bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentials and limitations of natural flood retention by forested land in headwater catchments: evidence from experimental and model studies
Authors: Wahren A. , Schwärzel K. , Feger K.‐H. 
Published: June 2012

AbstractAssessment of catchments water retention potential in the landscape is a common part of management plans as components of integrated flood risk management strategies. For forest land use, it has been stated that the promotion of sustainable forest management and the increase of forest land via afforestation will considerably improve flood retention. Notably, the latter should be efficient to re‐establish the natural water retention potential in anthropogenically disturbed river basins and to decrease the human‐made contribution to flood generation. However, due to obvious physical limitations (such as soil depth, porosity, and conductivity) and the frequent lack of available land for forest expansion, the role of afforestation in flood mitigation has been a topic of strong debate. This study assesses the ‘forest effect’ based on model calculations and suggests visualisations to communicate the results. For a catchment (6.8 ha) and two well‐founded land‐use scenarios, it could be shown that the peak reduction for flood events varies from 3% to 70% and is highly related to the event characteristics (especially pre‐event soil moisture). The cross compliance to other protection aims (i.e. water quality and soil protection) is part of the considerations.
Cataract prevalence and prevention in Europe: a literature review
Authors: Prokofyeva Elena , Wegener Alfred , Zrenner Eberhart 
Published: June 2012

Abstract.This literature review is aimed at the evaluation of the potential for cataract prevention in Europe. It was performed using PubMed with Mesh and free‐text terms. Studies included were (i) performed on a population of Caucasian origin at an age range of 40–95 years, (ii) cataract was clinically verified, (iii) drug record of prescriptions, their indication, a record of every diagnosis, dosage and quantity of prescribed medicine were available, (iv) sample size >300 and (v) published between 1990 and 2009. The results of 29 articles were reviewed. Former [3.75 (2.26–6.21)] or current smoking [2.34 (1.07–5.15)], diabetes of duration >10 years [2.72 (1.72–4.28)], asthma or chronic bronchitis [2.04 (1.04–3.81)], and cardiovascular disease [1.96 (1.22–3.14)] increased the risk of cataract. Cataract was more common in patients taking chlorpromazine during ≥90 days with a dosage ≥300 mg [8.8 (3.1–25.1)] and corticosteroids >5 years [3.25 (1.39–7.58)] in a daily dose >1600 mg [1.69 (1.17–2.43)]. Intake of a multivitamin/mineral formulation [2.00 (1.35–2.98)] or corticosteroids [2.12 (1.93–2.33)] also increased the risk of cataract. Corticosteroids applied orally [3.25 (1.39–7.58)], parenteral [1.56 (1.34–1.82)] or inhalational [1.58 (1.46–1.71)] lead to cataract more frequently than those applied topically: nasal [1.33 (1.21–1.45)], ear [1.31 (1.19–1.45)] or skin [1.43 (1.36–1.50)]. Outpatient cataract surgery was negatively associated with total cataract surgery costs, and chlorpromazine, corticosteroids and multivitamin/mineral formation increase the risk of posterior subcapsular cataract dependent on dose, treatment application and duration. This review presented a comprehensive overview of specific and general cataract risk factors and an update on most recent experimental studies and randomized control trials directed at cataract prevention.
Campylobacter Cross‐Contamination of Chicken Products at an Abattoir
Authors: Sasaki Y. , Maruyama N. , Zou B. , Haruna M. , Kusukawa M. , Murakami M. , Asai T. , Tsujiyama Y. , Yamada Y. 
Published: June 2012

SummaryConsumption of raw or undercooked poultry products contaminated with Campylobacter has been identified as a risk factor for human campylobacteriosis. We determined whether slaughtering of Campylobacter‐positive flocks was associated with contamination of chicken products derived from Campylobacter‐negative flocks slaughtered at the same abattoir. The presence of Campylobacter was investigated in 22 broiler farms 1 week prior to slaughter and in one abattoir on nine separate slaughter days. A total of 600 bulk packed chicken products were tested, with 198 (33.0%) of the products found to be Campylobacter positive. Of the 350 chicken products originating from Campylobacter‐positive flocks, 180 (51.1%) were contaminated with the bacteria. In contrast, only 18 (7.2%) of 250 chicken products derived from Campylobacter‐negative flocks were contaminated. In 14 of these 18 products, the Campylobacter isolates were identical to isolates obtained from the flock slaughtered immediately prior to the Campylobacter‐negative flock. Notably, on 4/6 slaughter days, Campylobacter‐negative flocks were slaughtered prior to the positive flocks, and Campylobacter was absent from all chicken products originating from the negative flocks. These results suggest that implementation of logistic slaughter (where Campylobacter‐negative flocks are slaughter first) significantly decreases the prevalence of Campylobacter‐positive chicken products.
Trends in general and abdominal obesity among Chinese children and adolescents 1993–2009
Authors: Liang Y‐J. , Xi B. , Song A‐Q. , Liu J‐X. , Mi J. 
Published: June 2012

SummaryObjectiveThis study aimed to examine the secular trends in body mass index (BMI) and waist circumference (WC), and the prevalence of general and abdominal obesity among Chinese children and adolescents from 1993 to 2009.MethodsData were obtained from the China Health and Nutrition Survey conducted from 1993 to 2009. 9693 children and adolescents aged 6–17 years were included in this study, with their height, weight and WC measured. General obesity was defined using the BMI cut‐offs for overweight recommended by the International Obesity Task Force, and abdominal obesity was assessed when a WC is above the 90th percentile for gender and age.ResultsAmong the total participants, mean BMI and WC increased significantly over the period 1993–2009: BMI increased from 17.6 to 17.8 kg m−2, and WC increased from 61.4 to 63.1 cm (both increases P < 0.001). The prevalence of general obesity and abdominal obesity increased significantly over the period: general obesity (including overweight) rose from 6.1% to 13.1% and abdominal obesity from 4.9% to 11.7% (both increases P < 0.001). WC and abdominal obesity increased at a relatively higher rate than BMI and general obesity. Upward trends in the prevalence of general and abdominal obesity were observed in all subgroups of gender, age and region (all increases P < 0.05), except for abdominal obesity in girls aged 13–17 years (P = 0.102).ConclusionGeneral and abdominal obesity increased significantly over the past 17 years in Chinese children.
Genome Sequence of the Halotolerant Bacterium Imtechella halotolerans K1
T
Authors: Kumar Shailesh , Vikram Surendra , Subramanian Srikrishna , Raghava Gajendra Pal Singh , Pinnaka Anil Kumar 
Published: June 2012

ABSTRACT

We report the 3.087-Mb genome sequence of
Imtechella halotolerans
K1
T
, isolated from an estuarine water sample collected from Kochi, Kerala, India. Strain K1 was recently reported as a novel genus of the family
Flavobacteriaceae
.
Activation of Thermogenesis in Brown Adipose Tissue and Dysregulated Lipid Metabolism Associated with Cancer Cachexia in Mice
Authors: Tsoli Maria , Moore Melissa , Burg Dominic , Painter Arran , Taylor Ryland , Lockie Sarah H. , Turner Nigel , Warren Alessandra , Cooney Greg , Oldfield Brian , Clarke Stephen , Robertson Graham 
Published: June 2012

Abstract
Cancer cachexia/anorexia is a complex syndrome that involves profound metabolic imbalances and is directly implicated as a cause of death in at least 20% to 30% of all cancers. Brown adipose tissue (BAT) plays a key role in thermogenesis and energy balance and potentially contributes to the physiologic perturbations associated with cachexia. In this study, we investigated the impact of cachexia-inducing colorectal tumor on BAT in mice. We found that brown adipocytes were smaller and exhibited profound delipidation in cachectic tumor–bearing mice. Diurnal expression profiling of key regulators of lipid accumulation and fatty acid β-oxidation and their corresponding target genes revealed dramatic molecular changes indicative of active BAT. Increased Ucp1, Pbe, and Cpt1α expression at specific points coincided with higher BAT temperatures during the dark cycle, suggestive of a temporal stimulation of thermogenesis in cachexia. These changes persisted when cachectic mice were acclimatized to 28°C confirming inappropriate stimulation of BAT despite thermoneutrality. Evidence of inflammatory signaling also was observed in the BAT as an energetically wasteful and maladaptive response to anorexia during the development of cachexia. Cancer Res; 72(17); 4372–82. ©2012 AACR.
DEDD Interacts with PI3KC3 to Activate Autophagy and Attenuate Epithelial–Mesenchymal Transition in Human Breast Cancer
Authors: Lv Qi , Wang Wei , Xue Jianfei , Hua Fang , Mu Rong , Lin Heng , Yan Jun , Lv Xiaoxi , Chen Xiaoguang , Hu Zhuo-Wei 
Published: June 2012

Abstract
Epithelial-to-mesenchymal transition (EMT), a crucial developmental program, contributes to cancer invasion and metastasis. In this study, we show that death-effector domain-containing DNA-binding protein (DEDD) attenuates EMT and acts as an endogenous suppressor of tumor growth and metastasis. We found that expression levels of DEDD were conversely correlated with poor prognosis in patients with breast and colon cancer. Both in vitro and in vivo, overexpression of DEDD attenuated the invasive phenotype of highly metastatic cells, whereas silencing of DEDD promoted the invasion of nonmetastatic cells. Via direct interaction with the class III PI-3-kinase (PI3KC3)/Beclin1, DEDD activated autophagy and induced the degradation of Snail and Twist, two master regulators of EMT. The DEDD–PI3KC3 interaction led to stabilization of PI3KC3, which further contributed to autophagy and the degradation of Snail and Twist. Together, our findings highlight a novel mechanism in which the intracellular signaling protein DEDD functions as an endogenous tumor suppressor. DEDD expression therefore may represent a prognostic marker and potential therapeutic target for the prevention and treatment of cancer metastasis. Cancer Res; 72(13); 3238–50. ©2012 AACR.
The Proinflammatory Myeloid Cell Receptor TREM-1 Controls Kupffer Cell Activation and Development of Hepatocellular Carcinoma
Authors: Wu Juan , Li Jiaqi , Salcedo Rosalba , Mivechi Nahid F. , Trinchieri Giorgio , Horuzsko Anatolij 
Published: June 2012

Abstract
Chronic inflammation drives liver cancer pathogenesis, invasion, and metastasis. Liver Kupffer cells have crucial roles in mediating the inflammatory processes that promote liver cancer, but the mechanistic basis for their contributions are not fully understood. Here we show that expression of the proinflammatory myeloid cell surface receptor TREM-1 expressed by Kupffer cells is a crucial factor in the development and progression of liver cancer. Deletion of the murine homolog Trem1 in mice attenuated hepatocellular carcinogenesis triggered by diethylnitrosamine (DEN). Trem1 deficiency attenuated Kupffer cell activation by downregulating transcription and protein expression of interleukin (IL)-6, IL-1β, TNF, CCL2, and CXCL10. In addition, Trem1 ablation diminished activation of the p38, extracellular regulated kinase 1/2, JNK, mitogen-activated protein kinase, and NF-κB signaling pathways in Kupffer cells, resulting in diminished liver injury after DEN exposure. Adoptive transfer of wild-type Kupffer cells to Trem1-deficient mice complemented these defects and reversed unresponsiveness to DEN-induced liver injury and malignant development. Together, our findings offer causal evidence that TREM-1 is a pivotal determinant of Kupffer cell activation in liver carcinogenesis, deepening mechanistic insights into how chronic inflammation underpins the development and progression of liver cancer. Cancer Res; 72(16); 3977–86. ©2012 AACR.
Carbonyl Reductase 1 Offers a Novel Therapeutic Target to Enhance Leukemia Treatment by Arsenic Trioxide
Authors: Jang Miran , Kim Yeonghwan , Won Hyeran , Lim Sangbin , K.R Jyothi , Dashdorj Amarjargal , Min Yoo Hong , Kim Si-Young , Shokat Kevan M. , Ha Joohun , Kim Sung Soo 
Published: June 2012

Abstract
Arsenic trioxide (As2O3) is used, in current practice, as an effective chemotherapeutic agent for acute promyelocytic leukemia (APL). However, the side effects and relatively low efficacy of As2O3 in treating other leukemias have limited its wider use in therapeutic applications. In the present study, we found that the expression of carbonyl reductase 1 (CBR1) affects the resistance to As2O3 in leukemias, including APL; As2O3 upregulated CBR1 expression at the transcriptional level by stimulating the activity of the transcription factor activator protein-1. Moreover, CBR1 overexpression was sufficient to protect cells against As2O3 through modulation of the generation of reactive oxygen species, whereas the attenuation of CBR1 was sufficient to sensitize cells to As2O3. A combination treatment with the specific CBR1 inhibitor hydroxy-PP-Me remarkably increased As2O3-induced apoptotic cell death compared with As2O3 alone, both in vitro and in vivo. These results were confirmed in primary cultured human acute and chronic myeloid leukemia cells, with no significant cell death observed in normal leukocytes. Taken together, our findings indicate that CBR1 contributes to the low efficacy of As2O3 and, therefore, is a rational target for the development of combination chemotherapy with As2O3 in diverse leukemias including APL. Cancer Res; 72(16); 4214–24. ©2012 AACR.
P1-17-01: Figitumumab Plus Exemestane Versus Exemestane as First-Line Treatment of Postmenopausal Hormone Receptor-Positive Advanced Breast Cancer: A Randomized, Open-Label Phase II Trial.
Authors: Ryan PD , Neven P , Blackwell KL , Dirix LY , Barrios CH , Miller WH , Fein LE , Fenton D , Benner RJ , Meech SJ , Paccagnella L , Sleight B , Yee D , Goss PE 
Published: June 2012

Abstract
Background Figitumumab (CP-751,871) is a fully human IgG2 monoclonal antibody that inhibits IGF-1R. Exemestane profoundly reduces estrogen production and has activity as first-line treatment in postmenopausal metastatic hormone receptor-positive (HR+) breast cancer (BC). Preclinical studies suggest cross-talk between the IGF-1R and estrogen receptor pathways. Combining agents that inhibit these pathways could benefit women with advanced BC.
Methods This was an open-label, multicenter, randomized, phase II trial of first-line figitumumab + exemestane (Arm A) vs. exemestane alone (Arm B) in HR+ postmenopausal advanced BC. Eligibility included: age &gt;18 yrs with Stage IIIB or IV disease; baseline ECOG PS ≤2. A high rate of grade [G] 3 and 4 hyperglycemia after figitumumab treatment prompted a protocol amendment in February 2010 requiring patients (pts) to have a baseline HbA1c &lt;5.7%. Patients received exemestane 25 mg po daily ± intravenous figitumumab 20 mg/kg every 21 days. The primary endpoint was progression-free survival (PFS) in pts with baseline HbA1c &lt;5.7%. Secondary endpoints included clinical benefit rate (CBR) and safety.
Results Between 2007 and February 2011, 103 pts were randomized to Arm A and 102 to Arm B. Of these, 37 pts in Arm A and 40 pts in Arm B had baseline HbA1c &lt;5.7%. These data are from an unplanned interim analysis which preceded premature study termination by the Sponsor for clinical development reasons and to expedite availability of data collected to date. Baseline demographics were balanced between arms. PFS, CBR and safety are summarized in Table 1.

The majority of AEs were G1/2. In the Arm A overall population, the most common G3/4 events (in decreasing frequency) were hyperglycemia, diabetes mellitus, weight loss, isolated GGT elevation and fatigue. Hyperglycemia was uncommon in Arm B and in all pts with HbA1c &lt;5.7%.[Table 2].

Conclusions The addition of figitumumab to exemestane was tolerable but overall did not improve PFS compared with exemestane alone in pts eligible for this trial. However, a trend toward benefit with figitumumab combined with exemestane in pts without evidence of baseline metabolic syndrome (HbA1c &lt;5.7%) was observed together with improved tolerability; further study with this combination may be warranted.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-17-01.
S5-6: Neoadjuvant Pertuzumab and Trastuzumab Concurrent or Sequential with an Anthracycline-Containing or Concurrent with an Anthracycline-Free Standard Regimen: A Randomized Phase II Study (TRYPHAENA).
Authors: Schneeweiss A , Chia S , Hickish T , Harvey V , Eniu A , Hegg R , Tausch C , Seo J-H , Tsai Y-F , Ackrill A , Ross G , Cortés J 
Published: June 2012

Abstract
Background: Pertuzumab (P) is a fully humanized investigational monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER2), preventing homo- and heterodimerization of HER2 and other HER family members and inducing antibody-dependent cell-mediated cytotoxicity. The NeoSphere study demonstrated significantly increased antitumor activity in the neoadjuvant setting for the combination of P and trastuzumab (H) plus docetaxel (T) compared with HT alone (Gianni et al. SABCS 2010), consistent with the hypothesis of complementary mechanisms of action of P and H. No increase in cardiac risk was observed with the addition of P to H and HT regimens. Anthracyclines have an important role in the treatment of breast cancer and may be especially efficacious in HER2−positive disease. In the TRYPHAENA study, P and H are being administered either sequentially or concurrently with an anthracycline-containing or concurrently with an anthracycline-free standard regimen in order to establish the tolerability profile of these regimens for testing in the adjuvant setting.
Methods: Patients with centrally confirmed stage II or III (including locally advanced and inflammatory disease) HER2−positive breast cancer (defined as centrally confirmed HER2 IHC 3+ or FISH/CISH+) were randomized to receive:

Study medication: P 840 mg loading dose and 420 mg maintenance; H 8 mg/kg loading dose and 6 mg/kg maintenance; T was given at 75 mg/m2 with dose escalation to 100 mg/m2 if the starting dose was well tolerated (no dose escalation in Arm C); FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 600 mg/m2) and carboplatin AUC 6. All treatments were given intravenously q3w. The study is ongoing. All patients will receive H for 1 year. The primary endpoint is assessment of the safety and tolerability of neoadjuvant treatment. During neoadjuvant treatment, left ventricular ejection fraction is assessed at Cycles 2, 4, and 6 by echocardiogram or multiple-gated acquisition. Safety data are supervised by a data and safety monitoring board. The key secondary endpoint is the rate of pathological complete response (pCR) defined as absence of invasive disease in the breast at surgery. Tissue specimens at baseline and post-surgery were required for all patients.
This study is registered at ClinicalTrials.gov: NCT00976989.
Results: 225 patients have been recruited. No arm has required modification due to safety concerns or to excessive incidence of disease progression. Analysis of the study results is anticipated in Q3 2011. Safety/tolerability and efficacy (pCR) data will be presented.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S5-6.
Molecular Pathways: The Hedgehog Signaling Pathway in Cancer
Authors: McMillan Ross , Matsui William 
Published: June 2012

AbstractThe Hedgehog (Hh) signaling pathway regulates embryonic development and may be aberrantly activated in a wide variety of human cancers. Efforts to target pathogenic Hh signaling have steadily progressed from the laboratory to the clinic, and the recent approval of the Hh pathway inhibitor vismodegib for patients with advanced basal cell carcinoma represents an important milestone. On the other hand, Hh pathway antagonists have failed to show significant clinical activity in other solid tumors. The reasons for these negative results are not precisely understood, but it is possible that the impact of Hh pathway inhibition has not been adequately measured by the clinical endpoints used thus far or that aberrancies in Hh signal transduction limits the activity of currently available pathway antagonists. Further basic and correlative studies to better understand Hh signaling in human tumors and validate putative antitumor mechanisms in the clinical setting may ultimately improve the success of Hh pathway inhibition to other tumor types. Clin Cancer Res; 18(18); 4883–8. ©2012 AACR.
Molecular Pathways: Tumor-Infiltrating Myeloid Cells and Reactive Oxygen Species in Regulation of Tumor Microenvironment
Authors: Lu Tangying , Gabrilovich Dmitry I. 
Published: June 2012

Abstract
Tumor-associated myeloid cells are the major type of inflammatory cells involved in the regulation of antitumor immune responses. One key characteristic of these cells is the generation of reactive oxygen (ROS) and reactive nitrogen species (RNS) in the tumor microenvironment. Recent studies have shown the important role of ROS and RNS, especially peroxynitrite, in immune suppression in cancer. ROS and RNS are involved in induction of antigen-specific T-cell tolerance, inhibition of T-cell migration to the tumor site, and tumor cell evasion of recognition by cytotoxic T cells. In preclinical settings, a number of potential therapeutic agents showed activity in blocking ROS/RNS in cancer and in improving the efficacy of cancer immune therapy. A better understanding of ROS/RNS-associated pathways in myeloid cells will help to identify more specific and direct targets to facilitate the development of more effective immune therapy for cancer. Clin Cancer Res; 18(18); 4877–82. ©2012 AACR.
The HSP90 Inhibitor, AT13387, Is Effective against Imatinib-Sensitive and -Resistant Gastrointestinal Stromal Tumor Models
Authors: Smyth Tomoko , Van Looy Thomas , Curry Jayne E. , Rodriguez-Lopez Ana M. , Wozniak Agnieszka , Zhu Meijun , Donsky Rachel , Morgan Jennifer G. , Mayeda Mark , Fletcher Jonathan A. , Schöffski Patrick , Lyons John , Thompson Neil T. , Wallis Nicola G. 
Published: June 2012

Abstract
The majority of gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT, an HSP90 client protein. Further secondary resistance mutations within KIT limit clinical responses to tyrosine kinase inhibitors, such as imatinib. The dependence of KIT and its mutated forms on HSP90 suggests that HSP90 inhibition might be a valuable treatment option for GIST, which would be equally effective on imatinib-sensitive and -resistant clones. We investigated the activity of AT13387, a potent HSP90 inhibitor currently being evaluated in clinical trials, in both in vitro and in vivo GIST models. AT13387 inhibited the proliferation of imatinib-sensitive (GIST882, GIST-T1) and -resistant (GIST430, GIST48) cell lines, including those resistant to the geldanamycin analogue HSP90 inhibitor, 17-AAG. Treatment with AT13387 resulted in depletion of HSP90 client proteins, KIT and AKT, along with their phospho-forms in imatinib-sensitive and -resistant cell lines, irrespective of KIT mutation. KIT signaling was ablated, whereas HSP70, a marker of HSP90 inhibition, was induced. In vivo, antitumor activity of AT13387 was showed in both the imatinib-sensitive, GIST-PSW, xenograft model and a newly characterized imatinib-resistant, GIST430, xenograft model. Induction of HSP70, depletion of phospho-KIT and inhibition of KIT signaling were seen in tumors from both models after treatment with AT13387. A combination of imatinib and AT13387 treatment in the imatinib-resistant GIST430 model significantly enhanced tumor growth inhibition over either of the monotherapies. Importantly, the combination of AT13387 and imatinib was well tolerated. These results suggest AT13387 is an excellent candidate for clinical testing in GIST in combination with imatinib. Mol Cancer Ther; 11(8); 1799–808. ©2012 AACR.