bluuebunny/crossref_metadata_2025 huggingface dataset:
Melanin, Radiation, and Energy Transduction in Fungi
Authors: Casadevall Arturo , Cordero Radames J. B. , Bryan Ruth , Nosanchuk Joshua , Dadachova Ekaterina
Published: March 2017

Melanin pigments are found in many diverse fungal species, where they serve a variety of functions that promote fitness and cell survival. Melanotic fungi inhabit some of the most extreme habitats on earth such as the damaged nuclear reactor at Chernobyl and the highlands of Antarctica, both of which are high-radiation environments. Melanotic fungi migrate toward radioactive sources, which appear to enhance their growth. This phenomenon, combined with the known capacities of melanin to absorb a broad spectrum of electromagnetic radiation and transduce this radiation into other forms of energy, raises the possibility that melanin also functions in harvesting such energy for biological usage. The ability of melanotic fungi to harness electromagnetic radiation for physiological processes has enormous implications for biological energy flows in the biosphere and for exobiology, since it provides new mechanisms for survival in extraterrestrial conditions. Whereas some features of the way melanin-related energy transduction works can be discerned by linking various observations and circumstantial data, the mechanistic details remain to be discovered.
Extraskeletal orbital mesenchymal chondrosarcoma: surgical approach and mini review
Authors: Jakhetiya Ashish , Shukla Nootan Kumar , Muduly Dillip , Kale Shashank S
Published: March 2017

Extraskeletal orbital mesenchymal chondrosarcoma (MC) is an extremely rare and highly aggressive tumour. It has characteristic radiological features and pathognomic histological biphasic pattern. Radical resection with negative margins is the mainstay of treatment; role of adjuvant chemotherapy and radiotherapy is yet not well defined. We report a rare case of 18-year-old man who was diagnosed to have orbital MC. He presented with locally advanced disease with no vision in the affected eye. He underwent right orbital exenteration; a transcranial intradural approach was used to divide the optic nerve, and the temporalis muscle flap was utilised to fill the exenterated orbit. Though optic nerve involvement is rare in orbital MCs, a transcranial approach may be used effectively to avoid traction on optic chiasma and ensure margin-free resection in case of optic nerve involvement up to orbital apex. Unfortunately, prognosis remains dismal in MCs despite treatment.
Correlation study of adenosine deaminase and its isoenzymes in type 2 diabetes mellitus
Authors: Sapkota Lokendra Bahadur , Thapa Sangita , Subedi Nuwadatta
Published: March 2017

Objective

Adenosine deaminase (ADA) plays an important role in cell-mediated immunity and modulation of insulin activity. Its clinical and diagnostic significance in Nepalese type 2 diabetes is not yet characterized. So, this study's objective was to determine the isoenzymatic activities of ADA (ADA1, ADA2, and total ADA) and show its correlation with demographic, anthropometric, and biochemical characteristics of type 2 Nepalese subjects with diabetes.

Research design and methods

This is a hospital-based cross-sectional study including 80 type 2 diabetes mellitus (DM) patients and same number of age-matched and sex-matched healthy controls. Data were collected using preformed set of questionnaires and biochemical data were obtained from the laboratory analysis of the patient's blood samples. Statistical analysis was performed with SPSS V.20.

Results

A significantly higher (p<0.001) mean values of body mass index (BMI), fasting blood sugar (FBS), postprandial blood sugar (PPBS), glycated hemoglobin (HbA1c), and lipid profiles except high-density lipoprotein cholesterol (HDL-C) were found in type 2 diabetic cases compared with controls. Serum ADA activities were significantly higher in cases compared with controls (p<0.001) showing significant positive correlation (p<0.05) with FBS, PPBS, HbA1c, and alcoholism; while no correlation was found with age, sex, ethnicity, BMI, waist–hip ratio, dietary habits, smoking, and duration of diabetes.

Conclusions

Serum ADA activities were significantly higher in type 2 diabetic patients compared with controls having significant positive correlation with glycemic parameters. Serum ADA and its isoenzymes could be used as biomarkers for assessing glycemic status in patients with type 2 DM.
Effectiveness of problem gambling interventions in a service setting: a protocol for a pragmatic randomised controlled clinical trial
Authors: Abbott M , Bellringer M , Vandal A C , Hodgins D C , Battersby M , Rodda S N
Published: March 2017

Introduction

The primary purpose of this study is to evaluate the relative effectiveness of 2 of the best developed and most promising forms of therapy for problem gambling, namely face-to-face motivational interviewing (MI) combined with a self-instruction booklet (W) and follow-up telephone booster sessions (B; MI+W+B) and face-to-face cognitive–behavioural therapy (CBT).

Methods and analysis

This project is a single-blind pragmatic randomised clinical trial of 2 interventions, with and without the addition of relapse-prevention text messages. Trial assessments take place pretreatment, at 3 and 12 months. A total of 300 participants will be recruited through a community treatment agency that provides services across New Zealand and randomised to up to 10 face-to-face sessions of CBT or 1 face-to-face session of MI+W+up to 5 B. Participants will also be randomised to 9 months of postcare text messaging. Eligibility criteria include a self-perception of having a current gambling problem and a willingness to participate in all components of the study (eg, read workbook). The statistical analysis will use an intent-to-treat approach. Primary outcome measures are days spent gambling and amount of money spent per day gambling in the prior month. Secondary outcome measures include problem gambling severity, gambling urges, gambling cognitions, mood, alcohol, drug use, tobacco, psychological distress, quality of life, health status and direct and indirect costs associated with treatment.

Ethics and dissemination

The research methods to be used in this study have been approved by the Ministry of Health, Health and Disability Ethics Committees (HDEC) 15/CEN/99. The investigators will provide annual reports to the HDEC and report any adverse events to this committee. Amendments will also be submitted to this committee. The results of this trial will be submitted for publication in peer-reviewed journals and as a report to the funding body. Additionally, the results will be presented at national and international conferences.

Trial registration number

ACTRN12615000637549.
Acceptability of the Cytosponge procedure for detecting Barrett's oesophagus: a qualitative study
Authors: Freeman Madeleine , Offman Judith , Walter Fiona M , Sasieni Peter , Smith Samuel G
Published: March 2017

Objective

To investigate the acceptability of the Cytosponge, a novel sampling device to detect Barrett's oesophagus (BE), a precursor to oesophageal adenocarcinoma (EAC), among people with risk factors for this condition.

Design

A qualitative study using semistructured interviews and focus group discussions. Data were explored by three researchers using thematic analysis.

Setting

Community setting in London, UK.

Participants

A recruitment company identified 33 adults (17 men, 16 women) aged 50–69 years with gastro-oesophageal reflux disease (GERD), a risk factor for BE. The majority of participants were white British (73%). The focus groups were stratified by gender and education. 10 individuals were interviewed and 23 participated in four focus groups.

Results

3 key themes emerged from the data: the anticipated physical experience, preferences for the content of information materials and comparisons with the current gold-standard test. Overall acceptability was high, but there was initial concern about the physical experience of taking the test, including swallowing and extracting the Cytosponge. These worries were reduced after handling the device and a video demonstration of the procedure. Knowledge of the relationship between GERD, BE and EAC was poor, and some suggested they would prefer not to know about the link when being offered the Cytosponge. Participants perceived the Cytosponge to be more comfortable, practical and economical than endoscopy.

Conclusions

These qualitative data suggest the Cytosponge was acceptable to the majority of participants with risk factors for BE, and could be used as a first-line test to investigate GERD symptoms. Concerns about the physical experience of the test were alleviated through multimedia resources. The development of patient information materials is an important next step to ensuring patients are adequately informed and reassured about the procedure. Patient stakeholders should be involved in this process to ensure their concerns and preferences are considered.

Trial registration number

ISRCTN68382401; pre-results.
Knowledge is Power. A quality improvement project to increase patient understanding of their hospital stay
Authors: Nicholson Thomas Eleanor , Edwards Lloyd , McArdle Paul
Published: March 2017

Patients frequently leave hospital uninformed about the details of their hospital stay with studies showing that only 59.9% of patients are able to accurately state their diagnosis and ongoing management after discharge. 1 2 This places patients at a higher risk of complications. Educating patients by providing them with accurate and understandable information enables them to take greater control, potentially reducing readmission rates, and unplanned visits to secondary services whilst providing safer care and improving patient satisfaction. 3 4

We wished to investigate whether through a simple intervention, we could improve the understanding and retention of key pieces of clinical information in those patients recently admitted to hospital.

A leaflet was designed to trigger patients to ask questions about key aspects of their stay. This was then given to inpatients who were interviewed two weeks later using telephone follow up to assess their understanding of their hospital admission. Patients were asked about their diagnosis, new medications, likely complications, follow up arrangements and recommended points of contact in case of difficulty. Sequential modifications were made using PDSA cycles to maximise the impact and benefit of the process.

Baseline data revealed that only 77% of patients could describe their diagnosis and only 27% of patients knew details about their new medications. After the leaflet intervention these figures improved to 100% and 71% respectively.

Too often patients are unaware about what happens to them whilst in hospital and are discharged unsafely and dissatisfied as a result. A simple intervention such as a leaflet prompting patients to ask questions and take responsibility for their health can make a difference in potentially increasing patient understanding and thereby reducing risk.
Patient values informing medical treatment: a pilot community and advance care planning survey
Authors: Milnes S , Corke C , Orford N R , Bailey M , Savulescu J , Wilkinson D
Published: March 2017

Medicine regards the prevention of death as an important priority. Yet patients may have a range of priorities of equal or greater importance. These other priorities are often not discussed or appreciated by treating doctors.

Objectives

We sought to identify priorities of care for patients attending an advance care planning (ACP) clinic and among the general population, and to identify factors associated with priorities other than prolonging life.

Methods

We used a locally developed survey tool ‘What Matters Most’ to identify values. Choices presented were: maintaining dignity, avoiding pain and suffering, living as long as possible, and remaining independent. Participants rated the importance of each and then selected a main priority for their doctor. Participant groups were a purposive sample of 382 lay people from the general population and 100 attendees at an ACP clinic.

Results

Living as long as possible was considered to be less important than other values for ACP patients and for the general population. Only 4% of ACP patients surveyed and 2.6% of our general population sample selected ‘living as long as possible’ as their top priority for medical treatment.

Conclusions

‘Living as long as possible’ was not the most important value for ACP patients, or for a younger general population. Prioritisation of other goals appeared to be independent of extreme age or illness. When end of life treatment is being discussed with patients, priorities other than merely prolonging life should be considered.
Impact thromboelastometry (ITEM) for point-of-injury detection of trauma-induced coagulopathy: a pilot study
Authors: Doyle Gerard S , Theodore Aristotle A , Hansen J Nicholas
Published: March 2017

Background

Acute coagulopathy of trauma is associated with high mortality and extensive use of blood products. Hemostatic resuscitation, the early administration of blood products with higher ratios of procoagulant components, may improve trauma outcomes in select cases, but can also worsen outcome if inappropriately used. Evolving approaches to hemostatic resuscitation utilize viscoelastic tests to provide a more rational basis for choosing blood component therapy regimens, but these tests are logistically rigorous. We hypothesized that coagulopathy could be detected by the failure of blood clots to remain intact when subjected to a predefined impact force.

Methods

We aim to develop a point-of-injury test for coagulopathy. We created coagulopathic blood using an ex vivo normal saline (NS) dilution model and allowed blood of varying dilutions to clot, then examined the behavior of the clotted blood when subjected to a uniform gravitationally induced sheer force.

Results

Clots created from coagulopatic blood (diluted to ≤50% with NS) failed under gravitational challenge at a significantly higher rate than non-coagulopathic blood dilutions.

Discussion

Impact thromboelastometry (ITEM) represents a simple, logistically lean method for detecting dilutional coagulopathy that may facilitate detection of trauma-induced coagulopathy. ITEM may thus function as a point-of-injury or point-of-care screening test for the presence of coagulopathy.

Level of evidence

Diagnostic studies, Level IV.
Successful treatment of chronic canine blastomycosis in a Labrador retriever with sterile histopathology
Authors: McFadden Rendina A , Heinrich Nicole A , Haarstad Amy C
Published: March 2017

A four‐year‐old, neutered male Labrador retriever from Minnesota, USA was presented to a dermatology referral clinic for evaluation of waxing and waning paronychia and multifocal cutaneous nodules of five months’ duration. The condition was managed before referral with antibiotics and glucocorticoids resulting in a partial response, but new lesions continued to develop. Skin biopsies made both before and after referral revealed pyogranulomatous dermatitis and fibrosis with negative fungal stains. However, acetate tape impression cytology performed at time of referral detected a single blastomyces organism; thus, a definitive diagnosis of blastomycosis was made. Treatment with fluconazole followed by generic itraconazole resulted in rapid, full recovery in three months’ time. Thoracic radiographs at the time of blastomycosis diagnosis were within normal limits, despite history of mild cough. This case highlights the potential pitfalls in diagnosis and treatment of canine blastomycosis.
Osthole prevents cerebral ischemia–reperfusion injury via the Notch signaling pathway
Authors: Guan Junhong , Wei Xiangtai , Qu Shengtao , Lv Tao , Fu Qiang , Yuan Ye
Published: March 2017

Stroke is a common cerebrovascular disease in aging populations, and constitutes the second highest principle cause of mortality and the principle cause of permanent disability, and ischemic stroke is the primary form. Osthole is a coumarin derivative extracted from the fruits of Cnidium monnieri (L.) Cusson. In this study, we established a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo and found that MCAO/R caused cerebral infarction, hippocampus neuronal injury and apoptosis, and also activated the Notch 1 signaling pathway. However, treatment with osthole further enhanced the activity of Notch 1 signaling and reduced the cerebral infarction as well as the hippocampus neuronal injury and apoptosis induced by MCAO/R in a dose-dependent manner. The same results were observed in a primary neuronal oxygen glucose deficiency/reperfusion (OGD/R) model in vitro, and the effect of osthole could be blocked by an inhibitor of Notch 1 signaling, N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine tert-butyl ester (DAPT). Therefore, we demonstrated that osthole injection prevented rat ischemia–reperfusion injury via activating the Notch 1 signaling pathway in vivo and in vitro in a dose-dependent manner, which may be significant for clinical treatment of ischemic stroke.
A green one-pot synthesis of nitrogen and sulfur co-doped carbon quantum dots for sensitive and selective detection of cephalexin
Authors: Akhgari Farhad , Samadi Naser , Farhadi Khalil , Akhgari Mehrdad
Published: March 2017

The article reports a simple, economic, and green method for preparing water-soluble, nitrogen and sulfur co-doped carbon quantum dots via a one-step hydrothermal method. Pomegranate juice served as the carbon source, and the L-cysteine provided nitrogen and sulfur. Co-doped carbon dots were characterized by X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy techniques. The co-doped carbon dots served as fluorescent probes for sensitive and selective detection of cephalexin. Briefly, the co-doped carbon dot systems showed quenching of photoluminescence intensity in the presence of cephalexin. The decrease of fluorescence intensity made it possible to analyze cephalexin with satisfactory detection limits and linear ranges. The Sterne–Volmer plot showed a linear relationship (R2 = 0.998) between F0/F and the concentration of cephalexin over the range from 0.3 to 10 μmol L−1. The limit of detection (LOD) was estimated to be 1 × 10−7 mol L−1 (at a signal to noise ratio of 3). To validate the applicability, the described method was successfully applied for the detection of cephalexin in human urine and raw milk samples.
The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract
Authors: Le Bars Pierre , Matamoros Sébastien , Montassier Emmanuel , Le Vacon Françoise , Potel Gilles , Soueidan Assem , Jordana Fabienne , de La Cochetière Marie-France
Published: March 2017

Many studies show that the human microbiome plays a critical role in the chronic pathologies of obesity, inflammatory bowel diseases, and diabetes. More recently, the interaction between cancer and the microbiome has been highlighted. Most studies have focused on the gut microbiota because it represents the most extensive bacterial community, and the body of evidence correlating it with gut syndromes is increasing. However, in the strict sense, the gastrointestinal (GI) tract begins in the oral cavity, and special attention should be paid to the specific flora of this cavity. This study reviewed the current knowledge about the various microbial ecosystems of the upper part of the GI tract and discussed their potential link to carcinogenesis. The overall composition of the microbial communities, as well as the presence or absence of “key species”, in relation to carcinogenesis is addressed. Alterations in the oral microbiota can potentially be used to predict the risk of cancer. Molecular advances and the further monitoring of the microbiota will increase our understanding of the role of the microbiota in carcinogenesis and open new perspectives for future therapeutic and prophylactic modalities.
Cause-effect analysis for sustainable development policy
Authors: Cucurachi Stefano , Suh Sangwon
Published: March 2017

The sustainable development goals (SDGs) launched by the United Nations (UN) set a new direction for development covering the environmental, economic, and social pillars. Given the complex and interdependent nature of the socioeconomic and environmental systems, however, understanding the cause-effect relationships between policy actions and their outcomes on SDGs remains as a challenge. We provide a systematic review of cause-effect analysis literature in the context of quantitative sustainability assessment. The cause-effect analysis literature in both social and natural sciences has significantly gained its breadth and depth, and some of the pioneering applications have begun to address sustainability challenges. We focus on randomized experiment studies, natural experiments, observational studies, and time-series methods, and the applicability of these approaches to quantitative sustainability assessment with respect to the plausibility of the assumptions, limitations and the data requirements. Despite the promising developments, however, we find that quantifying the sustainability consequences of a policy action, and providing unequivocal policy recommendations based on it is still a challenge. We recognize some of the key data requirements and assumptions necessary to design formal experiments as the bottleneck for conducting scientifically defensible cause-effect analysis in the context of quantitative sustainability assessment. Our study calls for the need of multi-disciplinary effort to develop an operational framework for quantifying the sustainability consequences of policy actions. In the meantime, continued efforts need to be made to advance other modeling platforms such as mechanistic models and simulation tools. We highlighted the importance of understanding and properly communicating the uncertainties associated with such models, regular monitoring and feedback on the consequences of policy actions to the modelers and decision-makers, and the use of what-if scenarios in the absence of well-formulated cause-effect analysis.
Spin jumping in the context of a QCD effective model
Authors: de Gracia G. B.
Published: March 2017

The tensor formulation for the effective theory of QCD vector resonances, whose model we denote by TEVR, is given by an antisymmetric tensor field and describes spin 1 particles. Our goal is to show, by different approaches, that the Abelian version of this model presents the so-called “spin jumping” when we consider its massless limit. Classically we find, by the use of the equations of motion and the Hamiltonian constraint analysis, that the massive phase of the model describes spin 1 particles while its massless phase describes spin 0 particles. From the quantum point of view, we derive these conclusions via tree-level unitarity analysis and the master action approach.
Research and design of underwater flow-induced vibration energy harvester based on Karman vortex street
Authors: Yao Gang , Wang Hai , Yang Chunlai , Wen Li
Published: March 2017

With the increasing development of wireless sensor network (WSN), power supply for WSN nodes had attracted increasing attention, and the energy harvesting system based on Karman vortex street has been widely used in underwater WSN. But the research of the influences of affecting factors towards the energy harvesting system is yet to be completed. So, in this paper, an underwater flow-induced vibration energy harvesting system based on Karman vortex street was proposed and tested. The influence of bluff body geometry and flow velocity towards the performance of the energy harvesting has been researched. The results showed that the output voltage increased as the diameter of bluff body and the water velocity increase. The power generation efficiency was the best when the shape of bluff body was circular.
Expression and localization of pannexin-1 and CALHM1 in porcine bladder and their involvement in modulating ATP release
Authors: Sana-Ur-Rehman Hafiz , Markus Irit , Moore Kate Hilda , Mansfield Kylie Jan , Liu Lu
Published: March 2017

ATP release from urinary bladder is vital for afferent signaling. The aims of this study were to localize calcium homeostasis modulator 1 (CALHM1) and pannexin-1 expression and to determine their involvement in mediating ATP release in the bladder. To determine gene expression and cellular distribution, PCR and immunohistochemistry were performed, respectively, in the porcine bladder. CALHM1 and pannexin-1-mediated ATP release in response to hypotonic solution (0.45% NaCl)-induced stretch, and extracellular Ca2+ depletion ([Ca2+]0) was measured in isolated urothelial, suburothelial, and detrusor muscle cells. CALHM1 and pannexin-1 mRNA and immunoreactivity were detected in urothelial, suburothelial, and detrusor muscle layers, with the highest expression on urothelium. Hypotonic stretch caused a 2.7-fold rise in ATP release from all three cell populations ( P < 0.01), which was significantly attenuated by the pannexin-1 inhibitor, 10Panx1, and by the CALHM1 antibody. Brefeldin A, a vesicular transport inhibitor, and ruthenium red, a nonselective CALHM1 channel blocker, also significantly inhibited stretch-mediated ATP release from urothelial cells. [Ca2+]0 caused a marked, but transient, elevation of extracellular ATP level in all three cell populations. CALHM1 antibody and ruthenium red inhibited [Ca2+]0-induced ATP release from urothelial cells, but their effects on suburothelial and detrusor cells were insignificant. 10Panx1 showed no significant inhibition of [Ca2+]0-induced ATP release in any types of cells. The results presented here provide compelling evidence that pannexin-1 and CALHM1, which are densely expressed in the porcine bladder, function as ATP release channels in response to bladder distension. Modulation of extracellular Ca2+ may also regulate ATP release in the porcine bladder through voltage-gated CALHM1 ion channels.
Bone Pain Induced by Multiple Myeloma Is Reduced by Targeting V-ATPase and ASIC3
Authors: Hiasa Masahiro , Okui Tatsuo , Allette Yohance M. , Ripsch Matthew S. , Sun-Wada Ge-Hong , Wakabayashi Hiroki , Roodman G. David , White Fletcher A. , Yoneda Toshiyuki
Published: March 2017

Multiple myeloma patients experience severe bone pain (MMBP) that is undertreated and poorly understood. In this study, we studied MMBP in an intratibial mouse xenograft model that employs JJN3 human multiple myeloma cells. In this model, mice develop MMBP associated in bone with increased sprouting of calcitonin gene-related peptide-positive (CGRP+) sensory nerves and in dorsal root ganglia (DRG) with upregulation of phosphorylated ERK1/2 (pERK1/2) and pCREB, two molecular indicators of neuron excitation. We found that JJN3 cells expressed a vacuolar proton pump (V-ATPase) that induced an acidic bone microenvironment. Inhibition of JJN3-colonized bone acidification by a single injection of the selective V-ATPase inhibitor, bafilomycin A1, decreased MMBP, CGRP+ sensory neuron sprouting, and pERK1/2 and pCREB expression in DRG. CGRP+ sensory nerves also expressed increased levels of the acid-sensing nociceptor ASIC3. Notably, a single injection of the selective ASIC3 antagonist APETx2 dramatically reduced MMBP in the model. Mechanistic investigations in primary DRG neurons cocultured with JJN3 cells showed increased neurite outgrowth and excitation inhibited by bafilomycin A1 or APETx2. Furthermore, combining APETx2 with bafilomycin A1 reduced MMBP to a greater extent than either agent alone. Finally, combining bafilomycin A1 with the osteoclast inhibitor zoledronic acid was sufficient to ameliorate MMBP, which was refractory to zoledronic acid. Overall, our results show that osteoclasts and multiple myeloma cooperate to induce an acidic bone microenvironment that evokes MMBP as a result of the excitation of ASIC3-activated sensory neurons. Furthermore, they present a mechanistic rationale for targeting ASIC3 on neurons along with the multiple myeloma-induced acidic bone microenvironment as a strategy to relieve MMBP in patients. Cancer Res; 77(6); 1283–95. ©2017 AACR.
Recommended Guidelines for Validation, Quality Control, and Reporting of TP53 Variants in Clinical Practice
Authors: Leroy Bernard , Ballinger Mandy L. , Baran-Marszak Fanny , Bond Gareth L. , Braithwaite Antony , Concin Nicole , Donehower Lawrence A. , El-Deiry Wafik S. , Fenaux Pierre , Gaidano Gianluca , Langerød Anita , Hellstrom-Lindberg Eva , Iggo Richard , Lehmann-Che Jacqueline , Mai Phuong L. , Malkin David , Moll Ute M. , Myers Jeffrey N. , Nichols Kim E. , Pospisilova Sarka , Ashton-Prolla Patricia , Rossi Davide , Savage Sharon A. , Strong Louise C. , Tonin Patricia N. , Zeillinger Robert , Zenz Thorsten , Fraumeni Joseph F. , Taschner Peter E.M. , Hainaut Pierre , Soussi Thierry
Published: March 2017

Accurate assessment of TP53 gene status in sporadic tumors and in the germline of individuals at high risk of cancer due to Li–Fraumeni Syndrome (LFS) has important clinical implications for diagnosis, surveillance, and therapy. Genomic data from more than 20,000 cancer genomes provide a wealth of information on cancer gene alterations and have confirmed TP53 as the most commonly mutated gene in human cancer. Analysis of a database of 70,000 TP53 variants reveals that the two newly discovered exons of the gene, exons 9β and 9γ, generated by alternative splicing, are the targets of inactivating mutation events in breast, liver, and head and neck tumors. Furthermore, germline rearrange-ments in intron 1 of TP53 are associated with LFS and are frequently observed in sporadic osteosarcoma. In this context of constantly growing genomic data, we discuss how screening strategies must be improved when assessing TP53 status in clinical samples. Finally, we discuss how TP53 alterations should be described by using accurate nomenclature to avoid confusion in scientific and clinical reports. Cancer Res; 77(6); 1250–60. ©2017 AACR.
Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future
Authors: Valent Peter , Akin Cem , Hartmann Karin , Nilsson Gunnar , Reiter Andreas , Hermine Olivier , Sotlar Karl , Sperr Wolfgang R. , Escribano Luis , George Tracy I. , Kluin-Nelemans Hanneke C. , Ustun Celalettin , Triggiani Massimo , Brockow Knut , Gotlib Jason , Orfao Alberto , Schwartz Lawrence B. , Broesby-Olsen Sigurd , Bindslev-Jensen Carsten , Kovanen Petri T. , Galli Stephen J. , Austen K. Frank , Arber Daniel A. , Horny Hans-Peter , Arock Michel , Metcalfe Dean D.
Published: March 2017

Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis, systemic mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic mastocytosis is further divided into indolent systemic mastocytosis and advanced systemic mastocytosis variants, including aggressive systemic mastocytosis and mast cell leukemia. The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis. In addition, new treatment options are available for patients with advanced systemic mastocytosis, including allogeneic hematopoietic stem cell transplantation and multikinase inhibitors directed against KIT D816V and other key signaling molecules. Our current article provides an overview of recent advances in the field of mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced systemic mastocytosis. Cancer Res; 77(6); 1261–70. ©2017 AACR.
Asymptomatic Carotid T1-High-Intense Plaque as a Risk Factor for a Subsequent Cerebrovascular Ischemic Event
Authors: Kurosaki Yoshitaka , Yoshida Kazumichi , Fukuda Hitoshi , Handa Akira , Chin Masaki , Yamagata Sen
Published: March 2017

Background: Intraplaque hemorrhage, detected as a high-signal intensity on carotid MRI, is also strongly associated with ischemic events in symptomatic patients. However, in asymptomatic patients, the relationship of the T1-high intense plaque and the subsequent stroke is not clear. The aim of this study is to test the hypothesis that asymptomatic carotid T1-high intense plaque is a risk factor for a subsequent cerebrovascular ischemic event. Methods: Of the 1,353 consecutive patients, who underwent head and carotid MRI as part of their annual medical check-up, the imaging quality of 13 was poor and 150 did not present for follow-up examination, thus leaving 1,190 subjects for evaluation. Of the 1,190 patients, 96 patients had findings of high-signal intensity on carotid MRI and 1,094 patients did not. Cerebrovascular events were retrospectively evaluated. Results: During a mean follow-up period of 53 months, 4 patients with high-signal intensities on carotid MRI (4%) and 3 with no findings (0.3%) had a cerebrovascular ischemic event, with the occurrences significantly higher in the high-signal-intensity group. (p < 0.01) Cox regression analysis indicated that the presence of the high-intense plaque on carotid MRI (hazard ratio [HR] 4.2; 95% CI 1.0-17.1; p = 0.04), age (HR 1.1; 95% CI 1.0-1.2; p = 0.003), and diabetes mellitus (HR 7.2; 95% CI 1.8-27.4; p = 0.004) were associated with the occurrence of subsequent ischemic cerebrovascular events. Conclusions: Asymptomatic carotid T1-high-intense plaque might be a potential high-risk factor for a subsequent cerebrovascular ischemic event.
Visual Loss Induced by Adalimumab Used for Plaque Psoriasis
Authors: Saffra Norman , Astafurov Konstantin
Published: March 2017

A 61-year-old Caucasian male with severe plaque psoriasis without joint involvement was initiated on adalimumab therapy. Shortly thereafter he presented to the emergency room with acute loss of vision in the right eye. A comprehensive systemic workup was instituted which included magnetic resonance imaging (MRI) with and without gadolinium of the brain and orbits. MRI revealed findings that were consistent with CNS demyelination and retrobulbar optic neuritis. Immediate cessation of adalimumab was instituted without any other systemic therapy. Complete return of vision occurred within 6 weeks. No additional psoriatic or neurologic treatment was instituted, and the patient has remained stable now for 14 months.
Diagnostic Accuracy of Fine Needle Aspiration in Thyroid Nodules Arising in Patients with Graves Disease
Authors: Hang Jen-Fan , Lilo Mohammed T. , Bishop Justin A. , Ali Syed Z.
Published: March 2017

Objective: Cytopathologic interpretation in Graves disease (GD) is considered challenging due to significant cellular atypia. Study Design: We retrospectively identified 55 fine needle aspirations (FNAs) from 43 patients with GD that subsequently underwent thyroidectomy from 1995 to 2016. Results: There were 5 patients with papillary thyroid carcinoma (PTC) and 4 with follicular adenoma (FA). Of the 5 patients with PTC, FNA was interpreted as PTC in 3, atypia of undetermined significance (AUS) in 1, and adenomatoid nodule (AN) in 1 (with a 0.5-cm incidental microcarcinoma). Of the 4 patients with FA, FNA was interpreted as follicular neoplasm (FN) in 2, AUS in 1, and AN in 1. Of the 46 nonneoplastic nodules, FNA was interpreted as nondiagnostic in 2, benign in 26, AUS in 15, FN in 1, and suspicious for PTC in 2. None was diagnosed as malignant. The sensitivity, specificity, positive predictive value, and negative predictive value of PTC diagnosis in FNA were 60, 100, 100, and 96.2%, respectively. Conclusion: FNA is a useful tool for identifying neoplastic nodules arising in GD. However, cytologic atypia often leads to indeterminate diagnoses (18/46, 39.1%). Awareness of clinical information regarding prior treatment for GD may be helpful to avoid overinterpretation.
MiR-15b-5p Regulates Collateral Artery Formation by Targeting AKT3 (Protein Kinase B-3)
Authors: Zhu Ling-Ping , Zhou Ji-Peng , Zhang Jia-Xiong , Wang Jun-Yao , Wang Zhen-Yu , Pan Miao , Li Ling-Fang , Chen Lin , Li Chuan-Chang , Wang Kang-Kai , Bai Yong-Ping , Zhang Guo-Gang
Published: March 2017

Objective—

To identify circulating microRNAs that are differentially expressed in severe coronary heart disease with well or poorly developed collateral arteries and to investigate their mechanisms of action in vivo and in vitro.

Approach and Results—

In our study, we identified a circulating microRNA, miR-15b-5p, with low expression that, nevertheless, characterized patients with sufficient coronary collateral artery function. Moreover, in murine hindlimb ischemia model, in situ hybridization identified that miR-15b-5p was specifically expressed in vascular endothelial cells of adductors in sham group and was remarkably downregulated after femoral artery ligation. Overexpressed miR-15b-5p significantly inhibited arteriogenesis and angiogenesis in mice. In vitro, both under basal and vascular endothelial growth factor stimulation, loss-of-function or gain-of-function studies suggested that miR-15b-5p significantly promoted or depressed the migration and proliferation of endothelial cells. We identified AKT3 (protein kinase B-3) as a direct target of miR-15b-5p. Interestingly, AKT3 deficiency by injection with Chol-AKT3-siRNA obviously suppressed arteriogenesis and the recovery of blood perfusion after femoral ligation in mice.

Conclusions—

These results indicate that circulating miR-15b-5p is a suitable biomarker for discriminating between patients with well-developed or poorly developed collaterals. Moreover, miR-15b-5p is a key regulator of arteriogenesis and angiogenesis, which may represent a potential therapeutic target for ischemic disease.
Beneficial Effect of Renal Denervation on Ventricular Premature Complex Induced Cardiomyopathy
Authors: Yamada Shinya , Lo Li‐Wei , Chou Yu‐Hui , Lin Wei‐Lun , Chang Shih‐Lin , Lin Yenn‐Jiang , Liu Shin‐Huei , Cheng Wen‐Han , Tsai Tsung‐Ying , Chen Shih‐Ann
Published: March 2017

Background

Frequent ventricular premature complexes (
VPC
s) can lead to the development of dilated cardiomyopathy and sudden cardiac death. Renal artery sympathetic denervation (
RDN
) may protect the heart from remodeling. This study aimed to investigate the effect of frequent
VPC
s on structural and electrical properties and whether
RDN
can protect the heart from remodeling.

Methods and Results

Eighteen rabbits were randomized to control (n=6),
VPC
(n=6), and
VPC
‐
RDN
(n=6) groups. Surgical and chemical
RDN
s were approached through bilateral retroperitoneal flank incisions in the
VPC
‐
RDN
group. Pacemakers were implanted to the left ventricular apex to produce 50%
VPC
burden for 5 weeks in the
VPC
and
VPC
‐
RDN
groups. In addition, ventricular myocardium was harvested for western blot and trichrome stain. Echocardiographic results showed left ventricular enlargement after 5‐week pacing in the
VPC
group, but not in the
VPC
‐
RDN
group, when compared to baseline. In biventricles, ion channel protein expressions of Nav1.5, Cav1.2, Kir2.1, and
SERCA
2 were similar among 3 groups. However, the degree of biventricular fibrosis was extensive in the
VPC
group, compared to the control and
VPC
‐
RDN
groups. Importantly, ventricular fibrillation inducibility was higher in the
VPC
group (41%) when comparing to the control (13%;
P
<0.05) and
VPC
‐
RDN
groups (13%;
P
<0.05), respectively.

Conclusions

Frequent
VPC
s are associated with the development of cardiac structural remodeling and high ventricular fibrillation inducibility.
RDN
prevents cardiac remodeling and the occurrence of ventricular arrhythmia through antifibrosis.
Two new terrestrial species of Hydraena Kugelann from the island of Bioko, Gulf of Guinea (Coleoptera: Hydraenidae)
Authors: HERNANDO CARLES , RIBERA IGNACIO
Published: March 2017

The knowledge of the Hydraenidae of sub-Saharan Africa, and in particular of the genus Hydraena Kugelann, 1794, is most incomplete. As an example, in southern Africa only three species were described before the revision of Perkins (2014), which raised the number to 31. Only 15 species are currently known from Central Africa, between the Sahel and South Africa, all belonging to subgenus Hydraenopsis Janssens, 1972 (Trizzino et al. 2013), but many more remain to be described and discovered. The islands of the Gulf of Guinea are no exception to this lack of knowledge (Jones 1994), and only one species of the family was previously known, H. (Hydraenopsis) pagaluensis Hernando & Ribera, 2001 from Annobón (Hernando & Ribera 2001; Trizzino et al. 2013). In this paper we describe the first known species of Hydraenidae from Bioko, the largest and closest to the continent of these islands. The species were collected by our friend and colleague Vasily Grebennikov during a survey of the forest litter fauna of Annobón and Bioko. Despite considerable efforts no Hydraenidae were found in Annobón, and only these two species, in a single locality, in Bioko.
A new species of Oncopeltus Stål, 1868 (Heteroptera: Lygaeidae) in the nominate subgenus from Ecuador
Authors: FAÚNDEZ EDUARDO I. , ROCCA JAVIERA R.
Published: March 2017

Oncopeltus Stål is a lygaeine genus currently comprising 39 species classified in two subgenera (Slater & O’Donnell, 1995). Oncopeltus is distributed in both hemispheres in tropical and temperate areas. Species on this genus are commonly known as milkweed bugs, because of their trophic association with plants in the family Apocynaceae (Scudder & Duffey, 1971). From these plants, the bugs sequester cardenolides making them unpalatable for predators (Duffey & Scudder, 1972). These habits are also accompanied with their brightly reddish coloration, which has been interpreted as aposematism (Duffey & Scudder, 1972, O’Rourke, 1979; Faúndez et al., 2016). As these bugs attack several plants in the subfamily Asclepiadoideae; they have an economic impact on several ornamentally used species, and may sometimes be considered as garden pests (Faúndez & Rocca, 2016; Faúndez et al., 2016). Species of this group are also well known for generating some natural hybrids (O’Rourke, 1979); because of this, their systematic treatment at specific level has been confused, and the identity of several taxa remain unclear. The purpose of this contribution is to describe a new species in this genus from Ecuador.
First description of the male of the easternmost Harpactea species, H. parthica (Araneae: Dysderidae)
Authors: ZAMANI ALIREZA , MARUSIK YURI M. , KOPONEN SEPPO
Published: March 2017

Within Dysderidae, Harpactea Bristowe, 1939 (178 species) is second only to Dysdera Latreille, 1804 (264 species) in number of species (WSC 2016). Harpactea is distributed from Portugal (Helsdingen 2015) to eastern Iran (Brignoli 1980) and, although there are many publications dealing with the taxonomy of Harpactea, an inclusive revision of the genus has never been done. In a paper on the Dysderidae of the Caucasus Dunin (1992) provided a regional revision of Harpactea.
Taxonomy and geographical distribution of Panchrysia Hübner, [1821] of China, with description of a new species (Lepidoptera, Noctuidae, Plusiinae)
Authors: HU YAN-QING , HUANG ZHEN-FU , WANG MIN
Published: March 2017

Panchrysia can be readily recognized by the brilliant silvery markings diffused on forewings except Panchrysia marmorea (Ronkay, 1986) and Panchrysia deaurata (Esper), which are characterized by the lack of silvery marking. As currently, this genus is consisted of six species, all of species have been recorded from Eurasian geographic distribution (Ronkay et al., 2008). In China, P. marmorea, Panchrysia tibetensis Chou & Lu, 1982, Panchrysia dives (Eversmann, 1844) and Panchrysia ornate (Bremer, 1864) have been recorded (Chou & Lu, 1978, 1979, 1982; Ronkay, 1986; Han et al., 2005; Ronkay et al., 2008). In this article, four species of Panchrysia are reviewed and a new species Panchrysia longcanggouensis sp. nov. is described herein. Their distribution patterns indicate that Panchrysia has a rather wide range from South-West China through the central China to North-East China, and absent in southeastern and northwestern China. A key to species of the genus in China is provided. Adults and genitalia are illustrated. Also a briefly outline the distribution of the component species is given.
Enhancing Dynamical Seasonal Predictions through Objective Regionalization
Authors: Satti Saleh , Zaitchik Benjamin F. , Badr Hamada S. , Tadesse Tsegaye
Published: March 2017

Improving seasonal forecasts in East Africa has great implications for food security and water resources planning in the region. Dynamically based seasonal forecast systems have much to contribute to this effort, as they have demonstrated ability to represent and, to some extent, predict large-scale atmospheric dynamics that drive interannual rainfall variability in East Africa. However, these global models often exhibit spatial biases in their placement of rainfall and rainfall anomalies within the region, which limits their direct applicability to forecast-based decision-making. This paper introduces a method that uses objective climate regionalization to improve the utility of dynamically based forecast-system predictions for East Africa. By breaking up the study area into regions that are homogenous in interannual precipitation variability, it is shown that models sometimes capture drivers of variability but misplace precipitation anomalies. These errors are evident in the pattern of homogenous regions in forecast systems relative to observation, indicating that forecasts can more meaningfully be applied at the scale of the analogous homogeneous climate region than as a direct forecast of the local grid cell. This regionalization approach was tested during the July–September (JAS) rain months, and results show an improvement in the predictions from version 4.5 of the Max Plank Institute for Meteorology’s atmosphere–ocean general circulation model (ECHAM4.5) for applicable areas of East Africa for the two test cases presented.
Northern Hemisphere Stratospheric Pathway of Different El Niño Flavors in Stratosphere-Resolving CMIP5 Models
Authors: Calvo N. , Iza M. , Hurwitz M. M. , Manzini E. , Peña-Ortiz C. , Butler A. H. , Cagnazzo C. , Ineson S. , Garfinkel C. I.
Published: March 2017

The Northern Hemisphere (NH) stratospheric signals of eastern Pacific (EP) and central Pacific (CP) El Niño events are investigated in stratosphere-resolving historical simulations from phase 5 of the Coupled Model Intercomparison Project (CMIP5), together with the role of the stratosphere in driving tropospheric El Niño teleconnections in NH climate. The large number of events in each composite addresses some of the previously reported concerns related to the short observational record. The results shown here highlight the importance of the seasonal evolution of the NH stratospheric signals for understanding the EP and CP surface impacts. CMIP5 models show a significantly warmer and weaker polar vortex during EP El Niño. No significant polar stratospheric response is found during CP El Niño. This is a result of differences in the timing of the intensification of the climatological wavenumber 1 through constructive interference, which occurs earlier in EP than CP events, related to the anomalous enhancement and earlier development of the Pacific–North American pattern in EP events. The northward extension of the Aleutian low and the stronger and eastward location of the high over eastern Canada during EP events are key in explaining the differences in upward wave propagation between the two types of El Niño. The influence of the polar stratosphere in driving tropospheric anomalies in the North Atlantic European region is clearly shown during EP El Niño events, facilitated by the occurrence of stratospheric summer warmings, the frequency of which is significantly higher in this case. In contrast, CMIP5 results do not support a stratospheric pathway for a remote influence of CP events on NH teleconnections.