bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light to Moderate Alcohol Consumption Is Associated With Lower Risk of Aortic Valve Sclerosis
Authors: Markus Marcello Ricardo Paulista , Lieb Wolfgang , Stritzke Jan , Siewert Ulrike , Troitzsch Paulina , Koch Manja , Dörr Marcus , Felix Stephan Burkhard , Völzke Henry , Schunkert Heribert , Baumeister Sebastian Edgar 
Published: March 2015

Objective—
In developed countries, sclerotic and calcific degeneration of the aortic valve is a common disorder showing pathophysiologic similarities with atherothrombotic coronary disease. Light to moderate alcohol consumption has been associated with a lower risk for atherothrombotic coronary disease and mortality. Whether alcohol consumption affects the development of aortic valve sclerosis (AVS) is not well known. In the present study, we aim to analyze the cross-sectional association between average daily alcohol consumption and AVS in the general population.

Approach and Results—

We analyzed cross-sectional data from 2022 men and women, aged 45 to 81 years, from the population-based Study of Health in Pomerania. We used a computer-assisted interview that included beverage-specific questions about quantity and frequency of alcohol over the last 30 days to calculate the average quantity of alcohol consumption (in grams of ethanol per day). AVS was ascertained by echocardiography. The prevalence of AVS was 32.3%. Average daily alcohol intake displayed a J-type relation with AVS (fully adjusted
P
value: 0.005). Compared with individuals with an average consumption of 10 g of alcohol per day, multivariable-adjusted odds ratios were 1.60 (95% confidence interval, 1.19–2.14) among current abstainers and 1.56 (95% confidence interval, 1.01–2.41) among individuals with an average consumption of 60 g per day.

Conclusions—
Our findings indicate that light to moderate alcohol consumption was associated with a lower odd of having AVS. Prospective data need to address whether alcohol consumption and related changes over time in several biological markers affect the progression of AVS.
Collectivization of Vascular Smooth Muscle Cells via TGF-β–Cadherin-11–Dependent Adhesive Switching
Authors: Balint Brittany , Yin Hao , Chakrabarti Subrata , Chu Michael W.A. , Sims Stephen M. , Pickering J. Geoffrey 
Published: March 2015

Objective—
Smooth muscle cells (SMCs) in healthy arteries are arranged as a collective. However, in diseased arteries, SMCs commonly exist as individual cells, unconnected to each other. The purpose of this study was to elucidate the events that enable individualized SMCs to enter into a stable and interacting cell collective.

Approach and Results—
Human SMCs stimulated to undergo programmed collectivization were tracked by time-lapse microscopy. We uncovered a switch in the behavior of contacting SMCs from semiautonomous motility to cell–cell adherence. Central to the cell-adherent phenotype was the formation of uniquely elongated adherens junctions, up to 60 μm in length, which appeared to strap adjacent SMCs to each other. Remarkably, these junctions contained both N-cadherin and cadherin-11. Ground-state depletion super-resolution microscopy revealed that these hybrid assemblies were comprised of 2 parallel nanotracks of each cadherin, separated by 50 nm. Blocking either N-cadherin or cadherin-11 inhibited collectivization. Cell–cell adhesion and adherens junction elongation were associated with reduced transforming growth factor-β signaling, and exogenous transforming growth factor-β1 suppressed junction elongation via the noncanonical p38 pathway. Imaging of fura-2–loaded SMCs revealed that SMC assemblies displayed coordinated calcium oscillations and cell–cell transmission of calcium waves which, together with increased connexin 43–containing junctions, depended on cadherin-11 and N-cadherin function.

Conclusions—
SMCs can self-organize, structurally and functionally, via transforming growth factor-β–p38–dependent adhesive switching and a novel adherens junction architecture comprised of hybrid nanotracks of cadherin-11 and N-cadherin. The findings define a mechanism for the assembly of SMCs into networks, a process that may be relevant to the stability and function of blood vessels.
Incidence of Secondary Intra-articular Injuries With Time to Anterior Cruciate Ligament Reconstruction
Authors: Ralles Steven , Agel Julie , Obermeier Michael , Tompkins Marc 
Published: March 2015

Background: Precise locations of chondral and meniscal damage with increased time to anterior cruciate ligament reconstruction (ACLR) have not been well described. Purpose/Hypothesis: The purpose of the study was to determine the relationship between delay in primary ACLR and incidence of secondary intra-articular injury. The hypothesis was that patients with increased time between initial injury and ACLR will exhibit greater incidence of secondary intra-articular injury when compared with those who receive surgical intervention promptly after injury. A second hypothesis was that patients with higher preinjury activity levels or older age will exhibit greater secondary injury when compared with those with minimal preinjury activity levels and younger age. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective review was performed on 1434 patients with an anterior cruciate ligament deficiency who underwent primary ACLR at a single institution between 2009 and 2013. Patients were grouped according to time to surgery after initial injury: 0-3, 4-12, and >12 months. Operative notes were used to analyze 10 variables across time-to-surgery groups: cartilage damage in the patella, trochlea, medial femoral condyle, lateral femoral condyle, medial tibial plateau, and lateral tibial plateau; medial and lateral meniscal injury; and the incidence of procedures involving either the meniscus or cartilage. Patient age and preinjury activity level were also analyzed for the 10 variables based on time-to-surgery groups. Results: An association was noted between time to surgery and increased incidence of injury in the trochlea, lateral femoral condyle, medial tibial plateau, and medial meniscus ( P < .001). Different significant findings within each age group were observed, but overall positive findings were seen in the same 4 locations described above. On the basis of preinjury activity level, the less active patients were most at risk for medial meniscal and trochlear injury, while the more active patients were most at risk for medial tibial plateau injury with increased time from injury to ACLR. Conclusion: Increasing time from injury to ACLR was associated with increased incidence of secondary injury seen in the trochlea, lateral femoral condyle, medial tibial plateau, and medial meniscus. Separate analyses of patient age and preinjury activity level showed similar findings, thus supporting the primary analysis.
Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina
Authors: Wang Jianxiang , Shen Zhi-Xiang , Saglio Giuseppe , Jin Jie , Huang He , Hu Yu , Du Xin , Li Jianyong , Meng Fanyi , Zhu Huanling , Hu Jianda , Wang Jianmin , Hou Ming , Hertle Sabine , Menssen Hans D. , Ortmann Christine-Elke , Tribouley Catherine , Yuan Ye , Baccarani Michele , Huang Xiaojun 
Published: March 2015

Key Points
Chinese patients with newly diagnosed CML-CP achieved higher rates of MMR with nilotinib vs imatinib. Nilotinib was well tolerated, and no new safety signals were observed.
A novel method to fabricate CoFe2O4/SrFe12O19 composite ferrite nanofibers with enhanced exchange coupling effect
Authors: Pan Lining , Cao Derang , Jing Panpan , Wang Jianbo , Liu Qingfang 
Published: March 2015

Abstract
Nanocomposite of CoFe2O4/SrFe12O19 has been synthesized by the electrospinning and calcination process. A novel method that cobalt powder was used to replace traditional cobalt salt in the precursor sol-gel for electrospinning was proposed. The crystal structures, morphologies, and magnetic properties of these samples have been characterized in detail. Moreover, when the average crystallite size of the hard/soft phases reached up to an optimal value, the CoFe2O4 have an enhanced saturation magnetization of 62.8 emu/g and a coercivity of 2,290 Oe. Significantly, the hysteresis loops for the nanocomposites show a single-phase magnetization behavior, and it has been found that the exchange coupling interaction strongly exists in the CoFe2O4/SrFe12O19 magnetic nanocomposite nanofibers.
Small Organic Molecule Disruptors of Cav3.2 - USP5 Interactions Reverse Inflammatory and Neuropathic Pain
Authors: Gadotti Vinicius M , Caballero Agustin Garcia , Berger N Daniel , Gladding Clare M , Chen Lina , Pfeifer Tom A , Zamponi Gerald W 
Published: March 2015

Background Cav3.2 channels facilitate nociceptive transmission and are upregulated in DRG neurons in response to nerve injury or peripheral inflammation. We reported that this enhancement of Cav3.2 currents in afferent neurons is mediated by deubiquitination of the channels by the deubiquitinase USP5, and that disrupting USP5/Cav3.2 channel interactions protected from inflammatory and neuropathic pain. Results Here we describe the development of a small molecule screening assay for USP5- Cav3.2 disruptors, and report on two hits of a ~5000 compound screen - suramin and the flavonoid gossypetin. In mouse models of inflammatory pain and neuropathic pain, both suramin and gossypetin produced dose-dependent and long-lasting mechanical anti-hyperalgesia that was abolished or greatly attenuated in Cav3.2 null mice. Suramin and Cav3.2/USP5 Tat-disruptor peptides were also tested in models of diabetic neuropathy and visceral pain, and provided remarkable protection. Conclusions Overall, our findings provide proof of concept for a new class of analgesics that target T-type channel deubiquitination.
Estimated dietary dioxin exposure and breast cancer risk among women from the French E3N prospective cohort
Authors: Danjou Aurélie MN , Fervers Béatrice , Boutron-Ruault Marie-Christine , Philip Thierry , Clavel-Chapelon Françoise , Dossus Laure 
Published: March 2015

Abstract
Introduction
Dioxins are environmental and persistent pollutants mostly emitted from combustion facilities (e.g. waste incinerators, metal and cement industries). Known to be endocrine disrupting chemicals, dioxins are suspected to increase breast cancer (BC) risk. Although diet is considered the primary source of dioxin exposure, no previous study has been published on dietary dioxin exposure in relation to BC risk. We aimed to assess dietary dioxin exposure among women from the E3N cohort and estimate BC risk associated with this exposure.

Methods
The study included 63,830 women from the E3N cohort who completed a diet history questionnaire (DHQ) in 1993 and were followed until 2008. Dietary dioxin exposure was estimated by combining consumption data from the E3N DHQ and food dioxin contamination data from a French national monitoring program. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox models adjusted for BC risk factors.

Results
Mean dietary dioxin exposure was estimated at 1.3 ± 0.4 pg/kg body weight (BW)/day. A 0.4 pg/kg BW/d increase in dioxin intake was not associated with overall BC risk (HR = 1.00; 95% CI: 0.96, 1.05). A significant decrease in risk of estrogen receptor negative (ER-)/progesterone receptor negative (PR-) tumors was observed among post-menopausal women in the upper quartile of estimated dioxin intake (HR for Q4 vs. Q1: 0.65; 95% CI: 0.45, 0.96; P for trend across quartiles = 0.0463).

Conclusions
Overall, no association between estimated dietary dioxin exposure and BC risk was found among E3N women. Further studies should include both dietary and environmental exposures to determine whether low-dose dioxin exposure is associated with BC risk.
Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice
Authors: Decock Julie , Hendrickx Wouter , Thirkettle Sally , Gutiérrez-Fernández Ana , Robinson Stephen D , Edwards Dylan R 
Published: March 2015

Abstract
Introduction
Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity that has oncosuppressive actions in numerous tumor types.

Methods
We have intercrossed Mmp8-null mice with the Polyoma virus middle T oncogene-driven (MMTV-PyMT) mouse model of mammary cancer to explore the effects of loss of MMP-8 on the incidence and progression of mammary carcinomas.

Results
In this aggressive mouse model of breast cancer, loss of MMP-8 accelerated tumor onset even further, such that 90% of MMTV-PyMT; Mmp8-null female mice were tumor-bearing at the time of weaning. Throughout the 14 weeks of the model, tumor burden increased in homozygous Mmp8-null mice compared to Mmp8-wild-type and -heterozygote animals. Likewise, lung metastasis dramatically increased in the MMTV-PyMT; Mmp8-null mice. Immunohistochemistry revealed that tumors in wild-type, Mmp8-heterozygotes and -null animals had similar vascular density at 8 weeks, but at 10 weeks Mmp8-wild-type tumors had a lower vascularity than their heterozygote and null counterparts. No differences in macrophage infiltration were apparent throughout primary tumor development, though at 10 weeks a drop in neutrophil infiltrates was observed in Mmp8-wild-type tumors. Using quantitative real-time RT-PCR, we tracked the expression of the entire Mmp and Timp gene families, observing a significant decrease in Mmp3 expression in Mmp8-null tumors compared to wild-type and heterozygotes throughout the time course of the model, which was confirmed at the protein level.

Conclusions
These findings provide novel insight into the suppressive action of MMP-8 on mammary tumorigenesis and metastasis, and indicate that the loss of MMP-8 likely has pleiotropic effects on innate immunity and angiogenesis that are reflected in changes in the protease web.
MUSiCC: a marker genes based framework for metagenomic normalization and accurate profiling of gene abundances in the microbiome
Authors: Manor Ohad , Borenstein Elhanan 
Published: March 2015

AbstractFunctional metagenomic analyses commonly involve a normalization step, where measured levels of genes or pathways are converted into relative abundances. Here, we demonstrate that this normalization scheme introduces marked biases both across and within human microbiome samples, and identify sample- and gene-specific properties that contribute to these biases. We introduce an alternative normalization paradigm, MUSiCC, which combines universal single-copy genes with machine learning methods to correct these biases and to obtain an accurate and biologically meaningful measure of gene abundances. Finally, we demonstrate that MUSiCC significantly improves downstream discovery of functional shifts in the microbiome.MUSiCC is available at http://elbo.gs.washington.edu/software.html.
HLAreporter: a tool for HLA typing from next generation sequencing data
Authors: Huang Yazhi , Yang Jing , Ying Dingge , Zhang Yan , Shotelersuk Vorasuk , Hirankarn Nattiya , Sham Pak Chung , Lau Yu Lung , Yang Wanling 
Published: March 2015

AbstractHuman leukocyte antigen (HLA) typing from next generation sequencing (NGS) data has the potential for widespread applications. Here we introduce a novel tool (HLAreporter) for HLA typing from NGS data based on read-mapping using a comprehensive reference panel containing all known HLA alleles, followed by de novo assembly of the gene-specific short reads. Accurate HLA typing at high-digit resolution was achieved when it was tested on publicly available NGS data, outperforming other newly developed tools such as HLAminer and PHLAT. HLAreporter can be downloaded from http://paed.hku.hk/genome/.
Heterogeneity of intratumoral 111In-ibritumomab tiuxetan and 18F-FDG distribution in association with therapeutic response in radioimmunotherapy for B-cell non-Hodgkin’s lymphoma
Authors: Hanaoka Kohei , Hosono Makoto , Tatsumi Yoichi , Ishii Kazunari , Im Sung-Woon , Tsuchiya Norio , Sakaguchi Kenta , Matsumura Itaru 
Published: March 2015

Abstract

Background
The purpose of this study was to quantitatively evaluate the tumor accumulation and heterogeneity of 111In-ibritumomab tiuxetan (Zevalin®) and tumor accumulation of 18F-fluoro-deoxyglucose (FDG) and compare them to the tumor response in B-cell non-Hodgkin’s lymphoma patients receiving 90Y-ibritumomab tiuxetan (Zevalin®) therapy.

Methods
Sixteen patients with histologically confirmed non-Hodgkin’s B-cell lymphoma who underwent 90Y-ibritumomab tiuxetan therapy along with 111In-ibritumomab tiuxetan single-photon emission computerized tomography (SPECT)/CT and FDG positron emission tomography (PET)/CT were enrolled in this retrospective study. On pretherapeutic FDG PET/CT images, the maximum standardized uptake value (SUVmax) was measured. On SPECT/CT images, a percentage of the injected dose per gram (%ID/g) and SUVmax of 111In-ibritumomab tiuxetan were measured at 48 h after its administration. The skewness and kurtosis of the voxel distribution were calculated to evaluate the intratumoral heterogeneity of tumor accumulation. As another intratumoral heterogeneity index, cumulative SUV-volume histograms describing the percentage of the total tumor volume above the percentage thresholds of pretherapeutic FDG and 111In-ibritumomab tiuxetan SUVmax (area under the curve of the cumulative SUV histograms (AUC-CSH)) were calculated. All lesions (n = 42) were classified into responders and non-responders lesion-by-lesion on pre- and post-therapeutic CT images.

Results
A positive correlation was observed between the FDG SUVmax and accumulation of 111In-ibritumomab tiuxetan in lesions. A significant difference in pretherapeutic FDG SUVmax was observed between responders and non-responders, while no significant difference in 111In-ibritumomab tiuxetan SUVmax was observed between the two groups. In contrast, voxel distribution of FDG demonstrated no significant differences in the three heterogeneity indices between responders and non-responders, while 111In-ibritumomab tiuxetan demonstrated skewness of 0.58 ± 0.16 and 0.73 ± 0.24 (p < 0.05), kurtosis of 2.39 ± 0.32 and 2.78 ± 0.53 (p < 0.02), and AUC-CSH of 0.37 ± 0.04 and 0.34 ± 0.05 (p < 0.05) for responders and non-responders.

Conclusions
Pretherapeutic FDG accumulation was predictive of the tumor response in 90Y-ibritumomab tiuxetan therapy. The heterogeneity of the intratumoral distribution rather than the absolute level of 111In-ibritumomab tiuxetan was correlated with the tumor response.
What is the influence of a reduction of planktivorous and benthivorous fish on water quality in temperate eutrophic lakes? A systematic review
Authors: Bernes Claes , Carpenter Stephen R , Gårdmark Anna , Larsson Per , Persson Lennart , Skov Christian , Speed James DM , Van Donk Ellen 
Published: March 2015

Abstract
Background
In recent decades, many attempts have been made to restore eutrophic lakes through biomanipulation. Reducing the populations of planktivorous and benthivorous fish (either directly or through stocking of piscivorous fish) may induce ecosystem changes that increase water transparency and decrease the risk of algal blooms and fish kills, at least in the short term. However, the generality of biomanipulation effects on water quality across lake types and geographical regions is not known. Therefore, we have undertaken a systematic review of such effects in eutrophic lakes in temperate regions throughout the world.

Methods
Searches for literature were made using online publication databases, search engines, specialist websites and bibliographies of literature reviews. Search terms were developed in English, Danish, Dutch and Swedish. Identified articles were screened for relevance using inclusion criteria set out in an a priori protocol. To reduce the risk of bias, we then critically appraised the combined evidence found on each biomanipulation. Data were extracted on outcomes such as Secchi depth and chlorophyll a concentration before, during and/or after manipulation, and on effect modifiers such as lake properties and amounts of fish removed or stocked.

Results
Our searches identified more than 14,500 articles. After screening for relevance, 233 of them remained. After exclusions based on critical appraisal, our evidence base included useful data on 128 biomanipulations in 123 lakes. Of these interventions, 85% had been made in Europe and 15% in North America. Meta-analysis showed that removal of planktivores and benthivores (with or without piscivore stocking) leads to increased Secchi depth and decreased chlorophyll a concentration during intervention and the first three years afterwards. Piscivore stocking alone has no significant effect. The response of chlorophyll a levels to biomanipulation is stronger in lakes where fish removal is intense, and in lakes which are small and/or have high pre-manipulation concentrations of total phosphorus.

Conclusions
Our review improves on previous reviews of biomanipulation in that we identified a large number of case studies from many parts of the world and used a consistent, repeatable process to screen them for relevance and susceptibility to bias. Our results indicate that removal of planktivorous and benthivorous fish is a useful means of improving water quality in eutrophic lakes. Biomanipulation tends to be particularly successful in relatively small lakes with short retention times and high phosphorus levels. More thorough fish removal increases the efficacy of biomanipulation. Nonetheless successes and failures have occurred across a wide range of conditions.
Anticancer effect of black tea extract in human cancer cell lines
Authors: Koňariková Katarína , Ježovičová Miriam , Keresteš Ján , Gbelcová Helena , Ďuračková Zdeňka , Žitňanová Ingrid 
Published: March 2015

Abstract
In this study we investigated effects of natural extract from the black tea Camellia sinensis (BTE) against human colon carcinoma cell line HT-29, human breast carcinoma cell line MCF-7, human alveolar carcinoma cell line A549 and healthy cell line NIH-3T3. We identified concentration range for cytotoxic/antiproliferative effects using MTT assay and the trypan blue assay, gel electrophoresis we employed to determine the type of cell death induced by BTE and DNA damage we determined by comet assay. Different concentrations of the extract (0.00078 - 5 μg/mL) we added to the cultured cells and incubated for 216 h. BTE showed cytotoxic effects against all carcinoma cell lines, however HT-29 and MCF-7 cells were more sensitive than A549. BTE showed no antiproliferative effect against healthy cells NIH-3T3 at tested concentrations. We found no apoptotic cell death in HT-29 and MCF-7 cells after 72 h of incubation in case of single administration of BTE but in case of repetitive administration of BTE (BTE was added to the cells each day) we found apoptotic cell death in HT-29 after 72 h incubation. BTE induced also DNA strand breaks and oxidative damage to DNA in carcinoma cells HT-29 and MCF-7.