bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proof of concept and feasibility studies examining the influence of combination ribose, adenine and allopurinol treatment on stroke outcome in the rat
Authors: Faller Kiterie M.E. , Leach Joshua , Johnston Pamela , Holmes William M. , Macrae I. Mhairi , Frenguelli Bruno G. 
Published: October 2017

Background: Cerebral ischaemia results in a rapid and profound depletion of adenosine triphosphate (ATP), the energy currency of the cell. This depletion leads to disruption of cellular homeostasis and cell death. Early replenishment of ATP levels might therefore have a neuroprotective effect in the injured brain. We have previously shown that the ATP precursors, D-ribose and adenine (RibAde), restored the reduced ATP levels in rat brain slices to values similar to those measured in the intact rodent brain. The aim of this study was to assess whether RibAde, either alone or in combination with the xanthine oxidase inhibitor allopurinol (RibAdeAll; to further increase the availability of ATP precursors), could improve outcome in an in vivo rodent model of transient cerebral ischaemia. Methods: After 60 min occlusion of the middle cerebral artery, and upon reperfusion, rats were administered saline, RibAde, or RibAdeAll for 6 h. Baseline lesion volume was determined by diffusion-weighted MRI prior to reperfusion and final infarct volume determined by T2-weighted MRI at Day 7. Neurological function was assessed at Days 1, 3 and 7. Results: Ischaemic lesion volume decreased between Days 1 and 7: a 50% reduction was observed for the RibAdeAll group, 38% for the RibAde group and 18% in the animals that received saline. Reductions in lesion size in treatment groups were accompanied by a trend for faster functional recovery. Conclusion: These data support the potential use of ribose, adenine and allopurinol in the treatment of cerebral ischaemic injury, especially since all compounds have been used in man.
Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?
Authors: Ng Kee Kwong Francois , Nicholson Andrew G. , Harrison Celeste L. , Hansbro Philip M. , Adcock Ian M. , Chung Kian Fan 
Published: October 2017

Chronic obstructive pulmonary disease (COPD) patients are at increased risk of developing nonsmall cell lung carcinoma, irrespective of their smoking history. Although the mechanisms behind this observation are not clear, established drivers of carcinogenesis in COPD include oxidative stress and sustained chronic inflammation. Mitochondria are critical in these two processes and recent evidence links increased oxidative stress in COPD patients to mitochondrial damage. We therefore postulate that mitochondrial damage in COPD patients leads to increased oxidative stress and chronic inflammation, thereby increasing the risk of carcinogenesis.The functional state of the mitochondrion is dependent on the balance between its biogenesis and degradation (mitophagy). Dysfunctional mitochondria are a source of oxidative stress and inflammasome activation. In COPD, there is impaired translocation of the ubiquitin-related degradation molecule Parkin following activation of the Pink1 mitophagy pathway, resulting in excessive dysfunctional mitochondria. We hypothesise that deranged pathways in mitochondrial biogenesis and mitophagy in COPD can account for the increased risk in carcinogenesis. To test this hypothesis, animal models exposed to cigarette smoke and developing emphysema and lung cancer should be developed. In the future, the use of mitochondria-based antioxidants should be studied as an adjunct with the aim of reducing the risk of COPD-associated cancer.
Practices regarding human Papillomavirus counseling and vaccination in head and neck cancer: A Canadian physician questionnaire
Authors: Anderson Scott , Isaac Andre , Jeffery Caroline C. , Robinson Joan L. , Isaac Daniela Migliarese , Korownyk Christina , Biron Vincent L. , Seikaly Hadi 
Published: October 2017

Background Human papillomavirus (HPV) has recently been implicated as a causative agent in a rapidly growing number of oropharyngeal cancers. Emerging literature supports the hypothesis that HPV vaccination may protect against HPV-related head and neck cancer (HNC) in addition to HPV-related cervical and anogenital disease. While the association between HPV infection and cervical cancer is widely understood, its relation to HNC is less well known. The purpose of this study was to better understand HPV counseling practices for infection and vaccination in relation to HNC of primary care physicians (PCPs), Obstetricians/Gynecologists (OBGYNs), and Otolaryngology - Head and Neck Surgeons (OHNSs) in Canada. Methods A Canada-wide electronic questionnaire regarding counseling practices on HPV infection, transmission, and vaccination was designed and distributed to PCPs, OBGYNs, and OHNSs across Canada through electronic and paper-based methods. Basic Descriptive statistics were used to analyze responses. Results In total, 337 physicians responded (239 family physicians, 51 OHNSs, 30 OBGYNs, and 17 pediatricians). Three out of four PCPs reported routine counseling of their patients regarding HPV infection, transmission, and vaccination. Among this group, 68% reported “never” or “rarely” counseling patients that HPV can cause HNC. The most commonly reported reason that PCPs cited for not counseling was a lack of knowledge. The majority of OHNSs (81%) and OBGYNs (97%) counseled patients regarding HPV infection, transmission, and vaccination. However, very few OHNSs (10%) regularly counseled patients with HPV-related HNC about HPV-related anogenital cancer. Similarly, very few OBGYNs (18%) regularly counseled patients with HPV related cervical/anogenital cancer about HPV related HNC. Conclusions The rate of counseling on HPV infection, transmission, and vaccination in relation to HNC among PCPs is low. The most common reason is a lack of knowledge. Specialists rarely counsel patients with confirmed HPV-related cancer about other HPV-related malignancies. More research is needed on the relationship between different HPV-related cancers in order to better inform counseling practices.
A new Fourier azimuthal amplitude variation fracture characterization method: Case study in the Haynesville Shale
Authors: Barone Anthony , Sen Mrinal K. 
Published: October 2017

We have evaluated a novel fracture characterization technique using azimuthal amplitude variations (AVAz) present in 3D seismic data, and we implemented it using synthetic and real seismic data targeting the Haynesville Shale. The method we evaluated overcomes many common AVAz limitations and differs from standard AVAz approaches in the following ways: (1) It was explicitly designed to model vertically fractured transverse isotropic (VFTI) media; (2) it can correctly resolve the fracture strike azimuth without a 90° ambiguity and uses a new magnitude-based method that is invariant to the sign of seismic reflectivity [Formula: see text]; and (3) it incorporates advanced inversion techniques to estimate a novel fracture density proxy that responds linearly to crack density. Our method is based on a newly derived relationship that relates seismic reflectivity directly to rock/fracture properties in VFTI media. We validated our method through rigorous testing on more than 400 synthetic seismic data sets. These synthetic tests indicate that our method excels at estimating fracture azimuth and fracture density from surface seismic data with overall success rates around 80%–85% for noisy data and 90%–95% for noise-free data. Applying our method to field data from the Haynesville Shale indicates that the dominant fracture set is oriented at approximately [Formula: see text] relative to geodetic north, i.e., rotated slightly counterclockwise of east–west. We assume a constant azimuth of 80° throughout our relatively small 20 square miles study area, and our method clearly identifies a general area with unusually high fracture density as well as several smaller subzones of dense fracturing. These smaller features appear to be connected by a pervasive large-scale fracture network covering the area with dominant features aligned at roughly parallel and perpendicular to our calculated fracture azimuth. Although we could not directly confirm these fracture characteristics, our results largely agree with previously published information about fracturing in our study area.
Fuzzy constrained Lp-norm inversion of direct current resistivity data
Authors: Singh Anand , Sharma Shashi Prakash , Akca İrfan , Baranwal Vikas Chand 
Published: October 2017

We evaluate the use of a fuzzy c-means clustering procedure to improve an inverted 2D resistivity model within the iterative error minimization procedure. The algorithm is coded in MATLAB language for the Lp-norm inversion of 2D direct current resistivity data and is referred to as fuzzy constrained inversion (FCI). Two additional input parameters are required to be provided by the interpreter: (1) the number of geologic units in the model (i.e., the number of clusters) and (2) the mean resistivity values of each geologic unit (i.e., cluster center values of the geologic units). The efficacy of our approach is evaluated by tests carried on the synthetic and field electrical resistivity tomography (ERT) data. Inversion results from the FCI algorithm are presented for conventional L1- and L2-norm minimization techniques. FCI indicates improvement over conventional inversion approaches in differentiating the geologic units if a proper number of the geologic units is provided to the algorithm. Inappropriate clustering information will affect the resulting resistivity models, particularly conductive geologic units existing in the model. We also determine that FCI is only effective when the observed ERT data can recognize the particular geologic units.
Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600–Mutant Anaplastic Thyroid Cancer
Authors: Subbiah Vivek , Kreitman Robert J. , Wainberg Zev A. , Cho Jae Yong , Schellens Jan H.M. , Soria Jean Charles , Wen Patrick Y. , Zielinski Christoph , Cabanillas Maria E. , Urbanowitz Gladys , Mookerjee Bijoyesh , Wang Dazhe , Rangwala Fatima , Keam Bhumsuk 
Published: October 2017

Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E–mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E–mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E–mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E–mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.
Efficacy and safety of ultrasound guided percutaneous glue embolization in iatrogenic haemorrhagic complications of paracentesis and thoracocentesis in cirrhotic patients
Authors: Mukund Amar , Kumar DP Vinay , Condati Naveen Kumar , Bhadoria Ajeet Singh , Sarin Shiv Kumar 
Published: October 2017

Objective:
To compare the safety and efficacy of ultrasound guided percutaneous glue (N-butyl-2-cyanoacrylate) embolization with transarterial embolization in the management of iatrogenically injured arteries while performing paracentesis or thoracocentesis in patients with chronic liver disease.

Methods:
Hospital database was searched for cirrhotic patients having abdominal/thoracic wall haemorrhage following paracentesis/thoracocentesis procedure from January 2011 to June 2016. Doppler ultrasound and/or CT angiography were used to localize the site of haemorrhage and patients were treated by transarterial embolization or ultrasound-guided percutaneous glue embolization. Technical success was defined as cessation of haemorrhage as evidenced by angiography/Doppler ultrasound and clinical success was evaluated in terms of stabilization of the vital signs without the need for further transfusion or pressors, and survival. In both groups, the time to “imaging diagnosis of haemorrhage” and “successful embolization” with the outcome was analysed.

Results:
23 cirrhotic patients had bleeding following a percutaneous procedure, 8 (Group 1) of them underwent transarterial embolization while 15 (Group 2) underwent ultrasound-guided percutaneous glue embolization. Mean time needed for embolization in Group 1 was 41 min while in Group 2 was 9 min (p &lt; 0.001). Technical success was achieved in all but one case requiring repeat glue embolization. Initial clinical improvement was noted in all cases but the 30-day mortality owing to all causes was not significantly different between treatment groups.

Conclusion:
The study and its outcome suggest that ultrasound guided percutaneous glue embolization is a quick and effective treatment for iatrogenic haemorrhage following paracentesis/thoracocentesis in cirrhotic patients with comparable results to transarterial embolotherapy.

Advances in knowledge:
This study details an innovative technique of ultrasound guided percutaneous glue embolization of the iatrogenically injured vessel in the management of active extravasation and pseudoaneurysm developing after paracentesis/thoracocentesis in patients with cirrhosis.
Dual-region-of-interest bolus-tracking technique for coronary computed tomographic angiography on a 320-row scanner: reduction in the interpatient variability of arterial contrast enhancement
Authors: Kai Noriyuki , Oda Seitaro , Utsunomiya Daisuke , Nakaura Takeshi , Funama Yoshinori , Kidoh Masafumi , Taguchi Narumi , Iyama Yuji , Nagayama Yasunori , Hirata Kenichiro , Yuki Hideaki , Sakabe Daisuke , Hatemura Masahiro , Yamashita Yasuyuki 
Published: October 2017

Objective:
We compared the effect of a dual-region-of-interest (ROI) bolus-tracking technique on interpatient variability of arterial contrast enhancement with that of the conventional bolus-tracking technique in coronary computed tomographic angiography (CTA) on a 320-row scanner.

Methods:
This study included 100 patients who underwent coronary CTA using one of two protocols: (1) 50 patients underwent scanning using a conventional single-ROI bolus-tracking technique (P-single) with an ROI placed in the ascending aorta, and (2) 50 patients underwent scanning using a dual-ROI technique (P-dual) with two ROIs placed in the pulmonary trunk and the ascending aorta. CT attenuation in the ascending aorta and coronary arteries, and the interpatient variability were compared between the two scanning protocols.

Results:
The mean CT attenuation of the ascending aorta and coronary arteries tended to be higher for P-dual than for P-single, but the difference was not significant (p = 0.08–0.30). The interpatient variability of contrast enhancement (SD of the CT attenuation) was significantly smaller for P-dual than for P-single (p &lt; 0.01).

Conclusion:
The dual-ROI bolus-tracking technique can reduce interpatient variability of arterial contrast enhancement in coronary CTA on a 320-row scanner.

Advances in knowledge:
The use of a dual-ROI bolus-tracking technique can provide sufficient and consistent arterial enhancement of coronary CTA.
Risk of solid cancer in patients with mast cell activation syndrome: Results from Germany and USA
Authors: Molderings Gerhard J. , Zienkiewicz Thomas , Homann Jürgen , Menzen Markus , Afrin Lawrence B. 
Published: October 2017

Background: It has been shown repeatedly that mast cells can promote or prevent cancer development and growth. If development and/or progression of a solid cancer is substantially influenced by mast cell activity, the frequencies of occurrence of solid cancers in patients with primary mast cells disorders would be expected to differ from the corresponding prevalence data in the general population. In fact, a recent study demonstrated that patients with systemic mastocytosis (i.e., a rare neoplastic variant of the primary mast cell activation disease) have increased risk for solid cancers, in particular melanoma and non-melanoma skin cancers. The aim of the present study is to examine whether the risk of solid cancer is increased in systemic mast cell activation syndrome (MCAS), the common systemic variant of mast cell activation disease. Methods: In the present descriptive study, we have analysed a large (n=828) patient group with MCAS, consisting of cohorts from Germany and the USA, for occurrence of solid forms of cancer and compared the frequencies of the different cancers with corresponding prevalence data for German and U.S. general populations. Results: Sixty-eight of the 828 MCAS patients (46 female, 22 male) had developed a solid tumor before the diagnosis of MCAS was made. Comparison of the frequencies of the malignancies in the MCAS patients with their prevalence in the general population revealed a significantly increased prevalence for melanoma and cancers of the breast, cervix uteri, ovary, lung, and thyroid in MCAS patients. Conclusions: Our data support the view that mast cells may promote development of certain malignant tumors. These findings indicate a need for increased surveillance of certain types of cancer in MCAS patients irrespective of its individual clinical presentation.
Pseudomonas expression of an oxygen sensing prolyl hydroxylase homologue regulates neutrophil host responses in vitro and in vivo
Authors: Dickinson Rebecca S. , Murphy Fiona , Doherty Catherine , Williams Sam , Mirchandani Ananda , Willson Joseph , Scotti John S. , Preston Gail , Schofield Christopher J. , Whyte Moira K.B. , Walmsley Sarah R. 
Published: October 2017

Background: Pseudomonas species are adapted to evade innate immune responses and can persist at sites of relative tissue hypoxia, including the mucus-plugged airways of patients with cystic fibrosis and bronchiectasis. The ability of these bacteria to directly sense and respond to changes in local oxygen availability is in part consequent upon expression of the 2-oxoglutarate oxygenase, Pseudomonas prolyl hydroxylase (PPHD), which acts on elongation factor Tu (EF-Tu), and is homologous with the human hypoxia inducible factor (HIF) prolyl hydroxylases. We report that PPHD expression regulates the neutrophil response to acute pseudomonal infection. Methods: In vitro co-culture experiments were performed with human neutrophils and PPHD-deficient and wild-type bacteria and supernatants, with viable neutrophil counts determined by flow cytometry. In vivo consequences of infection with PPHD deficient P. aeruginosa were determined in an acute pneumonia mouse model following intra-tracheal challenge. Results: Supernatants of PPHD-deficient bacterial cultures contained higher concentrations of the phenazine exotoxin pyocyanin and induced greater acceleration of neutrophil apoptosis than wild-type PAO1 supernatants in vitro. In vivo infection with PPHD mutants compared to wild-type PAO1 controls resulted in increased levels of neutrophil apoptosis and impaired control of infection, with higher numbers of P. aeruginosa recovered from the lungs of mice infected with the PPHD-deficient strain. This resulted in an overall increase in mortality in mice infected with the PPHD-deficient strain. Conclusions: Our data show that Pseudomonas expression of its prolyl hydroxylase influences the outcome of host-pathogen interactions in vitro and in vivo, demonstrating the importance of considering how both host and pathogen adaptations to hypoxia together define outcomes of infection. Given that inhibitors for the HIF prolyl hydroxylases are in late stage trials for the treatment of anaemia and that the active sites of PPHD and human HIF prolyl hydroxylases are closely related, the results are of current clinical interest.
The Diagnostic Yield of Noninvasive Microbiologic Sputum Sampling in a Cohort of Patients with Clinically Diagnosed Hospital‐Acquired Pneumonia
Authors: Naidus Elliot L. , Lasalvia Mary T. , Marcantonio Edward R. , Herzig Shoshana J. 
Published: October 2017

The clinical predictors of positive sputum culture have not been previously reported in hospital‐acquired pneumonia (HAP), and data on yield of sputum culture in this setting are scant. Current Infectious Disease Society of America guidelines for HAP recommend noninvasive sputum sampling, though the data for this practice are limited. We assessed the yield of sputum culture in HAP cases at an academic medical center from January 2007 to July 2013. HAP cases were identified by International Classification of Diseases, Ninth Revision‐Clinical Modification codes for bacterial pneumonia and all cases were validated by chart review. Our cohort had 1172 hospitalizations with a HAP diagnosis. At least 1 sputum specimen was collected noninvasively and sent for bacterial culture after hospital day 2 and within 7 days of HAP diagnosis in 344 of these hospitalizations (29.4%), with a total of 478 sputum specimens, yielding 63 (13.2%) positive, 109 (22.8%) negative, and 306 (64.0%) contaminated cultures (>10 epithelial cells per high power field). Significant predictors of a positive sputum culture were chronic lung disease (relative risk [RR] = 2.0; 95% confidence interval [CI], 1.2‐3.4) and steroid use (RR = 1.8; 95% CI, 1.1‐3.2). The most commonly identified organisms were Gram‐negative rods not further speciated (25.9%), Staphylococcus aureus (21.0%), and Pseudomonas aeruginosa (14.8%). Because of the ease of obtaining a sputum sample combined with the prevalence of commonly drug‐resistant organisms, we suggest that sputum culture in HAP is a potentially useful noninvasive diagnostic technique.
Fear, loss and meaningful play: Permadeath in DayZ
Authors: Carter Marcus , Allison Fraser 
Published: October 2017

Abstract
This article interrogates player experiences with permadeath in the massively multiplayer online first-person shooter (MMOFPS) DayZ. We analyse the differences between ‘good’ and ‘bad’ instances of permadeath and argue that meaningfulness – in accordance with Salen and Zimmerman’s concept of meaningful play – is a critical requirement for positive experiences with permadeath. In doing so, this article suggests new ontologies for meaningfulness in play, and demonstrates how meaningfulness can be a useful lens through which to understand player experiences with negatively valenced play. We conclude by relating the appeal of permadeath to the excitation transfer effect, drawing parallels between the appeal of DayZ and fear-inducing horror games such as Silent Hill 2 and gratuitously violent and gory games such as Mortal Kombat.