bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective Response Metric: a novel tool to predict relapse in childhood acute lymphoblastic leukaemia using time‐series gene expression profiling
Authors: Yeoh Allen E.‐J. , Li Zhenhua , Dong Difeng , Lu Yi , Jiang Nan , Trka Jan , Tan Ah Moy , Lin Hai Peng , Quah Thuan Chong , Ariffin Hany , Wong Limsoon 
Published: May 2018

SummaryAccurate risk assignment in childhood acute lymphoblastic leukaemia is essential to avoid under‐ or over‐treatment. We hypothesized that time‐series gene expression profiles (GEPs) of bone marrow samples during remission‐induction therapy can measure the response and be used for relapse prediction. We computed the time‐series changes from diagnosis to Day 8 of remission‐induction, termed Effective Response Metric (ERM‐D8) and tested its ability to predict relapse against contemporary risk assignment methods, including National Cancer Institutes (NCI) criteria, genetics and minimal residual disease (MRD). ERM‐D8 was trained on a set of 131 patients and validated on an independent set of 79 patients. In the independent blinded test set, unfavourable ERM‐D8 patients had >3‐fold increased risk of relapse compared to favourable ERM‐D8 (5‐year cumulative incidence of relapse 38·1% vs. 10·6%; P = 2·5 × 10−3). ERM‐D8 remained predictive of relapse [P = 0·05; Hazard ratio 4·09, 95% confidence interval (CI) 1·03–16·23] after adjusting for NCI criteria, genetics, Day 8 peripheral response and Day 33 MRD. ERM‐D8 improved risk stratification in favourable genetics subgroups (P = 0·01) and Day 33 MRD positive patients (P = 1·7 × 10−3). We conclude that our novel metric – ERM‐D8 – based on time‐series GEP after 8 days of remission‐induction therapy can independently predict relapse even after adjusting for NCI risk, genetics, Day 8 peripheral blood response and MRD.
Detection of platelet autoantibodies to identify immune thrombocytopenia: state of the art
Authors: Porcelijn Leendert , Huiskes Elly , Oldert Gonda , Schipperus Martin , Zwaginga Jaap J. , de Haas Masja 
Published: May 2018

SummaryImmune Thrombocytopenia (ITP) is diagnosed by exclusion of other causes for thrombocytopenia. Reliable detection of platelet autoantibodies would support the clinical diagnosis of ITP and prevent misdiagnosis. We optimized our diagnostic algorithm for suspected ITP using the direct monoclonal antibody immobilization of platelet antigens assay (MAIPA), which evaluates the presence of platelet autoantibodies on the glycoproteins (GP) IIb/IIIa, Ib/IX and V bound on the patient platelets. The direct MAIPA was shown to be a valuable technique for the detection of platelet autoantibodies and could possibly become a guide for optimizing therapy towards a more personalized treatment of ITP.
Clinical‐grade validation of whole genome sequencing reveals robust detection of low‐frequency variants and copy number alterations in CLL
Authors: Klintman Jenny , Barmpouti Katerina , Knight Samantha J. L. , Robbe Pauline , Dreau Hélène , Clifford Ruth , Ridout Kate , Burns Adam , Timbs Adele , Bruce David , Antoniou Pavlos , Sosinsky Alona , Becq Jennifer , Bentley David , Hillmen Peter , Taylor Jenny C. , Caulfield Mark , Schuh Anna H. 
Published: May 2018

SummaryThe 100 000 Genome Project aims to develop a diagnostics platform by introducing whole genome sequencing (WGS) into clinical practice. Samples from patients with chronic lymphocytic leukaemia were subjected to WGS. WGS detection of single nucleotide variants and insertion/deletions were validated by targeted next generation sequencing showing high concordance (96·3%), also for detection of sub‐clonal variants and low‐frequency TP53 variants. Copy number alteration detection was verified by fluorescent in situ hybridisation and genome‐wide single nucleotide polymorphism array (concordances of 86·7% and 92·9%, respectively), confirming adequate sensitivity by WGS. Our results confirm that WGS can provide comprehensive genomic characterisation for clinical trials, drug discovery and, ultimately, precision medicine.
Diagnostic markers for CNS lymphoma in blood and cerebrospinal fluid: a systematic review
Authors: van Westrhenen Anouk , Smidt Lisanne C. A. , Seute Tatjana , Nierkens Stefan , Stork Abraham C. J. , Minnema Monique C. , Snijders Tom J. 
Published: May 2018

SummaryDiagnosing central nervous system (CNS) lymphoma remains a challenge. Most patients have to undergo brain biopsy to obtain tissue for diagnosis, with associated risks of serious complications. Diagnostic markers in blood or cerebrospinal fluid (CSF) could facilitate early diagnosis with low complication rates. We performed a systematic literature search for studies on markers in blood or cerebrospinal fluid for the diagnosis CNS lymphoma and assessed the methodological quality of studies with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS‐2). We evaluated diagnostic value of the markers at a given threshold, as well as differences between mean or median levels in patients versus control groups. Twenty‐five studies were included, reporting diagnostic value for 18 markers in CSF (microRNAs ‐21, ‐19b, and ‐92a, RNU2‐1f, CXCL13, interleukins ‐6, ‐8, and ‐10, soluble interleukin‐2‐receptor, soluble CD19, soluble CD27, tumour necrosis factor‐alfa, beta‐2‐microglobulin, antithrombin III, soluble transmembrane activator and calcium modulator and cyclophilin ligand interactor, soluble B cell maturation antigen, neopterin and osteopontin) and three markers in blood (microRNA‐21 soluble CD27, and beta‐2‐microglobulin). All studies were at considerable risk of bias and there were concerns regarding the applicability of 15 studies. CXCL‐13, beta‐2‐microglobulin and neopterin have the highest potential in diagnosing CNS lymphoma, but further study is still needed before they can be used in clinical practice.
STED microscopy: A simplified method for liver sinusoidal endothelial fenestrae analysis
Authors: Di Martino Julie , Mascalchi Patrice , Legros Philippe , Lacomme Sabrina , Gontier Etienne , Bioulac‐Sage Paulette , Balabaud Charles , Moreau Violaine , Saltel Frédéric 
Published: May 2018

Background InformationLiver sinusoidal endothelial cells (LSECs) possess fenestrae, open transcellular pores with an average diameter of 100 nm. These fenestrae allow for the exchange between blood and hepatocytes. Alterations in their number or diameter in liver diseases have important implications for hepatic microcirculation and function. Although decades of studies, fenestrae are still observed into fixed cells and we have poor knowledge of their dynamics.ResultsUsing stimulated emission depletion (STED) super‐resolution microscopy, we have established a faster and simplest method to observe and quantify fenestrae. Indeed, using cytochalasin D, an actin depolymerising agent known to promote fenestrae formation, we measure the increase of fenestrae number. We adapted this methodology to develop an automated method to study fenestrae dynamics. Moreover, with two‐colour STED analysis, we have shown that this approach could be useful to study LSECs fenestrae molecular composition.ConclusionsOur approach demonstrates that STED microscopy is suitable for LSEC fenestrae study.SignificanceThis new way of analysing LSEC fenestrae will allow for expedited investigation of their dynamics, molecular composition and functions to better understand their function in liver pathophysiology.
Druggability of the guanosine/adenosine/cytidine nucleoside hydrolase from Trichomonas vaginalis
Authors: Alam Rayyan , Barbarovich Allen T. , Caravan Wagma , Ismail Mirna , Barskaya Angela , Parkin David W. , Stockman Brian J. 
Published: May 2018

Trichomonas vaginalis infects approximately 300 million people worldwide annually. Infected individuals have a higher susceptibility to more serious conditions such as cervical and prostate cancer. The parasite has developed increasing resistance to current drug therapies, with an estimated 5% of clinical cases resulting from resistant strains, creating the need for new therapeutic strategies with novel mechanisms of action. Nucleoside salvage pathway enzymes represent novel drug targets as these pathways are essential for the parasite's survival. The guanosine/adenosine/cytidine nucleoside hydrolase (GACNH) may be particularly important as its expression is upregulated under glucose‐limiting conditions mimicking those that occur during infection establishment. GACNH was screened against the NIH Clinical Collection to explore its druggability. Seven compounds were identified with IC50 values <20 μM. Extensive overlap was found between inhibitors of GACNH and the adenosine/guanosine nucleoside hydrolase (AGNH), but no overlap was found with inhibitors of the uridine nucleoside hydrolase. The guanosine analog ribavirin was the only compound found to be specific for GACNH. Compounds that inhibit both AGNH and GACNH purine salvage pathway enzymes may prove critical given the role that GACNH appears to play in the early stages of infection.
Insight into structural requirements of antiamoebic flavonoids: 3D‐QSAR and G‐QSAR studies
Authors: Fatima Shehnaz , Gupta Payal , Agarwal Subhash Mohan 
Published: May 2018

Plant‐based flavonoids have been found to exhibit strong inhibitory capability against Entamoeba histolytica. So, various QSAR models have been developed to identify the critical features that are responsible for the potency of these molecules. 3D‐QSAR analysis using k‐nearest neighbour molecular field analysis via stepwise forward–backward variable selection method showed best results for both internal and external predictive ability of the model (i.e., q2 = 0.64 and pred_r2 = 0.56). Also, a group‐based QSAR (G‐QSAR) model was developed based on partial least squares regression combined with stepwise forward–backward variable selection method. It gave best parametric results (r2 = 0.74, q2 = 0.56 and pred_r2 = 0.54) which implied that the model is highly predictive. 3D‐QSAR established that presence/absence of bulk near rings B and C is important in deciding the inhibitory potential of these molecules. Additionally, G‐QSAR provided site‐specific clue wherein modifications related to molecular weight, electronegativity and separation of an oxygen atom in rings A and C can result in enhanced biological activity. To the best of the author's knowledge, this is the first QSAR study of antiamoebic flavonoids, and therefore, we expect the results to be useful in the design of more potent antiamoebic inhibitors.
Are pregnancy, parity, menstruation and breastfeeding risk factors for thyroid cancer? Results from the Korea National Health and Nutrition Examination Survey, 2010‐2015
Authors: Kim Hosu , Kim Kyong Young , Baek Jong Ha , Jung Jaehoon 
Published: May 2018

SummaryContextIt is unclear whether reproductive factors such as pregnancy, parity, menstruation, and breastfeeding are risk factors for thyroid cancer. The aim of this study was to evaluate the association of reproductive factors with thyroid cancer risk.Design/SettingLarge‐scale nation‐wide cross‐sectional data were analysed from representative samples from the Korea National Health and Nutrition Examination Survey V‐VI (2010‐2015).ResultsIn this study, 38 086 people over the age of 18 years were enrolled, of which 241 had a diagnosis of thyroid cancer. Of 21 543 female subjects, 210 had thyroid cancer. In logistic regression analysis, pregnancy, parity and number of reproductive years (period between menarche and menopause, excluding breastfeeding period) were significantly associated with thyroid cancer after adjusting for age, body mass index and smoking. However, the number of pregnancies did not show a linear relationship with thyroid cancer. Among breastfeeding women, total duration of breastfeeding and number of babies breastfed significantly decreased the risk for thyroid cancer.ConclusionOur findings suggest that reproductive factors can be associated with the development of thyroid cancer. A large prospective cohort study is needed to clarify the causality.
Equine eosinophilic keratitis: An emergent ocular condition?
Authors: González‐Medina S. 
Published: May 2018

SummaryEosinophilic keratitis (EK) is considered an immune mediated disorder associated with an underlying type I orIVhypersensitivity reaction to parasitic or environment allergens. It is believed that the persistency of inflammatory mediators and recruitment of eosinophils into the conjunctival tissue have detrimental effects on the corneal surface. Epithelial cells are consequently damaged, particularly by eosinophilic toxic proteins, which determine the lack of epithelial healing and plaque formation. Although some clinical signs are common to other corneal diseases, the location of the lesion, presence of corneal plaques and time of the year, may help practitioners to identifyEK. Topical therapy with steroids or immune‐modulators seems to be the most effective treatment in small, localised lesions while large epithelial defects will benefit from a thorough debridement and/or early keratectomy, before secondary microbial infection may occur.
A unified and integrated numerical‐analytical approach for evaluation of Jk‐integrals of an interfacial crack in orthotropic and isotropic bimaterials
Authors: Tafreshi A. 
Published: May 2018

AbstractA new unified and integrated method for the numerical‐analytical calculation of Jk‐integrals of an in‐plane traction free interfacial crack in homogeneous orthotropic and isotropic bimaterials is presented. The numerical algorithm, based on the boundary element crack shape sensitivities, is generic and flexible. It applies to both straight and curved interfacial cracks in anisotropic and/or isotropic bimaterials. The shape functions of semidiscontinuous quadratic quarter point crack tip elements are correctly scaled to adapt the singular oscillatory near tip field of tractions. The length of crack is designated as the design variable to compute the strain energy release rate precisely. Although an analytical equation relating J1 and stress intensity factors (SIFs) exists, a similar relation for J2 in debonded anisotropic solids for decoupling SIFs is not available. An analytical expression was recently derived by this author for J2 in aligned orthotropic/orthotropic bimaterials with a straight interface crack. Using this new relation and the present computed Jk values, the SIFs can be decoupled without the need for an auxiliary equation. Here, the aforementioned analytical relation is reconstructed for cubic symmetry/isotropic bimaterials and used with the present numerical algorithm. An example with known analytical SIFs is presented. The numerical and analytical magnitudes of Jk for an interface crack in orthotropic/orthotropic and cubic symmetry/isotropic bimaterials show an excellent agreement.
Crack growth analysis and fatigue life estimation in the piston rod of a Kaplan hydro turbine
Authors: Liu X. , Presas A. , Luo Y. , Wang Z. 
Published: May 2018

AbstractLinear elastic fracture mechanics (LEFM) approaches are seldom used to analyze fatigue problems in hydraulic turbomachinery, where extremely simplified fatigue models are normally considered. In one of the largest Kaplan hydraulic turbines in the world, the piston rod, which is an important load transfer component, was found broken twice at the same location. This event, which leads to extremely high direct reparation costs and indirect costs, is a very useful case for research of fatigue problems in hydraulic turbines by means of LEFM. For this purpose, the crack growth progress in the piston rod is simulated with numerical LEFM techniques. A probabilistic model for the initial flaw size is considered. A reliability criterion, consisting in the probability of not having a critical crack or a fracture in the piston rod after a specific service time, is defined. Based on this model, the influence of initial crack models and operating services of the machine on the reliability of the unit is discussed. The calculated crack path and predicted number of loading cycles as a function of the initial crack size agree with the actual fracture section and operating time to fracture.
Spatiotemporal remote sensing of ecosystem change and causation across Alaska
Authors: Pastick Neal J. , Jorgenson M. Torre , Goetz Scott J. , Jones Benjamin M. , Wylie Bruce K. , Minsley Burke J. , Genet Hélène , Knight Joseph F. , Swanson David K. , Jorgenson Janet C. 
Published: May 2018

AbstractContemporary climate change in Alaska has resulted in amplified rates of press and pulse disturbances that drive ecosystem change with significant consequences for socio‐environmental systems. Despite the vulnerability of Arctic and boreal landscapes to change, little has been done to characterize landscape change and associated drivers across northern high‐latitude ecosystems. Here we characterize the historical sensitivity of Alaska's ecosystems to environmental change and anthropogenic disturbances using expert knowledge, remote sensing data, and spatiotemporal analyses and modeling. Time‐series analysis of moderate—and high‐resolution imagery was used to characterize land‐ and water‐surface dynamics across Alaska. Some 430,000 interpretations of ecological and geomorphological change were made using historical air photos and satellite imagery, and corroborate land‐surface greening, browning, and wetness/moisture trend parameters derived from peak‐growing season Landsat imagery acquired from 1984 to 2015. The time series of change metrics, together with climatic data and maps of landscape characteristics, were incorporated into a modeling framework for mapping and understanding of drivers of change throughout Alaska. According to our analysis, approximately 13% (~174,000 ± 8700 km2) of Alaska has experienced directional change in the last 32 years (±95% confidence intervals). At the ecoregions level, substantial increases in remotely sensed vegetation productivity were most pronounced in western and northern foothills of Alaska, which is explained by vegetation growth associated with increasing air temperatures. Significant browning trends were largely the result of recent wildfires in interior Alaska, but browning trends are also driven by increases in evaporative demand and surface‐water gains that have predominately occurred over warming permafrost landscapes. Increased rates of photosynthetic activity are associated with stabilization and recovery processes following wildfire, timber harvesting, insect damage, thermokarst, glacial retreat, and lake infilling and drainage events. Our results fill a critical gap in the understanding of historical and potential future trajectories of change in northern high‐latitude regions.
Influence of residential characteristics on the association between the oral health status and BMI of older adults in Indonesia
Authors: Hanindriyo Lisdrianto , Widita Elastria , Widyaningrum Rini , Priyono Bambang , Agustina Dewi 
Published: May 2018

ObjectiveTo assess the possible effects of residential characteristics on the association between oral hygiene and body mass index (BMI) of elderly people in Indonesia.MethodsThis cross‐sectional study involved 186 participants (87 males, 99 females) aged ≥60 years who were randomly recruited from 8 community health stations for the elderly people. Dentition status, oral hygiene index (OHI), probing pocket depth (PPD) and clinical attachment level (CAL) were assessed in accordance with WHO guidelines. Salivary condition was assessed through the unstimulated whole saliva collection method. Education status and oral health behaviours were evaluated using a standardised questionnaire. BMI was calculated as weight in kilograms divided by height in metres squared. Participants were grouped in accordance with their OHI status (poor, moderate or good) combined with their residential characteristic (rural or urban) to assess the independent effect of OHI and residential characteristic on BMI through linear regression analysis with confounder adjustment.ResultsIn the crude model of linear regression analysis, the poor OHI group is associated with low BMI regardless of their residential characteristic (rural/urban) when compared to the “good OHI, urban” group with P‐values of .045 and <.01 and regression coefficients (β) of −2.1 and −4.5, respectively. However, in the adjusted model, only the “poor OHI, rural” group showed a significant association with low BMI when compared to the “good OHI, urban” group (β = −3.4; P < .01).ConclusionLow BMI is significantly associated with poor OHI and rural residential characteristic among elderly people in Indonesia.
Vitamin D status in adult patients with nonmelanoma skin cancer in Cape Town, South Africa: a cross‐sectional study
Authors: van Deventer Linda , Kannenberg Susanna M.H. , du Toit Jacques 
Published: May 2018

AbstractBackgroundUltraviolet (UV) radiation is the most important environmental risk factor for the development of nonmelanoma skin cancer (NMSC). UV radiation is, however, also vital in the formation of vitamin D in humans. Strict sun protection advised to skin cancer patients may lead to vitamin D deficiency, yet vitamin D may have a protective effect against cancer formation.ObjectivesThe primary aim was to determine whether patients with nonmelanoma skin cancer at our institution were vitamin D deficient.Methods25‐Hydroxyvitamin D (25[OH]D) levels were determined in 109 patients with a diagnosis of basal cell carcinoma (BCC) and/or squamous cell carcinoma (SCC) during the summer and winter of 2015 at the Tygerberg Academic Hospital in Cape Town, South Africa. Associations between clinical and epidemiological data and the 25(OH)D level results were investigated. Vitamin D deficiency was defined as total 25(OH)D levels <20 ng/mL (<50 nmol/L).ResultsIt was found that 49.5% of NMSC patients were vitamin D deficient, and 41.3% had insufficient vitamin D levels. Females were more likely than males to be vitamin D deficient (P = 0.047). Winter was significantly associated with vitamin D deficiency, compared to summer (OR = 4.81, 95%CI = 2.09–11.09, P <0.001). Having a previous SCC appeared associated with not being vitamin D deficient (OR = 0.46, 95%CI = 0.20–1.11, P = 0.084).ConclusionsThe findings highlight the need for the development of recommendations and guidelines on sun protection in patients with NMSC, while still ensuring an adequate vitamin D status. High risk factors included winter and female gender.
Combining integer linear programming with a state‐of‐the‐art heuristic for the 2‐path network design problem
Authors: Clímaco Glaubos , Rosseti Isabel , Simonetti Luidi , Guerine Marcos 
Published: May 2018

AbstractIn communication network design, connections with few edges reduce the probability of delays and increase confidence. The 2‐path network design problem (2‐PNDP) raised in this context and aimed to build up a minimum‐cost network to satisfy a set of pairs of demands using a path with at most two edges. In this work, we propose two strategies that incorporate integer linear programming (ILP) into a state‐of‐the‐art heuristic for solving the 2‐PNDP. Our approaches collect information from specific components of the original heuristic and use it to reduce the solution space explored by the ILP solver, accelerating its resolution and improving the solution quality. Computational experiments conducted on a set of instances from the literature have shown the benefit of these combinations, achieving better solutions in almost all cases.