bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of faecal occult bloods in the diagnosis of iron deficiency anaemia
Authors: Chowdhury A T M Dilshad , Longcroft-Wheaton Gaius , Davis Andrew , Massey David , Goggin Patrick 
Published: January 2014

ObjectiveTo determine whether faecal occult blood (FOB) testing in patients with iron deficiency anaemia (IDA) can predict the presence of gastrointestinal cancer.DesignCohort study.SettingsSingle secondary care hospital UK.PatientsAll individuals aged 20 years and older referred for the investigation for IDA.InterventionsData was collected from all the patients regarding haemoglobin (Hb), mean corpuscular volume, age, sex, symptomatology and medication. All patients had FOB tests using laboratory guaiac and haemocell methods, and then underwent gastroscopy and colonoscopy.Main outcome measuresAccuracy, sensitivity and specificity of FOBs for identifying cancer in the upper or lower gastrointestinal tract.ResultsIn total, 292 patients completed the study; 37 patients were diagnosed with carcinoma (colon 34, gastro-oesophageal 3). Using an optimal combination of lab guiaic and haemocell test resulted in just one colorectal cancer being missed, a sensitivity of 97%, specificity of 49% and negative predictive value of 99%. The test was less effective for upper gastrointestinal cancer, with 2/3 tumours missed by the tests.ConclusionsPatients who have negative FOB tests are very unlikely to have a colorectal cancer, and the benefits to further colonic investigation is limited. This should be carefully considered in patients with significant comorbidities, where the risks of investigation may outweigh the benefits.
Camera selection for tracking in distributed smart camera networks
Authors: Tessens Linda , Morbee Marleen , Aghajan Hamid , Philips Wilfried 
Published: January 2014

Tracking persons with multiple cameras with overlapping fields of view instead of with one camera leads to more robust decisions. However, operating multiple cameras instead of one requires more processing power and communication bandwidth, which are limited resources in practical networks.When the fields of view of different cameras overlap, not all cameras are equally needed for localizing a tracking target. When only a selected set of cameras do processing and transmit data to track the target, a substantial saving of resources is achieved. The recent introduction of smart cameras with on-board image processing and communication hardware makes such a distributed implementation of tracking feasible.We present a novel framework for selecting cameras to track people in a distributed smart camera network that is based on generalized information-theory. By quantifying the contribution of one or more cameras to the tracking task, the limited network resources can be allocated appropriately, such that the best possible tracking performance is achieved.With the proposed method, we dynamically assign a subset of all available cameras to each target and track it in difficult circumstances of occlusions and limited fields of view with the same accuracy as when using all cameras.
New Strategies in Lung Cancer: Translating Immunotherapy into Clinical Practice
Authors: Forde Patrick M. , Kelly Ronan J. , Brahmer Julie R. 
Published: January 2014

Abstract
Recent breakthroughs in translating the early development of immunomodulatory antibodies into the clinic, notably with the anti–cytotoxic T-lymphocyte antigen-4 antibody, ipilimumab, have led to durable benefits and prolonged survival for a subgroup of patients with advanced melanoma. Subsequent studies have shown that related immune checkpoint antibodies, specifically those targeting the programmed death-1 pathway, have activity in non–small cell lung cancer. Non–small cell lung cancer is the commonest cause of cancer death worldwide and this exciting avenue of clinical investigation carries with it great promise and new challenges. In this article, we discuss recent developments in lung cancer immunotherapy, reviewing recent findings from therapeutic vaccine studies and in particular we focus on the refinement of immunomodulation as a therapeutic strategy in this challenging disease. Clin Cancer Res; 20(5); 1067–73. ©2014 AACR.
Phase Ib Study of Buparlisib plus Trastuzumab in Patients with HER2-Positive Advanced or Metastatic Breast Cancer That Has Progressed on Trastuzumab-Based Therapy
Authors: Saura Cristina , Bendell Johanna , Jerusalem Guy , Su Shaun , Ru Qinhua , De Buck Stefan , Mills David , Ruquet Sophie , Bosch Ana , Urruticoechea Ander , Beck Joseph T. , Di Tomaso Emmanuelle , Sternberg David W. , Massacesi Cristian , Hirawat Samit , Dirix Luc , Baselga Jose 
Published: January 2014

AbstractPurpose: Phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway activation in patients with HER2-positive (HER2+) breast cancer has been implicated in de novo and acquired trastuzumab resistance. The purpose of this study was to determine the clinical activity of the PI3K inhibitor buparlisib (BKM120) in patients with HER2+ advanced/metastatic breast cancer resistant to trastuzumab-based therapy.Experimental Design: In the dose-escalation portion of this phase I/II study, patients with trastuzumab-resistant locally advanced or metastatic HER2+ breast cancer were treated with daily oral doses of buparlisib and weekly intravenous trastuzumab (2 mg/kg). Dose escalation was guided by a Bayesian logistic regression model with overdose control.Results: Of 18 enrolled patients, 17 received buparlisib. One dose-limiting toxicity of grade 3 general weakness was reported at the 100-mg/day dose level (the single-agent maximum tolerated dose) and this dose level was declared the recommended phase II dose (RP2D) of buparlisib in combination with trastuzumab. Common (&gt;25%) adverse events included rash (39%), hyperglycemia (33%), and diarrhea (28%). The pharmacokinetic profile of buparlisib was not affected by its combination with trastuzumab. At the RP2D, there were two (17%) partial responses, 7 (58%) patients had stable disease (≥6 weeks), and the disease control rate was 75%. Pharmacodynamic studies showed inhibition of the PI3K/AKT/mTOR and RAS/MEK/ERK pathways.Conclusions: In this patient population, the combination of buparlisib and trastuzumab was well tolerated, and preliminary signs of clinical activity were observed. The phase II portion of this study will further explore the safety and efficacy of this combination at the RP2D. Clin Cancer Res; 20(7); 1935–45. ©2014 AACR.
RNA Helicase A Is a Downstream Mediator of KIF1Bβ Tumor-Suppressor Function in Neuroblastoma
Authors: Chen Zhi Xiong , Wallis Karin , Fell Stuart M. , Sobrado Veronica R. , Hemmer Marie C. , Ramsköld Daniel , Hellman Ulf , Sandberg Rickard , Kenchappa Rajappa S. , Martinson Tommy , Johnsen John I. , Kogner Per , Schlisio Susanne 
Published: January 2014

Abstract
Inherited KIF1B loss-of-function mutations in neuroblastomas and pheochromocytomas implicate the kinesin KIF1B as a 1p36.2 tumor suppressor. However, the mechanism of tumor suppression is unknown. We found that KIF1B isoform β (KIF1Bβ) interacts with RNA helicase A (DHX9), causing nuclear accumulation of DHX9, followed by subsequent induction of the proapoptotic XIAP-associated factor 1 (XAF1) and, consequently, apoptosis. Pheochromocytoma and neuroblastoma arise from neural crest progenitors that compete for growth factors such as nerve growth factor (NGF) during development. KIF1Bβ is required for developmental apoptosis induced by competition for NGF. We show that DHX9 is induced by and required for apoptosis stimulated by NGF deprivation. Moreover, neuroblastomas with chromosomal deletion of 1p36 exhibit loss of KIF1Bβ expression and impaired DHX9 nuclear localization, implicating the loss of DHX9 nuclear activity in neuroblastoma pathogenesis.
Significance: KIF1Bβ has neuroblastoma tumor-suppressor properties and promotes and requires nuclear-localized DHX9 for its apoptotic function by activating XAF1 expression. Loss of KIF1Bβ alters subcellular localization of DHX9 and diminishes NGF dependence of sympathetic neurons, leading to reduced culling of neural progenitors, and, therefore, might predispose to tumor formation. Cancer Discov; 4(4); 434–51. ©2014 AACR.
See related commentary by Bernards, p. 392
This article is highlighted in the In This Issue feature, p. 377
Impact of S-Adenosylmethionine Decarboxylase 1 on Pulmonary Vascular Remodeling
Authors: Weisel Friederike Christine , Kloepping Christina , Pichl Alexandra , Sydykov Akylbek , Kojonazarov Baktybek , Wilhelm Jochen , Roth Markus , Ridge Karen Marie , Igarashi Kazuei , Nishimura Kazuhiro , Maison Wolfgang , Wackendorff Claudia , Klepetko Walter , Jaksch Peter , Ghofrani Hossein Ardeschir , Grimminger Friedrich , Seeger Werner , Schermuly Ralph Theo , Weissmann Norbert , Kwapiszewska Grazyna 
Published: January 2014

Background—
Pulmonary hypertension (PH) is a life-threatening disease characterized by vascular remodeling and increased pulmonary vascular resistance. Chronic alveolar hypoxia in animals is often used to decipher pathways being regulated in PH. Here, we aimed to investigate whether chronic hypoxia–induced PH in mice can be reversed by reoxygenation and whether possible regression can be used to identify pathways activated during the reversal and development of PH by genome-wide screening.

Methods and Results—

Mice exposed to chronic hypoxia (21 days, 10% O
2
) were reoxygenated for up to 42 days. Full reversal of PH during reoxygenation was evident by normalized right ventricular pressure, right heart hypertrophy, and muscularization of small pulmonary vessels. Microarray analysis from these mice revealed s-adenosylmethionine decarboxylase 1 (AMD-1) as one of the most downregulated genes. In situ hybridization localized AMD-1 in pulmonary vessels. AMD-1 silencing decreased the proliferation of pulmonary arterial smooth muscle cells and diminished phospholipase Cγ1 phosphorylation. Compared with the respective controls, AMD-1 depletion by heterozygous in vivo knockout or pharmacological inhibition attenuated PH during chronic hypoxia. A detailed molecular approach including promoter analysis showed that AMD-1 could be regulated by early growth response 1, transcription factor, as a consequence of epidermal growth factor stimulation. Key findings from the animal model were confirmed in human idiopathic pulmonary arterial hypertension.

Conclusions—
Our study indicates that genome-wide screening in mice from a PH model in which full reversal of PH occurs can be useful to identify potential key candidates for the reversal and development of PH. Targeting AMD-1 may represent a promising strategy for PH therapy.
Circulation and Modification of Warm Deep Water on the Central Amundsen Shelf
Authors: Ha H. K. , Wåhlin A. K. , Kim T. W. , Lee S. H. , Lee J. H. , Lee H. J. , Hong C. S. , Arneborg L. , Björk G. , Kalén O. 
Published: January 2014

Abstract
The circulation pathways and subsurface cooling and freshening of warm deep water on the central Amundsen Sea shelf are deduced from hydrographic transects and four subsurface moorings. The Amundsen Sea continental shelf is intersected by the Dotson trough (DT), leading from the outer shelf to the deep basins on the inner shelf. During the measurement period, warm deep water was observed to flow southward on the eastern side of DT in approximate geostrophic balance. A northward outflow from the shelf was also observed along the bottom in the western side of DT. Estimates of the flow rate suggest that up to one-third of the inflowing warm deep water leaves the shelf area below the thermocline in this deep outflow. The deep current was 1.2°C colder and 0.3 psu fresher than the inflow, but still warm, salty, and dense compared to the overlying water mass. The temperature and salinity properties suggest that the cooling and freshening process is induced by subsurface melting of glacial ice, possibly from basal melting of Dotson and Getz ice shelves. New heat budgets are presented, with a southward oceanic heat transport of 3.3 TW on the eastern side of the DT, a northward oceanic heat transport of 0.5–1.6 TW on the western side, and an ocean-to-glacier heat flux of 0.9–2.53 TW, equivalent to melting glacial ice at the rate of 83–237 km3 yr−1. Recent satellite-based estimates of basal melt rates for the glaciers suggest comparable values for the Getz and Dotson ice shelves.
Ponatinib efficiently kills imatinib-resistant chronic eosinophilic leukemia cells harboring gatekeeper mutant T674I FIP1L1-PDGFRα: roles of Mcl-1 and β-catenin
Authors: Jin Yanli , Ding Ke , Li Honglin , Xue Mengzhu , Shi Xiaoke , Wang Chengyan , Pan Jingxuan 
Published: January 2014

Abstract
Background
T674I FIP1L1-PDGFRα in a subset of chronic eosinophilic leukemia (CEL) is a gatekeeper mutation that is resistant to many tyrosine kinase inhibitors (TKIs) (e.g., imatinib, nilotinib and dasatinib), similar to T315I Bcr-Abl. Therefore, novel TKIs effective against T674I FIP1L1-PDGFRα are needed. Ponatinib (AP24534) is a novel orally bioavailable TKI against T315I Bcr-Abl, but it is not clear whether ponatinib is effective against T674I FIP1L1-PDGFRα. The purpose of this study was to examine the effect of ponatinib on T674I FIP1L1-PDGFRα.

Methods
Molecular docking analysis in silico was performed. The effects of ponatinib on PDGFRα signaling pathways, apoptosis and cell cycling were examined in EOL-1, BaF3 cells expressing either wild type (WT) or T674I FIP1L1-PDGFRα. The in vivo antitumor activity of ponatinib was evaluated with xenografted BaF3-T674I FIP1L1-PDGFRα cells in nude mice models.

Results
Molecular docking analysis revealed that ponatinib could bind to the DFG (Asp-Phe-Gly)-out state of T674I PDGFRα. Ponatinib potently inhibited the phosphorylation of WT and T674I FIP1L1-PDGFRα and their downstream signaling molecules (e.g., Stat3, Stat5). Ponatinib strikingly inhibited the growth of both WT and T674I FIP1L1-PDGFRα-carrying CEL cells (IC50: 0.004–2.5 nM). It induced apoptosis in CEL cells with caspase-3-dependent cleavage of Mcl-1, and inhibited tyrosine phosphorylation of β-catenin to decrease its stability and pro-survival functions. In vivo, ponatinib abrogated the growth of xenografted BaF3-T674I FIP1L1-PDGFRα cells in nude mice.

Conclusions
Ponatinib is a pan-FIP1L1-PDGFRα inhibitor, and clinical trials are warranted to investigate its efficacy in imatinib-resistant CEL.
What are the effects of agricultural management on soil organic carbon (SOC) stocks?
Authors: Söderström Bo , Hedlund Katarina , Jackson Louise E , Kätterer Thomas , Lugato Emanuele , Thomsen Ingrid K , Bracht Jørgensen Helene 
Published: January 2014

Abstract
Background
Changes in soil organic carbon (SOC) stocks significantly influence the atmospheric C concentration. Agricultural management practices that increase SOC stocks thus may have profound effects on climate mitigation. Additional benefits include higher soil fertility since increased SOC stocks improve the physical and biological properties of the soil. Intensification of agriculture and land-use change from grasslands to croplands are generally known to deplete SOC stocks. The depletion is exacerbated through agricultural practices with low return of organic material and various mechanisms, such as oxidation/mineralization, leaching and erosion. However, a systematic review comparing the efficacy of different agricultural management practices to increase SOC stocks has not yet been produced. Since there are diverging views on this matter, a systematic review would be timely for framing policies not only nationally in Sweden, but also internationally, for promoting long-term sustainable management of soils and mitigating climate change.

Methods
The systematic review will examine how changes in SOC are affected by a range of soil-management practices relating to tillage management, addition of crop residues, manure or other organic “wastes”, and different crop rotation schemes. Within the warm temperate and the snow climate zones, agricultural management systems in which wheat, barley, rye, oats, silage maize or oilseed rape can grow in the crop rotation will be selected. The review will exclusively focus on studies conducted over at least 10 years. Searches will be made in 15 publication databases as well as in specialist databases. Articles found will be screened using inclusion/exclusion criteria at title, abstract and full-text levels, and screening consistency will be evaluated using Kappa tests. Data from articles that remain after critical appraisal will be extracted using a predefined spreadsheet. Subgroup analyses will be undertaken to elucidate statistical relationships that are specific to particular type of management interventions. Meta-regression within subgroups will be performed as well as sensitivity analysis to investigate the impact of removing groups of studies with low or unclear quality.
Microbes in the neonatal intensive care unit resemble those found in the gut of premature infants
Authors: Brooks Brandon , Firek Brian A , Miller Christopher S , Sharon Itai , Thomas Brian C , Baker Robyn , Morowitz Michael J , Banfield Jillian F 
Published: January 2014

Abstract

Background
The source inoculum of gastrointestinal tract (GIT) microbes is largely influenced by delivery mode in full-term infants, but these influences may be decoupled in very low birth weight (VLBW, <1,500 g) neonates via conventional broad-spectrum antibiotic treatment. We hypothesize the built environment (BE), specifically room surfaces frequently touched by humans, is a predominant source of colonizing microbes in the gut of premature VLBW infants. Here, we present the first matched fecal-BE time series analysis of two preterm VLBW neonates housed in a neonatal intensive care unit (NICU) over the first month of life.

Results
Fresh fecal samples were collected every 3 days and metagenomes sequenced on an Illumina HiSeq2000 device. For each fecal sample, approximately 33 swabs were collected from each NICU room from 6 specified areas: sink, feeding and intubation tubing, hands of healthcare providers and parents, general surfaces, and nurse station electronics (keyboard, mouse, and cell phone). Swabs were processed using a recently developed ‘expectation maximization iterative reconstruction of genes from the environment’ (EMIRGE) amplicon pipeline in which full-length 16S rRNA amplicons were sheared and sequenced using an Illumina platform, and short reads reassembled into full-length genes. Over 24,000 full-length 16S rRNA sequences were produced, generating an average of approximately 12,000 operational taxonomic units (OTUs) (clustered at 97% nucleotide identity) per room-infant pair. Dominant gut taxa, including Staphylococcus epidermidis, Klebsiella pneumoniae, Bacteroides fragilis, and Escherichia coli, were widely distributed throughout the room environment with many gut colonizers detected in more than half of samples. Reconstructed genomes from infant gut colonizers revealed a suite of genes that confer resistance to antibiotics (for example, tetracycline, fluoroquinolone, and aminoglycoside) and sterilizing agents, which likely offer a competitive advantage in the NICU environment.

Conclusions
We have developed a high-throughput culture-independent approach that integrates room surveys based on full-length 16S rRNA gene sequences with metagenomic analysis of fecal samples collected from infants in the room. The approach enabled identification of discrete ICU reservoirs of microbes that also colonized the infant gut and provided evidence for the presence of certain organisms in the room prior to their detection in the gut.
The relationship between lateral meniscus shape and joint contact parameters in the knee: a study using data from the Osteoarthritis Initiative
Authors: Zhang Kai Yu , Kedgley Angela E , Donoghue Claire R , Rueckert Daniel , Bull Anthony MJ 
Published: January 2014

Abstract
Introduction
The meniscus has an important role in force transmission across the knee, but a detailed three-dimensional (3D) morphometric shape analysis of the lateral meniscus to elucidate subject-specific function has not been conducted. The aim of this study was to perform 3D morphometric analyses of the lateral meniscus in order to correlate shape variables with anthropometric parameters, thereby gaining a better understanding of the relationship between lateral meniscus shape and its load-bearing function.

Methods
The lateral meniscus (LM) was manually segmented from magnetic resonance images randomly selected from the Osteoarthritis Initiative (OAI) non-exposed control subcohort. A 3D statistical shape model (SSM) was constructed to extract the principal morphological variations (PMV) of the lateral meniscus for 50 subjects (25 male and 25 female). Correlations between the principal morphological variations and anthropometric parameters were tested. Anthropometric parameters that were selected included height, weight, body mass index (BMI), femoral condyle width and axial rotation.

Results
The first principal morphological variation (PMV) was found to correlate with height (r = 0.569), weight (r = 0.647), BMI (r = 0.376), and femoral condyle width (r = 0.622). The third PMV was found to correlate with height (r = 0.406), weight (r = 0.312), and femoral condyle width (r = 0.331). The percentage of the tibial plateau covered by the lateral meniscus decreases as anthropometric parameters relating to size of the subject increase. Furthermore, when the size of the subject increases, the posterior and anterior horns become proportionally longer and wider.

Conclusion
The correlations discovered suggest that variations in meniscal shape can be at least partially explained by the levels of loads transmitted across the knee on a regular basis. Additionally, as the size of the subject increases and body weight rises, the coverage percentage of the meniscus is reduced, suggesting that there would be an increase in the load-bearing by the cartilage. However, this reduced coverage percentage is compensated by the proportionally wider and longer meniscal horn.
Randomized Controlled Trial of Expressive Writing for Patients With Renal Cell Carcinoma
Authors: Milbury Kathrin , Spelman Amy , Wood Christopher , Matin Surena F. , Tannir Nizar , Jonasch Eric , Pisters Louis , Wei Qi , Cohen Lorenzo 
Published: January 2014

Purpose This randomized controlled trial examined the quality-of-life benefits of an expressive writing (EW) intervention for patients with renal cell carcinoma (RCC) and identified a potential underlying mechanism of intervention efficacy. Patients and Methods Patients (N = 277) with stage I to IV RCC were randomly assigned to write about their deepest thoughts and feelings regarding their cancer (EW) or about neutral topics (neutral writing [NW]) on four separate occasions. Patients completed the Center for Epidemiologic Studies Depression Scale (CES-D), MD Anderson Symptom Inventory (MDASI), Brief Fatigue Inventory (BFI), Pittsburgh Sleep Quality Index (PSQI), Medical Outcomes Study Short Form-36 (SF-36), and Impact of Event Scale (IES) at baseline and 1, 4, and 10 months after the intervention. Results The mean age of participants (28% stage IV; 41% female) was 58 years. Multilevel modeling analyses, using a Bonferroni-corrected α = .021 for six outcomes adjusted for the correlation among outcomes, revealed that, relative to the NW group, patients in the EW group reported significantly lower MDASI scores (P = .003) and higher physical component summary scores on the SF-36 (P = .019) at 10 months after the intervention. Mediation analyses revealed that significant group differences for MDASI scores at 10 months were mediated by lower IES scores at 1 month after the intervention in the EW group (P = .042). No significant group differences were observed in the BFI, CES-D, PSQI, and mental component summary of the SF-36. Conclusion EW may reduce cancer-related symptoms and improve physical functioning in patients with RCC. Evidence suggests that this effect may occur through short-term improvements in cognitive processing.