bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of a validated screening tool for psoriatic arthritis in dermatology clinics
Authors: Ganatra Bella , Manoharan Dishan , Akhras Victoria 
Published: February 2015

AbstractDermatology clinics represent a key opportunity to screen patients with psoriasis for psoriatic arthritis (PA) which often remains unrecognised. A significant proportion of adults with psoriasis develop arthropathy [5] with around two-thirds having progressive arthritis.[6] NICE has recognised this by the annual use of a validated screening tool such as psoriasis epidemiological screening tool (PEST) on all psoriasis patients without PA. We introduced the PEST into our dermatology department since there was no established system of screening for PA. Twenty-one percent of patients that were identified through PEST as requiring a referral at baseline were not referred to rheumatology through the current system without PEST. This represented a significantly missed proportion of patients with possible PA.Using the PDSA cycle method, we introduced the PEST into cycle 1 and educated key staff about the tool. All eligible patients were referred appropriately. Through doctor and patient feedback, changes were adopted for cycle 2 and informative emails to all key staff about PEST were sent. We noted a drop in the number of PEST uptake in this cycle possibly due to lack of awareness on the purpose and use of PEST among staff, across the department. An educational teaching session was delivered to a wider audience and posters were placed in strategic areas of the department prior to the final cycle. This resulted in 100% PEST uptake and 100% of those with a score of >3 being referred. A total of 51 patients were studied, comprising of 30 eligible patients for PEST. Of these, 27 patients were actually screened (90%) and five with a PEST score of ≥ 3 were identified and referred appropriately (18.5%). We felt this represented a successful outcome in increasing PEST uptake within the department and in capturing a significant proportion of patients at risk of PA.
Improving inpatient care with the introduction of a hip fracture pathway
Authors: Chamberlain Mark , Pugh Hannah 
Published: February 2015

AbstractA system of payment by results exists for the management of hip fractures in England and Wales. Poor performance against the national standards was noted, reflecting failure to deliver optimal care. Through the introduction of a multi-disciplinary patient pathway and clerking pro forma, the proportion of patients earning the best practice tariff uplift increased from 44.4% to 91.7%. This demonstrates a significant improvement in patient care measured against the guidelines, also resulting in a substantial revenue increase for the department.
Depressive symptoms in the last days of life of patients with cancer: a nationwide retrospective mortality study
Authors: Janberidze Elene , Pereira Sandra Martins , Hjermstad Marianne Jensen , Knudsen Anne Kari , Kaasa Stein , van der Heide Agnes , Onwuteaka-Philipsen Bregje 
Published: February 2015

ObjectivesDepressive symptoms are common in patients with cancer and tend to increase as death approaches. The study aims were to examine the prevalence of depressive symptoms in patients with cancer in their final 24 h, and their association with other symptoms, sociodemographic and care characteristics.MethodsA stratified sample of deaths was drawn by Statistics Netherlands. Questionnaires on patient and care characteristics were sent to the physicians (N=6860) who signed the death certificates (response rate 77.8%). Adult patients with cancer with non-sudden death were included (n=1363). Symptoms during the final 24 h of life were assessed on a 1–5 scale and categorised as 1=no, 2–3=mild/moderate and 4–5=severe/very severe.ResultsDepressive symptoms were registered in 37.6% of the patients. Patients aged 80 years or more had a reduced risk of having mild/moderate depressive symptoms compared with those aged 17–65 years (OR 0.70; 95% CI 0.50 to 0.99). Elderly care physicians were more likely to assess patients with severe/very severe depressive symptoms than patients with no depressive symptoms (OR 4.18; 95% CI 1.48 to 11.76). Involvement of pain specialists/palliative care consultants and psychiatrists/psychologists was associated with more ratings of severe/very severe depressive symptoms. Fatigue and confusion were significantly associated with mild/moderate depressive symptoms and anxiety with severe/very severe symptoms.ConclusionsMore than one-third of the patients were categorised with depressive symptoms during the last 24 h of life. We recommend greater awareness of depression earlier in the disease trajectory to improve care.
Five anomalous structural aspects of rift basins in Thailand and their impact on petroleum systems
Authors: Morley Chris K. 
Published: February 2015

Abstract
The intracratonic, supra-subduction zone setting of the Thailand rift basins caused the rifts to evolve in several ways differently from other intracratonic rifts. Key differences include: widespread occurrence of low-angle normal faults; basin inversion alternating with rifting; diachronous initiation and cessation of rifting; rapid post-rift subsidence; and extensive, low-displacement post-rift faults. These characteristics are related to hot, weak continental lithosphere, rapid evolution of the plate boundaries and stresses during the Cenozoic, and the history of subduction and accretion. Low-angle normal faults impacted the Sirikit Field by controlling the location of fluvio-deltaic reservoirs interfingering lacustrine shales (source and seal). Basin inversion alternating with syn-rift section is detrimental to prospectivity of the southern half of the Phitsanulok Basin by destroying syn-rift structure, and halting hydrocarbon maturation early in the basin history. The diachronous timing of basin development resulted in large, gas-dominated hydrocarbon accumulations in the eastern Gulf of Thailand basins, but was detrimental for younger basins that lack the post-rift section, and the greater variety of petroleum systems and traps that post-rift basins offer. The extensive low displacement–length ratio post-rift faults form significant hydrocarbon traps in the Pattani and North Malay basins. They represent a structural style not usually found in post-rift basins.
Imaging Active Urokinase Plasminogen Activator in Prostate Cancer
Authors: LeBeau Aaron M. , Sevillano Natalia , Markham Kate , Winter Michael B. , Murphy Stephanie T. , Hostetter Daniel R. , West James , Lowman Henry , Craik Charles S. , VanBrocklin Henry F. 
Published: February 2015

Abstract
The increased proteolytic activity of membrane-bound and secreted proteases on the surface of cancer cells and in the transformed stroma is a common characteristic of aggressive metastatic prostate cancer. We describe here the development of an active site-specific probe for detecting a secreted peritumoral protease expressed by cancer cells and the surrounding tumor microenvironment. Using a human fragment antigen-binding phage display library, we identified a human antibody termed U33 that selectively inhibited the active form of the protease urokinase plasminogen activator (uPA, PLAU). In the full-length immunoglobulin form, U33 IgG labeled with near-infrared fluorophores or radionuclides allowed us to noninvasively detect active uPA in prostate cancer xenograft models using optical and single-photon emission computed tomography imaging modalities. U33 IgG labeled with 111In had a remarkable tumor uptake of 43.2% injected dose per gram (%ID/g) 72 hours after tail vein injection of the radiolabeled probe in subcutaneous xenografts. In addition, U33 was able to image active uPA in small soft-tissue and osseous metastatic lesions using a cardiac dissemination prostate cancer model that recapitulated metastatic human cancer. The favorable imaging properties were the direct result of U33 IgG internalization through an uPA receptor–mediated mechanism in which U33 mimicked the function of the endogenous inhibitor of uPA to gain entry into the cancer cell. Overall, our imaging probe targets a prostate cancer–associated protease, through a unique mechanism, allowing for the noninvasive preclinical imaging of prostate cancer lesions. Cancer Res; 75(7); 1225–35. ©2015 AACR.
Nonsteroidal Anti-Inflammatory Drug and Aspirin Use in Relation to Lung Cancer Risk among Postmenopausal Women
Authors: Baik Christina S. , Brasky Theodore M. , Pettinger Mary , Luo Juhua , Gong Zhihong , Wactawski-Wende Jean , Prentice Ross L. 
Published: February 2015

Abstract
Background: Results from prospective studies suggest that nonsteroidal anti-inflammatory drugs (NSAID) may decrease lung cancer risk; however, any protective effect appears to be most evident in men.
Methods: We evaluated the associations between NSAID use and lung cancer incidence in postmenopausal women in the Women's Health Initiative (WHI) adjusting for female-specific potential confounders such as hormone therapy in addition to smoking histories and other potential confounders. We identified 143,841 women from ages 50 to 79 and 1,902 centrally confirmed lung cancer cases were included in the analysis. We used Cox regression models to estimate HRs and their 95% confidence intervals (CI).
Results: Compared with nonuse, regular NSAID use was not associated with overall lung cancer incidence (NSAID use &gt;10 years HR 0.87; 95% CI, 0.71–1.08, Ptrend = 0.13). No statistically significant associations were found when examined by histologic subtypes and although there was a trend of decreased risk with longer duration of NSAID use in the adenocarcinoma subtype, this was not statistically significant (NSAID use &gt;10 years HR 0.80; 95% CI, 0.58–1.10; Ptrend = 0.07).
Conclusion: Our study did not show that NSAID use is associated with lung cancer risk in women even after adjusting for female-specific confounders. There was a trend of decreased risk in the adenocarcinoma subtype; however, this was not statistically significant.
Impact: Future studies will need to take in account the various molecular subtypes of non–small cell lung cancer to further elucidate the role of NSAIDs in lung cancer, especially for the adenocarcinoma subtype. Cancer Epidemiol Biomarkers Prev; 24(5); 790–7. ©2015 AACR.
13C-MR Spectroscopic Imaging with Hyperpolarized [1-13C]pyruvate Detects Early Response to Radiotherapy in SCC Tumors and HT-29 Tumors
Authors: Saito Keita , Matsumoto Shingo , Takakusagi Yoichi , Matsuo Masayuki , Morris H. Douglas , Lizak Martin J. , Munasinghe Jeeva P. , Devasahayam Nallathamby , Subramanian Sankaran , Mitchell James B. , Krishna Murali C. 
Published: February 2015

Abstract
Purpose: X-ray irradiation of tumors causes diverse effects on the tumor microenvironment, including metabolism. Recent developments of hyperpolarized 13C-MRI enabled detecting metabolic changes in tumors using a tracer [1-13C]pyruvate, which participates in important bioenergetic processes that are altered in cancers. Here, we investigated the effects of X-ray irradiation on pyruvate metabolism in squamous cell carcinoma (SCCVII) and colon cancer (HT-29) using hyperpolarized 13C-MRI.
Experimental Design: SCCVII and HT-29 tumors were grown by injecting tumor cells into the hind legs of mice. [1-13C]pyruvate was hyperpolarized and injected intravenously into tumor-bearing mice, and 13C-MR signals were acquired using a 4.7 T scanner.
Results: [1-13C]pyruvate and [1-13C]lactate were detected in the tumor-bearing legs immediately after hyperpolarized [1-13C]pyruvate administration. The [1-13C]lactate to [1-13C]pyruvate ratio (Lac/Pyr) increased as the tumors grew in nonirradiated SCCVII tumors. The increase in Lac/Pyr was suppressed modestly with a single 10 Gy of irradiation, but it significantly decreased by further irradiation (10 Gy × 3). Similar results were obtained in HT-29; Lac/Pyr significantly dropped with fractionated 30 Gy irradiation. Independent ex vivo measurements revealed that the lactate dehydrogenase (LDH) activity and protein level were significantly smaller in the irradiated SCCVII tumors compared with the nonirradiated tumors, indicating that a decrease in LDH activity was one of the main factors responsible for the decrease of Lac/Pyr observed on 13C-MRI.
Conclusions: Robust changes of Lac/Pyr observed in the HT-29 after the radiation suggested that lactate conversion from pyruvate monitored with hyperpolarized 13C-MRI could be useful for the evaluation of early response to radiotherapy. Clin Cancer Res; 21(22); 5073–81. ©2015 AACR.
See related commentary by Lai et al., p. 4996
Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors
Authors: Sinha Sutapa , Boysen Justin , Nelson Michael , Secreto Charla , Warner Steven L. , Bearss David J. , Lesnick Connie , Shanafelt Tait D. , Kay Neil E. , Ghosh Asish K. 
Published: February 2015

Abstract
Purpose: B-cell chronic lymphocytic leukemia (CLL) is an incurable disease despite aggressive therapeutic approaches. We previously found that Axl receptor tyrosine kinase (RTK) plays a critical role in CLL B-cell survival. Here, we explored the possibility of using a high-affinity Axl inhibitor as a single agent or in combination with Bruton's tyrosine kinase (BTK) inhibitors for future clinical trial to treat patients with CLL.
Experimental Design: Expression/activation status of other members of the TAM (e.g., Tyro3, Axl, and MER) family of RTKs in CLL B cells was evaluated. Cells were treated with a high-affinity orally bioavailable Axl inhibitor TP-0903 with or without the presence of CLL bone marrow stromal cells (BMSCs). Inhibitory effects of TP-0903 on the Axl signaling pathway were also evaluated in CLL B cells. Finally, cells were exposed to TP-0903 in combination with BTK inhibitors to determine any synergistic/additive effects of the combination.
Results: CLL B cells overexpress Tyro3, but not MER. Of interest, Tyro3 remains as constitutively phosphorylated and forms a complex with Axl in CLL B cells. TP-0903 induces massive apoptosis in CLL B cells with LD50 values of nanomolar ranges. Importantly, CLL BMSCs could not protect the leukemic B cells from TP-0903–induced apoptosis. A marked reduction of the antiapoptotic proteins Mcl-1, Bcl-2, and XIAP and upregulation of the proapoptotic protein BIM in CLL B cells was detected as a result of Axl inhibition. Finally, combination of TP-0903 with BTK inhibitors augments CLL B-cell apoptosis.
Conclusions: Administration of TP-0903 either as a single agent or in combination with BTK inhibitors may be effective in treating patients with CLL. Clin Cancer Res; 21(9); 2115–26. ©2015 AACR.
The effect of calcium plus vitamin D supplementation on the risk of venous thromboembolism
Authors: Rodabough Rebecca J. , Budrys Nicole , Johnson Karen C. , Berger Jeffrey S. , Shikany James M. , Raiesdana Azad , Heckbert Susan R , Manson JoAnn E. , LaCroix Andrea Z. , Siscovick David , Kestenbaum Bryan , Smith Nicholas L. , de Boer Ian H. , Blondon Marc 
Published: February 2015

SummaryExperimental and epidemiological studies suggest that vitamin D may be implicated in haemostatic regulations and influence the risk of venous thromboembolism (VTE). The aim of this study was to investigate whether oral supplementation of vitamin D3 combined with calcium reduces the risk of VTE. In the randomised, double-blind, placebo-controlled Women’s Health Initiative Calcium Plus Vitamin D trial, 36,282 postmenopausal women aged 50-79 years were randomised to receive 1,000 mg of calcium carbonate and 400 IU of vitamin D3 per day (n=18,176) or a matching placebo (n=18,106) during an average of seven years. This secondary analysis of the trial compared the incidence of VTE by treatment group using an intention-to-treat Cox regression analysis. The incidence of VTE did not differ between women randomised to calcium plus vitamin D and women randomised to placebo (320 vs 348 VTE events, respectively; hazard ratio (HR) 0.92, 95 % confidence interval (CI) 0.79-1.07). Results were not modified in an analysis using inverse-probability weights to take non-adherence into account (HR 0.94, 95 %CI 0.73-1.22) or in multiple subgroups. Whereas the risk of a non-idiopathic VTE was similar between groups, the risk of idiopathic VTE was lower in women randomised to calcium plus vitamin D (40 vs 65 events; HR 0.62, 95 %CI 0.42-0.92). In conclusion, daily supplementation with 1,000 mg of calcium and 400 IU of vitamin D did not reduce the overall incidence of VTE in generally healthy postmenopausal women. However, the observed reduced risk of idiopathic VTE in women randomised to calcium and vitamin D warrants further investigations.Trial Registration: NCT00000611 (www.clinicaltrials.gov).
Dissociation of SERPINE1 mRNA from the translational repressor proteins Ago2 and TIA-1 upon platelet activation
Authors: Corduan Aurélie , Plé Hélène , Laffont Benoit , Wallon Thérèse , Plante Isabelle , Landry Patricia , Provost Patrick 
Published: February 2015

SummaryPlatelets play an important role in haemostasis, as well as in thrombosis and coagulation processes. They harbour a wide variety of messenger RNAs (mRNAs), that can template de novo protein synthesis, and an abundant array of microRNAs, which are known to mediate mRNA translational repression through proteins of the Argonaute (Ago) family. The relationship between platelet microRNAs and proteins capable of mediating translational repression, however, remains unclear. Here, we report that half of platelet microRNAs is associated to mRNA-regulatory Ago2 protein complexes, in various proportions. Associated to these Ago2 complexes are platelet mRNAs known to support de novo protein synthesis. Reporter gene activity assays confirmed the capacity of the platelet microRNAs, found to be associated to Ago2 complexes, to regulate translation of these platelet mRNAs through their 3’UTR. Neither the microRNA repertoire nor the microRNA composition of Ago2 complexes of human platelets changed upon activation with thrombin. However, under conditions favoring de novo synthesis of Plasminogen Activator Inhibitor-1 (PAI-1) protein, we documented a rapid dissociation of the encoding platelet SERPINE1 mRNA from Ago2 protein complexes as well as from the translational repressor protein T-cell-restricted intracellular antigen-1 (TIA-1). These findings are consistent with a scenario by which lifting of the repressive effects of Ago2 and TIA-1 protein complexes, involving a rearrangement of protein•mRNA complexes rather than disassembly of Ago2•microRNA complexes, would allow translation of SERPINE1 mRNA into PAI-1 in response to platelet activation.
Assessment of Regional Myocardial Work in Rats
Authors: Espe Emil K.S. , Aronsen Jan Magnus , Eriksen Guro S. , Zhang Lili , Smiseth Otto A. , Edvardsen Thor , Sjaastad Ivar , Eriksen Morten 
Published: February 2015

Background—
Left ventricular (LV) motion and deformation is dependent on mechanical load and do therefore not reflect myocardial energy consumption directly. Regional myocardial work, however, constitutes a more complete assessment of myocardial function.

Methods and Results—

Strain was measured using high-resolution phase-contrast MRI in 9 adult male rats with myocardial infarction (MI) and in 5 sham-operated control animals. Timing of LV valvular events and LV dimensions were evaluated by cine MRI. A separate cohort of 14 animals (MI/sham=9/5) underwent measurement of LV pressure concurrent with identification of valvular events by Doppler-echocardiography for the purpose of generating a standard LV pressure curve, normalized to valvular events. The infarctions were localized to the anterolateral LV wall. Combining strain with timing of valvular events and a measurement of peak arterial pressure, regional myocardial work could be calculated by applying the standard LV pressure curves. Cardiac output and stroke work was preserved in the MI hearts, suggesting a compensatory redistribution of myocardial work from the infarcted region to the viable tissue. In the septum, regional work was indeed increased in MI rats compared with sham (median work per unit long-axis length in a mid-ventricular slice: 241.2 [224.1–271.2] versus 137.2 [127.0–143.8] mJ/m;
P
<0.001). Myocardial work in infarcted regions was zero. Additionally, eccentric work was increased in the MI hearts.

Conclusions—
Phase-contrast MRI, in combination with measurement of peak arterial pressure and MRI-derived timing of valvular events, represent a noninvasive approach for estimation of regional myocardial work in rodents.
Cortical Selective Neuronal Loss, Impaired Behavior, and Normal Magnetic Resonance Imaging in a New Rat Model of True Transient Ischemic Attacks
Authors: Ejaz Sohail , Emmrich Julius V. , Sawiak Stephen J. , Williamson David J. , Baron Jean-Claude 
Published: February 2015

Background and Purpose—
New-definition transient ischemic attacks (TIAs) are frequent but difficult to diagnose because magnetic resonance imaging (MRI)-negative by definition. However, hidden underlying cell damage might be present and account for the reported long-lasting cognitive impairment after TIAs. Most prior rodent models of true TIA targeted the striatum or have not been fully characterized. Here we present the MRI, behavioral, and quantitative cell changes characterizing a new rodent model of true TIA targeting the more behaviorally relevant cerebral cortex.

Methods—
Fifteen-minute distal middle cerebral artery occlusion was performed in 29 spontaneously hypertensive rats allowed to survive for 7 to 60 days. Behavior was assessed serially using both global neurological and fine sensorimotor tests. Diffusion- and T2-weighted MRI was obtained 20 min postreperfusion and again 7 to 60 days later, and then changes in neurons and microglia were quantified across the middle cerebral artery territory using immunohistochemistry.

Results—
No MRI changes or pan-necrosis were observed at any time point, but patchy cortical selective neuronal loss affected 28/29 rats, regardless of survival interval, together with topographically congruent microglial activation that gradually declined over time. The Neuroscore was unchanged, but there was marked contralateral sensorimotor impairment, still recovering by day 28.

Conclusions—
Our new rodent model mimicking true cortical TIA is characterized by normal MRI, but consistent cortical selective neuronal loss and microglial activation and long-lasting sensorimotor deficits. By causing selective neuronal loss, TIAs and silent microemboli might affect neuronal reserve, thereby increasing long-term cognitive impairment risk. Selective neuronal loss and microglial activation might represent novel therapeutic targets that could be detectable in vivo after TIAs using appropriate imaging tracers.
Lead Me Beside Still Waters
Authors: Hickman Lisa Nichols 
Published: February 2015

Artist Ena Swansea paints a provocative paradox in “One” from her “4 Seasons” quadtych: Is the child in the bathtub playfully holding a bubble, the orb of our global commons, or a crystal ball that portends an ominous future? As the viewer is confronted with the image of a child who, in the middle of an ordinary daily routine, is up to his armpits in a pool of blood red water, the question of water toxicity becomes central in the painting.
Working from that image, this paper explores the interaction between water toxicity and Trisomy 21, proposing the need for a “precautionary principle” to guide decision-making. The rationale for that principle is developed here through a study of communities with heightened links between water toxicity and Trisomy 21, a deepened theology of water across worldviews drawing on the work of John Hart’s Sacramental Commons, and a proposed model for “eco-social disability.” Because scientific studies linking toxic water and Trisomy 21 are inconclusive, the precautionary principle serves as a guide to prevent the potential disabling effects of toxic water causing unjust generation of disablement.