bluuebunny/crossref_metadata_2025 huggingface dataset:
Republished: Real-time MRI guidance for intra-arterial drug delivery in a patient with a brain tumor: technical note
Authors: Zawadzki Michal , Walecki Jerzy , Kostkiewicz Boguslaw , Kostyra Kacper , Pearl Monica Smith , Solaiyappan Meiyappan , Walczak Piotr , Janowski Miroslaw
Published: May 2019

Patients suffering from malignant brain tumors are burdened with a grim prognosis. The blood brain barrier is considered a primary obstacle in therapeutic drug delivery to the brain. Intra-arterial (IA) delivery of therapeutic agents following osmotic BBB opening has been attempted for years, but high variability has limited its widespread implementation. It has been recently shown in animal studies that MRI is superior to X-ray for guiding IA infusions, as it allows direct visualization of the brain parenchyma perfused and facilitates predictable drug targeting. Moreover, PET imaging has revealed that IA, not intravenous, delivery of bevacizumab results in brain accumulation, providing strong rationale for utilizing the IA route. Here, we present our experience in a patient with recurrent butterfly glioblastoma enrolled in first-in-man MRI-guided neurointervention for targeted IA drug delivery.
Occupational exposure to organic particles and combustion products during pregnancy and birth outcome in a nationwide cohort study in Sweden
Authors: Norlén Filip , Gustavsson Per , Wiebert Pernilla , Rylander Lars , Westgren Magnus , Plato Nils , Albin Maria , Selander Jenny
Published: May 2019

Objective

To study if children of women exposed to organic particles and combustion products at work during pregnancy, have an increased risk of low birth weight, preterm birth or small for gestational age.

Methods

A nationwide cohort of all occupationally active mothers and their children from single births during 1994 to the end of 2012 (1 182 138 observations) was formed. Information on birth outcome was obtained from the medical birth register. Information on absence from work, education, occupation, age, nationality and smoking habits was obtained from national registers. A job exposure matrix (FINJEM) was used to assess the exposure.

Results

Pregnant women with low absence from work and high (>50th percentile) exposure to organic particles had an increased risk of giving birth to children with low birth weight (OR=1.19; 95% CI: 1.07 to 1.32), small for gestational age (OR=1.22; 95% CI: 1.07 to 1.38) or preterm birth (OR=1.17; 95% CI: 1.08 to 1.27). Subgroup analyses showed an increased risk of small for gestational age in association with exposure to oil mist. Exposure to oil mist and cooking fumes was associated with low birth weight. Paper and other organic dust was associated with preterm birth. Exposure to combustion products showed an increased risk of small for gestational age (OR=1.40; 95% CI: 1.15 to 1.71).

Conclusions

The results indicate that occupational exposure to organic particles or combustion products during pregnancy is associated with restriction of fetal growth and preterm birth. More studies are needed to confirm a casual association.
Pleistocene mammals from Extinction Cave, Belize
Authors: Churcher C.S.
Published: May 2019

A small mammalian fauna is recorded from Extinction Cave (also called Sibun Cave), east of Belmopan, on the Sibun River, Belize, Central America. The animals recognized are armadillo (†Dasypus bellus), American lion (†Panthera atrox), jaguar (Panthera onca), puma or mountain lion (Puma concolor), Florida spectacled bear (†Tremarctos floridanus), javelina or collared peccary (Pecari tajacu), llama (Camelidae indet., †?Palaeolama mirifica), red brocket deer (Mazama americana), bison (Bison sp.) and Mexican half-ass (†Equus conversidens); sabre-toothed cat (†Smilodon fatalis) may also be represented. “†” indicates an extinct taxon. Bear and bison are absent from the region today. The bison record is one of the more southerly known. The bear record is almost the most westerly known and a first for Central America.
Structural, dielectric, ferroelectric and impedance spectroscopic studies on Ba1−xSrxTiO3(0.15 ≤ x ≤ 0.35)
Authors: Pandey Shukdev , Parkash Om , Kumar Devendra
Published: May 2019

Compositions with x = 0.15, 0.20, 0.25, 0.30 and 0.35 were synthesized in the system [Formula: see text] using conventional solid state reaction method and characterized by X-Ray Diffraction (XRD), Raman spectroscopy and Scanning Electron Microscopy (SEM). Tetragonal phase was confirmed in all the samples using Rietveld refinement of the XRD patterns and observation of their Raman spectra. Dielectric and impedance measurements were carried out in the temperature range 300–723 K in the frequency range 1 Hz to 1 MHz. The samples exhibit diffuse phase transition (DPT). Equivalent circuit model involving combination of Constant Phase angle Elements (CPE) and resistances (R) was developed which represents the data well. Expressions for the values of resistances (R) were established in terms of composition and temperature empirically. P-E loops indicated normal ferroelectric behavior for all the samples. Dielectric constant was also measured in the frequency range 8–12 GHz in the X band of microwaves.
New complex hyperbolic and trigonometric solutions for the generalized conformable fractional Gardner equation
Authors: Rezazadeh Hadi , Kumar Dipankar , Sulaiman Tukur Abdulkadir , Bulut Hasan
Published: May 2019

This study focuses on acquiring new complex hyperbolic and trigonometric function solutions to the generalized conformable fractional Gardner equation by using two distinct integration schemes, namely: the modified Kudryashov method and the hyperbolic function method with the help of symbolic computation package. We generate new closed-form solitary wave solutions to the governing model. Implemented schemes are pragmatically effective for solving various types of nonlinear partial differential equations with integer or fractional order arising in various fields of applied sciences.
Do we come from a quantum anomaly?
Authors: Basilakos Spyros , Mavromatos Nick E. , Solà Peracaula Joan
Published: May 2019

We present a string-based picture of the cosmological evolution in which (CP-violating) gravitational anomalies acting during the inflationary phase of the universe cause the vacuum energy density to “run” with the effective Hubble parameter squared, [Formula: see text], thanks to the axion field of the bosonic string multiplet. This leads to baryogenesis through leptogenesis with massive right-handed neutrinos. The generation of chiral matter after inflation helps in cancelling the anomalies in the observable radiation- and matter-dominated eras. The present era inherits the same “running vacuum” structure triggered during the inflationary time by the axion field. The current dark energy is thus predicted to be mildly dynamical, and dark matter should be made of axions. Paraphrasing Carl Sagan [ https://www.goodreads.com/author/quotes/10538.Carl_Sagan .]: we are all anomalously made from starstuff.
Hyperonic stars within the Bogoliubov quark meson model for nuclear matter
Authors: Panda Prafulla K. , Providência Constança , Moszkowski Steven A. , Bohr Henrik , da Providência João
Published: May 2019

We generalize the Bogoliubov quark-meson coupling (QMC) model to also include hyperons. The hyperon-[Formula: see text]-meson couplings are fixed by the model and the hyperon-[Formula: see text]-meson couplings are fitted to the hyperon potentials in symmetric nuclear matter. The present model predicts neutron stars with masses above 2[Formula: see text] and the radius of a 1.4[Formula: see text] star [Formula: see text]14[Formula: see text]km. In the most massive stars, bags overlap at the core of the star, and this may be interpreted as a transition to deconfined quark matter.
Geographical Information Science (GIS), spatial sampling and sediment variability examined using a case of manslaughter
Authors: McKinley Jennifer , Ruffell Alastair
Published: May 2019

The body of a missing person was found adjacent to a 3 km long sand-covered forest track in an upland area of Northern Ireland (UK). Geological trace evidence in the form of sand was found in the passenger footwell and on the foot pedals of a vehicle belonging to the last known associates of the deceased. A Geographical Information Science (GIS) methodology was used to integrate regional geological and soil databases to confirm the provenance of the sand and to find geographical locations for control (or alibi) samples. To complement the forensic examination in the case, 77 samples were taken at the scene in order to test whether such a collection assists knowledge of the scene, or whether fewer, targeted samples at access points to the body would have sufficed. The results demonstrate the potential applications of a GIS approach and show the usefulness of employing a spatial sampling scheme to understand the degree of local variability between samples. The findings from this study demonstrated that fewer samples would have been sufficient to associate the questioned items with the scene, yet would not have demonstrated how other areas of the track could be progressively excluded from comparison.
Role of Discourse Information in Urdu Sentiment Classification
Authors: Awais Dr. Muhammad , Shoaib Dr. Muhammad
Published: May 2019

In computational linguistics, sentiment analysis refers to the classification of opinions in a positive class or a negative class. There exist a lot of different methods for sentiment analysis of the English language, but the literature lacks the availability of methods and techniques for Urdu, which is the largely spoken language in the South Asian sub-continent and the national language of Pakistan. The currently available techniques, such as adjective count method known as Bag of Words (BoW), is not sufficient for classification of complex sentiment written in the Urdu language. Also, the performance of available machine-learning techniques (with legacy features), for classification of Urdu sentiments, are not comparable with the achieved accuracy of other languages. In the case of the English language, the discourse information (sub-sentence-level information) boosts the performance of both the BoW method and machine-learning techniques, but there are very few works available that have tested the context-level information for the sentiment analysis of the Urdu language. This research aims to extract the discourse information from the Urdu sentiments and utilise the discourse information to improve the performance and reduce the error rate of existing techniques for Urdu Sentiment classification. The proposed solution extracts the discourse information, suggests a new set of features for machine-learning techniques, and introduces a set of rules to extend the capabilities of the BoW model. The results show that the task has been enhanced significantly and the performance metrics such as recall, precision, and accuracy are increased by 31.25%, 8.46%, and 21.6%, respectively. In future, the proposed technique can be extended to sentiments with more than two sub-opinions, such as for blogs, reviews, and TV talk shows.
Incorporating Computing Professionals’ Know-how
Authors: Sánchez Ana , Domínguez César , Blanco Jose Miguel , Jaime Arturo
Published: May 2019

It is important for both computer science academics and students to clearly comprehend the differences between academic and professional perspectives in terms of assessing a deliverable. It is especially interesting to determine whether the aspects deemed important to evaluate by a computer science expert are the same as those established by academics and students. Such potential discrepancies are indicative of the unexpected challenges students may encounter once they graduate and begin working. In this article, we propose a learning activity in which computer science students made a video about their future profession after hearing an expert in the field who discussed about the characteristics and difficulties of his or her work. Academics, professional experts, and students assessed the videos by means of a questionnaire. This article reports a quantitative study of the results of this experience, which was conducted for three academic years. The study involved 63 students, 6 academics, and 4 computing professionals with extensive experience, and 14 videos were evaluated. Professional experts proved to be the most demanding in the assessment, followed by academics. The least demanding group was the students. These differences are more salient if more substantial issues are examined. The experts focused more on aspects of content, whereas the student preferred to concentrate on format. The academics’ focus falls between these two extremes. Understanding how experts value knowledge can guide educators in their search for effective learning environments in computing education.
Source-code Similarity Detection and Detection Tools Used in Academia
Authors: Novak Matija , Joy Mike , Kermek Dragutin
Published: May 2019

Teachers deal with plagiarism on a regular basis, so they try to prevent and detect plagiarism, a task that is complicated by the large size of some classes. Students who cheat often try to hide their plagiarism (obfuscate), and many different similarity detection engines (often called plagiarism detection tools) have been built to help teachers. This article focuses only on plagiarism detection and presents a detailed systematic review of the field of source-code plagiarism detection in academia. This review gives an overview of definitions of plagiarism, plagiarism detection tools, comparison metrics, obfuscation methods, datasets used for comparison, and algorithm types. Perspectives on the meaning of source-code plagiarism detection in academia are presented, together with categorisations of the available detection tools and analyses of their effectiveness. While writing the review, some interesting insights have been found about metrics and datasets for quantitative tool comparison and categorisation of detection algorithms. Also, existing obfuscation methods classifications have been expanded together with a new definition of “source-code plagiarism detection in academia.”
The April 2019 issue
Authors: Bonaventure Olivier
Published: May 2019

Brief description of the contents of the April 2019 issue of CCR.
Workshop on Internet Economics (WIE2018) Final Report
Authors: claffy kc , Clark David
Published: May 2019

On 12-13 December 2018, CAIDA hosted the 9th interdisciplinary Workshop on Internet Economics (WIE) at the UC San Diego’s Supercomputer Center. This workshop series provides a forum for researchers, Internet facilities and service providers, technologists, economists, theorists, policy makers, and other stakeholders to exchange views on current and emerging regulatory and policy debates. To add clarity to a range of vigorous policy debates, and in pursuit of actionable objectives, this year’s meeting used a different approach to structuring the agenda. Each attendee chose a specific policy goal or harm, and structured their presentation to answer three questions: (1) What data is needed to measure progress toward/away from this goal/harm? (2) What methods do you propose to gather such data? (3) Who are the right entities to gather such data, and how should such data be managed and shared? With a specific focus on measurement challenges, the topics we discussed included: analyzing the evolution of the Internet in a layered-platform context to gain new insights; measurement and analysis of economic impacts of new technologies using old tools; security and trustworthiness, reach (universal service) and reachability, sustainability of investment into Internet infrastructure, as well as infrastructure to measure the Internet. All slides made available at https://www.caida.org/workshops/wie/1812/.
Vibration‐Based Damage Assessment in Gravity‐Based Wind Turbine Tower under Various Waves
Authors: Nguyen Cong-Uy , Lee So-Young , Kim Heon-Tae , Kim Jeong-Tae
Published: May 2019

In this study, the feasibility of vibration‐based damage assessment in a wind turbine tower (WTT) with gravity‐based foundation (GBF) under various waves is numerically investigated. Firstly, a finite element model is constructed for the GBF WTT which consists of a tower, caisson, and foundation bed. Eigenvalue analysis is performed to identify a few vibration modes of interest, which represent complex behaviors of a flexible tower, rigid caisson, and deformable foundation. Secondly, wave‐induced dynamic pressures are analyzed for a few selected wave conditions and damage scenarios are also designed to simulate the main components of the target GBF WTT. Thirdly, forced vibration responses of the GBF WTT are analyzed for the wave‐induced excitation. Then modal parameters (i.e., natural frequencies and mode shapes) are extracted by using a combined use of time‐domain and frequency‐domain modal identification methods. Finally, the variation of modal parameters is estimated by measuring relative changes in natural frequencies and mode shapes in order to quantify the damage‐induced effects. Also, the wave‐induced variation of modal parameters is estimated to relatively assess the effect of various wave actions on the damage‐induced variation of modal parameters.
Insights on the Multifunctional Activities of Magnolol
Authors: Zhang Jianhong , Chen Zhixi , Huang Xianhua , Shi Weimei , Zhang Rui , Chen Meiling , Huang Hao , Wu Longhuo
Published: May 2019

Over years, various biological constituents are isolated from Traditional Chinese Medicine and confirmed to show multifunctional activities. Magnolol, a hydroxylated biphenyl natural compound isolated fromMagnolia officinalis, has been extensively documented and shows a range of biological activities. Many signaling pathways include, but are not limited to, NF-κB/MAPK, Nrf2/HO-1, and PI3K/Akt pathways, which are implicated in the biological functions mediated by magnolol. Thus, magnolol is considered as a promising therapeutic agent for clinic research. However, the low water solubility, the low bioavailability, and the rapid metabolism of magnolol dramatically limit its clinical application. In this review, we will comprehensively discuss the last five-year progress of the biological activities of magnolol, including anti-inflammatory, antimicroorganism, antioxidative, anticancer, neuroprotective, cardiovascular protection, metabolism regulation, and ion-mediating activity.
Low-Cost and Secure Communication System for SCADA System of Remote Microgrids
Authors: Iqbal Amjad , Iqbal M. Tariq
Published: May 2019

Renewable energy-based local microgrids are gaining popularity despite the unavailability of low-cost, power efficient, and secure communication system for its supervisory control and data acquisition (SCADA) system. This research has been carried out to address this issue along with the additional features such as data uploading to a server through a gateway, local data logging, and alerting the concerned crew in case of any fault to minimize the outage time. This paper presents the design of a communication system for the SCADA system of microgrid. ESP32 with LoRa has been used for communication between two nodes or a node and central SCADA unit. Communication security has been achieved by implementing AES cryptography. Data authenticity has been achieved by introducing a unique message authentication code (MAC) for each message. A mesh-like network has been implemented to improve the LoRa range. ESP32 and dragino-uno based LoRa gateways have been tried for uploading the data to the server, and local data storage has been achieved using an SD card. The main controller working as the SCADA unit has the feature of sending emails. Detailed system design and test results are presented in this paper.
Similarity Solution and Heat Transfer Characteristics for a Class of Nonlinear Convection‐Diffusion Equation with Initial Value Conditions
Authors: Xu Yunbin
Published: May 2019

A class of nonlinear convection‐diffusion equation is studied in this paper. The partial differential equation is converted into nonlinear ordinary differential equation by introducing a similarity transformation. The asymptotic analytical solutions are obtained by using double‐parameter transformation perturbation expansion method (DPTPEM). The influences of convection functional coefficient k(z) and power law index n on the heat transport characteristics are discussed and shown graphically. The comparison with the numerical results is presented and it is found to be in excellent agreement. The method and technique used in this paper have the significance in studying other engineering problems.
A Mathematical Model for Variable Chlorine Decay Rates in Water Distribution Systems
Authors: Tiruneh Ababu T. , Debessai Tesfamariam Y. , Bwembya Gabriel C. , Nkambule Stanley J.
Published: May 2019

A model for relating the time-dependent variable rate of reaction to the decay of chlorine residual in water is developed based on the initial chlorine dose, molar concentrations of reactants, and the rate constant itself. The mathematical model, while retaining its second order nature, simplifies the solution as the residual chlorine and aggregate parameters such as molar concentration of reactants can be estimated. The model is based on molar-averaged reaction rates involving arithmetic and harmonic means of reactants that eliminate the individual reaction rates that are difficult to determine. Part of the mathematical assumption used in the derivation of the equations using molar averaging is tested for its validity through theoretical as well as Monte Carlo simulation of the error term over wide ranges of assumed reaction rates and molar concentration of reactants. The second-order variation of the rate of reaction with respect to the initial chlorine concentration has been verified through experimental tests of bulk chlorine decay carried out at different chlorine doses.
Recycling of Oily Sludge as a Roadbed Material Utilizing Phosphogypsum‐Based Cementitious Materials
Authors: Xiao Wei , Yao Xiao , Zhang Fuyang
Published: May 2019

Oily sludge is a hazardous waste containing emulsified petroleum hydrocarbons, water, heavy metals, and solid particles. The objective of this work is to employ solidification/stabilization (S/S) techniques to utilize oily sludge as a roadbed material with ordinary Portland cement (OPC), fly ash (FA), and silica fume (SF) as binders and phosphogypsum (PG) as a stabilizer. The efficacy of the S/S process is assessed mainly through an unconfined compressive strength (UCS) test and a toxicity leaching test. Road performance, including water stability, freeze‐thaw resistance, and volume stability, is also tested on the solidified samples. The mineralogical compositions, microstructures, and pore structure are characterized through X‐ray diffractometry (XRD), scanning electron microscopy (SEM), and mercury intrusion porosimetry (MIP). The results show that the addition of 20% binders (OPC : FA : SF = 1 : 0.7 : 0.8) in combination with phosphogypsum to the oily sludge not only increases the 28‐day compressive strength of the solidified samples and remarkably decreases the release of heavy metals but also refines the pore structure and compacts the microstructure. The solidified body had sufficient strength and good water stability performance, freeze‐thaw resistance, and volumetric stability. This solidification/stabilization (S/S) process, which combines oily sludge treatment and phosphogypsum resource utilization, significantly enhances environmental protection and renders the solidified product economically profitable.
A Perspective Review on the Role of Nanomedicine in the Modulation of TNF-TNFR2 Axis in Breast Cancer Immunotherapy
Authors: Al-Hatamleh Mohammad A. I. , Ahmad Suhana , Boer Jennifer C. , Lim JitKang , Chen Xin , Plebanski Magdalena , Mohamud Rohimah
Published: May 2019

In the past decade, nanomedicine research has provided us with highly useful agents (nanoparticles) delivering therapeutic drugs to target cancer cells. The present review highlights nanomedicine applications for breast cancer immunotherapy. Recent studies have suggested that tumour necrosis factor (TNF) and its receptor 2 (TNFR2) expressed on breast cancer cells have important functional consequences. This cytokine/receptor interaction is also critical for promoting highly immune-suppressive phenotypes by regulatory T cells (Tregs). This review generally provides a background for nanoparticles as potential drug delivery agents for immunomodulators and further discusses in depth the potential of TNF antagonists delivery to modulate TNF-TNFR2 interactions and inhibit breast cancer progression.
Esophageal Cancer: Should Gender Be Considered as an Influential Factor for Patient Safety in Drug Treatment?
Authors: Liu Fengxia , Feng Helin , Guo Sumin , Chen Yuhan , Liu Qingyi , Wu Feng , Gu Weikuan , Shan Baoen
Published: May 2019

Aim. Analyze the gender difference of esophageal cancer patients in response to drug treatment. Methods. All publications on clinical trials were collected from PubMed, Scopus, and PMC. Each publication was examined to determine whether the publication is a clinical trial and whether data on gender difference were reported. Results. Selected from a total of 191 publications, data from 7 trials with a total of 2041 patients were evaluated for gender differences. These clinical trials involve different drugs and disease phenotype. A significant difference was obtained between male and female groups from Student’s t-test. There is no conclusive result on age, ethnicity, tumor size, and drug influence. Conclusions. Gender difference in response to treatment potentially most likely exists in esophageal cancer patients, regardless of age, race, and drugs.
Nonlinear Frequency Response Analysis as a Tool for Identification of Adsorption Kinetics: Case Study—Pore‐Surface Diffusion Control
Authors: Brzić Danica V. , Petkovska Menka T.
Published: May 2019

In the present paper, the Nonlinear Frequency Response (NFR) analysis is applied for theoretical study of kinetics of adsorption governed by pore‐surface diffusion. The concept of higher‐order frequency response functions (FRFs) is used. Based on a nonlinear mathematical model for adsorption of pure gas and spherical adsorbent particles, the theoretical first‐ and second‐order FRFs, which relate the adsorbate concentration in the particle to the surrounding pressure (F1(ω) and F2(ω,ω)), have been derived. The obtained FRFs have been simulated for different steady‐state pressures and different ratios (between zero and one) of surface to pore diffusion coefficients. The results show that, unlike F1(ω), F2(ω,ω) exhibits features which unambiguously distinguish the pore‐surface diffusion model from pure pore diffusion and micropore diffusion. Based on the characteristic features of F1(ω) and F2(ω,ω), a new methodology for direct estimation of the separate values of the pore and surface diffusion coefficients has been established.
Asporin Restricts Mesenchymal Stromal Cell Differentiation, Alters the Tumor Microenvironment, and Drives Metastatic Progression
Authors: Hughes Robert M. , Simons Brian W. , Khan Hamda , Miller Rebecca , Kugler Valentina , Torquato Samantha , Theodros Debebe , Haffner Michael C. , Lotan Tamara , Huang Jessie , Davicioni Elai , An Steven S. , Riddle Ryan C. , Thorek Daniel L.J. , Garraway Isla P. , Fertig Elana J. , Isaacs John T. , Brennen W. Nathaniel , Park Ben H. , Hurley Paula J.
Published: May 2019

Tumor progression to metastasis is not cancer cell autonomous, but rather involves the interplay of multiple cell types within the tumor microenvironment. Here we identify asporin (ASPN) as a novel, secreted mesenchymal stromal cell (MSC) factor in the tumor microenvironment that regulates metastatic development. MSCs expressed high levels of ASPN, which decreased following lineage differentiation. ASPN loss impaired MSC self-renewal and promoted terminal cell differentiation. Mechanistically, secreted ASPN bound to BMP-4 and restricted BMP-4–induced MSC differentiation prior to lineage commitment. ASPN expression was distinctly conserved between MSC and cancer-associated fibroblasts (CAF). ASPN expression in the tumor microenvironment broadly impacted multiple cell types. Prostate tumor allografts in ASPN-null mice had a reduced number of tumor-associated MSCs, fewer cancer stem cells, decreased tumor vasculature, and an increased percentage of infiltrating CD8+ T cells. ASPN-null mice also demonstrated a significant reduction in lung metastases compared with wild-type mice. These data establish a role for ASPN as a critical MSC factor that extensively affects the tumor microenvironment and induces metastatic progression.

Significance:

These findings show that asporin regulates key properties of mesenchymal stromal cells, including self-renewal and multipotency, and asporin expression by reactive stromal cells alters the tumor microenvironment and promotes metastatic progression.
Factors Associated with the Development of Immune Tolerance in Children with Cow’s Milk Allergy
Authors: Sánchez-Valverde Félix , Etayo Verónica , Gil Francisco , Aznal Elena , Martínez Diana , Amézqueta Ana , Mendizábal Mikel , Galbete Arkaitz , Pastor Nítida , Vanderhoof Jon
Published: May 2019

Introduction: Cow’s milk allergy (CMA) is a common diagnosis in infants, requiring the exclusion of cow’s milk until tolerance is recovered. In the present study, we aim to determine which factors are associated with the development of tolerance. Methods: Retrospective, observational study of subjects who underwent the same clinical follow-up methodology. We studied 245 cases of CMA (125 IgE-mediated and 120 non-IgE-mediated). The following variables were analysed: age at diagnosis, gender, type of delivery, type of feeding received, feeding during the first months of life, clinical features, and type of feed received as treatment: casein hydrolysates or casein hydrolysates with Lactobacillus rhamnosus GG (LGG). Results: Factors associated with earlier tolerance were non-IgE-mediated CMA (HR = 2.92; 95% CI: 2.20–3.88) and patients receiving casein hydrolysate with LGG (HR = 1.79; 95% CI: 1.33–2.42). Later tolerance was associated with caesarean delivery (HR = 0.78; 95% CI: 0.58–1.05) and breastfeeding for a period of at least 3 days (HR = 0.64; 95% CI: 0.44–0.93). The multivariate study shows that the type of formula (HR = 1.61; 95% CI: 1.19–2.18) and the type of CMA (HR = 2.82; 95% CI: 2.12–3.85) have an effect on the recovery time. Casein hydrolysates with LGG reduces the recovery time in IgE-mediated (HR = 1.88; 95% CI: 1.17–3.01) and non-IgE-mediated CMA (HR = 1.46; 95% CI: 0.98–2.17). Conclusions: Tolerance acquisition is faster in non-IgE-mediated CMA subjects and in those who received casein hydrolysate with LGG.
Neutrophils in Nail Clipping Histology: A Retrospective Review of 112 Cases
Authors: Neves José Miguel , Cunha Nélia , João Alexandre , Lencastre André
Published: May 2019

Background: Nail clipping histology is more sensitive than mycology for detecting nail fungi. However, in the absence of fungi, established diagnostic clues for this and other nail dystrophy causes are lacking, namely for nail psoriasis. Neutrophils have been reported in onychomycosis and nail psoriasis samples but have been insufficiently characterized. Objectives: The aim of this paper is to differentiate neutrophil-containing nail clipping samples in nail psoriasis and onychomycosis regarding histology. Methods: We performed a 3-year retrospective review of all nail clipping test results included in our department’s database and re-analyzed samples containing neutrophils. Results: In total,112 neutrophil-containing nail clipping samples were accounted. Onychomycosis was the commonest diagnosis (74.1%), followed by nail psoriasis (18.8%). Onychomycosis samples had more abundant neutrophils, more often arranged in collections (60.2%) (p = 0.002) and with smaller quantities of parakeratosis, in a lamellar distribution. In nail psoriasis, neutrophils were mostly aggregated (57.1%) with parakeratosis in all samples, in increased amounts, and showing no predominant pattern. Conclusions: Neutrophils are present in both nail psoriasis and onychomycosis, warranting careful interpretation. However, less dense aggregates of neutrophils with more abundant parakeratosis are clues of nail psoriasis when all other fungal tests are negative.
Uncommon Endoscopic Findings in a Tylosis Patient: A Case Report
Authors: Surapaneni Balarama K. , Kancharla Pragnan , Vinayek R. , Dutta Sudhir K. , Goldfinger Mendel
Published: May 2019

Palmoplantar tylosis is a focal non epidermolytic palmoplantar hyperkeratosis and is associated with a very high lifetime risk of developing squamous cell carcinoma of the esophagus (OSCC). It is generally inherited as an autosomal dominant trait with complete penetrance involving the RHBDF2 gene located on 17q25.1. The data regarding endoscopic appearance of the mucosa in patients with tylosis before development of cancer is limited. Surveillance endoscopy is recommended in family members which include annual esophagogastroscopy with biopsy of suspicious lesion with quadratic biopsies from upper, middle and lower esophagus. We describe characteristic endoscopy findings in a tylosis with no evidence of cancer. Prospective documentation of endoscopic findings of similar mucosal changes and disease process to establish a better screening protocol and supplemental intervention with agents like carotenoids (beta-carotene, alpha-carotene, lycopene, beta-cryptoxanthin, lutein, and zeaxanthin) may delay the progression and possibly revert to normal.
Angiography and En Face Optical Coherence Tomography Findings in Acute Syphilitic Posterior Placoid Chorioretinopathy
Authors: Moll-Udina Aina , Figueroa-Vercellino Juan P. , Llorenç Victor , Miguel Lucía , Adán Alfredo
Published: May 2019

Acute syphilitic posterior placoid chorioretinopathy (ASPPC) is one of the rarest ocular manifestations of syphilis. The pathophysiology of this entity is still unknown. We report the outer retinal findings on en face optical coherence tomography (OCT) and the alteration of choriocapillaris flow findings on OCT angiography in a patient with ASPPC at the time of presentation, after penicillin treatment completion and during follow-up.
The Incidence of Childhood Thyrotoxicosis Is Increasing in Both Girls and Boys in Sweden
Authors: Rodanaki Maria , Lodefalk Maria , Forssell Katharina , Arvidsson Carl-Göran , Forssberg Maria , Åman Jan
Published: May 2019

Background: We found an increase in the incidence rate (IR) of childhood thyrotoxicosis (CT) during the 1990s in central Sweden. The optimal treatment method for CT is a subject that is still debated upon. Objectives: To investigate whether the increase in IR of CT in Sweden persists and to study the treatment outcome. Method: Children <16 years of age diagnosed with CT during 2000–2009 and living in 1 of 5 counties in central Sweden were identified retrospectively using hospital registers. Data on clinical and biochemical characteristics and outcomes of treatment were collected from medical records. The corresponding data from 1990 to 1999 were pooled with the new data. Results: In total, 113 children were diagnosed with CT during 1990–2009 in the study area. The overall IR was 2.2/100,000 person-years (95% CI 1.2–2.5/100,000 person-years). The IR was significantly higher during 2000–2009 than during 1990–1999 (2.8/100,000 [2.2–3.6] vs. 1.6/100,000 person-years [1.2–2.2], p = 0.006). The increase was significant for both sexes. Seventy percent of the patients who completed the planned initial treatment with antithyroid drugs (ATDs) and were not lost to follow-up relapsed within 3 years. Boys tended to relapse earlier than girls (6.0 months after drug withdrawal [95% CI 1.9–10.0] vs. 12.0 months [95% CI 6.8–17.3], p = 0.074). Conclusions: The IR of CT is increasing in both girls and boys. Relapse rate after withdrawal of ATD treatment is 70%. Boys tend to relapse earlier than girls, and this needs to be further investigated.
No Wound for Stones <2 cm in Horseshoe Kidney: A Systematic Review of Comparative Studies
Authors: Chen Han , Chen Gang , Pan Yang , Zhu Yunxiao , Xiong Chaoyu , Chen Hualin , Yang Ziyi
Published: May 2019

Introduction: No wound to the patients is the pursuit of surgeons. Extracorporeal shock wave lithotripsy (SWL) and ureteroscopy (URS) are minimally invasive modalities for treating horseshoe kidney (HSK) stone <2 cm. We aimed to review the outcomes and complications of comparing SWL and URS in HSK stone. Methods: The literature was reviewed in the Embase, PubMed, and Cochrane Library up to March 1, 2018. Only 4 articles were available for analysis. Inclusion criteria were all English language articles reporting on the comparison between SWL and URS. Results: URS tends to be performed in a relatively heavier stone burden. The higher initial stone-free rate and success rate were demonstrated for URS than for SWL (p < 0.00001, p = 0.02, respectively). The less retreatment rate was found in URS than SWL (p = 0.04). There was no difference in minor complications in the 2 groups (p = 0.57). Renal colic episodes were more likely to be observed in the SWL group (p = 0.02). There were no major complications found in the review. Conclusion: For a stone <2 cm in HSK, both SWL and URS are safe treatment modalities. URS alone is a more feasible and sufficient option for stone in HSK <2 cm than SWL with possibilities of a second session.
Original Method to Repigment Achromic Laser Tattoo Removal Scars
Authors: Arbache Samir , Roth Dirlene , Arbache Samia Trigo , Hirata Sergio Henrique
Published: May 2019

Laser tattoo removal is expensive, painful, and time-consuming. Even with the use of the right laser equipment, it is often impossible to eliminate all pigments. Incomplete tattoo removal, one of the undesired effects of laser treatment, is widely disseminated in the media and accepted by most patients. However, few patients know that laser tattoo removal can cause permanent scars. Some patients who develop achromic scars can feel disappointed with the results of laser tattoo removal and take legal action against the physician responsible for the treatment. This paper describes our experience with a drug delivery treatment called MMP® (“Microinfusão de Medicamentos na Pele,” Portuguese acronym for “Microinfusion of Drugs in the Skin”) that repigments and improves the final esthetic results of achromic laser tattoo removal scars.
Nuclear Imaging
Authors: Hyafil Fabien , Vigne Jonathan
Published: May 2019

Noninvasive imaging technologies offer to identify several anatomic and molecular features of high-risk plaques. For the noninvasive molecular imaging of atherosclerotic plaques, nuclear medicine constitutes one of the best imaging modalities, thanks to its high sensitivity for the detection of probes in tissues. 18F-fluorodeoxyglucose (FDG) is currently the most widely used radiopharmaceutical for molecular imaging of atherosclerotic plaques with positron emission tomography. The intensity of FDG uptake in the vascular wall correlates closely with the degree of macrophage infiltration in atherosclerotic plaques. FDG positron emission tomographic imaging has become a powerful tool to identify and monitor noninvasively inflammatory activities in atherosclerotic plaques over time. This review examines how FDG positron emission tomographic imaging has given us deeper insight into the role of inflammation in atherosclerotic plaque progression and discusses perspectives for alternative radiopharmaceuticals to FDG that could provide a more specific and simple identification of high-risk lesions and help improve risk stratification of atherosclerotic patients.

Visual Overview—

An online visual overview is available for this article.
Anthracycline and Peripartum Cardiomyopathies
Authors: Cowgill Joshua A. , Francis Sanjeev A. , Sawyer Douglas B.
Published: May 2019

Anthracycline-associated cardiomyopathy and peripartum cardiomyopathy are nonischemic cardiomyopathies that often afflict previously healthy young patients; both diseases have been well described since at least the 1970s and both occur in the settings of predictable stressors (ie, cancer treatment and pregnancy). Despite this, the precise mechanisms and the ability to reliably predict who exactly will go on to develop cardiomyopathy and heart failure in the face of anthracycline exposure or childbirth have proven elusive. For both cardiomyopathies, recent advances in basic and molecular sciences have illuminated the complex balance between cardiomyocyte and endothelial homeostasis via 3 broad pathways: reactive oxidative stress, interference in apoptosis/growth/metabolism, and angiogenic imbalance. These advances have already shown potential for specific, disease-altering therapies, and as our mechanistic knowledge continues to evolve, further clinical successes are expected to follow.
Leveraging Signaling Pathways to Treat Heart Failure With Reduced Ejection Fraction
Authors: Pinilla-Vera Miguel , Hahn Virginia S. , Kass David A.
Published: May 2019

Advances in the treatment of heart failure with reduced ejection fraction due to systolic dysfunction are engaging an ever-expanding compendium of molecular signaling targets. Well established approaches modifying hemodynamics and cell biology by neurohumoral receptor blockade are evolving, exploring the role and impact of modulating intracellular signaling pathways with more direct myocardial effects. Even well-tread avenues are being reconsidered with new insights into the signaling engaged and thus opportunity to treat underlying myocardial disease. This review explores therapies that have proven successful, those that have not, those that are moving into the clinic but whose utility remains to be confirmed, and those that remain in the experimental realm. The emphasis is on signaling pathways that are tractable for therapeutic manipulation. Of the approaches yet to be tested in humans, we chose those with a well-established experimental history, where clinical translation may be around the corner. The breadth of opportunities bodes well for the next generation of heart failure therapeutics.
Excess Mortality Associated With Functional Tricuspid Regurgitation Complicating Heart Failure With Reduced Ejection Fraction
Authors: Benfari Giovanni , Antoine Clemence , Miller Wayne L. , Thapa Prabin , Topilsky Yan , Rossi Andrea , Michelena Hector I. , Pislaru Sorin , Enriquez-Sarano Maurice
Published: May 2019

Background:

Functional tricuspid regurgitation (FTR) is common in heart failure with reduced ejection fraction and mostly consequent to pulmonary hypertension. However, the intrinsic clinical implications of FTR are not fully understood.

Methods:

The cohort of all Mayo Clinic patients from 2003 to 2011 diagnosed with heart failure stage B-C and ejection fraction<50%, with FTR grading and systolic pulmonary artery pressure estimation by Doppler echocardiography was identified and outcomes were analyzed. Patients with pacemakers/defibrillators, organic valve disease, or previous valve surgery were excluded. The primary outcome measure was overall mortality (censored at implantation of a defibrillator, ventricular assist device, or cardiac transplantation), adjusting for clinical and echocardiographic associates with mortality and major comorbidities.

Results:

Among 13 026 patients meeting inclusion criteria, FTR was detected in 88% (N=11 507: 33% trivial, 32% mild, 17% moderate, and 6% severe), aged 68±14 years, 35% women, ejection fraction 36±10%, systolic pulmonary artery pressure 41±14 mm Hg with 20% atrial fibrillation. Covariates independently associated with FTR included elevated systolic pulmonary artery pressure, older age, female sex, lower ejection fraction, mitral regurgitation, and atrial fibrillation (all
P
<0.0001). FTR was independently associated with more dyspnea, impaired kidney function, and lower cardiac output (
P
<0.003 for all). For long-term outcome, higher FTR degree compared with trivial tricuspid regurgitation was independently associated with higher mortality (adjusted hazard ratios 1.09 [1.01-1.17] for mild FTR, 1.21 [1.11-1.33] for moderate FTR and 1.57 [1.39-1.78] for severe FTR); hence, 5-year survival was substantially lower with increasing severity of functional FTR, 68±1% for trivial FTR, 58±2% for mild FTR, 45±2% for moderate FTR, and 34±4% for severe FTR.

Conclusions:

In this large cohort of patients with heart failure with reduced ejection fraction, FTR was common and independently associated with pulmonary hypertension, atrial fibrillation, and more severe heart failure presentation. Long-term, higher FTR severity is associated with considerably worse survival, independently of baseline characteristics. Given these untoward outcomes associated with FTR in patients with heart failure with reduced ejection fraction, clinical trials should be directed at testing FTR treatment.
Effect of Depth and Width on Local Minima in Deep Learning
Authors: Kawaguchi Kenji , Huang Jiaoyang , Kaelbling Leslie Pack
Published: May 2019

In this paper, we analyze the effects of depth and width on the quality of local minima, without strong overparameterization and simplification assumptions in the literature. Without any simplification assumption, for deep nonlinear neural networks with the squared loss, we theoretically show that the quality of local minima tends to improve toward the global minimum value as depth and width increase. Furthermore, with a locally induced structure on deep nonlinear neural networks, the values of local minima of neural networks are theoretically proven to be no worse than the globally optimal values of corresponding classical machine learning models. We empirically support our theoretical observation with a synthetic data set, as well as MNIST, CIFAR-10, and SVHN data sets. When compared to previous studies with strong overparameterization assumptions, the results in this letter do not require overparameterization and instead show the gradual effects of overparameterization as consequences of general results.
Three new Fragilaria species (Bacillariophyta) from low-conductivity mountain freshwaters (Alps and Apennines)
Authors: CANTONATI MARCO , ANGELI NICOLA , LANGE-BERTALOT HORST
Published: May 2019

More or less needle-shaped species of Fragilaria s.s. are difficult to identify. Here we contribute to the taxonomy of this difficult group by describing three species new to science from very low conductivity mountain freshwater environments. Two of the new species resemble taxa established by Kützing in the early 19th century: F. rumpens and F. vaucheriae. Fragilaria spinaspeciosa sp. nov., from a seepage (helocrenic spring) in the northern Apennines, is superficially similar to F. rumpens, but has a lower stria density. Fragilaria tridentina sp. nov. is distinguished from F. gracilis by its smaller length-to-breadth ratio and more closely spaced areolae. Fragilaria vaucheriaeraetica sp. nov. is distinguished from F. vaucheriae and F. microvaucheriae by its outline and denser striae. These last three species also have distinctly different ecologies. Fragilaria vaucheriaeraetica sp. nov. is found in very low conductivity, very low nitrate, ultra-oligotrophic waters, while F. vaucheriae and F. microvaucheriae are found in medium conductivity, high total phosphorus, and relatively high nitrate streams. Accurate species identification and knowledge of each species’ ecological preferences are critically important if diatoms are to be used effectively as indicators of environmental impact and climate change. Weakly buffered, low alkalinity, low nutrient and low conductivity mountain freshwater habitats are sensitive to human disturbance and biotopes for many rare (Red List) diatoms. As such, they serve as valuable early warning systems for detecting the effects of climate change and other human activities.