bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of emergency hospital admissions for drug poisoning and major diseases: a retrospective observational study using a nationwide administrative discharge database
Authors: Okumura Yasuyuki , Shimizu Sayuri , Ishikawa Koichi B , Matsuda Shinya , Fushimi Kiyohide , Ito Hiroto 
Published: December 2012

ObjectiveTo compare the clinical and procedural characteristics of emergency hospital admissions for drug poisoning and major diseases.DesignRetrospective observational study.SettingDischarged patients from 855 acute care hospitals from 1 July to 31 December in 2008 in Japan.ResultsThere were a total of 1 157 893 emergency hospital admissions. Among the top 100 causes, drug poisoning was ranked higher in terms of the percentage of patients using ambulance services (74.1%; second) and tertiary emergency medical services (37.8%; first). Despite higher utilisation of emergency care resources, drug poisoning ranked lower in terms of the median length of stay (2 days; 100th), percentage of requirement for surgical procedures (1.7%; 91st) and inhospital mortality ratio (0.3%; 74th).ConclusionsDrug poisoning is unique among the top 100 causes of emergency admissions. Our findings suggest that drug poisoning imposes a greater burden on emergency care resources but has a less severe clinical course than other causes of admissions. Future research should focus on strategies to reduce the burden of drug poisoning on emergency medical systems.
Molecular epidemiology of gonorrhoea in Wales (UK)
Authors: Cole Michelle J , Thomas Daniel Rh , Chisholm Stephanie A , Abdullah Adel N , Birley Humphrey , Hosein Ian , Kubiak Elizabeth , White Diana , Martin Iona , Ison Catherine A 
Published: December 2012

ObjectivesAfter a trend of increasing incidence of gonorrhoea in the 1990s, by 2004 the incidence was declining in England, but continuing to increase in Wales. This prompted an investigation of the epidemiology of gonorrhoea in Wales to inform future prevention and control measures.MethodsAs an extension to Gonococcal Resistance to Antimicrobials Surveillance Programme, between May 2005 and September 2006, 540 consecutive gonococcal isolates were collected from three microbiology laboratories in South Wales. Isolates were typed usingNeisseria gonorrhoeaeMulti Antigen Sequence Typing tested for susceptibility to therapeutic agents and demographic and behavioural data were collected retrospectively from patient notes.Results163 sequence types (STs) were identified in 475N gonorrhoeaeisolates from 502 patient episodes. The most frequently observed STs (>20 isolates) were: 2, 752, 471, 249 and 8, all of which were susceptible to the antimicrobial agents tested. A significant association between ST and sexual orientation was identified, the most frequently observed STs occurring in young (median age <25 years) heterosexuals. STs 147, 4, 1634 and 64 predominated in men who have sex with men.ConclusionsWe confirm the existence of common STs across the UK, as well as identify a number of types that were novel to Wales. Discrete sexual networks were identified, the most localised being in young heterosexuals. Molecular typing provides a method for identifying local clusters of gonorrhoea, and could assist in the implementation and evaluation of targeted interventions.
Observation of a cytopathogenic effect on cell lines used for routine viral cultures led to the diagnosis of lymphogranuloma venereum
Authors: Busson Laurent , Crucitti Tania , De Foor Marc , Van den Wijngaert Sigi , Vandenberg Olivier 
Published: December 2012

ObjectivesThis article reports the fortuitous recovery of nineChlamydia trachomatisserovar L strains in cell cultures (Vero and LLC-MK2cell line) designed for viral culture.MethodsNine ano-genital swabs were inoculated on confluent Vero, MRC5 and LLC-MK2cell cultures. They were collected from HIV-positive patients who were primarily men who have sex with men (MSM) presenting ulcerations that mimicked herpes simplex infections.ResultsA cytopathogenic effect was observed on Vero and LLC-MK2cells on day 14. The presence ofC trachomatisserovar L in the cell lines was confirmed by Real Time–PCR.ConclusionsC trachomatisserovar L can grow on Vero and LLC-MK2cell lines designed for viral cultures. Lymphogranuloma venereum must be considered as a differential diagnosis for herpes-like lesions, particularly in MSM with high-risk behaviours.
Neuropilin-1 Identifies a Subset of Bone Marrow Gr1− Monocytes That Can Induce Tumor Vessel Normalization and Inhibit Tumor Growth
Authors: Carrer Alessandro , Moimas Silvia , Zacchigna Serena , Pattarini Lucia , Zentilin Lorena , Ruozi Giulia , Mano Miguel , Sinigaglia Milena , Maione Federica , Serini Guido , Giraudo Enrico , Bussolino Federico , Giacca Mauro 
Published: December 2012

AbstractImproving tumor perfusion, thus tempering tumor-associated hypoxia, is known to impair cancer progression. Previous work from our laboratory has shown that VEGF-A165 and semaphorin 3A (Sema3A) promote vessel maturation through the recruitment of a population of circulating monocytes expressing the neuropilin-1 (Nrp1) receptor (Nrp1-expressing monocytes; NEM). Here, we define the characteristics of bone marrow NEMs and assess whether these cells might represent an exploitable tool to induce tumor vessel maturation. Gene expression signature and surface marker analysis have indicated that NEMs represent a specific subset of CD11b+ Nrp1+ Gr1− resident monocytes, distinctively recruited by Sema3A. NEMs were found to produce several factors involved in vessel maturation, including PDGFb, TGF-β, thrombospondin-1, and CXCL10; consistently, they were chemoattractive for vascular smooth muscle cells in vitro. When directly injected into growing tumors, NEMs, isolated either from the bone marrow or from Sema3A-expressing muscles, exerted antitumor activity despite having no direct effects on the proliferation of tumor cells. NEM inoculation specifically promoted mural cell coverage of tumor vessels and decreased vascular leakiness. Tumors treated with NEMs were smaller, better perfused and less hypoxic, and had a reduced level of activation of HIF-1α. We conclude that NEMs represent a novel, unique population of myeloid cells that, once inoculated into a tumor, induce tumor vessel normalization and inhibit tumor growth. Cancer Res; 72(24); 6371–81. ©2012 AACR.
Obesity and Overfeeding Affecting Both Tumor and Systemic Metabolism Activates the Progesterone Receptor to Contribute to Postmenopausal Breast Cancer
Authors: Giles Erin D. , Wellberg Elizabeth A. , Astling David P. , Anderson Steven M. , Thor Ann D. , Jindal Sonali , Tan Aik-Choon , Schedin Pepper S. , MacLean Paul S. 
Published: December 2012

Abstract
Obese postmenopausal women have increased risk of breast cancers with poorer clinical outcomes than their lean counterparts. However, the mechanisms underlying these associations are poorly understood. Rodent model studies have recently identified a period of vulnerability for mammary cancer promotion, which emerges during weight gain after the loss of ovarian function (surgical ovariectomy; OVX). Thus, a period of transient weight gain may provide a life cycle–specific opportunity to prevent or treat postmenopausal breast cancer. We hypothesized that a combination of impaired metabolic regulation in obese animals prior to OVX plus an OVX-induced positive energy imbalance might cooperate to drive tumor growth and progression. To determine if lean and obese rodents differ in their metabolic response to OVX-induced weight gain, and whether this difference affects later mammary tumor metabolism, we performed a nutrient tracer study during the menopausal window of vulnerability. Lean animals preferentially deposited excess nutrients to mammary and peripheral tissues rather than to the adjacent tumors. Conversely, obese animals deposited excess nutrients into the tumors themselves. Notably, tumors from obese animals also displayed increased expression of the progesterone receptor (PR). Elevated PR expression positively correlated with tumor expression of glycolytic and lipogenic enzymes, glucose uptake, and proliferation markers. Treatment with the antidiabetic drug metformin during ovariectomy-induced weight gain caused tumor regression and downregulation of PR expression in tumors. Clinically, expression array analysis of breast tumors from postmenopausal women revealed that PR expression correlated with a similar pattern of metabolic upregulation, supporting the notion that PR+ tumors have enhanced metabolic capacity after menopause. Our findings have potential explanative power in understanding why obese, postmenopausal women display an increased risk of breast cancer. Cancer Res; 72(24); 6490–501. ©2012 AACR.
Role of Chemokines and Chemokine Receptors in Shaping the Effector Phase of the Antitumor Immune Response
Authors: Franciszkiewicz Katarzyna , Boissonnas Alexandre , Boutet Marie , Combadière Christophe , Mami-Chouaib Fathia 
Published: December 2012

Abstract
Immune system–mediated eradication of neoplastic cells requires induction of a strong long-lasting antitumor T-cell response. However, generation of tumor-specific effector T cells does not necessarily result in tumor clearance. CTL must first be able to migrate to the tumor site, infiltrate the tumor tissue, and interact with the target to finally trigger effector functions indispensable for tumor destruction. Chemokines are involved in circulation, homing, retention, and activation of immunocompetent cells. Although some of them are known to contribute to tumor growth and metastasis, others are responsible for changes in the tumor microenvironment that lead to extensive infiltration of lymphocytes, resulting in tumor eradication. Given their chemoattractive and activating properties, a role for chemokines in the development of the effector phase of the antitumor immune response has been suggested. Here, we emphasize the role of the chemokine–chemokine receptor network at multiple levels of the T-cell–mediated antitumor immune response. The identification of chemokine-dependent molecular mechanisms implicated in tumor-specific CTL trafficking, retention, and regulation of their in situ effector functions may offer new perspectives for development of innovative immunotherapeutic approaches to cancer treatment. Cancer Res; 72(24); 6325–32. ©2012 AACR.
TLRs as miRNA Receptors
Authors: Fabbri Muller 
Published: December 2012

Abstract
MicroRNAs (miRNA) are small noncoding RNAs with gene regulatory functions. Their expression is frequently dysregulated in almost all human tumors and they can be found circulating within exosomes secreted by cancer cells. In addition to being promising cancer biomarkers with diagnostic, prognostic, and theranostic implications, circulating miRNAs have also important biologic functions: they can be engulfed by immune cells surrounding cancer cells within the tumor microenvironment and bind to toll-like receptors (TLR7 in mice and TLR8 in human) expressed by the immune cells. As a result, the binding miRNAs function as agonists of these single-stranded RNA-binding TLRs, leading to NF-κB signaling activation and secretion of interleukin (IL)-6 and TNF-α, which promote cancer cell growth and metastasization. This novel miRNA mechanism of action suggests that these small noncoding RNAs can act as hormones (we call these miRNAs hormone miRNAs or H-miRNAs). The discovery that miRNAs released by cancer cells can bind to a receptor in a surrounding immune cell is completely novel. Other receptors (in addition to TLR7 and TLR8) are likely to be found, but this is the first identified miRNA receptor and it is relevant to cancer. This review discusses the meaning of this discovery and comments on the exciting future implications of these findings in the context of tumor microenvironment biology as well as of other human diseases. Cancer Res; 72(24); 6333–7. ©2012 AACR.
Dual Functions of the Homeoprotein DLX4 in Modulating Responsiveness of Tumor Cells to Topoisomerase II-Targeting Drugs
Authors: Trinh Bon Q. , Ko Song Yi , Barengo Nicolas , Lin Shiaw-Yih , Naora Honami 
Published: December 2012

Abstract
Topoisomerase II (TOP2)-targeting poisons such as anthracyclines and etoposide are commonly used for cancer chemotherapy and kill tumor cells by causing accumulation of DNA double-strand breaks (DSB). Several lines of evidence indicate that overexpression of TOP2A, the gene encoding topoisomerase IIα, increases sensitivity of tumor cells to TOP2 poisons, but it is not clear why some TOP2A-overexpressing (TOP2A-High) tumors respond poorly to these drugs. In this study, we identified that TOP2A expression is induced by DLX4, a homeoprotein that is overexpressed in breast and ovarian cancers. Analysis of breast cancer datasets revealed that TOP2A-high cases that also highly expressed DLX4 responded more poorly to anthracycline-based chemotherapy than TOP2A-high cases that expressed DLX4 at low levels. Overexpression of TOP2A alone in tumor cells increased the level of DSBs induced by TOP2 poisons. In contrast, DLX4 reduced the level of TOP2 poison-induced DSBs irrespective of its induction of TOP2A. DLX4 did not stimulate homologous recombination–mediated repair of DSBs. However, DLX4 interacted with Ku proteins, stimulated DNA-dependent protein kinase activity, and increased erroneous end-joining repair of DSBs. Whereas DLX4 did not reduce levels of TOP2 poison-induced DSBs in Ku-deficient cells, DLX4 stimulated DSB repair and reduced the level of TOP2 poison–induced DSBs when Ku was reconstituted in these cells. Our findings indicate that DLX4 induces TOP2A expression but reduces sensitivity of tumor cells to TOP2 poisons by stimulating Ku-dependent repair of DSBs. These opposing activities of DLX4 could explain why some TOP2A-overexpressing tumors are not highly sensitive to TOP2 poisons. Cancer Res; 73(2); 1000–10. ©2012 AACR.
Number of Target Lesions for EASL and Modified RECIST to Predict Survivals in Hepatocellular Carcinoma Treated with Chemoembolization
Authors: Kim Beom Kyung , Kim Seung Up , Kim Myeong-Jin , Kim Kyung Ah , Kim Do Young , Park Jun Yong , Ahn Sang Hoon , Han Kwang-Hyub , Chon Chae Yoon 
Published: December 2012

Abstract
Purposes: To date, most studies about the optimal number of target lesions for enhancement criteria for hepatocellular carcinoma (HCC) have focused on cross-sectional analyses of concordance. We investigated the optimal number of target lesions for European Association for the Study of the Liver (EASL) and modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines in predicting overall survival (OS).
Experimental Design: We analyzed 254 consecutive treatment-naïve patients with HCC having at least 2 measurable target lesions undergoing transarterial chemoembolization. Kappa values for intermethod agreement of treatment responses were calculated for comparisons between use of maximum of 1, 2, 3, 4, or 5 targets versus use of all target lesions. Prognostic values of radiologic assessments according to number of target lesions for predicting OS were expressed as C-index.
Results: By EASL and mRECIST guidelines, κ values between responses assessing the longest 2, 3, 4, or 5 targets and assessing all targets were 0.924, 0.977, 1.000, or 1.000 and 0.907, 0.959, 1.000, or 1.000, respectively, whereas those between responses assessing only one target and assessing all target lesions were 0.723 and 0.666, respectively. C-index when measuring the longest 1, 2, 3, 4, 5, and all targets was similar, ranging from 0.739 to 0.749 for EASL criteria and from 0.750 to 0.759 for mRECIST. From Cox regression analyses, radiologic response from each calculation method showed independently significant effects on OS for both guidelines, regardless of number of target lesions.
Conclusions: Prognostic values for predicting OS were similar regardless of number of target lesions. Assessing the 2 largest targets rather than only 1 index lesion could be recommended considering high concordances from cross-sectional analyses. Clin Cancer Res; 19(6); 1503–11. ©2012 AACR.
Parental Efficacy and Role Responsibility for Assisting in Child’s Healthful Behaviors
Authors: Ice Christa L. , Neal William A. , Cottrell Lesley 
Published: December 2012

The epidemic of childhood obesity, and its subsequent impact on negative health outcomes, continues to plague the United States. Better health outcomes have been linked to increased child achievement in school. Due to the strong influence parents have on children’s healthful behaviors particularly in younger years, it’s imperative to examine the social cognitive impact parents have on this aspect of children’s development. The objective of this study was to determine the impact parental self-efficacy and parental role responsibility have on child’s nutritional, physical activity, and weight categories. Parents ( N = 820) responded to a questionnaire after participating in a child health screening project. Parental self-efficacy for assisting in their child’s healthful behaviors has a strong association with the child’s weight status, nutrition and physical activity. In order to make an effective change on child health behaviors, which lead to increased child academic test scores, these results suggest that school health interventionists and clinicians need to target basic psychological motivators of parental involvement.
Outcomes of Cartilage Tympanoplasty in the Pediatric Population
Authors: Friedman Adva B. , Gluth Michael B. , Moore Page C. , Dornhoffer John L. 
Published: December 2012

ObjectiveTo justify the successful use of a patient selection algorithm based on age for primary cartilage tympanoplasty.Study DesignCase series with chart review.SettingTertiary care pediatric hospital.Subjects and MethodsWe performed a retrospective chart review of patients between ages 4 and 13 years who underwent cartilage tympanoplasty for tympanic membrane perforations from August 2005 to November 2011. Demographics, complication data, and auditory outcomes were collected.ResultsPatients were subdivided into 3 age groups. Group 1 consisted of patients younger than 7 years (n = 43); group 2, ages 7 to 10 years (n = 40); and group 3, ages 10 to 13 years (n = 36). Mean follow‐up was 595 days (range, 48‐1742). Complication rates respective to the 3 groups were as follows: remnant perforation (6.97%, 5.00%, 2.78%), revision tympanoplasty (2.33%, 2.50%, 0%), and need for tympanostomy tubes (4.65%, 2.50%, 0%). Logistic regression models were used to evaluate complication rates between groups. No significant differences were found (remnant perforation, P =. 710; repeat tympanoplasty, P =. 998; tympanostomy tubes, P =. 875). No significance was found among audiological outcomes between the 3 groups.ConclusionThese data suggest cartilage tympanoplasty can be performed effectively in young children when appropriate conditions exist.
Weight change associated with corticosteroid therapy in adolescents with systemic lupus erythematosus
Authors: Manaboriboon B , Silverman ED , Homsanit M , Chui H , Kaufman M 
Published: December 2012

Physical appearance is very important to adolescents and weight gain secondary to corticosteroid (CS) treatment may have a direct impact on adolescent development. Understanding weight gain in adolescents with SLE who are being treated with CS will help clinicians develop strategies for prevention of nonadherence, obesity and eating disorders in this population. Methods: Patients aged 11–18 years old with newly diagnosed SLE between January,1995 and December, 2006 were identified through the Rheumatology database at the Sickkids hospital, Canada. All charts were reviewed. Patients were categorized based on final BMI status as normal, overweight and obese. Risk factors for being obese were examined by logistic regression model analysis. Results: Of 236 patients, 78% fulfilled the criteria. 85% were female with mean age at onset of diagnosis was 14 ± 1.7 years. Mean duration of CS treatment was 50 ± 31 months and mean cumulative CS dosage was 34.11 ± 32.7 g of prednisone. At baseline, 10% had BMI >25 kg/m2 while at the end of the study, 20% were overweight and 10.4% were obese. In addition, 61% gained <10 kg while 15% gained ≥20 kg. Initial BMI was a significant predictors for final BMI (OR = 27.59, 95%CI = 6.04–126.09, p < .001) while male (OR = 8.50, 95%CI = 2.95–24.5, p < 0.000) and cumulative CS dosage (OR = 1.53, 95%CI = 1.05–2.23, p < .05) were the significant predictors for weight gain >10 kg. Duration of CS treatment did not correlate with obesity. Conclusion: Although a significant number of patients became overweight or obese after being treated with CS, most gained <10 kg. Obesity secondary to CS treatment in SLE patients was significantly correlated with baseline BMI, gender and cumulative CS dosage.
Effectiveness and response predictive factors of erlotinib in a non-small cell lung cancer unselected European population previously treated: A retrospective, observational, multicentric study
Authors: Cioffi Pasquale , Marotta Valerio , Fanizza Caterina , Giglioni Adriano , Natoli Clara , Petrelli Fabio , Grappasonni Iolanda 
Published: December 2012

Aims and background: Erlotinib approval was supported by the positive results of a large multicentric phase III trial (BR.21 study) that included 10% Asiatic patients and the remaining were North-American Caucasian. It is well-known that the efficacy of tyrosine kinase inhibitors is strongly influenced by ethnicity and other genetic factors. It is, therefore, relevant to establish whether the same profile of efficacy is seen in an unselected population and whether the results of BR.21 can be generalized to other patient populations, such as that described here. Methods: In this retrospective, observational, multicentric study, we assessed effectiveness and potentially response predictive factors in 222 unselected Italian patients, with stage IIIB/IV non-small-cell lung cancer, with performance status from 0 to 3, who had received at least one line of chemotherapy, treated with the standard dose of erlotinib (150 mg once daily) until disease progression or unacceptable toxicity. Results: The disease control rate was 60.9% (135 patients). Median progression-free survival and overall survival times were 3.1 months and 7.97 months, respectively. The characteristics of non-smoker, female gender, performance status 0 or 1 were associated with a significantly better prognosis in terms of disease control rate and were also predictive of longer overall survival and progression-free survival. The 1-year survival rate was 38.79%. Even though Italian patients baseline characteristics were strongly different to those reported in pivotal BR.21 trial in terms of age, performance status, line treatment and ethnic group, our study confirms the favorable effectiveness profile in real clinical practice of erlotinib according to results from the pivotal study BR.21. Conclusions: Today, we know that epidermal growth factor receptor (EGFR) status assessment is mandatory before starting first-line therapy and that the presence of only certain clinical characteristics initially associated with sensitivity to EGFR-tyrosine kinase inhibitors, as reported in this study, is not sufficient in selecting patients candidates to such treatments.