhanced visual short-term memory for angry faces.

Although some views of face perception posit independent processing of face identity and expression, recent studies suggest interactive processing of these 2 domains. The authors examined expression-identity interactions in visual short-term memory (VSTM) by assessing recognition performance in a VSTM task in which face identity was relevant and expression was irrelevant. Using study arrays of between 1 and 4 faces and a 1,000-ms retention interval, the authors measured recognition accuracy for just-seen faces. Results indicated that significantly more angry face identities can be stored in VSTM than happy or neutral face identities. Furthermore, the study provides evidence to exclude accounts for this angry face benefit based on physiological arousal, opportunity to encode, face discriminability, low-level feature recognition, expression intensity, or specific face sets. Perhaps processes activated by the presence of specifically angry expressions enhance VSTM because memory for the identities of angry people has particular behavioral relevance.

Identification of SEPTIN12 as a novel target of the androgen and estrogen receptors in human testicular cells.

SEPTIN12 (SEPT12) is a testis-enriched gene that is downregulated in the testis of infertile men with severe spermatogenic defects. While SEPT12 is involved in spermatogenic failure and sperm motility disorder, SEPT12 transcriptional regulation is still unknown. Here we report the promoter region of SEPT12 as a 245 bp segment upstream of the transcription start site. One androgen receptor (AR) and two estrogen receptor α (ERα) binding sites in this region were initially identified by bioinformatics prediction and confirmed by chromatin immunoprecipitation assay. Truncated ERα or AR binding sites decreased the promoter activity, which indicated that the ERα and AR are essential for the SEPT12 promoter. On the other hand, the promoter activity was enhanced by the treatment with 17ß-estradiol (E2) and 5α-dihydrotestosterone (5α-DHT). Thus, one androgen and two estrogen hormone responsive elements located in the promoter of SEPT12 gene can regulate SEPT12 expression. Two single nucleotide polymorphisms (SNPs), rs759992 T > C and rs3827527 C > T, were observed in the SEPT12 gene promoter region and were able to decrease the promoter activity. In conclusion, the current work identified the promoter of the human SEPT12 gene and provided key evidence about its transcriptional regulation via E2 and 5α-DHT. Since SEPT12 has an important role in spermatogenesis, SEPT12 expression analysis can be developed as a potential tool for the assessment of environmental or food pollution by hormones or for the evaluation of the risk of endocrine-disrupting chemicals (EDCs) in general.