bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian Inference for Latent Biologic Structure With Determinantal Point Processes (DPP)
Authors: Xu Yanxun , Müller Peter , Telesca Donatello 
Published: February 2016

Summary
We discuss the use of the determinantal point process (DPP) as a prior for latent structure in biomedical applications, where inference often centers on the interpretation of latent features as biologically or clinically meaningful structure. Typical examples include mixture models, when the terms of the mixture are meant to represent clinically meaningful subpopulations (of patients, genes, etc.). Another class of examples are feature allocation models. We propose the DPP prior as a repulsive prior on latent mixture components in the first example, and as prior on feature-specific parameters in the second case. We argue that the DPP is in general an attractive prior model for latent structure when biologically relevant interpretation of such structure is desired. We illustrate the advantages of DPP prior in three case studies, including inference in mixture models for magnetic resonance images (MRI) and for protein expression, and a feature allocation model for gene expression using data from The Cancer Genome Atlas. An important part of our argument are efficient and straightforward posterior simulation methods. We implement a variation of reversible jump Markov chain Monte Carlo simulation for inference under the DPP prior, using a density with respect to the unit rate Poisson process.
Sparse Estimation of Cox Proportional Hazards Models via Approximated Information Criteria
Authors: Su Xiaogang , Wijayasinghe Chalani S. , Fan Juanjuan , Zhang Ying 
Published: February 2016

SummaryWe propose a new sparse estimation method for Cox (1972) proportional hazards models by optimizing an approximated information criterion. The main idea involves approximation of the norm with a continuous or smooth unit dent function. The proposed method bridges the best subset selection and regularization by borrowing strength from both. It mimics the best subset selection using a penalized likelihood approach yet with no need of a tuning parameter. We further reformulate the problem with a reparameterization step so that it reduces to one unconstrained nonconvex yet smooth programming problem, which can be solved efficiently as in computing the maximum partial likelihood estimator (MPLE). Furthermore, the reparameterization tactic yields an additional advantage in terms of circumventing postselection inference. The oracle property of the proposed method is established. Both simulated experiments and empirical examples are provided for assessment and illustration.
Retinal ganglion cell neuronal damage in diabetes and diabetic retinopathy
Authors: Ng Dorothy SK , Chiang Peggy PC , Tan Gavin , Cheung CM Gemmy , Cheng Ching‐Yu , Cheung Carol Y , Wong Tien Y , Lamoureux Ecosse L , Ikram Mohammad K 
Published: February 2016

AbstractBackgroundTo examine the association of diabetes and diabetic retinopathy (DR) with retinal ganglion cell (RGC) loss.DesignObservational case–control study.ParticipantsType 2 diabetes cases and age‐gender matched controls without diabetes.MethodsSpectral‐domain optical coherence tomography (OCT) parameters of RGCs were calculated after automated segmentation of macular scans. DR severity was graded on fundus photographs using the modified Airlie House Classification system. Generalized estimating equation was used to compare OCT parameters between cases and controls, adjusted for covariates.Main Outcome MeasuresAverage ganglion cell‐inner plexiform layer (GC‐IPL) and average retinal nerve fibre layer (RNFL) thicknesses.ResultsWe analyzed 227 cases and 227 controls. The mean age (years) of cases was 58.3 and controls was 58.1 (P = 0.13). Among cases, 101 had none, 25 had mild and 101 had moderate or severe DR. Compared with controls, GC‐IPL and RNFL were thinner in all cases [mean difference (95% confidence interval [CI]): GC‐IPL −4.49 µm (−2.92; −6.06), RNFL −0.93 µm (−0.09; −1.85)], including cases with no DR [mean difference (95% CI), GC‐IPL −4.37 µm (−2.72; −6.02), RNFL −1.06 µm (−0.10; −2.02)]. Cases with any DR had thinner GC‐IPL than controls [mean difference (95% CI): GC‐IPL −4.81 µm (−2.12; −7.50)]. Among cases, subjects with moderate or severe DR had thinner GC‐IPL than subjects with no DR [mean difference (95% CI): GC‐IPL −2.07 µm (−0.08; −4.07)].ConclusionsRGC loss is present in subjects with diabetes and no DR, and is progressive in moderate or severe DR. RGC neuronal damage in diabetes and DR can be clinically detected using OCT.
Effects of white‐nose syndrome on regional population patterns of 3 hibernating bat species
Authors: Ingersoll Thomas E. , Sewall Brent J. , Amelon Sybill K. 
Published: February 2016

AbstractHibernating bats have undergone severe recent declines across the eastern United States, but the cause of these regional‐scale declines has not been systematically evaluated. We assessed the influence of white‐nose syndrome (an emerging bat disease caused by the fungus Pseudogymnoascus destructans, formerly Geomyces destructans) on large‐scale, long‐term population patterns in the little brown myotis (Myotis lucifugus), the northern myotis (Myotis septentrionalis), and the tricolored bat (Perimyotis subflavus). We modeled population trajectories for each species on the basis of an extensive data set of winter hibernacula counts of more than 1 million individual bats from a 4‐state region over 13 years and with data on locations of hibernacula and first detections of white‐nose syndrome at each hibernaculum. We used generalized additive mixed models to determine population change relative to expectations, that is, how population trajectories differed with a colony's infection status, how trajectories differed with distance from the point of introduction of white‐nose syndrome, and whether declines were concordant with first local observation of the disease. Population trajectories in all species met at least one of the 3 expectations, but none met all 3. Our results suggest, therefore, that white‐nose syndrome has affected regional populations differently than was previously understood and has not been the sole cause of declines. Specifically, our results suggest that in some areas and species, threats other than white‐nose syndrome are also contributing to population declines, declines linked to white‐nose syndrome have spread across large geographic areas with unexpected speed, and the disease or other threats led to declines in bat populations for years prior to disease detection. Effective conservation will require further research to mitigate impacts of white‐nose syndrome, renewed attention to other threats to bats, and improved surveillance efforts to ensure early detection of white‐nose syndrome.
Genetic diversity and population structure of Raffaelea quercus‐mongolicae, a fungus associated with oak mortality in South Korea
Authors: Kim M.‐S. , Hohenlohe P. A. , Kim K.‐H. , Seo S.‐T. , Klopfenstein N. B. 
Published: February 2016

SummaryRaffaelea quercus‐mongolicae is a fungus associated with oak wilt and deemed to cause extensive oak mortality in South Korea. Since the discovery of this fungus on a dead Mongolian oak (Quercus mongolica) in 2004, the mortality continued to spread southwards in South Korea. Despite continued expansion of the disease and associated significant impacts on forest ecosystems, information is lacking about the origin and genetic diversity of R. quercus‐mongolicae. Restriction‐site‐associated DNA (RAD) sequencing was used to assess genetic diversity and population structure among five populations (provinces) of R. quercus‐mongolicae in South Korea. In total, 179 single nucleotide polymorphisms (SNPs) were identified among 2,639 RAD loci across the nuclear genome of the 54 R. quercus‐mongolicae isolates (0.0012 SNPs per bp), which displayed an overall low expected heterozygosity and no apparent population structure. The low genetic diversity and no apparent population structure among South Korean populations of this ambrosia beetle‐vectored fungus support the hypothesis that this fungus was introduced to South Korea.
Season of diagnosis is associated with overall survival in patients with diffuse large B‐cell lymphoma but not with Hodgkin's lymphoma – A population‐based Swedish Lymphoma Register study
Authors: Székely Elisabeth , Lindén Ola , Peterson Stefan , Jerkeman Mats 
Published: February 2016

AbstractObjective and methodsThe aim of this study was to investigate the effect of season of diagnosis on the outcome of patients with diffuse large B‐cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). In this study, we included curatively treated DLBCL (n = 5875) and HL (n = 1693) patients, diagnosed between 2000 and 2011, based on data from the Swedish Lymphoma Register.ResultsOverall survival was significantly better for patients diagnosed with DLBCL during the summer months, but not for patients diagnosed with HL. The difference remained in a multivariable analysis adjusted for age, stage, performance status, number of extra nodal sites and year of diagnosis (HR 1.08; 95% CI 1.02–1.14, P = 0.0069). When analyzing the DLBCL patients according to gender in the multivariable model, the effect of season was shown to be restricted to male patients (HR = 1.09, 95% CI 1.01–1.17, P = 0.0269.ConclusionsIn summary, season of diagnosis was shown to have impact on overall survival in male patients with DLBCL. Possible explanations of our results are the higher vitamin D level during the summer months, the effects of sunlight on the circadian rhythm and the immune system, or the lower risk of infectious disease during the summer. Further investigations are needed to explore these hypotheses.
The role of tumour‐infiltrating eosinophils, mast cells and macrophages in Classical and Nodular Lymphocyte Predominant Hodgkin Lymphoma in children
Authors: Englund Annika , Molin Daniel , Enblad Gunilla , Karlén Jonas , Glimelius Ingrid , Ljungman Gustaf , Amini Rose‐Marie 
Published: February 2016

AbstractObjectivesTo study Hodgkin lymphoma (HL) microenvironment in a Swedish paediatric population and its relation to clinical parameters.MethodsTumour tissue from classical HL (cHL) (n = 87) and nodular lymphocyte predominant HL (NLPHL) (n = 11) was investigated for Epstein‐Barr Virus (EBV) and analysed for eosinophils, mast cells and macrophages.ResultsIn cHL, EBV positivity was more common in low age (P < 0.001) and in mixed cellularity (MC) (P < 0.001). Higher mast cell infiltration was seen in stage III‐IV (P < 0.001), and with presence of B‐symptoms (P = 0.01). Cases with high mast cell counts displayed higher erythrocyte sedimentation rate (ESR), lower haemoglobin and albumin levels. Higher macrophage infiltration was seen in stage III‐IV (P = 0.02) and there was elevated ESR and neutrophil count. All NLPHL cases were EBV negative, had lower rates of inflammatory cells and lower degree of inflammatory reaction in laboratory parameters. There was no difference in survival estimates with regard to infiltration of inflammatory cells.ConclusionsHigher levels of mast cells and macrophages in cHL tumours reflected the clinical presentation in laboratory parameters, B‐symptoms and more advanced stages. NLPHL differs from cHL in numbers of inflammatory cells in the tumour, and in laboratory parameters.
Epilepsy in young Tsc1+/− mice exhibits age‐dependent expression that mimics that of human tuberous sclerosis complex
Authors: Gataullina Svetlana , Lemaire Eric , Wendling Fabrice , Kaminska Anna , Watrin Françoise , Riquet Audrey , Ville Dorothée , Moutard Marie‐Laure , de Saint Martin Anne , Napuri Silvia , Pedespan Jean‐Michel , Eisermann Monika , Bahi‐Buisson Nadia , Nabbout Rima , Chiron Catherine , Dulac Olivier , Huberfeld Gilles 
Published: February 2016

SummaryObjectiveTo describe the epileptic phenotype of Tsc1+/− mice pups in comparison with age‐related seizures in human tuberous sclerosis complex (TSC).MethodsTsc1+/− and control mice underwent intracranial electroencephalography (EEG) recording at postnatal ages (P)8 to P33, with linear silicon probe implanted in the somatosensory cortex of one or both hemispheres for 8–24 h. Ictal events were classified visually by independent analyzers; distinct EEG patterns were related to age and analyzed to quantify field potential characteristics and signal dynamics between hemispheres. We collected retrospectively 20 infants with prenatally diagnosed TSC and EEG before seizure onset, and analyzed the electroclinical course of epilepsy, taking into account a first‐line treatment by vigabatrin.ResultsSpontaneous seizures were disclosed in 55% of Tsc1+/− mice at P9–18. Three ictal patterns were identified: from P9 to P12 “spike clusters” consisted of recurring large spikes without clinical correlate; “spasm‐like” discharges dominated from P13 to P16 consisting of high amplitude large field potential superimposed with or followed by fast activity repeated every 2–10 s for at least 20 s, accompanied by rhythmic limb contractions; from P14 to P18 a “tonic–clonic like” pattern comprised rhythmic spikes of increasing amplitude with tonic–clonic movements. Early onset “spike clusters” were mainly unilateral, whereas “spasm‐like” and “tonic–clonic like” patterns were bilateral. Interhemispheric propagation was significantly faster for “tonic–clonic like” than for “spasm‐like” events. In infants diagnosed prenatally with TSC, clusters of sharp waves or spikes preceded the first seizure, and vigabatrin prevented the development of seizures. Patients treated after seizure onset developed spasms or focal seizures that were pharmacoresistant in 66.7% of cases.SignificanceTsc1+/− mice pups exhibit an age‐dependent seizure pattern sequence mimicking early human TSC epilepsy features. Spike clusters before seizure onset in TSC should be considered as a first stage of epilepsy reinforcing the concept of preventive antiepileptic therapy.
Physiological responses of Arundo donax ecotypes to drought: a common garden study
Authors: Haworth Matthew , Cosentino Salvatore Luciano , Marino Giovanni , Brunetti Cecilia , Scordia Danilo , Testa Giorgio , Riggi Ezio , Avola Giovanni , Loreto Francesco , Centritto Mauro 
Published: February 2016

AbstractGenetic analyses have suggested that the clonal reproduction of Arundo donax has resulted in low genetic diversity. However, an earlier common garden phenotyping experiment identified specimens of A. donax with contrasting biomass yields (ecotypes 6 and 20). We utilized the same well‐established stands to investigate the photosynthetic and stress physiology of the A. donax ecotypes under irrigated and drought conditions. Ecotype 6 produced the largest yields in both treatments. The A. donax ecotypes exhibited identical high leaf‐level rates of photosynthesis (PN) and stomatal conductance (Gs) in the well‐watered treatment. Soil drying induced reductions in PN and Gs, decreased use of light energy for photochemistry, impaired function of photosystem II and increased heat dissipation similarly in the two ecotypes. Levels of biologically active free‐abscisic acid (ABA) and fixed glycosylated‐ABA increased earlier in response to the onset of water deficit in ecotype 6; however, as drought progressed, the ecotypes showed similar increases in both forms of ABA. This may suggest that because of the low genetic variability in A. donax the genes responding to drought might have been activated similarly in the two ecotypes, resulting in identical physiological responses to water deficit. Despite the lack of physiological ecotypic differences that could be associated with yield, A. donax retained a high degree of PN and biomass gain under water deficit stress conditions. This may enable utilization of A. donax as a fast growing biomass crop in rain‐fed marginal lands in hot drought prone climates.
Diagnostic value of telecytology in tertiary teledermatological consultation: a retrospective analysis of 75 cases
Authors: Durdu Murat , Harman Mehmet 
Published: February 2016

AbstractBackgroundThe addition of dermatoscopic images to clinical images is reported to increase the diagnostic value of teledermatology. No study has investigated the contribution of telecytology to teledermatology. We aimed to assess the diagnostic accuracy of telecytology in tertiary teledermatological evaluation.MethodsThe study included 75 patients for whom no diagnosis could be established at face‐to‐face clinical examinations and cytological evaluations, who therefore consulted with a dermatologist experienced in cytology through the store‐and‐forward method. Telecytological diagnosis was then compared with the final diagnosis, and diagnostic accuracy was calculated.ResultsIn the past 2 years, 75 patients (38 [50.7%] female, 37 [49.3%] male) were evaluated by telecytology. According to definitive diagnoses, 31 patients (41.3%) had erosive–vesiculobullous, 25 (33.3%) had tumoral, and 19 (15.8%) had granulomatous disease. Diagnostic accuracy of telecytology was 90.7%.LimitationsOur study was a retrospective study, and cytological images were evaluated by one dermatologist only; therefore, no reliability analysis could be performed.ConclusionThis study revealed that the cytological images should be used in tertiary teledermatological evaluation. Further studies should therefore be carried out to investigate the diagnostic value of different telecytological methods.
Building a global teledermatology collaboration
Authors: Bobbs Melanie , Bayer Michelle , Frazer Tifany , Humphrey Stephen , Wilson Barbara , Olasz Edit , Holland Kristen , Kuzminski Jacquelyn 
Published: February 2016

AbstractSkin disease is common in low‐resource countries and is associated with significant morbidity. The disease burden is often heightened by lack of access to adequate diagnosis and treatment. Teledermatology is a growing healthcare delivery modality that allows access to subspecialty care at a distance. This article describes how a low‐cost teledermatology program was launched through collaboration between the Medical College of Wisconsin and Hillside Healthcare International. Several factors are required for a teledermatology program to be successful, beginning with a partnership between two entities that targets a locally identified need and is mutually beneficial to invested partners. The program should utilize the expertise of each partner, be based on an agreed upon process with clearly defined objectives, and protect patient privacy. After a program is implemented, adaptation to address challenges and best meet the needs of all parties involved will allow for continued success and sustainability. This process can serve as a model for other programs desiring to establish similar teledermatology partnerships in an academic setting.
Lenalidomide treatment of cutaneous lupus erythematosus: the Mayo Clinic experience
Authors: Kindle Scott A. , Wetter David A. , Davis Mark D. P. , Pittelkow Mark R. , Sciallis Gabriel F. 
Published: February 2016

AbstractBackgroundPublished case series describe lenalidomide as an effective treatment of refractory cutaneous lupus erythematosus (CLE).ObjectivesThe present study aimed to further characterize lenalidomide use in the treatment of CLE.MethodsA retrospective review of patients treated with lenalidomide for CLE from January 1, 2000, to December 17, 2014, was conducted.ResultsEight of the nine patients (89%) were women. Their median age at initiation of lenalidomide was 62 years (range: 41–86 years). Subtypes of CLE included discoid lupus erythematosus (DLE) (n = 6), lupus panniculitis (n = 2), and subacute CLE (n = 1). Before the initiation of lenalidomide, all patients had been previously treated unsuccessfully or were intolerant to at least one antimalarial and one immunosuppressive agent. With lenalidomide, five patients achieved a complete response (CR), two a partial response, and two had no response (lupus panniculitis). Time to initial response (dose range: 2.5–10.0 mg/d) varied from 2 weeks to 3 months; the median time to CR in five patients was 3 months (range: 3–6 months). The median duration of lenalidomide therapy was 12 months (range: 2–67 months). The median duration of follow‐up was 48 months (range: 20–103 months). Adverse effects included mild leukopenia; one patient had deep vein thrombosis of unclear etiology during a hospitalization. No patients developed or showed progression of systemic LE while receiving lenalidomide.ConclusionsLenalidomide was effective for the treatment of CLE (particularly DLE) but not for the treatment of lupus panniculitis in this series.
Lichen planus and dyslipidemia: a systematic review and meta‐analysis of observational studies
Authors: Lai Yi C. , Yew Yik W. , Schwartz Robert A. 
Published: February 2016

AbstractBackgroundLichen planus (LP) is a chronic inflammatory disease that has been shown to be positively associated with dyslipidemia. However, the magnitude and types of the underlying lipid abnormalities have not been investigated. This study aims to conduct a systematic review and meta‐analysis to investigate the qualitative and quantitative association between LP and dyslipidemia.MethodsA systematic search of studies published from inception to April 1, 2015, was conducted using MEDLINE, EMBASE, Web of Science, and Cochrane library databases. Meta‐analyses of observational studies with both categorical and continuous outcome were performed. DerSimonian and Lard random effects models were utilized to calculate the pooled odds ratio and weighted mean difference (WMD). Publication bias was evaluated by funnel plot and Egger's test.ResultsSeven studies with 5242 subjects were included in this meta‐analysis. Patients with LP were significantly more likely to have dyslipidemia, with a pooled odds ratio of 1.74 (95% confidence interval [CI]: 1.19–2.54, P = 0.004). LP was associated with higher levels of triglycerides (WMD 83.37 mg/dl, 95% CI 0.62–166.12, P = 0.048), low‐density lipoprotein (18.75 mg/dl, 95% CI −17.21 to 54.72, P = 0.307), total cholesterol (19.22 mg/dl, 95% CI −8.80 to 47.25, P = 0.179), and lower levels of high‐density lipoprotein cholesterol (−8.96 mg/dl, 95% CI −21.22 to 3.30, P = 0.152).ConclusionsDespite considerable heterogeneity, this study demonstrated that LP was significantly associated with an increased risk of dyslipidemia and higher triglyceride levels. For patients presenting with LP, physicians should be cognizant of this association and consider screening them for dyslipidemia.
Is timolol an effective treatment for pyogenic granuloma?
Authors: Gupta Divya , Singh Nidhi , Thappa Devinder Mohan 
Published: February 2016

AbstractBackgroundPyogenic granuloma (PG) is a benign vascular tumor that can be treated by cautery (chemical or thermal), laser, excision, curettage, sclerotherapy, and cryotherapy. Topical timolol is emerging as a non‐invasive modality for the treatment of PGs.MethodsWe recruited a series of 10 patients with PG, who received treatment with 0.5% timolol maleate ophthalmic solution applied 4 times a day, 2 drops per dose. No other medication, topical or systemic, was given. Pulse rate, blood pressure, and blood glucose were monitored at baseline and weekly thereafter for the duration of treatment. ECG was done at baseline. The efficacy of the treatment was evaluated by considering a complete response, a partial response, and no response.ResultsOf 10 patients, four showed complete response within 3–24 days, with no recurrence at 3‐month follow‐up. Three patients each showed partial or no response. No local or systemic side effects were reported in any of the patients.ConclusionsThe response of PGs to β blockers seems to be variable. Although topical timolol has the advantage of minimal adverse events, ease of administration, and better cosmetic outcomes, it's efficacy in PG may not be universal unlike in infantile hemangiomas. Topical timolol may be a treatment option in young children, incapacitated elderly, and over delicate areas like face, nails, and gums where invasive modalities are not desirable.