bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical prophylaxis after hip fracture: what is the risk of deep vein thrombosis? A retrospective observational study
Authors: Protty Majd B , Aithal Shridhar , Hickey Ben , Pettit Rebecca , Johansen Antony 
Published: February 2015

Graduated compression stockings carry a potential risk of pressure, vascular and other complications. Current understanding of deep vein thrombosis (DVT) risk leaves it uncertain whether patients with hip fracture should wear stockings on both legs.ObjectivesTo determine the association between the side of the hip fracture and the subsequent occurrence of symptomatic lower limb DVT.SettingSingle tertiary trauma centre, Wales.ParticipantsAll 3657 patients presenting with hip fracture between 2007 and 2013 were identified from our unit's National Hip Fracture Database. We excluded 404 patients (11.0%) resident outside our catchment area, leaving a total of 3253. Median age was 83 years (±12.4).Primary/secondary outcome measuresWe cross-linked patient details with Medical Physics records, to identify 634 (19.5%) who had undergone one or more lower-limb Doppler-ultrasound scans at some point during the study period. The distribution rates of DVT were calculated from this resulting data set.ResultsMany of the total 634 scans were unrelated to the hip fracture, including 225 (35.5%) performed prior to the fracture. We calculated a baseline rate of DVT of 3.7/1000 patients per year, for the 3-month period immediately before the hip fracture. Scans performed following hip fracture showed DVT risk to be highest in the 3-month period after fracture (35.7/1000 patients per year). This resulted from a six-fold increase in DVTs on the side of the fracture (29.5/1000 patients per year, p<0.01). We found only a very small non-significant increase in DVT on the contralateral leg (6.1/1000 patients per year)ConclusionsThe additional risk of DVT after hip fracture is essentially confined to the fractured limb—the leg to which it is most painful to apply stockings. There appears little justification for the cost and potential risk of using stockings on the contralateral leg.
Catheter based selective hypothermia reduces stroke volume during focal cerebral ischemia in swine
Authors: Mattingly Thomas K , Denning Lynn M , Siroen Karen L , Lehrbass Barb , Lopez-Ojeda Pablo , Stitt Larry , Pelz David M , Das Sumit , Ang Lee-Cyn , Lee Donald H , Lownie Stephen P 
Published: February 2015

BackgroundTotal body hypothermia is an established neuroprotectant in global cerebral ischemia. The role of hypothermia in acute ischemic stroke remains uncertain. Selective application of hypothermia to a region of focal ischemia may provide similar protection with more rapid cooling and elimination of systemic side effects. We studied the effect of selective endovascular cooling in a focal stroke model in adult domestic swine.MethodsAfter craniotomy under general anesthesia, a proximal middle cerebral artery branch was occluded for 3 h, followed by 3 h of reperfusion. In half of the animals, selective hypothermia was induced during reperfusion using a dual lumen balloon occlusion catheter placed in the ipsilateral common carotid artery. Following reperfusion, the animals were sacrificed. Brain MRI and histology were evaluated by experts who were blinded to the intervention.Results25 animals were available for analysis. Using selective hypothermia, hemicranial temperature was successfully cooled to a mean of 26.5°C. Average time from start of perfusion to attainment of moderate hypothermia (<30°C) was 25 min. Mean MRI stroke volumes were significantly reduced by selective cooling (0.050±0.059 control, 0.005±0.011 hypothermia (ratio stroke:hemisphere volume) (p=0.046). Stroke pathology volumes were reduced by 42% compared with controls (p=0.256).ConclusionsSelective moderate hypothermia was rapidly induced using endovascular techniques in a clinically realistic swine stroke model. A significant reduction in stroke volume on MRI was observed. Endovascular selective hypothermia can provide neuroprotection within time frames relevant to acute ischemic stroke treatment.
Sexual harassment of psychiatric trainees: experiences and attitudes
Authors: Morgan John F , Porter Sally 
Published: February 2015

Summary
A survey was carried out of psychiatric trainees' work-related experiences of unwanted sexual contact. A structured postal questionnaire was administered to 100 psychiatric trainees from senior house officer to specialist registrar level in a large psychiatric rotation. There was an 85% response rate; 86% (73) of the sample had experienced unwanted sexual contact, with 47% (40) experiencing deliberate touching, leaning over or cornering, and 18% (15) receiving letters, telephone calls or material of a sexual nature. Three-quarters (64) of respondents had experienced unwanted sexual contact from patients and 64% (54) from staff. Experiences and attitudes did not generally differ by gender, grade or training experience. Four out of 48 female respondents described stalking by patients. Of the 39 respondents who had reported harassment by patients, 31 felt supported by colleagues, while of the 13 who had reported harassment by colleagues, eight felt supported. Two-thirds of the respondents considered sexual harassment ‘sometimes’ or ‘frequently’ a problem for the profession. Diagnoses of confusional states, mania or schizophrenia made subjects less likely to consider unwanted sexual behaviour to be ‘sexual harassment’ (86%, 80%, and 67%, respectively), but not for other diagnoses. Levels of threatening and intrusive sexual harassment are unacceptably high in this study group. Health trusts should adopt policies of ‘zero tolerance’ and all incidents should be reported. Psychological impact on victims should be acknowledged even when the behaviour of the perpetrator can be explained by diagnosis. Key pointspsychiatric trainees commonly experience intrusive sexual harassment from patients and sometimes colleagueslevels are unacceptably high and Health Trusts should adopt ‘zero tolerance’ policiespsychological impact of harassment should not be underestimated, even when a patient's behaviour is explicable by diagnoses of psychosis or confusional stateslevels of sexual harassment need to be established among other medical specialties, particularly those involving community-based treatments
Clearance of acanthosis nigricans associated with the HAIR-AN syndrome after partial pancreatectomy: an 11-year follow-up
Authors: Pfeifer S L E , Wilson R M , Gawkrodger D J 
Published: February 2015

Summary
We describe a woman with the syndrome characterised by hyperandrogenism, insulin resistance and acanthosis nigricans (the HAIR-AN syndrome), and an associated insulinoma (islet B-cell tumour), whose signs and symptoms cleared after partial pancreatectomy.
Calcium phosphate stones during long-term acetazolamide treatment for epilepsy
Authors: Paisley K E , Tomson C R V 
Published: February 2015

Summary
We report a case of recurrent renal calculi containing calcium phosphate associated with long-term acetazolamide treatment for epilepsy. Unfortunately, the cause of stone formation was not recognised for many years, by which time irreversible renal damage had occurred.
Thermodynamical behavior of the variable Chaplygin gas
Authors: Panigrahi D. 
Published: February 2015

The thermodynamical behavior of the variable Chaplygin gas (VCG) model is studied, using an equation-of-state (EoS) like [Formula: see text], where [Formula: see text]. Here B0 is a positive universal constant, n is also a constant and V is the volume of the fluid. From the consideration of thermodynamic stability, it is seen that only if the values of n are allowed to be negative, then [Formula: see text] throughout the evolution. Again thermal capacity at constant volume cV shows positive expression. Using the best fit value of n = -3.4 as previously found by Guo and Zhang (Phys. Lett. B. 645 (2007) 326) gives that the fluid is thermodynamically stable throughout the evolution. The effective EoS for the special case of n = 0 goes to Λ Cold Dark Matter (ΛCDM) model. Again for n < 0, it favors phantom-like cosmology which is in agreement with the current SNe Ia constraints like VCG model. The deceleration parameter is also studied in the context of thermodynamics and the analysis shows that the flip occurs for the value of n < 4. Finally, the thermal EoS is discussed which is an explicit function of temperature only. It is also observed that the third law of thermodynamics is satisfied in this model. As expected, the volume increases as temperature falls during adiabatic expansions. In this case, for T → 0, the thermal EoS reduces to [Formula: see text], which is identical with the EoS for the case of large volume.
STUDY OF THE INFLUENCE BETWEEN BARIUM IONS AND CALCIUM IONS ON MORPHOLOGY AND SIZE OF COPRECIPITATION IN MICROEMULSION
Authors: WANG NONG , MENG QING LUO 
Published: February 2015

In this paper, we systematically drew a series of inverse-microemulsion quasi-ternary system phase diagrams of OP -10+ C8H17OH + C6H12+ brine ( CaCl2/ BaCl2) by adjusting the ratio of CaCl2and BaCl2. On this basis, microemulsions have been prepared with seven different molar ratios of Ca2+/ Ba2+, and calcium carbonate and barium carbonate coprecipitation products were obtained by reaction with an equimolar amount of sodium carbonate. The influence of barium ion to morphology and composition of nanometer calcium carbonate were studied. These samples were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The SEM photographs indicated that when the content of Ca2+was higher, some incomplete large cube of coprecipitation particles were formed in solution, but with the content of Ba2+increased gradually, they formed a large number of small spherical particles, with the further increase of Ba2+concentration, the particles mainly had structures of irregular polyhedron eventually. The measurement results of FTIR and XRD indicated that CaCO3coprecipitation products gradually changed from calcite to the vaterite, eventually turned into being aragonite with the further increase of Ba2+concentration.
Chemotherapy Rescues Hypoxic Tumor Cells and Induces Their Reoxygenation and Repopulation—An Effect That Is Inhibited by the Hypoxia-Activated Prodrug TH-302
Authors: Saggar Jasdeep K. , Tannock Ian F. 
Published: February 2015

Abstract
Purpose: Chemotherapy targets rapidly proliferating tumor cells, but spares slowly proliferating hypoxic cells. We hypothesized that nutrition of hypoxic cells would improve in intervals between chemotherapy, and that hypoxic cells destined to die without treatment would survive and proliferate.
Experimental Design: We therefore evaluated repopulation and reoxygenation following chemotherapy, and the effects of the hypoxia-activated prodrug TH-302 on these processes. Tumor-bearing mice were treated with doxorubicin or docetaxel ± TH-302. Pimonidazole (given concurrent with chemotherapy) and EF5 (given 24 to 120 hours later) identified hypoxic cells. Proliferation (Ki67) and oxygen status (EF5 uptake) of formerly hypoxic (pimo positive) cells were quantified by immunohistochemistry.
Results: Chronically hypoxic cells had limited proliferation in control tumors. After chemotherapy, we observed reoxygenation and increased proliferation of previously hypoxic cells; these processes were inhibited by TH-302.
Conclusions: Chemotherapy leads to paradoxical sparing of hypoxic cells destined to die in solid tumors in absence of treatment, and their reoxygenation and proliferation: TH-302 inhibits these processes. Clin Cancer Res; 21(9); 2107–14. ©2015 AACR.
The Tumor-Suppressor WWOX and HDAC3 Inhibit the Transcriptional Activity of the β-Catenin Coactivator BCL9-2 in Breast Cancer Cells
Authors: El-Hage Perla , Petitalot Ambre , Monsoro-Burq Anne-Hélène , Maczkowiak Frédérique , Driouch Keltouma , Formstecher Etienne , Camonis Jacques , Sabbah Michèle , Bièche Ivan , Lidereau Rosette , Lallemand François 
Published: February 2015

Abstract
The WW domain containing oxidoreductase (WWOX) has recently been shown to inhibit of the Wnt/β-catenin pathway by preventing the nuclear import of disheveled 2 (DVL2) in human breast cancer cells. Here, it is revealed that WWOX also interacts with the BCL9-2, a cofactor of the Wnt/β-catenin pathway, to enhance the activity of the β-catenin–TCF/LEF (T-cell factor/lymphoid enhancer factors family) transcription factor complexes. By using both a luciferase assay in MCF-7 cells and a Xenopus secondary axis induction assay, it was demonstrated that WWOX inhibits the BCL9-2 function in Wnt/β-catenin signaling. WWOX does not affect the BCL9-2–β-catenin association and colocalizes with BCL9-2 and β-catenin in the nucleus of the MCF-7 cells. Moreover, WWOX inhibits the β-catenin–TCF1 interaction. Further examination found that HDAC3 associates with BCL9-2, enhances the inhibitory effect of WWOX on BCL9-2 transcriptional activity, and promotes the WWOX–BCL9-2 interaction, independent of its deacetylase activity. However, WWOX does not influence the HDAC3–BCL9-2 interaction. Altogether, these results strongly indicate that nuclear WWOX interacts with BCL9-2 associated with β-catenin only when BCL9-2 is in complex with HDAC3 and inhibits its transcriptional activity, in part, by inhibiting the β-catenin–TCF1 interaction. The promotion of the WWOX–BCL9-2 interaction by HDAC3, independent of its deacetylase activity, represents a new mechanism by which this HDAC inhibits transcription.
Implications: The inhibition of the transcriptional activity of BCL9-2 by WWOX and HDAC3 constitutes a new molecular mechanism and provides new insight for a broad range of cancers. Mol Cancer Res; 13(5); 902–12. ©2015 AACR.
HuR Suppresses Fas Expression and Correlates with Patient Outcome in Liver Cancer
Authors: Zhu Haifeng , Berkova Zuzana , Mathur Rohit , Sehgal Lalit , Khashab Tamer , Tao Rong-Hua , Ao Xue , Feng Lei , Sabichi Anita L. , Blechacz Boris , Rashid Asif , Samaniego Felipe 
Published: February 2015

Abstract
Hepatocellular carcinomas (HCC) show resistance to chemotherapy and have blunt response to apoptotic stimuli. HCC cell lines express low levels of the Fas death receptor and are resistant to FasL stimulation, whereas immortalized hepatocytes are sensitive. The variable Fas transcript levels and consistently low Fas protein in HCC cells suggest posttranscriptional regulation of Fas expression. The 3′-untranslated region (UTR) of Fas mRNA was found to interact with the ribonucleoprotein Human Antigen R (HuR) to block mRNA translation. Silencing of HuR in HCC cells increased the levels of cell surface Fas and sensitized HCC cells to FasL. Two AU-rich domains within the 3′-UTR of Fas mRNA were identified as putative HuR-binding sites and were found to mediate the translational regulation in reporter assay. Hydrodynamic transfection of HuR plasmid into mice induced downregulation of Fas expression in livers and established functional resistance to the killing effects of Fas agonist. Human HCC tumor tissues showed significantly higher overall and cytoplasmic HuR staining compared with normal liver tissues, and the high HuR staining score correlated with worse survival of patients with early-stage HCC. Combined, the protumorigenic ribonucleoprotein HuR blocks the translation of Fas mRNA and effectively prevents Fas-mediated apoptosis in HCC, suggesting that targeting HuR would sensitize cells to apoptotic stimuli and reverse tumorigenic properties.
Implications: Demonstrating how death receptor signaling pathways are altered during progression of HCC will enable the development of better methods to restore this potent apoptosis mechanism. Mol Cancer Res; 13(5); 809–18. ©2015 AACR.
Cross-Presentation of the Oncofetal Tumor Antigen 5T4 from Irradiated Prostate Cancer Cells—A Key Role for Heat-Shock Protein 70 and Receptor CD91
Authors: Salimu Josephine , Spary Lisa K. , Al-Taei Saly , Clayton Aled , Mason Malcolm D. , Staffurth John , Tabi Zsuzsanna 
Published: February 2015

Abstract
Immune responses contribute to the success of radiotherapy of solid tumors; however, the mechanism of triggering CD8+ T-cell responses is poorly understood. Antigen cross-presentation from tumor cells by dendritic cells (DC) is a likely dominant mechanism to achieve CD8+ T-cell stimulation. We established a cross-presentation model in which DCs present a naturally expressed oncofetal tumor antigen (5T4) from irradiated DU145 prostate cancer cells to 5T4-specific T cells. The aim was to establish which immunogenic signals are important in radiation-induced cross-presentation. Radiation (12 Gy) caused G2–M cell-cycle arrest and cell death, increased cellular 5T4 levels, high-mobility protein group-B1 (HMGB1) release, and surface calreticulin and heat-shock protein-70 (Hsp70) expression in DU145 cells. DCs phagocytosed irradiated tumor cells efficiently, followed by upregulation of CD86 on phagocytic DCs. CD8+ 5T4-specific T cells, stimulated with these DCs, proliferated and produced IFNγ. Inhibition of HMGB1 or the TRIF/MyD88 pathway only had a partial effect on T-cell stimulation. Unlike previous investigators, we found no evidence that DCs carrying Asp299Gly Toll-like receptor-4 (TLR4) single-nucleotide polymorphism had impaired ability to cross-present tumor antigen. However, pretreatment of tumor cells with Hsp70 inhibitors resulted in a highly statistically significant and robust prevention of antigen cross-presentation and CD86 upregulation on DCs cocultured with irradiated tumor cells. Blocking the Hsp70 receptor CD91 also abolished cross-presentation. Together, the results from our study demonstrate that irradiation induces immunologically relevant changes in tumor cells, which can trigger CD8+ T-cell responses via a predominantly Hsp70-dependent antigen cross-presentation process. Cancer Immunol Res; 3(6); 678–88. ©2015 AACR.
Novel Role of Reactive Oxygen Species–Activated
trp
Melastatin Channel-2 in Mediating Angiogenesis and Postischemic Neovascularization
Authors: Mittal Manish , Urao Norifumi , Hecquet Claudie M. , Zhang Min , Sudhahar Varadarajan , Gao Xiao-pei , Komarova Yulia , Ushio-Fukai Masuko , Malik Asrar B. 
Published: February 2015

Objective—

Transient receptor potential melastatin-2 (TRPM2) channel is a nonselective cation channel that mediates influx of Ca
2+
and Na
+
with relative permeability of
P
Ca:
P
Na ≈0.6 in response to cellular oxidative stress. As angiogenesis and ischemic neovascularization are both significantly dependent on oxidant signaling, here we investigated the possible role of vascular endothelial growth factor (VEGF)–induced reactive oxygen species production in activating TRPM2-dependent Ca
2+
signaling and in the mechanism of angiogenesis and ischemic neovascularization.

Approach and Results—

We observed that VEGF stimulation rapidly induced the association of TRPM2 and cellular Src kinase with vascular endothelial-cadherin forming a signalplex at vascular endothelial-cadherin junctions in endothelial cells. Using endothelial cells isolated from
TRPM2

−/−

mice or after small interfering RNA depletion of TRPM2, we demonstrated that TRPM2-activated Ca
2+
signaling was required for cellular Src kinase–induced phosphorylation of vascular endothelial-cadherin at Y658 and Y731, the crucial sites involved in vascular endothelial-cadherin internalization in response to VEGF. VEGF-induced reactive oxygen species generation activated TRPM2-induced Ca
2+
entry, whereas the reactive oxygen species–insensitive TRPM2 mutant (C1008→A) showed impaired Ca
2+
entry. Endothelial cells depleted of TRPM2 also displayed significantly perturbed migratory phenotype and impaired activation of cellular Src in response to VEGF.
TRPM2
−/−
mice reconstituted with wild-type myeloid cells demonstrated aberrant angiogenesis and neovascularization in the hindlimb ischemia model as compared with wild-type mice.

Conclusions—
VEGF-induced angiogenesis and postischemic neovascularization in mice required reactive oxygen species generation in endothelial cells and resultant TRPM2 activation. Thus, our findings provide novel insight into the role of TRPM2 in mechanism of angiogenesis and ischemic neovascularization.
Central Nervous System Regulation of Intestinal Lipoprotein Metabolism by Glucagon-Like Peptide-1 via a Brain–Gut Axis
Authors: Farr Sarah , Baker Christopher , Naples Mark , Taher Jennifer , Iqbal Jahangir , Hussain Mahmood , Adeli Khosrow 
Published: February 2015

Objective—
Intestinal overproduction of atherogenic chylomicron particles postprandially is an important component of diabetic dyslipidemia in insulin-resistant states. In addition to enhancing insulin secretion, peripheral glucagon-like peptide-1 (GLP-1) receptor stimulation has the added benefit of reducing this chylomicron overproduction in patients with type 2 diabetes mellitus. Given the presence of central GLP-1 receptors and GLP-1–producing neurons, we assessed whether central GLP-1 exerts an integral layer of neuronal control during the production of these potentially atherogenic particles.

Approach and Results—
Postprandial production of triglyceride-rich lipoproteins was assessed in Syrian hamsters administered a single intracerebroventricular injection of the GLP-1 receptor agonist exendin-4. Intracerebroventricular exendin-4 reduced triglyceride-rich lipoprotein-triglyceride and -apolipoprotein B48 accumulation relative to vehicle-treated controls. This was mirrored by intracerebroventricular MK-0626, an inhibitor of endogenous GLP-1 degradation, and prevented by central exendin9–39, a GLP-1 receptor antagonist. The effects of intracerebroventricular exendin-4 were also lost during peripheral adrenergic receptor and central melanocortin-4 receptor inhibition, achieved using intravenous propranolol and phentolamine and intracerebroventricular HS014, respectively. However, central exendin9–39 did not preclude the effects of peripheral exendin-4 treatment on chylomicron output.

Conclusions—
Central GLP-1 is a novel regulator of chylomicron production via melanocortin-4 receptors. Our findings point to the relative importance of central accessibility of GLP-1–based therapies and compel further studies examining the status of this brain–gut axis in the development of diabetic dyslipidemia and chylomicron overproduction.
Exploratory Longitudinal Cohort Study of Associations of Fatigue After Stroke
Authors: Duncan Fiona , Lewis Susan J. , Greig Carolyn A. , Dennis Martin S. , Sharpe Michael , MacLullich Alasdair M.J. , Mead Gillian E. 
Published: February 2015

Background and Purpose—
The pathogenesis of poststroke fatigue is unclear. In this prospective study, we explored whether reduced physical activity might contribute to poststroke fatigue or be a consequence of it.

Methods—
Patients with a recent acute stroke were assessed at 1, 6, and 12 months with, Fatigue Assessment Scale (FAS), a fatigue case definition, Hospital Anxiety and Depression Score, sleepiness, quality of life, and accelerometry (ActivPAL). Bivariate analyses determined associations between fatigue and step count at each time point. Multiple linear regression tested whether 1-month step count independently predicted 6- and 12-month FAS.

Results—

A total of 136 participants (mean age, 72 years; 64% men) attended ≥1 assessment. ActivPAL data were available for 84 (64%), 69 (66%), and 58 (64%) participants at 1, 6, and 12 months, respectively. At 6 and 12 months, a positive fatigue case definition was associated with lower daily step counts (
P
=0.014 and 0.013, respectively). At 1, 6, and 12 months, higher FAS (more fatigue) was associated with lower step count (
P
<0.001, 0.01, and 0.007), higher depression (
P
<0.001), anxiety scores (
P
<0.001) and sleepiness (
P
<0.001), and poorer quality of life (
P
<0.001). Lower daily step count (
P
<0.002 and 0.006) and greater anxiety (
P
<0.001 for both) at 1 month independently predicted higher FAS at 6 and 12 months.

Conclusions—
Lower step counts at 1 month independently predicted greater FAS for ≤12 months. Physical activity might be a therapeutic target for poststroke fatigue.