bluuebunny/crossref_metadata_2025 huggingface dataset:
Low vitamin D status is associated with anaemia in hospitalised cats
Authors: Titmarsh Helen Faye , Woods Glynn Alan , Cartwright Jennifer A , Kilpatrick Scott , Gaylor Donna , Berry Jaqueline , Gow Adam , Bommer Nick X , Gunn‐Moore Danielle , Handel Ian , Mellanby Richard J
Published: February 2020

Background

The major physiological role of vitamin D has traditionally been considered to be the regulation of calcium homeostasis and maintenance of skeletal health. However, there is increasing evidence that vitamin D influences a wider range of physiological processes including erythropoiesis. Vitamin D (25‐hydroxyvitamin D, 25(OH)D) deficiency concentrations have been associated with anaemia in human beings. In contrast, the relationship between vitamin D status and erythropoiesis has not been investigated in cats.

Methods

Clinical records of cats consecutively presenting between November 2013 and February 2015 were reviewed. For each cat, data including sex, age, breed, serum albumin and creatinine concentrations, and appetite scores were extracted. A multivariable linear regression model was constructed to examine the relationship between 25(OH)D concentrations and these variables.

Results

Cats with anaemia had significantly lower 25(OH)D concentrations (median 49.5 nmol/l, n=31) than cats with packed cell volume above the lower limit of the reference range (median 109.0 nmol/l, n=130) (P<0.001). A binary logistic regression found that red blood cell count and mean corpuscular volume were negatively correlated with serum 25(OH)D concentrations (P<0.001 and P=0.007, respectively).

Conclusion

Vitamin D (25(OH)D) concentration is positively associated with red blood cell count and mean corpuscular volume in cats with a wide range of different illnesses.
Lepton collider indirect signatures of dark CP-violation
Authors: Cordero-Cid A. , Hernández-Sánchez J. , Keus V. , Moretti S. , Rojas D. , Sokołowska D.
Published: February 2020

We study an extension of the Standard Model (SM) in which two copies of the SM Higgs doublet are added to the scalar sector. These extra doublets do not develop a vacuum expectation value, hence, they areinert. This essentially leads to a 3-Higgs Doublet Model (3HDM) with 2 inert and 1 active scalar doublets, which we denote as I(2+1)HDM. We allow for CP-violation in theinertsector, where the lightestinertstate is protected from decaying to SM particles through the conservation of a$$Z_2$$Z2symmetry, so that it is a Dark Matter (DM) candidate. For this scenario, we identify a smoking gun signature of dark CP-violation in the form of production thresholds of pairs ofinertneutral Higgs bosons at an$$e^+e^-$$e+e-collider.
Study on electron state density and optical properties of IIIA main group element-doped ZnO
Authors: Yang Chao , Guo Juan , Yuan Xiaoming , Yang Ping
Published: February 2020

The electronic structures and optical properties of pure ZnO and IIIA group elements Al-, Ga- and In-doped wurtzite ZnO are studied by using first-principles plane density of states pseudopotential method based on the density functional theory. Considering the difference between doped and undoped situation, the band structure, total/partial wave density and dielectric function, refractive index, reflectivity, absorption spectrum and loss function are investigated. The results show that all the three doped elements transform the pure ZnO into [Formula: see text]-type direct band gap semiconductor materials, and the band gap becomes smaller and smaller with the enhancement of the gold property of the doped elements. In addition, it is found by comparison that Al doping has the highest conductivity. In the visible light region, Ga-doped ZnO has a good transmittance and is an ideal transparent conductive material. In-doped ZnO has higher absorption rate and emission rate, and has a great application prospect in ultraviolet protection. The results have a positive reference value for IIIA main group elements in ZnO doping design.
Functional Correlations in the Pursuit of Performance Assessment of Classifiers
Authors: Gribkova Nadezhda , Zitikis Ričardas
Published: February 2020

In statistical classification and machine learning, as well as in social and other sciences, a number of measures of association have been proposed for assessing and comparing individual classifiers, raters, as well as their groups. In this paper, we introduce, justify, and explore several new measures of association, which we call CO-, ANTI-, and COANTI-correlation coefficients, that we demonstrate to be powerful tools for classifying confusion matrices. We illustrate the performance of these new coefficients using a number of examples, from which we also conclude that the coefficients are new objects in the sense that they differ from those already in the literature.
Primitivity of the group of a cipher involving the action of the key-schedule
Authors: Calderini Marco
Published: February 2020

The algebraic structure of the group generated by the encryption functions of a block cipher depends on the key schedule algorithm used for generating the round keys. For such a reason, in general, studying this group does not appear to be an easy task. Previous works, focusing on the algebraic properties of groups associated to a cipher, have studied the group generated by the round functions of the cipher considering independent round keys.

In this paper, we want to study the more realistic group generated by the encryption functions, where the key schedule satisfies certain requirements. In this context, we are able to identify sufficient conditions that permit to guarantee the primitivity of this group and the security of the cipher with respect to the partition-based trapdoor. This type of trapdoor has been recently introduced by Bannier et al. in 2016 and it is a generalization of that introduced by Paterson in 1999.
Three-dimensional generalized thermoelasticity with variable thermal conductivity
Authors: Youssef Hamdy M. , Oreijah Mowffaq , Alsharif Hunaydi S.
Published: February 2020

In this paper, a three-dimensional model of the generalized thermoelasticity with one relaxation time and variable thermal conductivity is constructed. The resulting nondimensional governing equations, together with the Laplace and double Fourier transform techniques have been applied to a three-dimensional half-space subjected to thermal loading with rectangular pulse and traction free surface. The inverses of double Fourier transforms and Laplace transforms have been obtained numerically. Numerical results for the temperature increment, the invariant stress, the invariant strain, and the displacement are represented graphically. The variability of thermal conductivity has significant effects on all the studied fields.
Exotic properties of materials and the necessity to invoke the dimension of angle (𝜃) and the orbital degrees of freedom of s electrons
Authors: Iyakutti K. , Kawazoe Y. , Surya V. J. , Lakshmi I. , Rajeswarapalanichamy R.
Published: February 2020

Currently, many new materials including nanomaterials exhibit exotic properties like, mention a few, unconventional superconductivity, reduced magnetism, reduced Pauli repulsion. These exotic properties could not be explained completely with the existing quantum mechanical theories which did not take into account the dimension of angle. Now, there arises a necessity to invoke the forgotten dimension of angle, for explaining these exotic interesting properties. So far angle is considered as a dimensionless quantity even though its all time partner [Formula: see text] is endowed with dimension. In materials, where surface plays a dominant role, this new dimension, of angle becomes an important tool for exploring their morphology and exotic properties. This new dimension of angle restores the orbital degrees of freedom to the s electrons whose orbital degrees of freedom are suppressed ([Formula: see text]). It compensates for the missed signature of s electron orbital angular momentum.
Digital Government
Authors: Scholl Hans J.
Published: February 2020

Digital Government refers to the use of information technology to support government operations, engage citizens, and provide government services, as the Digital Government Society declares in its mission statement. While modern information technologies provide the necessary underpinnings expressed by the terms “digital” or the outdated “electronic,” for this public-sector phenomenon, technology in and by itself is not sufficient to capture the scope and various dimensions of Digital Government, which, unobserved at first, and later even disputed, continue to have increasingly transformational influences on the business of government in all its aspects, on all levels, and in all branches. In this disquisition, the evolution of Digital Government is portrayed and discussed from its humble beginnings to the intermediary present along with a projection and a preview of where this fascinating multidisciplinary domain of research and practice might lead in the next two decades. It is claimed that the transformation of the business of government is just beginning, and it is argued that major and undeniable instances of transition can be observed in the next decade.
Computing Optimal Repairs for Functional Dependencies
Authors: Livshits Ester , Kimelfeld Benny , Roy Sudeepa
Published: February 2020

We investigate the complexity of computing an optimal repair of an inconsistent database, in the case where integrity constraints are Functional Dependencies (FDs). We focus on two types of repairs: an optimal subset repair (optimal S-repair), which is obtained by a minimum number of tuple deletions, and an optimal update repair (optimal U-repair), which is obtained by a minimum number of value (cell) updates. For computing an optimal S-repair, we present a polynomial-time algorithm that succeeds on certain sets of FDs and fails on others. We prove the following about the algorithm. When it succeeds, it can also incorporate weighted tuples and duplicate tuples. When it fails, the problem is NP-hard and, in fact, APX-complete (hence, cannot be approximated better than some constant). Thus, we establish a dichotomy in the complexity of computing an optimal S-repair. We present general analysis techniques for the complexity of computing an optimal U-repair, some based on the dichotomy for S-repairs. We also draw a connection to a past dichotomy in the complexity of finding a “most probable database” that satisfies a set of FDs with a single attribute on the left-hand side; the case of general FDs was left open, and we show how our dichotomy provides the missing generalization and thereby settles the open problem.
Network Pharmacology Study on the Pharmacological Mechanism of Cinobufotalin Injection against Lung Cancer
Authors: Mao Yun , Peng Xi , Xue Peng , Lu Dianrong , Li Linlu , Zhu Shijie
Published: February 2020

Cinobufotalin injection, extracted from the skin of Chinese giant salamander or black sable, has good clinical effect against lung cancer. However, owing to its complex composition, the pharmacological mechanism of cinobufotalin injection has not been fully clarified. This study aimed to explore the mechanism of action of cinobufotalin injection against lung cancer using network pharmacology and bioinformatics. Compounds of cinobufotalin injection were determined by literature retrieval, and potential therapeutic targets of cinobufotalin injection were screened from Swiss Target Prediction and STITCH databases. Lung‐cancer‐related genes were summarized from GeneCards, OMIM, and DrugBank databases. The pharmacological mechanism of cinobufotalin injection against lung cancer was determined by enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes, and protein‐protein interaction network was constructed. We identified 23 compounds and 506 potential therapeutic targets of cinobufotalin injection, as well as 70 genes as potential therapeutic targets of cinobufotalin injection in lung cancer by molecular docking. The antilung cancer effect of cinobufotalin injection was shown to involve cell cycle, cell proliferation, antiangiogenesis effect, and immune inflammation pathways, such as PI3K‐Akt, VEGF, and the Toll‐like receptor signaling pathway. In network analysis, the hub targets of cinobufotalin injection against lung cancer were identified as VEGFA, EGFR, CCND1, CASP3, and AKT1. A network diagram of “drug‐compounds‐target‐pathway” was constructed through network pharmacology to elucidate the pharmacological mechanism of the antilung cancer effect of cinobufotalin injection, which is conducive to guiding clinical medication.
Practice and Associated Factors among Adult Residents towards Traditional Eye Medicine in Gondar City, North West Ethiopia
Authors: Munaw Minychil Bantihun , Assefa Natnael Lakachew , Anbesse Dereje Hayilu , Mulusew Tegegne Mebratu
Published: February 2020

Traditional medicines are commonly used in Africa. About 13.2–82.3% of the population use traditional eye medicine. The aim of this study was to assess practice and associated factors among adult residents towards traditional eye medicine in Gondar city, North West Ethiopia. Methods. A community-based cross-sectional study was conducted on 600 participants by using a pretested structured questionnaire. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 20 computer software. Association and strength between dependent and independent variables were determined using odds ratio with a 95% confidence interval. Results. A total of 600 respondents participated in the study with a 95 % response rate. From the total study participants, 73 (12.2%) (95% CI: 10–15%) had used traditional eye medicine in the past two years. Variables such as being unmarried (AOR = 0.48 (95% CI: 0.17–0.83)), being illiterate (AOR = 5.40 (95% CI: 5.3–12.3)), living in traditional healers available area (AOR = 2.84 (95% CI: 1.44–7.56)), poor access to modern eye care services (AOR = 2.11 (95% CI: 1.06–4.19)), and positive family history of traditional eye medicine use (AOR = 4.00 (95% CI: 1.84–8.67)) were significantly associated with traditional eye medicine practice. Conclusion. The proportion of traditional eye medicine practice was low in the past two years in Gondar city, Ethiopia, as compared to most African and Asian studies like south East Nigeria and Nepal, respectively. This may be due to the presence of tertiary eye care centers in the city that lets the residents prefer modern eye medicines over traditional eye medicines. Positive family history of traditional eye medicine use, being unmarried, being illiterate, poor access to modern eye care service, and availability of traditional healers had a significant association with the practice of traditional eye medicine. Community awareness about traditional eye medicine use is important to reduce the risk of complications even if the proportion is low.
Trimethylamine N-Oxide Generated by the Gut Microbiota Is Associated with Vascular Inflammation: New Insights into Atherosclerosis
Authors: Liu Yarong , Dai Min
Published: February 2020

Trimethylamine N-oxide (TMAO) is a biologically active molecule generated by the gut microbiota. Accumulating evidences have indicated a close association between high plasma TMAO levels and the risk of developing atherosclerosis (AS). AS is considered a chronic inflammatory disease initiated by vascular endothelial inflammatory injury. Both observational and experimental studies suggest that TMAO can cause endothelial inflammatory injury. However, a clear mechanistic link between TMAO and vascular inflammation of AS is not yet summarized. In this review, we discuss the association between TMAO and AS and focus on the potential role of TMAO in endothelial inflammatory injury. Finally, the utility of TMAO-targeted therapeutic strategies for the treatment of AS is also analyzed.
Preservative Effect of Novel Combined Treatment with Electrolyzed Active Water and Lysozyme Enzyme to Increase the Storage Life of Vacuum-Packaged Carp
Authors: Palotás Péter , Palotás Péter , Jónás Gábor , Lehel József , Friedrich László
Published: February 2020

In the present study, common carp (Cyprinus carpio), a highly valuable worldwide commercial fish species, was used as a model. One sample group of fresh, skin-on carp fillets was placed in a bath of acidic electrolyzed oxidizing (AEO) water containing a solution of 100 mg/kg chloride ion concentration for 5 minutes. Another sample group was treated with acidic electrolyzed water and 0.5% lysozyme enzyme solution. Another set of samples were washed after the AEO water treatment. Within the study, a storage test was performed to examine the effect of the new combined treatment on the samples’ shelf-life and quality while kept at 2°C. During the storage period, chemical (chlorate) and microbiological (TVC, mesophilic anaerobic plate count, and Enterobacteriaceae count) tests and sensory evaluation were conducted. The combination of AEO water and lysozyme enzyme showed additional bactericidal efficacy on the surface of the carp fillets, which has never been reported before. Both the AEO water and the combined treatment effectively increased the shelf life of the samples, causing 2.4–3.1 log CFU/g difference compared to the control by the end of the 7-day storage. The measured residual chlorate content exceeded the legal threshold, but washing the samples resulted in values below the theoretical threshold limit. The applied preservation methods did not have an adverse effect on the organoleptic properties of the samples.
Model of Driver’s Eye Movement and ECG Index under Tunnel Environment Based on Spatiotemporal Data
Authors: Qi Weiwei , Shen Bin , Wang Linhong
Published: February 2020

In order to improve the driver’s physiological and psychological state, the driver’s mental load which is caused by sight distance, lighting, and other factors in the tunnel environment should be quantified via modeling the spatiotemporal data. The experimental schemes have been scientifically designed based on methods of traffic engineering and human factor engineering, which aims to test the driver’s spatiotemporal data of eye movement and ECG (electrocardiogram) index in the tunnel environment. Firstly, the changes in the driver’s spatiotemporal data are analyzed to judge the changing trend of the driver’s workload in the tunnel environment. The results show that the cubic spline interpolation function model can fit the dynamic changes of average pupil diameter and heart rate (HR) growth rate well, and the goodness of fit for the model group is above 0.95. So, tunnel environment makes the driver’s typical physiological indicators fluctuate in the coordinates of time and space, which can be modeled and quantified. Secondly, in order to analyze the classification of tunnel risk level, a fusion model has been built based on the functions of average pupil diameter and HR growth rate. The tunnel environmental risk level has been divided into four levels via the fusion model, which can provide a guidance for the classification of tunnel risk level. Furthermore, the fusion model allows tunnel design and construction personnel to adopt different safety design measures for different risk levels, and this method can effectively improve the economy of tunnel operating safety design.
Nonlocal Conformable-Fractional Differential Equations with a Measure of Noncompactness in Banach Spaces
Authors: Bouaouid Mohamed , Hannabou Mohamed , Hilal Khalid
Published: February 2020

This paper deals with the existence of mild solutions for the following Cauchy problem: dαxt/dtα=Axt+ft,xt,x0=x0+gx,t∈0,τ, where dα./dtα is the so-called conformable fractional derivative. The linear part A is the infinitesimal generator of a uniformly continuous semigroup Ttt≥0 on a Banach space X, f and g are given functions. The main result is proved by using the Darbo–Sadovskii fixed point theorem without assuming the compactness of the family Ttt>0 and the Lipshitz condition on the nonlocal part g.
Enhancing Stock Price Trend Prediction via a Time-Sensitive Data Augmentation Method
Authors: Teng Xiao , Wang Tuo , Zhang Xiang , Lan Long , Luo Zhigang
Published: February 2020

Stock trend prediction refers to predicting future price trend of stocks for seeking profit maximum of stock investment. Although it has aroused broad attention in stock markets, it is still a tough task not only because the stock markets are complex and easily volatile but also because real short-term stock data is so limited that existing stock prediction models could be far from perfect, especially for deep neural networks. As a kind of time-series data, the underlying patterns of stock data are easily influenced by any tiny noises. Thus, how to augment limited stock price data is an open problem in stock trend prediction, since most data augmentation schemes adopted in image processing cannot be brutally used here. To this end, we devise a simple yet effective time-sensitive data augmentation method for stock trend prediction. To be specific, we augment data by corrupting high-frequency patterns of original stock price data as well as preserving low-frequency ones in the frame of wavelet transformation. The proposed method is motivated by the fact that low-frequency patterns without noisy corruptions do not hurt the true patterns of stock price data. Besides, a transformation technique is proposed to recognize the importance of the patterns at varied time points, that is, the information is time-sensitive. A series of experiments carried out on a real stock price dataset including 50 corporation stocks verify the efficacy of our data augmentation method.
Precancerous Gastric Lesions with Helicobacter pylori vacA+/babA2+/oipA+ Genotype Increase the Risk of Gastric Cancer
Authors: Bartpho Theeraya Simawaranon , Wattanawongdon Wareeporn , Tongtawee Taweesak , Paoin Chatchanok , Kangwantas Kokiet , Dechsukhum Chavaboon
Published: February 2020

Objective. The clinical outcomes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer have been attributed to the interplay of virulence factors of Helicobacter pylori (H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. Methods. Chronic gastritis, atrophic gastritis, and intestinal metaplasia specimens were obtained from patients who underwent endoscopy and surgical resection between January 2017 and December 2018; specimens from gastric cancer patients treated between January 2014 and December 2018 were also added. H. pylori infection and virulence genes (cagA, vacA, iceA2, babA2, and oipA) were determined using real‐time PCR. The association between H. pylori genotypes and clinical outcomes were evaluated using multivariate regression model analysis. The overall survival of gastric cancer patients was compared between genotype combinations. Results. H. pylori was positive in 166 patients with chronic gastritis, precancerous gastric lesions, and gastric cancer. The genes vacA, babA2, and oipA were most prevalent in chronic gastritis (73%), precancerous gastric lesions (62%), and gastric cancer (91%), respectively. The vacA, babA2, and oipA genes were associated with increased risk of gastric cancer (OR = 1.23; 95% CI = 1.13–3.32; P = 0.033, OR = 2.64; 95% CI = 1.44–4.82, P = 0.024, and OR = 2.79; 95% CI = 1.58–5.41; P = 0.031, respectively). Interestingly, H. pylori vacA+/babA2+/oipA+ genotype infection was associated with increased risk of gastric cancer (OR = 3.85, 95% CI = 1.67–5.77, P = 0.014). Conclusion. In this present study, we reported on the virulence genes of H. pylori infection to reveal their association with increased risk of chronic gastritis, precancerous gastric lesions, and gastric cancer. Precancerous gastric lesions with H. pylori vacA+/babA2+/oipA+ genotype increased the risk of gastric cancer.
Relationships of Stresses on Alveolar Bone and Abutment of Dental Implant from Various Bite Forces by Three‐Dimensional Finite Element Analysis
Authors: Kang Xiaoning , Li Yiming , Wang Yixi , Zhang Yao , Yu Dongsheng , Peng Yun
Published: February 2020

Occlusal trauma caused by improper bite forces owing to the lack of periodontal membrane may lead to bone resorption, which is still a problem for the success of dental implant. In our study, to avoid occlusal trauma, we put forward a hypothesis that a microelectromechanical system (MEMS) pressure sensor is settled on an implant abutment to track stress on the abutment and predict the stress on alveolar bone for controlling bite forces in real time. Loading forces of different magnitudes (0 N–100 N) and angles (0–90°) were applied to the crown of the dental implant of the left central incisor in a maxillary model. The stress distribution on the abutment and alveolar bone were analyzed using a three‐dimensional finite element analysis (3D FEA). Then, the quantitative relation between them was derived using Origin 2017 software. The results show that the relation between the loading forces and the stresses on the alveolar bone and abutment could be described as 3D surface equations associated with the sine function. The appropriate range of stress on the implant abutment is 1.5 MPa–8.66 MPa, and the acceptable loading force range on the dental implant of the left maxillary central incisor is approximately 6 N–86 N. These results could be used as a reference for the layout of MEMS pressure sensors to maintain alveolar bone dynamic remodeling balance.
Experimental Study on Performance Influencing Factors and Reasonable Mixture Ratio of Desert Sand Ceramsite Lightweight Aggregate Concrete
Authors: Zhang Songlin , Yuan Kang , Zhang Jiaming , Guo Junlin
Published: February 2020

The utilization of desert sand for making ceramsite lightweight aggregate concrete is proposed to make full use of local natural resources in the development of a new type of lightweight and load‐bearing wall material with good energy conservation, waste utilization, and thermal insulation performances. An orthogonal test was conducted to analyze the effects of the water‐binder ratio, sand ratio, desert sand substitution rate, and fly ash content on the slump, apparent density, and tube crushing strength of desert sand ceramsite lightweight aggregate concrete. Thus, the optimal mixture ratio of the desert sand ceramsite concrete was obtained for the LC20 and LC25 strength grades. Based on two reasonable mixture ratios, the physical and mechanical properties of the desert sand ceramsite concrete were investigated. The results revealed that the water‐binder ratio, sand ratio, and desert sand substitution rate were the main influencing factors, and the influence law is essentially consistent with that of ordinary desert sand concrete. Based on the reasonable substitution rate of desert sand, the main physical and mechanical properties of the desert sand ceramsite lightweight aggregate concrete, such as the tube crushing strength, tensile strength, and thermal conductivity, satisfied the requirements of the Chinese code’s specifications. In summary, desert sand can replace ordinary sand in ceramsite lightweight aggregate concrete for the production of new lightweight and load‐bearing wall materials.
Leveraging Digital Data to Inform and Improve Quality Cancer Care
Authors: Hernandez-Boussard Tina , Blayney Douglas W. , Brooks James D.
Published: February 2020

Background:

Efficient capture of routine clinical care and patient outcomes is needed at a population-level, as is evidence on important treatment-related side effects and their effect on well-being and clinical outcomes. The increasing availability of electronic health records (EHR) offers new opportunities to generate population-level patient-centered evidence on oncologic care that can better guide treatment decisions and patient-valued care.

Methods:

This study includes patients seeking care at an academic medical center, 2008 to 2018. Digital data sources are combined to address missingness, inaccuracy, and noise common to EHR data. Clinical concepts were identified and extracted from EHR unstructured data using natural language processing (NLP) and machine/deep learning techniques. All models are trained, tested, and validated on independent data samples using standard metrics.

Results:

We provide use cases for using EHR data to assess guideline adherence and quality measurements among patients with cancer. Pretreatment assessment was evaluated by guideline adherence and quality metrics for cancer staging metrics. Our studies in perioperative quality focused on medications administered and guideline adherence. Patient outcomes included treatment-related side effects and patient-reported outcomes.

Conclusions:

Advanced technologies applied to EHRs present opportunities to advance population-level quality assessment, to learn from routinely collected clinical data for personalized treatment guidelines, and to augment epidemiologic and population health studies. The effective use of digital data can inform patient-valued care, quality initiatives, and policy guidelines.

Impact:

A comprehensive set of health data analyzed with advanced technologies results in a unique resource that facilitates wide-ranging, innovative, and impactful research on prostate cancer. This work demonstrates new ways to use the EHRs and technology to advance epidemiologic studies and benefit oncologic care.

See all articles in this CEBP Focus section, “Modernizing Population Science.”
Rituximab Twice Weekly for Refractory Thrombotic Thrombocytopenic Purpura in a Critically Ill Patient with Acute Respiratory Distress Syndrome
Authors: Azrieh Bahjat , Alsaud Arwa , Obeidat Khaldun , Ashour Amr , Elebbi Seham , Mohamed Shehab F. , Abdelaty Mohamed Adel , Akkari Abdelraouf , Elbuzidi Abdurrahman Ali , Yassin Mohamed A.
Published: February 2020

Thrombotic thrombocytopenic purpura (TTP) is a rare, serious, life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and hypercoagulability. The etiology is a deficiency of ADAMTS13 which is usually caused by acquired antibodies. Plasma exchange and steroids is the standard of care in the treatment of TTP. However, there are refractory cases of TTP which require further management. Rituximab appears to be a safe and effective therapy for refractory and relapsing TTP. Here we report a challenging case of TTP that responded to treatment with rituximab twice weekly. According to our knowledge, rituximab twice weekly has never been used for TTP before.
Treatment of Rectal Cancer-Induced Disseminated Carcinomatosis of the Bone Marrow with FOLFOX plus Cetuximab and Panitumumab
Authors: Ehara Takehito , Kitazawa Masato , Hondo Nao , Takahata Shugo , Yamamoto Yuta , Koyama Makoto , Okumura Motohiro , Nakamura Satoshi , Tokumaru Shigeo , Muranaka Futoshi , Miyagawa Yusuke , Soejima Yuji
Published: February 2020

Disseminated carcinomatosis of the bone marrow (DCBM) in colorectal cancer is an extremely rare complication with a poor prognosis. Here, we report a case of DCBM due to rectal cancer successfully treated with a combination of FOLFOX and an anti-epidermal growth factor receptor (EGFR) agent. The patient was a 38-year-old man diagnosed with rectal cancer with multiple bone and para-aortic lymph node metastases complicated by disseminated intravascular coagulation (DIC). He first recovered from DIC following cotreatment with FOLOX plus cetuximab; subsequently, the second attack was successfully treated with FOLFOX plus panitumumab. His initial condition was extremely poor, but he survived with two FOLFOX plus anti-EGFR regimens and died 333 days after introduction of chemotherapy.
Deep Learning–Based Quantification of Epicardial Adipose Tissue Volume and Attenuation Predicts Major Adverse Cardiovascular Events in Asymptomatic Subjects
Authors: Eisenberg Evann , McElhinney Priscilla A. , Commandeur Frederic , Chen Xi , Cadet Sebastien , Goeller Markus , Razipour Aryabod , Gransar Heidi , Cantu Stephanie , Miller Robert J.H. , Slomka Piotr J. , Wong Nathan D. , Rozanski Alan , Achenbach Stephan , Tamarappoo Balaji K. , Berman Daniel S. , Dey Damini
Published: February 2020

Background:

Epicardial adipose tissue (EAT) volume (cm
3
) and attenuation (Hounsfield units) may predict major adverse cardiovascular events (MACE). We aimed to evaluate the prognostic value of fully automated deep learning-based EAT volume and attenuation measurements quantified from noncontrast cardiac computed tomography.

Methods:

Our study included 2068 asymptomatic subjects (56±9 years, 59% male) from the EISNER trial (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) with long-term follow-up after coronary artery calcium measurement. EAT volume and mean attenuation were quantified using automated deep learning software from noncontrast cardiac computed tomography. MACE was defined as myocardial infarction, late (>180 days) revascularization, and cardiac death. EAT measures were compared to coronary artery calcium score and atherosclerotic cardiovascular disease risk score for MACE prediction.

Results:

At 14±3 years, 223 subjects suffered MACE. Increased EAT volume and decreased EAT attenuation were both independently associated with MACE. Atherosclerotic cardiovascular disease risk score, coronary artery calcium, and EAT volume were associated with increased risk of MACE (hazard ratio [95%CI]: 1.03 [1.01–1.04]; 1.25 [1.19–1.30]; and 1.35 [1.07–1.68],
P
<0.01 for all) and EAT attenuation was inversely associated with MACE (hazard ratio, 0.83 [95% CI, 0.72–0.96];
P
=0.01), with corresponding Harrell C statistic of 0.76. MACE risk progressively increased with EAT volume ≥113 cm
3
and coronary artery calcium ≥100 AU and was highest in subjects with both (
P
<0.02 for all). In 1317 subjects, EAT volume was correlated with inflammatory biomarkers C-reactive protein, myeloperoxidase, and adiponectin reduction; EAT attenuation was inversely related to these biomarkers.

Conclusions:

Fully automated EAT volume and attenuation quantification by deep learning from noncontrast cardiac computed tomography can provide prognostic value for the asymptomatic patient, without additional imaging or physician interaction.
Efficient 1-Hour Technetium-99 m Pyrophosphate Imaging Protocol for the Diagnosis of Transthyretin Cardiac Amyloidosis
Authors: Masri Ahmad , Bukhari Syed , Ahmad Shahzad , Nieves Ricardo , Eisele Yvonne S. , Follansbee William , Brownell Amy , Wong Timothy C. , Schelbert Erik , Soman Prem
Published: February 2020

Background:

Technetium-99 m pyrophosphate protocols for transthyretin cardiac amyloidosis diagnosis have variably used 1- and 3-hour imaging time points. We investigated whether imaging at 1 hour with superior efficiency had comparable diagnostic accuracy as 3-hour imaging.

Methods:

This is a registry analysis of patients with suspected transthyretin cardiac amyloidosis referred for technetium-99 m pyrophosphate at a single tertiary center from June 2015 through January 2019. Patients underwent planar and single-photon emission computed tomography (SPECT) imaging at 1 and 3 hours. A positive Tc-99m pyrophosphate study was defined by the presence of diffuse myocardial tracer uptake on SPECT. For planar imaging, visual semiquantitative (grades 0-3, ≥2 considered positive) and quantitative heart to contralateral ratios (≥1.5 considered positive) were used.

Results:

Two hundred thirty-three patients (69% men; median age, 77 [69–83] years) underwent the study protocol. There were 60 (25.8%) patients with diffuse myocardial uptake, 1 (0.4%) with regional uptake, and 172 (73.8%) with no myocardial uptake. Results of SPECT were identical at 1 and 3 hours. Planar imaging at 1 hour had 98% sensitivity and 96% specificity. Planar grade 0 uptake or heart to contralateral ratio ≤1.2 and planar grade 3 uptake or heart to contralateral ratio ≥2.0 were always associated with negative and positive SPECT, respectively. For planar grades 1 and 2 uptake and heart to contralateral ratio 1.3 to 1.9, SPECT was needed to make a diagnosis. No patient with light-chain cardiac amyloidosis had positive SPECT.

Conclusions:

An efficient 1-hour technetium-99 m pyrophosphate protocol had comparable diagnostic performance to a 3-hour protocol.
SUPPORT-AF II: Supporting Use of Anticoagulants Through Provider Profiling of Oral Anticoagulant Therapy for Atrial Fibrillation
Authors: Kapoor Alok , Amroze Azraa , Vakil Fatima , Crawford Sybil , Der Jacqueline , Mathew Jomol , Alper Eric , Yogaratnam Dinesh , Javed Saud , Elhag Rasha , Lin Abraham , Narayanan Siddhartha , Bartlett Donna , Nagy Ahmed , Shagoury Bevin Kathleen , Fischer Michael A. , Mazor Kathleen M. , Saczynski Jane S. , Ashburner Jeffrey M. , Lopes Renato , McManus David D.
Published: February 2020

Background:

Previous provider-directed electronic messaging interventions have not by themselves improved anticoagulation use in patients with atrial fibrillation. Direct engagement with providers using academic detailing coupled with electronic messaging may overcome the limitations of the prior interventions.

Methods and Results:

We randomized outpatient providers affiliated with our health system in a 2.5:1 ratio to our electronic profiling/messaging combined with academic detailing intervention. In the intervention, we emailed providers monthly reports of their anticoagulation percentage relative to peers for atrial fibrillation patients with elevated stroke risk (CHA
2
DS
2
-VASc ≥2). We also sent electronic medical record-based messages shortly before an appointment with an anticoagulation-eligible but untreated atrial fibrillation patient. Providers had the option to send responses with explanations for prescribing decisions. We also offered to meet with intervention providers using an academic detailing approach developed based on knowledge gaps discussed in provider focus groups. To assess feasibility, we tracked provider review of our messages. To assess effectiveness, we measured the change in anticoagulation for patients of intervention providers relative to controls. We identified 85 intervention and 34 control providers taking care of 3591 and 1908 patients, respectively; 33 intervention providers participated in academic detailing. More than 80% of intervention providers read our emails, and 98% of the time a provider reviewed our in-basket messages. Replies to messages identified patient refusal as the most common reason for patients not being on anticoagulation (11.2%). For the group of patients not on anticoagulation at baseline assigned to an intervention versus control provider, the adjusted percent increase in the use of anticoagulation over 6 months was 5.2% versus 7.4%, respectively (
P
=0.21).

Conclusions:

Our electronic messaging and academic detailing intervention was feasible but did not increase anticoagulation use. Patient-directed interventions or provider interventions targeting patients declining anticoagulation may be necessary to raise the rate of anticoagulation.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT03583008.
Sex Differences in Symptom Phenotypes Among Patients With Acute Myocardial Infarction
Authors: Brush John E. , Krumholz Harlan M. , Greene Erich J. , Dreyer Rachel P.
Published: February 2020

Background:

The diagnosis of acute myocardial infarction (AMI) is missed more frequently in young women than men, which may be related to the cognitive psychology of the diagnostic process. Physicians start the diagnostic process by intuitively recognizing familiar symptom phenotypes, but little is known about how symptoms combine in individuals as unique symptom phenotypes. We examined how symptoms of AMI combine as unique symptom phenotypes in individual patients to compare the distribution of symptom phenotypes in women versus men.

Methods and Results:

The VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) was a multicenter, observational cohort study of 3501 young adults hospitalized with AMI. Data were collected on presenting symptoms with standardized interviews and from medical record abstraction. The number and distribution of unique symptom phenotypes were compared between women and men. Because of the 2:1 female-to-male enrollment ratio, women and men were compared with permutation testing and repeated subsampling. There were 426 interview-symptom phenotypes in women and 280 in men. The observed difference between women and men of 146 phenotypes was significant, even allowing for the greater enrollment of women (permutation
P
=0.004, median difference 110 under the null hypothesis of no association between sex and phenotype). The repeated subsample analysis also showed significantly more interview-symptom phenotypes in women than men (206.8±7.3 versus 188.6±6.0,
P
<0.001). Women were more broadly distributed among symptom phenotype subgroups than men (
P
<0.001). Similar findings were observed in the analysis of symptoms abstracted from the medical record.

Conclusions:

Women exhibited substantially more variation in unique symptom phenotypes than men, regardless of whether the symptoms were derived from structured interviews or abstracted from the medical record. These findings may provide an explanation for the higher missed diagnosis rate in young women with AMI and may have important implications for teaching and improving clinicians’ ability to recognize the diagnosis of AMI in women.
Genomic Characterization of Endothelial Enhancers Reveals a Multifunctional Role for NR2F2 in Regulation of Arteriovenous Gene Expression
Authors: Sissaoui Samir , Yu Jun , Yan Aimin , Li Rui , Yukselen Onur , Kucukural Alper , Zhu Lihua Julie , Lawson Nathan D.
Published: February 2020

Rationale:

Significant progress has revealed transcriptional inputs that underlie regulation of artery and vein endothelial cell fates. However, little is known concerning genome-wide regulation of this process. Therefore, such studies are warranted to address this gap.

Objective:

To identify and characterize artery- and vein-specific endothelial enhancers in the human genome, thereby gaining insights into mechanisms by which blood vessel identity is regulated.

Methods and Results:

Using chromatin immunoprecipitation and deep sequencing for markers of active chromatin in human arterial and venous endothelial cells, we identified several thousand artery- and vein-specific regulatory elements. Computational analysis revealed that NR2F2 (nuclear receptor subfamily 2, group F, member 2) sites were overrepresented in vein-specific enhancers, suggesting a direct role in promoting vein identity. Subsequent integration of chromatin immunoprecipitation and deep sequencing data sets with RNA sequencing revealed that NR2F2 regulated 3 distinct aspects related to arteriovenous identity. First, consistent with previous genetic observations, NR2F2 directly activated enhancer elements flanking cell cycle genes to drive their expression. Second, NR2F2 was essential to directly activate vein-specific enhancers and their associated genes. Our genomic approach further revealed that NR2F2 acts with ERG (ETS-related gene) at many of these sites to drive vein-specific gene expression. Finally, NR2F2 directly repressed only a small number of artery enhancers in venous cells to prevent their activation, including a distal element upstream of the artery-specific transcription factor,
HEY2
(hes related family bHLH transcription factor with YRPW motif 2). In arterial endothelial cells, this enhancer was normally bound by ERG, which was also required for arterial
HEY2
expression. By contrast, in venous endothelial cells, NR2F2 was bound to this site, together with ERG, and prevented its activation.

Conclusions:

By leveraging a genome-wide approach, we revealed mechanistic insights into how NR2F2 functions in multiple roles to maintain venous identity. Importantly, characterization of its role at a crucial artery enhancer upstream of
HEY2
established a novel mechanism by which artery-specific expression can be achieved.
Cardiovascular Health Among Pregnant Women, Aged 20 to 44 Years, in the United States
Authors: Perak Amanda M. , Ning Hongyan , Khan Sadiya S. , Van Horn Linda V. , Grobman William A. , Lloyd‐Jones Donald M.
Published: February 2020

Background

Pregnancy is a cardiometabolic stressor and thus a critical period to address women's lifetime cardiovascular health (CVH). However, CVH among US pregnant women has not been characterized.

Methods and Results

We analyzed cross‐sectional data from National Health and Nutrition Examination Surveys 1999 to 2014 for 1117 pregnant and 8200 nonpregnant women, aged 20 to 44 years. We assessed 7 CVH metrics using American Heart Association definitions modified for pregnancy; categorized metrics as ideal, intermediate, or poor; assigned these categories 2, 1, or 0 points, respectively; and summed across the 7 metrics for a total score of 0 to 14 points. Total scores 12 to 14 indicated high CVH; 8 to 11, moderate CVH; and 0 to 7, low CVH. We applied survey weights to generate US population‐level estimates of CVH levels and compared pregnant and nonpregnant women using demographic‐adjusted polytomous logistic and linear regression. Among pregnant women, the prevalences (95% CIs) of ideal levels of CVH metrics were 0.1% (0%–0.3%) for diet, 27.3% (22.2%–32.3%) for physical activity, 38.9% (33.7%–44.0%) for total cholesterol, 51.1% (46.0%–56.2%) for body mass index, 77.7% (73.3%–82.2%) for smoking, 90.4% (87.5%–93.3%) for blood pressure, and 91.6% (88.3%–94.9%) for fasting glucose. The mean total CVH score was 8.3 (95% CI, 8.0–8.7) of 14, with high CVH in 4.6% (95% CI, 0.5%–8.8%), moderate CVH in 60.6% (95% CI, 52.3%–68.9%), and low CVH in 34.8% (95% CI, 26.4%–43.2%). CVH levels were significantly lower among pregnant versus nonpregnant women; for example, 13.0% (95% CI, 11.0%–15.0%) of nonpregnant women had high CVH (adjusted, comparison
P
=0.01).

Conclusions

From 1999 to 2014, <1 in 10 US pregnant women, aged 20 to 44 years, had high CVH.
Stereochilus arunachalensis, a new orchid species of Orchidaceae (Epidendroideae: Vandeae: Aeridinae) from Arunachal Pradesh, India

Authors: CHOWLU KRISHNA , RAO A. NAGESWARA
Published: February 2020

Stereochilus Lindley (1858: 38) is a small orchid genus of about seven species distributed from northeastern India to Vietnam (Govaerts et al. 2019). It is characterised by a long, erect footless column with firmly attached saccate lip, long subulate rostellum projection and long slender somewhat clavate stipes with a small viscidium carrying four equal, ovate pollinia with short caudicles, the sac inside with back wall callus, front wall callus and septum (Seidenfaden 1988).
Lycopodiaceae in Colombia: Subfamilies Lycopodioideae and Lycopodielloideae.
Authors: ØLLGAARD BENJAMIN
Published: February 2020

Following the treatment of the Colombian species belonging to the genus Phlegmariurus (Lycopodiaceae, subfamily Huperzioideae) by Øllgaard (2019), the present study deals with the remaining genera of the family, belonging to the subfamilies Lycopodioideae (Austrolycopodium, Diphasiastrum, Diphasium, and Lycopodium s.str.,) and Lycopodielloideae (Lycopodiella s.str., Palhinhaea, and Pseudolycopodiella).