bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Simple Estimator of Two‐Dimensional Copulas, with Applications1
Authors: Anderson Eddie , Prokhorov Artem , Zhu Yajing 
Published: May 2020

AbstractCopulas are distributions with uniform marginals. Non‐parametric copula estimates may violate the uniformity condition in finite samples. We look at whether it is possible to obtain valid piecewise linear copula densities by triangulation. The copula property imposes strict constraints on design points, making an equi‐spaced grid a natural starting point. However, the mixed‐integer nature of the problem makes a pure triangulation approach impractical on fine grids. As an alternative, we study the ways of approximating copula densities with triangular functions which guarantees that the estimator is a valid copula density. The family of resulting estimators can be viewed as a non‐parametric MLE of B‐spline coefficients on possibly non‐equally spaced grids under simple linear constraints. As such, it can be easily solved using standard convex optimization tools and allows for a degree of localization. A simulation study shows an attractive performance of the estimator in small samples and compares it with some of the leading alternatives. We demonstrate empirical relevance of our approach using three applications. In the first application, we investigate how the body mass index of children depends on that of parents. In the second application, we construct a bivariate copula underlying the Gibson paradox from macroeconomics. In the third application, we show the benefit of using our approach in testing the null of independence against the alternative of an arbitrary dependence pattern.
When ESKD complicates the management of pain
Authors: Jhamb Manisha , Tucker Laura , Liebschutz Jane 
Published: May 2020

AbstractPain is one of the most common symptoms reported by patients with end‐stage kidney disease (ESKD) and negatively impacts their health‐related quality of life (HRQOL), dialysis adherence, healthcare utilization, and mortality. There are a number of patient‐related and health system‐related barriers that make it very challenging to treat pain in these patients. Moreover, the limited availability of efficacious and safe nonopiate analgesic options has led to over‐use of opioids in this population. We propose a framework for pain assessment and tailored treatment using nonpharmacological and pharmacological approaches to optimize pain management and opioid use. Additionally, we recommend system‐level changes to improve care coordination and pain management in ESKD patients.
Hepatitis B Immunoglobulin discontinuation in long‐term liver transplant patients
Authors: Dobrindt Eva Maria , Keshi Eriselda , Salim Yones , Gillespie Allan , Saipbaev Akylbek , Schöning Wenzel , Öllinger Robert , Pratschke Johann , Eurich Dennis 
Published: May 2020

AbstractBackgroundHepatitis B immunoglobulin (HBIG)—as a monotherapy or combined with nucleos(t)ide analogs (NUCs)—has effectively lowered Hepatitis B virus (HBV) reinfection after liver transplantation. However, it is associated with high costs and viral resistance. HBIG‐free prophylaxis with novel NUCs (tenofovir, entecavir) composes a viable alternative. We evaluated reinfection rate, histological changes, and outcome associated with HBIG discontinuation.MethodsA retrospective analysis was performed of patients undergoing liver transplantation due to HBV‐induced liver disease at our center since 1988. A controlled HBIG discontinuation was conducted between 2015 and 2017 in 65 patients. Recurrent infection was determined by HbsAg values. Fibrosis and inflammation were evaluated by routine biopsy. The survival of patients after HBIG discontinuation was compared to a control population on HBIG for prophylaxis.ResultsFrom 1988 to 2013, 352 patients underwent liver transplantation due to HBV‐induced liver disease. 169 patients could be included for analysis. 104 (51.5%) patients continued a prophylaxis containing HBIG. HBIG was discontinued in 65 (38.5%) patients in a controlled manner, maintaining an oral NUC. None of those patients showed HBV reinfection or graft dysfunction. No significant changes of inflammation grades (P = .067) or fibrosis stages (P = .051) were detected. The survival of patients after HBIG discontinuation was comparable to the control (P = .95).ConclusionHBIG withdrawal under continuation of oral NUC therapy is safe and not related to graft dysfunction, based on blood tests and histology. HBIG‐free prophylaxis is not associated with a worse outcome and displays a financial relief as well as a logistic simplification during long‐term follow‐up.
Progressive multifocal leukoencephalopathy presenting with acute sensorineural hearing loss in an intestinal transplant recipient
Authors: Lippa Andrew M. , Ocwieja Karen E. , Iglesias Julie , Fawaz Rima , Elisofon Scott , Lee Christine , Sharma Tanvi S. 
Published: May 2020

AbstractA 20‐year‐old male presented 3.5 years after intestinal transplantation with rapidly progressive sensorineural hearing loss. Initial brain imaging was consistent with inflammation and/or demyelination. Lumbar puncture was initially non‐diagnostic and a broad infectious workup was unrevealing. Three months after presentation, a repeat LP detected JC virus for which tests had not earlier been conducted. He continued to deteriorate despite withdrawal of prior immunosuppression and addition of mirtazapine, maraviroc, and steroids. He died of progressive neurologic decompensation 5 months after his initial presentation. This case highlights progressive multifocal leukoencephalopathy (PML) as a rare complication after solid organ transplantation and acute sensorineural hearing loss as an unusual first presenting symptom of PML. JC virus should be considered in the differential diagnosis of acute sensorineural hearing loss in any immunocompromised patient.
Automatic wheat ear counting using machine learning based on RGB UAV imagery
Authors: Fernandez‐Gallego Jose A. , Lootens Peter , Borra‐Serrano Irene , Derycke Veerle , Haesaert Geert , Roldán‐Ruiz Isabel , Araus Jose L. , Kefauver Shawn C. 
Published: May 2020

SummaryIn wheat (Triticum aestivum L) and other cereals, the number of ears per unit area is one of the main yield‐determining components. An automatic evaluation of this parameter may contribute to the advance of wheat phenotyping and monitoring. There is no standard protocol for wheat ear counting in the field, and moreover it is time consuming. An automatic ear‐counting system is proposed using machine learning techniques based on RGB (red, green, blue) images acquired from an unmanned aerial vehicle (UAV). Evaluation was performed on a set of 12 winter wheat cultivars with three nitrogen treatments during the 2017–2018 crop season. The automatic system uses a frequency filter, segmentation and feature extraction, with different classification techniques, to discriminate wheat ears in micro‐plot images. The relationship between the image‐based manual counting and the algorithm counting exhibited high levels of accuracy and efficiency. In addition, manual ear counting was conducted in the field for secondary validation. The correlations between the automatic and the manual in‐situ ear counting with grain yield were also compared. Correlations between the automatic ear counting and grain yield were stronger than those between manual in‐situ counting and GY, particularly for the lower nitrogen treatment. Methodological requirements and limitations are discussed.
AtNOT1 is required for gametophyte development in Arabidopsis
Authors: Pereira Patrícia A. , Boavida Leonor C. , Santos Mário R. , Becker Jörg D. 
Published: May 2020

SummaryIn flowering plants, pollen development is under a dynamic and well‐orchestrated transcriptional control, characterized by an early phase with high transcript diversity and a late post‐mitotic phase skewed to a cell‐type‐specific transcriptome. Such transcriptional changes require a balance between synthesis and degradation of mRNA transcripts, the latter being initiated by deadenylation. The CCR4‐NOT complex is the main evolutionary conserved deadenylase complex in eukaryotes, and its function is essential during germline specification in animals. We hypothesized that the CCR4‐NOT complex might play a central role in mRNA turnover during microgametogenesis in Arabidopsis. Disruption of NOT1 gene, which encodes the scaffold protein of the CCR4‐NOT complex, showed abnormal seed set. Genetic analysis failed to recover homozygous progeny, and reciprocal crosses confirmed reduced transmission through the male and female gametophytes. Concordantly, not1 embryo sacs showed delayed development and defects in embryogenesis. not1 pollen grains exhibited abnormal male germ unit configurations and failed to germinate. Transcriptome analysis of pollen from not1/+ mutants revealed that lack of NOT1 leads to an extensive transcriptional deregulation during microgametogenesis. Therefore, our work establishes NOT1 as an important player during gametophyte development in Arabidopsis.
Analgesic effect of topical and subconjunctival morphine in dogs after phacoemulsification: A pilot study
Authors: Spertus Chloe B. , Espinheira Gomes Filipe , Martin‐Flores Manuel , Parry Stephen A. , Ledbetter Eric C. 
Published: May 2020

AbstractObjectiveTo determine the efficacy of a single treatment of topical and subconjunctival 0.1% preservative‐free morphine sulfate (PFMS) in providing analgesia following phacoemulsification in dogs.Animals studiedTen diabetic and ten non‐diabetic client‐owned dogs treated with bilateral phacoemulsification.ProceduresA prospective, randomized, masked, negative‐controlled clinical trial was performed. All dogs received topical (0.2 mL) and subconjunctival (0.1 mL) 0.1% PFMS in one eye following phacoemulsification. The other eye received an equal volume and mode of administration of balanced salt solution (BSS). Ophthalmic examination, blinking rates, tearing, conjunctival hyperemia, aqueous flare, and central corneal esthesiometry (CCE) were evaluated in all eyes 1 day prior to surgery and at 4, 24, and 48 hours after surgery. Complete physical examination, ocular ultrasound, electroretinogram, hemogram, and serum biochemistry panel were performed in all dogs prior to phacoemulsification. All dogs received the standard of care treatment before and after surgery, including uniform anesthetic protocol.ResultsBaseline ophthalmic exams were unremarkable, except for the presence of cataracts, in all dogs. The mean CCE (±SD) at 4 hours post‐operatively was 1.76 ± 1.27 g/mm2 and 1.85 ± 1.5 g/mm2 for the negative control and PFMS groups, respectively. There were no statistical differences in blepharospasm, conjunctival hyperemia, tearing, aqueous flare, blinking rates, CCE, or intraocular pressure (IOP) between the treatment groups for any of the time points for the non‐diabetic and diabetic dogs, or for all dogs combined (P > .05).ConclusionsTopical and subconjunctival 0.1% PFMS did not affect the evaluated parameters after phacoemulsification in the study dogs at the timepoints assessed.
10 Innovative Institutes
Authors: González Carlos M. 
Published: May 2020

Abstract
Engineering is a major that is continuously evolving. To meet the demand of a changing world, educational institutions are implementing new instructional models that can rise to the changes occurring today and tomorrow. What does the future of engineering education look like? This article explores some of the unique program offerings available to today’s engineers, ranging from research opportunities, global collaboration, diversity inclusion programs, entrepreneurship education, and STEM mentoring.
Focus on Methodology: A sense of sociomaterialism: How sociomaterial perspectives might illuminate health professions education
Authors: Burm Sarah , MacLeod Anna 
Published: May 2020

Emerging from the field of socio-technical studies (STS), “sociomaterial” refers to a diverse group of theoretical approaches that, broadly speaking, share a commitment to symmetrically privileging both social and material elements. Not surprisingly, the ways in which a sociomaterial researcher engages in the process of collecting and analysing data will differ from studies that foreground a more human-centered point of view. This paper introduces researchers to the principles informing sociomaterial research and demonstrates their application in the context of a problem that has reached rampant levels among healthcare professionals—burnout. In this paper, we provide an accessible, in-depth description of what we mean by the sociomaterial, describe its historical roots and elucidate what it means to engage in empirical sociomaterial work. In so doing, our goal is to illuminate the potential of sociomaterial studies for exploring the complexity of health professions education.
Clinicopathological characteristics of 8697 patients with COVID-19 in China: a meta-analysis
Authors: Zhu Jieyun , Zhong Zhimei , Ji Pan , Li Hongyuan , Li Bocheng , Pang Jielong , Zhang Jianfeng , Zhao Chunling 
Published: May 2020

ObjectiveOur study aims to present a summary of the clinicopathological characteristics of patients affected by the coronavirus disease 2019 (COVID-19) that can be used as a reference for further research and clinical decisions.DesignStudies were included in the meta-analysis if they had cohort, case–control or case series designs and provided sufficient details on clinical symptoms, laboratory outcomes and asymptomatic patients.SettingPubMed, Embase, Chinese Biomedical Literature Database, Wanfang, China Science and Technology Journal Database and China National Knowledge Infrastructure databases were electronically searched to identify related studies published between 1 January 2020 and 16 March 2020. Three reviewers independently examined the literature, extracted relevant data and assessed the risk of publication bias before including the studies in the meta-analysis.ParticipantsThe confirmed cases of COVID-19.ResultsA total of 55 unique retrospective studies involving 8697 patients with COVID-19 were identified. Meta-analysis showed that a higher proportion of infected patients were male (53.3%), and the two major symptoms observed were fever (78.4%) and cough (58.3%). Other common symptoms included fatigue (34%), myalgia (21.9%), expectoration (23.7%), anorexia (22.9%), chest tightness (22.9%) and dyspnoea (20.6%). Minor symptoms included nausea and vomiting (6.6%), diarrhoea (8.2%), headache (11.3%), pharyngalgia (11.6%), shivering (15.2%) and rhinorrhea (7.3%). About 5.4% of the patients were asymptomatic. Most patients showed normal leucocyte counts (64.7%) and elevated C reactive protein levels (65.9%). Lymphopaenia was observed in about 47.6% of the infected patients, along with abnormal levels of myocardial enzymes (49.4%) and liver function (26.4%). Other findings included leucopenia (23.5%), elevated D-dimer (20.4%), elevated erythrocyte sedimentation rate (20.4%), leucocytosis (9.9%), elevated procalcitonin (16.7%) and abnormal renal function (10.9%).ConclusionsThe most commonly experienced symptoms of patients with COVID-19 were fever and cough. Myalgia, anorexia, chest tightness and dyspnoea were found in some patients. A relatively small percentage of patients were asymptomatic and could act as carriers of the disease. Most patients showed normal leucocyte counts, elevated levels of C reactive protein and lymphopaenia, confirming the viral origin of the disease.
Association between rectal douching and HIV acquisition: the mediating role of condom use and rectal bleeding in a national online sample of Chinese men who have sex with men
Authors: Lu Tianyi , Mao Xiang , Peng Erlei , Gao Yangyang , Chu Zhenxing , Dong Willa , Zhang Wenran , Jiang Yong-Jun , Xu Junjie 
Published: May 2020

ObjectivesPrevious studies have demonstrated that rectal douching (RD) is associated with HIV acquisition among men who have sex with men (MSM). However, the precise mechanism underlying the association between RD and HIV remains unclear.MethodsWe recruited participants over WeChat from October 2017 to October 2018. Respondents received mailed HIV self-testing kits, uploaded images of HIV self-test results and completed an online electronic questionnaire simultaneously. The questionnaire assessed sociodemographic characteristics, RD practices and sexual risk behaviours. HIV status was measured as the result of the HIV self-testing. The Baron and Kenny statistical method was used to assess the association between RD and HIV, controlling for condomless anal intercourse (CAI) and rectal bleeding.ResultsOf 1365 participants, 39.93% (545/1365) reported RD in the past 6 months, 60.07% had multiple male sexual partners and 43.08% had CAI in the past 6 months. The prevalence of HIV, based on self-testing, was 3.37% (46/1365). Multivariable logistic analysis showed RD was significantly associated with bottom sexual role (adjusted OR (aOR) 14.0; 95% CI 9.8 to 20.2), having multiple male sexual partners (aOR 1.8; 95% CI 1.4 to 2.2), CAI (aOR 1.3; 95% CI 1.0 to 1.6), rectal bleeding (aOR 2.0; 95% CI 1.6 to 2.6) and HIV infection (aOR 1.9; 95% CI 1.0 to 3.4). Baron and Kenny analysis found both CAI (aOR 2.2; 95% CI 1.2 to 4.1) and rectal bleeding (aOR 1.9; 95% CI 1.0 to 3.4) play a mediating role in the association between RD and HIV.ConclusionsOur study results confirmed the relationship between RD and HIV, and found CAI and rectal bleeding mediated HIV infection in Chinese MSM who douched. Strategies should be encouraged to strengthen health education and reduce high-risk sexual behaviour in order to reduce the risk of HIV in MSM who use enemas. Rectal microbicides may represent an efficient means of providing HIV prophylaxis among MSM.
Physical activity perceptions, experiences, and beliefs of older adults with mild cognitive impairment or Alzheimer’s disease and their care partners
Authors: Bechard Lauren E. , Beaton Dorcas , McGilton Katherine S. , Tartaglia Maria Carmela , Black Sandra E. 
Published: May 2020

Physical activity (PA) participation provides functional and social benefits for persons with mild cognitive impairment (MCI) and Alzheimer’s disease (AD), but PA participation in these populations is low. To support health promotion initiatives for cognitively impaired older adults, this study explored the perceptions, experiences, and beliefs of older adults with cognitive impairment and their caregivers concerning PA. Ten care dyads (community-dwelling adult aged ≥65 years diagnosed with MCI or mild-to-moderate AD and their care partner) participated in semi-structured interviews informed by the Theoretical Domains Framework about their PA perceptions, experiences, and beliefs. Interpretive phenomenological analysis of interview transcripts yielded 4 emergent themes: (1) PA as a meaningful activity, (2) experience versus evidence as motivating, (3) participation is possible despite dementia, and (4) care partners as enablers. Findings from this study address a research gap concerning the PA perceptions, experiences, and beliefs of cognitively impaired older adults and their care partners. Novelty Older adults with MCI/AD want to and are capable of engaging in PA. Care partners are critical supporters of PA participation in MCI/AD. Adapted health promotion strategies could enhance PA in MCI/AD.
Benchmarking of water consumption and waste management in multi-unit residential buildings (MURBs) in Toronto
Authors: Ghajarkhosravi Mahssa , Huang Yirong , Fung Alan S. , Kumar Rakesh , Straka Vera 
Published: May 2020

Water and solid waste benchmarking and developing meaningful performance indicators can help government and building owners to make effective decisions on improving their buildings’ efficiency and sustainability. For this study, information on 120 multi-unit residential buildings (MURBs) has been collected and analyzed. The study entails the following steps: performing water and solid waste benchmarking for the 120 MURBs, developing meaningful performance indicators; determining performance ranking; and estimating different levels of savings (water, solid waste, cost, and GHG emissions). The most appropriate performance indicator and the benchmarking range for water and solid waste are as follows: water consumption normalized by square metre, 1.06–4.19 m3/m2; solid waste benchmarking normalized by number of units, 1.58–17.4 yd3/unit. Also, the MURBs domestic hot water system efficiencies are found to be very low (with overall system efficiency in the range of 35% to 45%). A relatively strong correlation is found between annual natural gas consumption and annual water consumption.
Synthetic Lethality with Trifluridine/Tipiracil and Checkpoint Kinase 1 Inhibitor for Esophageal Squamous Cell Carcinoma
Authors: Ohashi Shinya , Kikuchi Osamu , Nakai Yukie , Ida Tomomi , Saito Tomoki , Kondo Yuki , Yamamoto Yoshihiro , Mitani Yosuke , Nguyen Vu Trang H. , Fukuyama Keita , Tsukihara Hiroshi , Suzuki Norihiko , Muto Manabu 
Published: May 2020

Abstract
Esophageal squamous cell carcinoma (ESCC) is a disease characterized by a high mutation rate of the TP53 gene, which plays pivotal roles in the DNA damage response (DDR) and is regulated by checkpoint kinase (CHK) 2. CHK1 is another key DDR-related protein, and its selective inhibition is suggested to be particularly sensitive to TP53-mutated cancers, because a loss of both pathways (CHK1 and/or CHK2–p53) is lethal due to the serious impairment of DDR. Such a therapeutic strategy is termed synthetic lethality. Here, we propose a novel therapeutic strategy based on synthetic lethality combining trifluridine/tipiracil and prexasertib (CHK1 inhibitor) as a treatment for ESCC. Trifluridine is a key component of the antitumor drug combination with trifluridine/tipiracil (an inhibitor of trifluridine degradation), also known as TAS-102. In this study, we demonstrate that trifluridine increases CHK1 phosphorylation in ESCC cells combined with a reduction of the S-phase ratio as well as the induction of ssDNA damage. Because CHK1 phosphorylation is considered to be induced as DDR for trifluridine-mediated DNA damage, we examined the effects of CHK1 inhibition on trifluridine treatment. Consequently, CHK1 inhibition by short hairpin RNA or treatment with the CHK1 inhibitor, prexasertib, markedly enhanced trifluridine-mediated DNA damage, represented by an increase of γH2AX expression. Moreover, the combination of trifluridine/tipiracil and CHK1 inhibition significantly suppressed tumor growth of ESCC-derived xenograft tumors. Furthermore, the combination of trifluridine and prexasertib enhanced radiosensitivity both in vitro and in vivo. Thus, the combination of trifluridine/tipiracil and a CHK1 inhibitor exhibits effective antitumor effects, suggesting a novel therapeutic strategy for ESCC.
A Novel Peptidylarginine Deiminase 4 (PAD4) Inhibitor BMS-P5 Blocks Formation of Neutrophil Extracellular Traps and Delays Progression of Multiple Myeloma
Authors: Li Marina , Lin Cindy , Deng Hui , Strnad Joann , Bernabei Luca , Vogl Dan T. , Burke James J. , Nefedova Yulia 
Published: May 2020

Abstract
Multiple myeloma is a plasma cell malignancy, which grows in the bone marrow (BM). The major population of cells in the BM is represented by neutrophils and they can form neutrophil extracellular traps (NET). Here, we investigated whether multiple myeloma cells induce NET formation and whether targeting this process would delay multiple myeloma progression. We demonstrated that murine and human multiple myeloma cells stimulate citrullination of histone H3 and NET formation by neutrophils and that this process is abrogated by pharmacological targeting of peptidylarginine deiminase 4 (PAD4) with a novel-specific small molecule inhibitor BMS-P5. Administration of BMS-P5 to multiple myeloma-bearing mice delays appearance of symptoms and disease progression. Taken together, our data demonstrate that targeting PAD4 may be beneficial for treatment of multiple myeloma.