bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality and HRQoL in ICU patients with delirium: Protocol for 1‐year follow‐up of AID‐ICU trial
Authors: Mortensen Camilla B. , Poulsen Lone M. , Andersen‐Ranberg Nina C. , Perner Anders , Lange Theis , Estrup S Stine , Ebdrup Bjørn H. , Egerod Ingrid , Rasmussen Bodil S. , Hästbacka Johanna , Caballero Jesús , Citerio Giuseppe , Morgan Matthew P.G. , Samuelson Karin , Mathiesen Ole 
Published: July 2020

BackgroundIntensive care unit (ICU)‐acquired delirium is frequent and associated with poor short‐ and long‐term outcomes for patients in ICUs. It therefore constitutes a major healthcare problem. Despite limited evidence, haloperidol is the most frequently used pharmacological intervention against ICU‐acquired delirium.Agents intervening against Delirium in the ICU (AID‐ICU) is an international, multicentre, randomised, blinded, placebo‐controlled trial investigates benefits and harms of treatment with haloperidol in patients with ICU‐acquired delirium. The current pre‐planned one‐year follow‐up study of the AID‐ICU trial population aims to explore the effects of haloperidol on one‐year mortality and health related quality of life (HRQoL).Methods The AID‐ICU trial will include 1000 participants. One‐year mortality will be obtained from the trial sites; we will validate the vital status of Danish participants using the Danish National Health Data Registers. Mortality will be analysed by Cox‐regression and visualized by Kaplan‐Meier curves tested for significance using the log‐rank test. We will obtain HRQoL data using the EQ‐5D instrument. HRQoL analysis will be performed using a general linear model adjusted for stratification variables. Deceased participants will be designated the worst possible value.ResultsWe expect to publish results of this study in 2022.ConclusionWe expect that this one‐year follow‐up study of participants with ICU‐acquired delirium allocated to haloperidol vs. placebo will provide important information on the long‐term consequences of delirium including the effects of haloperidol. We expect that our results will improve the care of this vulnerable patient group.
Occupancy patterns of an apex avian predator across a forest landscape
Authors: Cisterne Adam , Crates Ross , Bell Phil , Heinsohn Rob , Stojanovic Dejan 
Published: July 2020

AbstractApex predators are integral parts of every ecosystem, having top‐down roles in food web maintenance. Understanding the environmental and habitat characteristics associated with predator occurrence is paramount to conservation efforts. However, detecting top order predators can be difficult due to small population sizes and cryptic behaviour. The endangered Tasmanian masked owl (Tyto novaehollandiae castanops) is a nocturnal predator with a distribution understood to be associated with high mature forest cover at broad scales. With the aim to gather monitoring data to inform future conservation effort, we trialled an occupancy survey design to model masked owl occurrence across ~800 km2in the Tasmanian Southern Forests. We conducted 662 visits to assess masked owl occupancy at 160 sites during July–September 2018. Masked owl site occupancy was 12%, and estimated detectability was 0.26 (±0.06 SE). Cumulative detection probability of masked owls over four visits was 0.7. Occupancy modelling suggested owls were more likely to be detected when mean prey count was higher. However, low detection rates hindered the development of confident occupancy predictions. To inform effective conservation of the endangered Tasmanian masked owl, there is a need to develop novel survey techniques that better account for the ecology of this rare, wide‐ranging and cryptic predator. We discuss the potential to combine novel census approaches that exploit different aspects of masked owl ecology to obtain more robust and detailed data.
Role of testosterone in cognition and mobility of aging men
Authors: Kaufman Jean‐Marc , Lapauw Bruno 
Published: July 2020

AbstractBackgroundCognitive decline and impairment of physical performance and mobility are age‐related clinical problems with major negative impact on quality of life of elderly men. In how far the decline of testosterone production contributes to these problems in older men and whether testosterone therapy can contribute to slow down, prevent, or reverse their development remains subjects of debate.ObjectivesThis narrative review presents the current knowledge on association of sex steroid status with cognitive decline and impairment of physical function and mobility in elderly men and on the effects of testosterone therapy on cognition and on physical performance and mobility in elderly men.Materials and MethodThe review is based on electronic database searches with primary focus on evidence from larger prospective observational studies and from controlled randomized trials, respectively.ResultsIn most observational studies, testosterone levels do not predict cognitive decline or development of Alzheimer's disease. In randomized trials, testosterone therapy did not significantly affect cognition in men with low or low‐to‐normal serum testosterone, regardless of whether they have preexisting cognitive impairment. Overall, observational data indicate that the usually moderate decline of androgen exposure in older men cannot fully account for the parallel decline of physical performance and mobility. Trials of testosterone therapy in older men with low or low‐normal serum testosterone, whether they were generally healthy or suffered from physical function impairments, either did not show any effect on mobility and physical performance or showed limited effects of uncertain clinical relevancy.Discussion and ConclusionsThe whole of the evidence tends to downplay the role of sex steroid status in the decline of cognitive function and impairment of physical function and mobility in older men. Based on the available evidence, prevention or treatment of cognitive decline or of impairment of mobility and physical function are not valid indications for testosterone treatment in older men with low or low‐to‐normal serum testosterone levels.
Predictive values of initial semi‐quantitative assessment of relative afferent pupillary defect for neovascularization in central retinal vein occlusion
Authors: Ducloyer Jean‐Baptiste , Bensaber Sonia , Khanna Raoul Kanav , Cochard Catherine , Lebreton Olivier , Le Meur Guylène , Lebranchu Pierre , Arsene Sophie , Weber Michel 
Published: July 2020

AbstractPurposeTo measure the predictive values of relative afferent pupillary defect (RAPD) assessed semi‐quantitatively, and visual acuity (VA) at onset of central retinal vein occlusion (CRVO), for neovascularization.MethodsRetrospective analysis of the TROXHEMO trial that included patients with CRVO within 30 days after the onset. Inclusion criteria were as follows: semi‐quantitative RAPD assessment at diagnosis and/or at one month. RAPD was ‘severe’ if ≥ 0.9 log. Exclusion criteria were as follows: prophylactic panretinal photocoagulation (PRP) before neovascularization.ResultsAmong the 119 patients enrolled in the main centre, 101 were analysed. 26 had a neovascular complication during the twelve months of follow‐up: rubeosis (19), glaucoma (7) and posterior neovascularization (15). The mean time to onset of a neovascular complication was 4.7 months (1 to 12, median 3 months). All the patients who had a neovascular complication had RAPD at first examination or at one month (negative predictive value (NPV) = 100%) but the positive predictive value (PPV) was low (31%, 95% CI [21%; 42%]). The association ‘severe RAPD or VA < 35 letters (ETDRS) at inclusion or at one month’ was the best compromise between PPV (53%, [39%; 68%]) and NPV (96%, [92%; 100%]).ConclusionTo predict neovascularization, RAPD should be routinely evaluated with filters: the risk of neovascular complication is (a) almost nil if there is no RAPD, (b) very low if there is no severe RAPD and if VA is higher than 35 letters, and (c) higher than 50% if RAPD is ≥ 0.9 log or if VA is less than 35 letters.
Randomised clinical trial: significant biochemical and colonic transit effects of the farnesoid X receptor agonist tropifexor in patients with primary bile acid diarrhoea
Authors: Camilleri Michael , Nord Sara Linker , Burton Duane , Oduyebo Ibironke , Zhang Yiming , Chen Jin , Im Koeun , Bhad Prafulla , Badman Michael K. , Sanders David S. , Walters Julian R. F. 
Published: July 2020

SummaryBackgroundIn primary bile acid diarrhoea, feedback by farnesoid X receptor (FXR) and fibroblast growth hormone 19 (FGF19) on hepatic bile acid production is impaired.AimsTo evaluate the safety, mechanisms and efficacy of negative feedback by FXR activation with tropifexor, a non‐bile acid FXR agonist, in patients with primary bile acid diarrhoea.MethodsIn this double‐blind, multicentre, randomised, cross‐over study, patients received tropifexor 60 µg or placebo once daily for 14 days in each of two treatment periods. Primary objectives included tropifexor safety and tolerability, and on stool frequency and form. Other assessments included pharmacokinetic and pharmacodynamic measures, biochemical markers and gastrointestinal transit.ResultsTwenty patients (tropifexor 60 µg/placebo [N = 10]; placebo/tropifexor 60 µg [N = 10]) were enrolled. Adverse event rates were lower with tropifexor vs placebo (52.9% vs 73.7%). No patient had pruritus during tropifexor intake. There were no significant differences in stool frequency, stool form or loperamide use between treatments. Tropifexor increased FGF19 and decreased 7α‐hydroxy‐4‐cholesten‐3‐one (C4) levels for up to 8 h. Plasma tropifexor concentrations peaked at 5 hours post‐dose on days 1 and 12. At day 12, tropifexor caused reduction in peak total bile acid concentration (33%, P = 0.032) and exposure (36%, P = 0.005). Moreover, tropifexor showed a significant increase in ascending colon half‐emptying time (P = 0.036).ConclusionsTropifexor 60 µg once daily had acceptable safety and tolerability. Changes in FGF19 and C4 showed effective target engagement; however, higher doses may be required to observe stool frequency changes. Slowing of ascending colon emptying suggests therapeutic potential of tropifexor in patients with primary bile acid diarrhoea.ClinicalTrials.gov number: NCT02713243.
Statistical inference for natural language processing algorithms with a demonstration using type 2 diabetes prediction from electronic health record notes
Authors: Egleston Brian L. , Bai Tian , Bleicher Richard J. , Taylor Stanford J. , Lutz Michael H. , Vucetic Slobodan 
Published: July 2020

AbstractThe pointwise mutual information statistic (PMI), which measures how often two words occur together in a document corpus, is a cornerstone of recently proposed popular natural language processing algorithms such as word2vec. PMI and word2vec reveal semantic relationships between words and can be helpful in a range of applications such as document indexing, topic analysis, or document categorization. We use probability theory to demonstrate the relationship between PMI and word2vec. We use the theoretical results to demonstrate how the PMI can be modeled and estimated in a simple and straight forward manner. We further describe how one can obtain standard error estimates that account for within‐patient clustering that arises from patterns of repeated words within a patient's health record due to a unique health history. We then demonstrate the usefulness of PMI on the problem of predictive identification of disease from free text notes of electronic health records. Specifically, we use our methods to distinguish those with and without type 2 diabetes mellitus in electronic health record free text data using over 400 000 clinical notes from an academic medical center.
Preoperative detection of Vesical Imaging‐Reporting and Data System (VI‐RADS) score 5 reliably identifies extravesical extension of urothelial carcinoma of the urinary bladder and predicts significant delayed time to cystectomy: time to reconsider the need for primary deep transurethral resection of bladder tumour in cases of locally advanced disease?
Authors: Del Giudice Francesco , Leonardo Costantino , Simone Giuseppe , Pecoraro Martina , De Berardinis Ettore , Cipollari Stefano , Flammia Simone , Bicchetti Marco , Busetto Gian Maria , Chung Benjamin I. , Gallucci Michele , Catalano Carlo , Panebianco Valeria 
Published: July 2020

Objectives(I) To determine Vesical Imaging‐Reporting and Data System (VI‐RADS) score 5 accuracy in predicting locally advanced bladder cancer (BCa), so as to potentially identify those patients who could avoid the morbidity of deep transurethral resection of bladder tumour (TURBT) in favour of histological sampling‐TUR prior to radical cystectomy (RC). (II) To explore the predictive value of VI‐RADS score 5 on time‐to‐cystectomy (TTC) outcomes.Patients and MethodsWe retrospectively reviewed patients’ ineligible or refusing cisplatin‐based combination neoadjuvant chemotherapy who underwent multiparametric magnetic resonance imaging (mpMRI) of the bladder prior to staging TURBT followed by RC for muscle‐invasive BCa. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated for VI‐RADS score 5 vs. score 2–4 cases to assess the accuracy of mpMRI for extravesical BCa detection (≥pT3). VI‐RADS score performance was assessed by receiver operating characteristics curve analysis. A Κ statistic was calculated to estimate mpMRI and pathological diagnostic agreement. The risk of delayed TTC (i.e. time from initial BCa diagnosis of >3 months) was assessed using multivariable logistic regression model.ResultsA total of 149 T2–T4a, cN0–M0 patients (VI‐RADS score 5, n = 39 vs VI‐RADS score 2–4, n = 110) were examined. VI‐RADS score 5 demonstrated sensitivity, specificity, PPV and NPV, in detecting extravesical disease of 90.2% (95% confidence interval [CI] 84–94.3), 98.1% (95% CI 94–99.6), 94.9% (95% CI 89.6–97.6) and 96.4% (95% CI 91.6–98.6), respectively. The area under the curve was 94.2% (95% CI 88.7–99.7) and inter‐reader agreement was excellent (Κinter 0.89). The mean (SD) TTC was 4.2 (2.3) and 2.8 (1.1) months for score 5 vs 2–4, respectively (P < 0.001). VI‐RADS score 5 was found to independently increase risk of delayed TTC (odds ratio 2.81, 95% CI 1.20–6.62).ConclusionThe VI‐RADS is valid and reliable in differentiating patients with extravesical disease from those with muscle‐confined BCa before TURBT. Detection of VI‐RADS score 5 was found to predict significant delay in TTC independently from other clinicopathological features. In the future, higher VI‐RADS scores could potentially avoid the morbidity of extensive primary resections in favour of sampling‐TUR for histology. Further prospective, larger, and multi‐institutional trials are required to validate clinical applicability of our findings.
Lightning‐caused disturbance in the Peruvian Amazon
Authors: Gora Evan M. , Yanoviak Stephen P. 
Published: July 2020

AbstractWe surveyed seven lightning strike sites in the northern Peruvian Amazon. An average of 17.3 trees were damaged per strike; large trees (> 60 cm diameter) were disproportionately affected. The results contribute to a growing body of evidence that lightning is an important agent of disturbance pantropically.Abstract in Spanish is available with online material.
Perceived discrimination in health services and preventive dental attendance in Brazilian adults
Authors: Junior Orlando Luiz do Amaral , Menegazzo Gabriele Rissotto , Fagundes Maria Laura Braccini , de Sousa Jailson Lopes , Tôrres Luisa Helena do Nascimento , Giordani Jessye Melgarejo do Amaral 
Published: July 2020

AbstractObjectivesIt is evident that discriminatory attitudes affect different dimensions of personal life, including health. This study aimed to verify the association between perceived discrimination in health services and preventive dental attendance in Brazilian adults.MethodsThis cross‐sectional study used secondary data from the 2013 National Health Survey (PNS), a representative survey of the Brazilian population. The response rate was 91.9%, with 60,202 adults agreeing to complete the oral health self‐perception questionnaire. Data were analysed using the software STATA 14.0. A descriptive sample analysis was conducted that considered sample weight as well as an association between health discrimination and factors associated with preventive dental attendance through Poisson regression models.ResultsAdjusted analysis demonstrated that, regarding the reasons that led to discrimination, lack of money, social class and type of working occupation showed a negative association with preventive dental attendance.ConclusionOur findings show that discrimination perpetuates health inequities. Those with worse social conditions need more assistance as they struggle with discrimination and end up going for a check‐up after the disease is established or advanced. Preventive care, which could change the health condition of the disadvantaged population, is often a reality only for those less vulnerable.
Evaluating the outcomes of genetic rescue attempts
Authors: Robinson Zachary L. , Bell Donovan A. , Dhendup Tashi , Luikart Gordon , Whiteley Andrew R. , Kardos Marty 
Published: July 2020

AbstractAugmenting gene flow is a powerful tool for the conservation of small, isolated populations. However, genetic rescue attempts have largely been limited to populations at the brink of extinction, in part due to concerns over negative outcomes (e.g., outbreeding depression). Increasing habitat fragmentation may necessitate more proactive genetic management. Broader application of augmented gene flow will, in turn, require rigorous evaluation to increase confidence and identify pitfalls in this approach. To date, there has been no assessment of best monitoring practices for genetic rescue attempts. We used genomically explicit, individual‐based simulations to examine the effectiveness of common approaches (i.e., tests for increases in fitness, migrant ancestry, heterozygosity, and abundance) for determining whether genetic rescue or outbreeding depression occurred. Statistical power to detect the effects of gene flow on fitness was high (≥0.8) when effect sizes were large, a finding consistent with those from previous studies on severely inbred populations. However, smaller effects of gene flow on fitness can appreciably affect persistence probability but current evaluation approaches fail to provide results from which reliable inferences can be drawn. The power of the metrics we examined to evaluate genetic rescue attempts depended on the time since gene flow and whether gene flow was beneficial or deleterious. Encouragingly, the use of multiple metrics provided nonredundant information and improved inference reliability, highlighting the importance of intensive monitoring efforts. Further development of best practices for evaluating genetic rescue attempts will be crucial for a responsible transition to increased use of translocations to decrease extinction risk.
PRAME expression in melanocytic proliferations with intermediate histopathologic or spitzoid features
Authors: Raghavan Shyam S. , Wang Jennifer Y. , Kwok Shirley , Rieger Kerri E. , Novoa Roberto A. , Brown Ryanne A. 
Published: July 2020

AbstractBackgroundPRAME (PReferentially expressed Antigen in MElanoma) has shown utility in distinguishing melanoma from benign melanocytic lesions, but knowledge of its expression pattern in intermediate melanocytic and spitzoid proliferations is limited.MethodsImmunohistochemical expression of PRAME was examined in 112 melanocytic proliferations with intermediate histopathologic or spitzoid features.ResultsAny intensity of nuclear PRAME staining in at least 60% of lesional melanocytes was determined as the best threshold for diffuse staining in this cohort. Nearly all non‐spitzoid melanomas (23/24; 95.8%) demonstrated diffuse PRAME expression. PRAME was completely negative in 95.6% (43/45) of mitotically‐active nevi, traumatized nevi, nevi with persistent/recurrent features, and dysplastic nevi. Most Spitz nevi (15/20) and atypical Spitz tumors (10/13) entirely lacked PRAME expression. One Spitz nevus, one atypical Spitz tumor, and one spitzoid melanoma (1/2) demonstrated diffuse PRAME expression.ConclusionsAlthough diffuse PRAME expression is generally limited to malignant melanoma, benign Spitz nevi and atypical Spitz tumors can infrequently express diffuse PRAME. PRAME immunohistochemistry can be useful in the evaluation of atypical melanocytic proliferations with intermediate histopathologic features but should be interpreted with caution in the setting of spitzoid neoplasms.
A Study on Operational Risk and Credit Portfolio Risk Estimation Using Data Analytics*
Authors: Chen Rongda , Wang Ze , Yang Liu , Ng Chi To , Cheng T.C.E. 
Published: July 2020

ABSTRACTIn this article we consider operational risk and use data analytics to estimate the credit portfolio risk. Specifically, we consider situations in which managers need to make the optimal operational decision on total provision for risk to hedge against the potential risk in the entire supply chain. We build a new structural credit model integrated with data analytics to analyze the joint default risk of credit portfolio. Our model enables the decision maker to better assess the risk of a supply chain, so that they could determine the optimal operational decisions with total provision for risk, and react in a timely manner to economic and environmental changes. We propose an efficient simulation method to estimate the default probability of the credit portfolio with the risk factors having the multivariate t‐copula. Moreover, we develop a three‐step importance sampling (IS) method for the t‐copula credit portfolio risk measurement model to achieve an accurate estimation of the tail probability of the credit portfolio loss distribution. We apply the Levenberg–Marquardt algorithm to estimate the mean‐shift vector of the systematic risk factors after the probability measure change. Besides, we empirically examine the changes in the credit portfolio risks of 60 listed Chinese firms in different industries using our proposed method. The results show that our model can help the decision maker make the optimal operational decisions with total provision for risk, which hedges against the potential risk in the entire supply chain.