bluuebunny/crossref_metadata_2025 huggingface dataset:
EPR reversible signature of self-trapped holes in fictive temperature-treated silica glass
Authors: Lancry Matthieu , Ollier Nadège , Babu B. H. , Herrero Christian , Poumellec Bertrand
Published: March 2018

Post-mortem electron paramagnetic resonance spectroscopy experiments have been carried out between room temperature and 20 K to examine the radiation-induced defects in fictive temperature (Tf) treated Heraeus F300 silica (0.1 ppm OH, 1500 ppm Cl2). In particular, we focus our attention on Self-Trapped Hole (STH) centers detected in 1000 °C, 1100 °C, and 1200 °C Tf treated samples irradiated at room temperature by gamma rays at 6 kGy. By repeating annealing cycles between 77 and 300 K on the same samples, we observed that the EPR signal attributed to STH decreases as the temperature increases but in a reversible manner. We evidenced a deviation from the Curie law for T > 70 K and suggested an interpretation based on the decrease in the “strain-assisted TH” population by reversible excitation of the trapped hole to a delocalized state with an activation energy of 7.8 meV. This also means that the precursors of hole trapping sites (a local strain atomic configuration) remain stable until 300 K at least.
Plane shock loading on mono- and nano-crystalline silicon carbide
Authors: Branicio Paulo S. , Zhang Jingyun , Rino José P. , Nakano Aiichiro , Kalia Rajiv K. , Vashishta Priya
Published: March 2018

The understanding of the nanoscale mechanisms of shock damage and failure in SiC is essential for its application in effective and damage tolerant coatings. We use molecular-dynamics simulations to investigate the shock properties of 3C-SiC along low-index crystallographic directions and in nanocrystalline samples with 5 nm and 10 nm grain sizes. The predicted Hugoniot in the particle velocity range of 0.1 km/s–6.0 km/s agrees well with experimental data. The shock response transitions from elastic to plastic, predominantly deformation twinning, to structural transformation to the rock-salt phase. The predicted strengths from 12.3 to 30.9 GPa, at the Hugoniot elastic limit, are in excellent agreement with experimental data.
A hybrid physics-based and machine learning approach tackles molecular modeling
Authors: Kim Meeri
Published: March 2018

A new study describes modeling of large molecular systems with an approach that combines classical physics-based potentials with machine learning methods.
Synthesis of Chiral Polyaniline Induced by Modified Hemoglobin
Authors: Chen Jian-bo , Kong Xiang-ling , Huang Liu
Published: March 2018

The synthesis of chiral polyaniline (PANI) induced by modified hemoglobin (Hb) was profoundly explored for the first time. Results revealed that after being separated, inactivated or immobilized, Hb can still induce the formation of chiral PANI successfully, suggesting that Hb can be used as the chiral inducers regardless of harsh reaction conditions. By examining the properties of PANI induced by modified Hb, it was found that Hb(inactivated)-PANI possessed excellent chirality, stability, and crystalline structure. The globin separated from Hb was demonstrated to have the ability of inducing the production of chiral PANI whereas the hematin from Hb had no capacity to direct enantio specificity for the PANI chains. Results indicated that Hb(immobilized)-PANI exhibited poor yield, doping state, and crystalline structure, indicating that the immobilization of Hb by entrapment was not beneficial to the polymerization reaction. Results also showed that the structure of Hb may have significant effects on the morphologies of chiral PANI.
Perception of formulaic and novel expressions under acoustic degradation
Authors: Rammell C. Sophia , Van Lancker Sidtis Diana , Pisoni David B.
Published: March 2018

Background: Formulaic expressions, including idioms and other fixed expressions, comprise a significant proportion of discourse. Although much has been written about this topic, controversy remains about their psychological status. An important claim about formulaic expressions, that they are known to native speakers, has seldom been directly demonstrated. This study tested the hypothesis that formulaic expressions are known and stored as whole unit mental representations by performing three perceptual experiments.

Method: Listeners transcribed two kinds of spectrally-degraded spoken sentences, half formulaic, and half novel, newly created expressions, matched for grammar and length. Two familiarity ratings, usage and exposure, were obtained from listeners for each expression. Text frequency data for the stimuli and their constituent words were obtained using a spoken corpus.

Results: Participants transcribed formulaic more successfully than literal utterances. Usage and familiarity ratings correlated with accuracy, but formulaic utterances with low ratings were also transcribed correctly. Phrase types differed significantly in text frequency, but word frequency counts did not differentiate the two kinds of expressions.

Discussion: These studies provide new converging evidence that formulaic expressions are encoded and processed as whole units, supporting a dual-process model of language processing, which assumes that grammatical and formulaic expressions are differentially processed.
Commonly stabilized cytochromes c from deep-sea Shewanella and Pseudomonas
Authors: Fujii Sotaro , Masanari-Fujii Misa , Kobayashi Shinya , Kato Chiaki , Nishiyama Masayoshi , Harada Yoshie , Wakai Satoshi , Sambongi Yoshihiro
Published: March 2018

Two cytochromes c5 (SBcytc and SVcytc) have been derived from Shewanella living in the deep-sea, which is a high pressure environment, so it could be that these proteins are more stable at high pressure than at atmospheric pressure, 0.1 MPa. This study, however, revealed that SBcytc and SVcytc were more stable at 0.1 MPa than at higher pressure. In addition, at 0.1–150 MPa, the stability of SBcytc and SVcytc was higher than that of homologues from atmospheric-pressure Shewanella, which was due to hydrogen bond formation with the heme in the former two proteins. This study further revealed that cytochrome c551 (PMcytc) of deep-sea Pseudomonas was more stable than a homologue of atmospheric-pressure Pseudomonas aeruginosa, and that specific hydrogen bond formation with the heme also occurred in the former. Although SBcytc and SVcytc, and PMcytc are phylogenetically very distant, these deep-sea cytochromes c are commonly stabilized through hydrogen bond formation.
Romo1 is a mitochondrial nonselective cation channel with viroporin-like characteristics
Authors: Lee Gi Young , You Deok-gyun , Lee Hye-Ra , Hwang Sun Wook , Lee C. Justin , Yoo Young Do
Published: March 2018

Reactive oxygen species (ROS) modulator 1 (Romo1) is a nuclear-encoded mitochondrial inner membrane protein known to regulate mitochondrial ROS production and to act as an essential redox sensor in mitochondrial dynamics. Although its physiological roles have been studied for a decade, the biophysical mechanisms that explain these activities of Romo1 are unclear. In this study, we report that Romo1 is a unique mitochondrial ion channel that differs from currently identified eukaryotic ion channels. Romo1 is a highly conserved protein with structural features of class II viroporins, which are virus-encoded nonselective cation channels. Indeed, Romo1 forms a nonselective cation channel with its amphipathic helical transmembrane domain necessary for pore-forming activity. Notably, channel activity was specifically inhibited by Fe2+ ions, an essential transition metal ion in ROS metabolism. Using structural bioinformatics, we designed an experimental data–guided structural model of Romo1 with a rational hexameric structure. We propose that Romo1 establishes a new category of viroporin-like nonselective cation channel in eukaryotes.
CMV: visualization for RNA and protein family models and their comparisons
Authors: Eggenhofer Florian , Hofacker Ivo L , Backofen Rolf , Höner zu Siederdissen Christian
Published: March 2018

A standard method for the identification of novel RNAs or proteins is homology search via probabilistic models. One approach relies on the definition of families, which can be encoded as covariance models (CMs) or Hidden Markov Models (HMMs). While being powerful tools, their complexity makes it tedious to investigate them in their (default) tabulated form. This specifically applies to the interpretation of comparisons between multiple models as in family clans. The Covariance model visualization tools (CMV) visualize CMs or HMMs to: I) Obtain an easily interpretable representation of HMMs and CMs; II) Put them in context with the structural sequence alignments they have been created from; III) Investigate results of model comparisons and highlight regions of interest.

Availability and implementation

Source code (http://www.github.com/eggzilla/cmv), web-service (http://rna.informatik.uni-freiburg.de/CMVS).

Supplementary information

Supplementary data are available at Bioinformatics online.
ADPredict: ADP-ribosylation site prediction based on physicochemical and structural descriptors
Authors: Lo Monte Matteo , Manelfi Candida , Gemei Marica , Corda Daniela , Beccari Andrea Rosario
Published: March 2018

Motivation

ADP-ribosylation is a post-translational modification (PTM) implicated in several crucial cellular processes, ranging from regulation of DNA repair and chromatin structure to cell metabolism and stress responses. To date, a complete understanding of ADP-ribosylation targets and their modification sites in different tissues and disease states is still lacking. Identification of ADP-ribosylation sites is required to discern the molecular mechanisms regulated by this modification. This motivated us to develop a computational tool for the prediction of ADP-ribosylated sites.

Results

Here, we present ADPredict, the first dedicated computational tool for the prediction of ADP-ribosylated aspartic and glutamic acids. This predictive algorithm is based on (i) physicochemical properties, (ii) in-house designed secondary structure-related descriptors and (iii) three-dimensional features of a set of human ADP-ribosylated proteins that have been reported in the literature. ADPredict was developed using principal component analysis and machine learning techniques; its performance was evaluated both internally via intensive bootstrapping and in predicting two external experimental datasets. It outperformed the only other available ADP-ribosylation prediction tool, ModPred. Moreover, a novel secondary structure descriptor, HM-ratio, was introduced and successfully contributed to the model development, thus representing a promising tool for bioinformatics studies, such as PTM prediction.

Availability and implementation

ADPredict is freely available at www.ADPredict.net.

Supplementary information

Supplementary data are available at Bioinformatics online.
RapidRMSD: rapid determination of RMSDs corresponding to motions of flexible molecules
Authors: Neveu Emilie , Popov Petr , Hoffmann Alexandre , Migliosi Angelo , Besseron Xavier , Danoy Grégoire , Bouvry Pascal , Grudinin Sergei
Published: March 2018

Motivation

The root mean square deviation (RMSD) is one of the most used similarity criteria in structural biology and bioinformatics. Standard computation of the RMSD has a linear complexity with respect to the number of atoms in a molecule, making RMSD calculations time-consuming for the large-scale modeling applications, such as assessment of molecular docking predictions or clustering of spatially proximate molecular conformations. Previously, we introduced the RigidRMSD algorithm to compute the RMSD corresponding to the rigid-body motion of a molecule. In this study, we go beyond the limits of the rigid-body approximation by taking into account conformational flexibility of the molecule. We model the flexibility with a reduced set of collective motions computed with e.g. normal modes or principal component analysis.

Results

The initialization of our algorithm is linear in the number of atoms and all the subsequent evaluations of RMSD values between flexible molecular conformations depend only on the number of collective motions that are selected to model the flexibility. Therefore, our algorithm is much faster compared to the standard RMSD computation for large-scale modeling applications. We demonstrate the efficiency of our method on several clustering examples, including clustering of flexible docking results and molecular dynamics (MD) trajectories. We also demonstrate how to use the presented formalism to generate pseudo-random constant-RMSD structural molecular ensembles and how to use these in cross-docking.

Availability and implementation

We provide the algorithm written in C++ as the open-source RapidRMSD library governed by the BSD-compatible license, which is available at http://team.inria.fr/nano-d/software/RapidRMSD/. The constant-RMSD structural ensemble application and clustering of MD trajectories is available at http://team.inria.fr/nano-d/software/nolb-normal-modes/.

Supplementary information

Supplementary data are available at Bioinformatics online.
DeepSol: a deep learning framework for sequence-based protein solubility prediction
Authors: Khurana Sameer , Rawi Reda , Kunji Khalid , Chuang Gwo-Yu , Bensmail Halima , Mall Raghvendra
Published: March 2018

Motivation

Protein solubility plays a vital role in pharmaceutical research and production yield. For a given protein, the extent of its solubility can represent the quality of its function, and is ultimately defined by its sequence. Thus, it is imperative to develop novel, highly accurate in silico sequence-based protein solubility predictors. In this work we propose, DeepSol, a novel Deep Learning-based protein solubility predictor. The backbone of our framework is a convolutional neural network that exploits k-mer structure and additional sequence and structural features extracted from the protein sequence.

Results

DeepSol outperformed all known sequence-based state-of-the-art solubility prediction methods and attained an accuracy of 0.77 and Matthew’s correlation coefficient of 0.55. The superior prediction accuracy of DeepSol allows to screen for sequences with enhanced production capacity and can more reliably predict solubility of novel proteins.

Availability and implementation

DeepSol’s best performing models and results are publicly deposited at https://doi.org/10.5281/zenodo.1162886 (Khurana and Mall, 2018).

Supplementary information

Supplementary data are available at Bioinformatics online.
Arioc: GPU-accelerated alignment of short bisulfite-treated reads
Authors: Wilton Richard , Li Xin , Feinberg Andrew P , Szalay Alexander S
Published: March 2018

Motivation

The alignment of bisulfite-treated DNA sequences (BS-seq reads) to a large genome involves a significant computational burden beyond that required to align non-bisulfite-treated reads. In the analysis of BS-seq data, this can present an important performance bottleneck that can be mitigated by appropriate algorithmic and software-engineering improvements. One strategy is to modify the read-alignment algorithms by integrating the logic related to BS-seq alignment, with the goal of making the software implementation amenable to optimizations that lead to higher speed and greater sensitivity than might otherwise be attainable.

Results

We evaluated this strategy using Arioc, a short-read aligner that uses GPU (general-purpose graphics processing unit) hardware to accelerate computationally-expensive programming logic. We integrated the BS-seq computational logic into both GPU and CPU code throughout the Arioc implementation. We then carried out a read-by-read comparison of Arioc's reported alignments with the alignments reported by well-known CPU-based BS-seq read aligners. With simulated reads, Arioc's accuracy is equal to or better than the other read aligners we evaluated. With human sequencing reads, Arioc's throughput is at least 10 times faster than existing BS-seq aligners across a wide range of sensitivity settings.

Availability and implementation

The Arioc software is available for download at https://github.com/RWilton/Arioc. It is released under a BSD open-source license.

Supplementary information

Supplementary data are available at Bioinformatics online.
SCOTCH: subtype A coreceptor tropism classification in HIV-1
Authors: Löchel Hannah F , Riemenschneider Mona , Frishman Dmitrij , Heider Dominik
Published: March 2018

Motivation

The V3 loop of the gp120 glycoprotein of the Human Immunodeficiency Virus 1 (HIV-1) is considered to be responsible for viral coreceptor tropism. gp120 interacts with the CD4 receptor of the host cell and subsequently V3 binds either CCR5 or CXCR4. Due to the fact that the CCR5 coreceptor is targeted by entry inhibitors, a reliable prediction of the coreceptor usage of HIV-1 is of great interest for antiretroviral therapy. Although several methods for the prediction of coreceptor tropism are available, almost all of them have been developed based on only subtype B sequences, and it has been shown in several studies that the prediction of non-B sequences, in particular subtype A sequences, are less reliable. Thus, the aim of the current study was to develop a reliable prediction model for subtype A viruses.

Results

Our new model SCOTCH is based on a stacking approach of classifier ensembles and shows a significantly better performance for subtype A sequences compared to other available models. In particular for low false positive rates (between 0.05 and 0.2, i.e. recommendation in the German and European Guidelines for tropism prediction), SCOTCH shows significantly better prediction performances in terms of partial area under the curves and diagnostic odds ratios compared to existing tools, and thus can be used to reliably predict coreceptor tropism for subtype A sequences.

Availability and implementation

SCOTCH can be downloaded/accessed at http://www.heiderlab.de.
Conditional expectation estimation through attributable components
Authors: Tabak Esteban G , Trigila Giulio
Published: March 2018

A general methodology is proposed for the explanation of variability in a quantity of interest x in terms of covariates z = (z1, …, zL). It provides the conditional mean $\bar{x}(z)$ as a sum of components, where each component is represented as a product of non-parametric one-dimensional functions of each covariate zl that are computed through an alternating projection procedure. Both x and the zl can be real or categorical variables; in addition, some or all values of each zl can be unknown, providing a general framework for multi-clustering, classification and covariate imputation in the presence of confounding factors.

The procedure can be considered as a preconditioning step for the more general determination of the full conditional distribution $\boldsymbol{\rho}(x|z) $ through a data-driven optimal-transport barycenter problem. In particular, just iterating the procedure once yields the second order structure (i.e. the covariance) of $\boldsymbol{\rho}(x|z) $.

The methodology is illustrated through examples that include the explanation of variability of ground temperature across the continental United States and the prediction of book preference among potential readers.
Framing Public Health and Pharmacy
Authors: Hanson Ardis , Levin Bruce Lubotsky , Hurd Peter D.
Published: March 2018

This chapter incorporates a number of global perspectives of pharmacy and public health, including international perspectives (e.g., World Health Organization, macro-level), regional perspectives (e.g., European Union, meso-level), and national (e.g., country, micro-level) perspectives. This chapter provides a broader understanding of how issues in pharmacy and public health are framed and reframed as the field moves from a national understanding of pharmacy and public health to broader regional and global understandings. It also shows show there are significant commonalities and differences in the practice, education, and research in the disciplines and careers of pharmacy and public health. Topics covered include integrated delivery of health care, preventive health services, public–private sector partnerships, global health, public health engagement, public health surveillance, public health practice, and public health systems research.
Disease Prevention and Health Promotion
Authors: Hurd Peter D , Guyton Justinne , Hanson Ardis
Published: March 2018

Changing human behavior is challenging; however, having a long-term impact on the improved health of a population is a compelling reason for an increased public health commitment by individuals in pharmacy. Any of the activities that individuals and populations pursue have a direct effect on their health, from drinking clean water to breathing fresh air. Health behaviors mitigate or exacerbate chronic diseases, such as heart disease, cancer, diabetes, and stroke, and human behaviors can affect the resurgence of infectious diseases (and the emergence of new infectious diseases). Other behavioral factors, such as tobacco use, poor diet, lack of exercise, alcohol consumption, at-risk sexual behaviors, and avoidable injuries, contribute prominently to increased morbidity and mortality. This chapter addresses basic public health principles of disease prevention and health promotion, looking at consumer health education, health literacy, social media, and program design and evaluation.
Cultural Perspectives in Public Health
Authors: Bleidt Barry A , Coleman Carmita A , Hurd Peter D
Published: March 2018

In order to deliver effective health care and public health services, an awareness of and appreciation for culture’s influence on the social determinants of health is fundamental. In addition, culturally competent delivery of care is a primary contributor to reducing the more expansive concern of health disparities. This chapter defines culture, including its role and influence as a social determinant of health, and discusses the concepts of cultural awareness and cultural competency, which are the foundation of a patient-centered approach to better health outcomes and wellness. It also discusses the status of cultural consideration in health care as a public health problem and presents the need for culturally competent service delivery, along with an exploration of what is involved in the cultural-integration journey.
Behavioral Health
Authors: Hanson Ardis , Ott Carol A , Levin Bruce Lubotsky
Published: March 2018

Seven of the top 20 disorders affecting morbidity are mental illnesses: major depressive disorders, drug use disorders, anxiety disorders, alcohol use disorders, schizophrenia, bipolar disorder, and dysthymia. Behavioral health disorders are important determinants of work role disability and quality of life. Behavioral health disorders also have generally stronger “cross-domain” effects, exacerbating the diagnosis and treatment of many physical disorders and chronic medical conditions. In addition to the persistent stigma surrounding behavioral health disorders, there are issues of reimbursement, costs of care, availability of care based on provider and/or geographic availability, policy limitations, formulary restrictions, transportation, provider knowledge, patient knowledge, attitudinal/evaluative barriers, medication compliance, family support (or lack of it), inconvenience or inability to obtain an appointment, and refusal of treatment. This chapter provides an overview of the issues surrounding behavioral health care from a population health perspective, including pharmaceutical treatment and competencies for community-based pharmacists.
Public Health Nutrition
Authors: Wright Lauri , Chavez Melody
Published: March 2018

The importance of nutrition and the prevention of illness and disease in public health has long been recognized and encouraged in the United States. These issues are now being recognized as key opportunities for pharmacists to engage in improving individual and population health as the Accreditation Council for Pharmacy Education Standards 2016 report emphasizes the importance of patient-centered care, health and wellness, and population-based care. This chapter starts with an overview of nutritional needs throughout the lifespan. It then discusses specific strategies and programs pharmacists can refer to in order to support healthy lifestyles and public health prevention strategies focused on nutrition.
Evidence-Based Practice and Public Health
Authors: Bryant Patrick , Hurd Peter D , Hanson Ardis
Published: March 2018

The most difficult step of evidence-based medicine (EBM) and evidence-based public health (EBPH) is to link the evidence with current clinical knowledge and experience, especially with the continued focus on using evidence in decision-making. Standards of care and clinical practice guidelines are now established and reported using nationally and globally recognized protocols to ensure standard nomenclature and clinical crosswalks. This chapter examines relevant background issues, including concepts underlying EBM, EBPH, and definitions of evidence; describes key analytic tools to enhance the adoption of evidence-based decision-making; and finishes with challenges and opportunities for implementation in public health practice.
Education and Training
Authors: Garcia Angela S , Forrister Daniel , Bullers Krystal , Hurd Peter D
Published: March 2018

The growing focus on training pharmacists in public health has influenced each iteration of the pharmacy education guidelines of the Center for the Advancement of Pharmaceutical Education Educational Outcomes produced by the American Association of Colleges of Pharmacy. Starting with population-based health improvement, wellness, and disease prevention, the American Council on Pharmaceutical Education now requires pharmacy candidates be provided opportunities to participate in public health focused skills, such as immunization delivery. This chapter examines training and certification in public health, including unique specializations for pharmacy students and practitioners, career options in public health pharmacy, the continued need for public health education and training in pharmacy, and developing leadership skills.
Neuroanatomy
Authors: Fisch Adam J
Published: March 2018

Neuroanatomy: Draw It to Know It, Third Edition teaches neuroanatomy in a purely kinesthetic way. In using this book, the reader draws each neuroanatomical pathway and structure, and in the process, creates memorable and reproducible schematics for the various learning points in Neuroanatomy in a hands-on, enjoyable and highly effective manner. In addition to this unique method, Neuroanatomy: Draw it to Know It also provides a remarkable repository of reference materials, including numerous anatomic and radiographic brain images and illustrations from many other classic texts to enhance the learning experience.
In the third edition of this classic text, the author completely reorganized the book based on user feedback, taking a more intuitive and easy-to-use approach. For the first time, the illustrations are in full color. No other text in neuroanatomy engages the reader in as direct a manner as this book and none covers the advanced level of detail found while retaining the simplistic approach to the learning which has become the cornerstone of the text. Neuroanatomy: Draw It to Know It is singular in its ability to engage and instruct without overwhelming any level of neuroanatomy student. The most effective model for learning neuroanatomy is Neuroanatomy: Draw It to Know It.
Introduction to Neuroanatomy
Authors: Fisch Adam J
Published: March 2018

This chapter focuses on learning the origination and organization of the nervous system and how to draw all the various elements that comprise it. Instructions are given for drawing the cerebrum, basal ganglia, thalamus, limbic systems, brainstem, cranial nerves, vertebral column, spinal cord, peripheral nervous system (PNS), autonomic nervous system (ANS), formation of neural plates, and neural tubes. Additionally, the chapter addresses how the elements of the nervous system are related to each other, notes their function, and outlines their respective sensorimotor and cognitive activities.
Cerebral Vasculature, Cerebrospinal Fluid, & Meninges
Authors: Fisch Adam J
Published: March 2018

This chapter focuses on learning about the cerebral vasculature, cerebrospinal fluid, and the meninges. Instructions are given for drawing the circle of Willis, brainstem, cerebellar arteries, intracranial hemorrhage, brain herniation, cerebral ventricles, cerebrospinal fluid (CSF) pathways, and spinal meninges. The chapter also covers specific areas that are vulnerable to lesions and to illness such as stroke and other disorders, and indicates where procedures such a lumbar puncture take place.
The Brainstem & Cranial Nerves
Authors: Fisch Adam J
Published: March 2018

This chapter focuses on learning about the brainstem and cranial nerves—their components, function, and anatomy. The chapter provides instruction on how to draw the brainstem, the midbrain, the pons, the medulla, cranial nerves, the skull base, the somatomotor set, pharyngeal arch set, and solely sensory set. Also discussed are neurological disorders associated with the brainstem and cranial nerves and their mechanisms, and the mechanics of the extraocular muscles and their associated disorders.
Normal Breast Anatomy and Histology
Authors: Apple Sophia K. , Bassett Lawrence W.
Published: March 2018

In this chapter, normal breast anatomy is discussed, with a succinct pictorial summary of breast glandular elements, the chest wall, and the axilla. The locations of breast lesions are often arbitrarily divided into upper outer, upper inner, lower inner, and upper inner quadrants. However, the lobes within a specific quadrant cross over into adjacent quadrants. The terminal duct lobular unit (TDLU) is composed of an interlobular duct and associated lobules with multiple grape-like structures where the milk is secreted and drains into the terminal ducts, interlobular ducts, excretory ducts, lactiferous sinus, lactiferous duct, and the nipple. Axillary lymph nodes are divided into three levels, based on their location in relation to the pectoralis minor muscle. Level I axillary lymph nodes are located below the edge of the pectoralis minor; level II lies posterior to the pectoralis minor; and level III lies medial to the pectoralis minor.
Circumscribed Mass: Cysts, Complicated Cysts, Clustered Microcysts
Authors: Kettler Mark D.
Published: March 2018

Benign cysts can occur in women of all ages, but they have a predilection for women in their 40s and 50s, and are far less common in younger and older women. Most cysts arise at the level of the terminal duct-lobular unit (TDLU); less commonly, cysts are caused by ectasia of central ducts. This chapter, appearing in the section on circumscribed mass, reviews the key clinical and imaging features, differential diagnosis, and management recommendations for primary cystic masses, including simple cysts, complicated cysts, and clustered microcysts. Careful assessment of sonographic features usually allows a definitive diagnosis of these benign entities that do not typically require tissue sampling. Some complex masses containing fluid and/or cystic-appearing components may require tissue sampling for diagnosis.
Spiculated Masses
Authors: Andrejeva Liva , Geisel Jaime L. , Harigopal Malini
Published: March 2018

A spiculated mass is a centrally dense lesion seen on mammography with sharp lines radiating from its margin. The spicules can vary greatly in length, from a few millimeters to several centimeters. In malignant lesions, spicules represent a mixture of tumor cells and fibrosis invading the normal tissue surrounding the lesion. Although a spiculated mass is thought of as a classic finding of malignancy on mammography, ultrasound, and MRI, its differential diagnosis includes benign lesions. However, unless clinical history strongly supports a benign diagnosis, a spiculated mass on any modality typically will require additional workup and biopsy. This chapter reviews the key imaging and clinical features, imaging protocols and pitfalls, differential diagnoses, radiology–pathology correlations, and clinical management recommendations for a spiculated mass. Topics discussed include both malignant and benign masses.
Mass in Lactating Female
Authors: Woldenberg Nina , Joines Melissa M.
Published: March 2018

Timely and accurate diagnosis of a mass in the lactating patient requires comprehensive understanding of the indicated imaging workup. During lactation it is not uncommon for patients to present with a palpable mass that requires evaluation. In patients with a palpable abnormality, diagnostic evaluation should not be delayed due to pregnancy or lactation. In addition, a mass that requires further evaluation may be identified at the time of screening mammography in lactating patients. This chapter, appearing in the section on asymmetry, mass, and distortion, reviews the key imaging and clinical features, imaging protocols and pitfalls, differential diagnoses, and management recommendations for a mass in the lactating patient. Topics discussed include differential considerations of benign and malignant masses in the lactating breast including cysts, focal lobular hyperplasia (focal fibrocystic change), galactocele, abscess, fibroadenoma, lactating adenoma, and pregnancy-associated breast cancer.
Architectural Distortion (Cancer)
Authors: Durand Melissa A.
Published: March 2018

An architectural distortion (AD) is an alteration of the breast parenchyma, which results in radiating lines or spicules emanating from a point without a distinct mass. It can occur as the primary finding, or it may be an associated feature of a mass, asymmetry, or calcifications. AD is a mammographic finding with a high positive predictive value for malignancy and is a major cause of false-negative screening exams. This chapter, appearing in the section on asymmetry, mass, and distortion, reviews the key imaging and clinical features, imaging protocols, differential diagnoses, management recommendations, and potential pitfalls for a malignant architectural distortion. Topics discussed include superimposition of breast tissue, localization, workup of tomosynthesis-detected architectural distortion, and image-guided biopsy options.
Vascular Calcifications
Authors: Holbrook Anna I.
Published: March 2018

Vascular calcifications lie within the artery wall, and appear to be linear, usually in association with blood vessels. The parallel or “tram-track” appearance of the calcifications in opposite walls of the artery is pathognomonic. They are more prevalent with age. They are also associated with diabetes, renal disease, hyperparathyroidism, parity, and history of lactation, and possibly, cardiovascular disease. Vascular calcifications in the breast are within the arterial wall media, where they are known as Mönckeberg medial calcific sclerosis. This chapter reviews the key imaging features, imaging protocols, differential diagnoses, and management recommendations for vascular calcifications. Topics discussed include demographics and comorbidities, linear calcifications, and diagnostic workup.
Milk of Calcium
Authors: Ho Christopher P.
Published: March 2018

Milk of calcium (MOC) is simply calcium oxalate crystals precipitated within the microcysts (acini) of the breast lobules. MOC has a very distinct mammographic appearance. It is a benign entity, and when seen and properly identified, it requires no further workup or follow-up. It is, however, important to recognize the proper initial evaluation of MOC so as to avoid misdiagnosis or potential unnecessary biopsies.

This chapter, appearing in the section on calcifications, reviews the key imaging and clinical features, imaging protocols and pitfalls, differential diagnoses, and management recommendations for milk of calcium. Topics discussed include appropriate use of magnification views, hints to recognize the distinct appearance of milk of calcium, and management.
Amorphous/Indistinct Calcifications (Regional/Diffuse)
Authors: Wang Lilian
Published: March 2018

Amorphous calcifications are calcifications that are sufficiently small and/or hazy that a more specific morphological classification cannot be made. Historically, such calcifications were referred to as “indistinct” calcifications. The likelihood of malignancy and the management of amorphous calcifications largely depend on their distribution. The majority of amorphous calcifications are benign, most often due to fibrocystic change (60%). Sclerosing adenosis commonly occurs in perimenopausal women and is associated with a 1.5–2.1x relative risk for development of breast cancer. This chapter, appearing in the section on calcifications, reviews the key imaging and clinical features, imaging protocols and pitfalls, differential diagnosis, and management recommendations for amorphous/indistinct calcifications in a regional or diffuse distribution. Topics discussed include influence of distribution on risk of malignancy and pathological entities, including sclerosing adenosis.
Fine, Linear/Branching Calcifications
Authors: Doepke Laura
Published: March 2018

Of all of the calcifications identified on mammography, fine, linear/branching calcifications are the most suspicious for malignancy, most commonly ductal carcinoma in situ (DCIS). The risk of malignancy associated with fine, linear/branching calcifications is approximately 70%. A recent study evaluating the positive predictive value of suspicious calcifications based on the fifth edition of BI-RADS found the positive predictive value of fine pleomorphic/linear or segmental calcifications was 93.8%. This chapter, which appears in the section on calcifications, reviews the key imaging features, imaging protocols for evaluating calcifications, management, and potential pitfalls or mimics of fine, linear/branching calcifications. Topics discussed will include magnification views, stereotactic core needle biopsy, and radiology–pathology correlation.
Duct Ectasia
Authors: Winkler Nicole S.
Published: March 2018

Duct ectasia is a term used to describe benign dilation of fluid-filled mammary ducts. Duct ectasia is characterized by tubular fluid-filled structures >2 mm in diameter that are commonly bilateral and subareolar in location. Ductal dilation is due to weakened wall elasticity that occurs with age. The ducts fill with secretions that may result in intermittent nipple discharge or chronic inflammation. When duct ectasia involves multiple ducts bilaterally, it can be dismissed on screening mammography; however, a solitary dilated duct should be further evaluated, given the potential for associated non-calcified DCIS. This chapter, appearing in the section on nipple, skin, and lymph nodes, reviews the key imaging and clinical features, imaging protocols and pitfalls, differential diagnoses, and management recommendations for duct ectasia. Topics discussed include solitary dilated duct, nipple discharge, and sonographic evaluation of ducts.
Ductography
Authors: Harvey Susan C.
Published: March 2018

Ductography or galactography is a technique used in the diagnostic workup of unilateral, single duct, spontaneous, and bloody or clear nipple discharge. Mammographic imaging with magnification may reveal the source of the discharge. The technique is challenging, yet it can be mastered with attention to detail, a well thought-out protocol, and practice. Imaging findings can be non-specific, yet may guide biopsy or surgical excision. Now with the wide use of breast magnetic resonance imaging (MRI), which has been shown to be more sensitive for lesion detection, ductography is used less frequently. This chapter, appearing in the section on interventions and surgical changes, reviews the indications, procedure protocols, and pitfalls, as well as the management and imaging follow-up for ductography or galactography.
The Biological Basis of Depression
Authors: Nestler Eric J.
Published: March 2018

Most major advances in biomedical research have relied on the use of animal and cell models of disease. This is a particularly difficult challenge in psychiatry, because many core symptoms of mental illnesses are inherently inaccessible in animals. Moreover, because still today there are no bona fide molecular-cellular abnormalities that are pathogenomic for these illnesses, cell models are even more far afield. This chapter reviews efforts to overcome these obstacles and use animal and cell studies to better understand the biological basis of depression and to develop improved treatments. An important distinction is made between acute vs. chronic stress models as well as differentiating the changes that stress induces in brain that mediate deleterious maladaptations as opposed to homeostatic adaptations that help the individual cope with the stress. Studies along these lines are making major strides in identifying candidate molecular pathways that should be mined for new antidepressant treatments. However, a major gap in the field is the great difficulty in testing novel mechanisms in humans; closing this gap is one of the highest priorities for the field.
Diabetes and Depression
Authors: Navarro Eduardo A. Colón
Published: March 2018

Diabetes is a chronic disorder accompanied by a significant illness burden, risk of complications, and with significant impact on psychosocial function. Rates of depression in diabetes are elevated in various studies. Our current understanding indicates a bidirectional relationship, with depression resulting from the illness, but also representing a predisposing factor. As we learn more about this relationship, the role of biological determinants becomes more apparent, including changes in neuroendocrine parameters, and the inflammatory mediators of depression.
Wound Healing and Depression
Authors: Stoddard Frederick J. , Sheridan Robert L.
Published: March 2018

Depression and wound healing are bidirectional processes for adults and children consistent with the conception of depression as systemic. This systemic interaction is similar to the “bidirectional impact of mood disorder on risk for development, progression, treatment, and outcomes of medical illness” generally. And, evidence is growing that the bidirectional impact of mood disorder may be true for injuries and for trauma surgery. Animal models have provided some support that treatment of depression may improve wound healing. An established biological model for a mechanism delaying wound healing is increased cortisol secretion secondary to depression and/or stress, and impaired immune response, in addition or together with the other factors such as genetic or epigenetic risk for depression. Cellular models relate both to wound healing and to depression include cytokines, the inflammatory response (Miller et al, 2008), and cellular aging (Telgenhoff and Shroot, 2005) reflected in shorter leukocyte telomere length (LTL) (Verhoeven et al, 2016). Another model of stress impacting wound healing investigated genetic correlates—immediate early gene expression or IEG from the medial prefrontal cortex, and locomotion, in isolation-reared juvenile rats. Levine et al (2008) compared isolation reared to group reared samples, and found that, immediate gene expression in the medial prefrontal cortex (mPFC) was reduced, and behavioral hyperactivity increased, in juvenile rats with 20% burn injuries. Wound healing in the isolation reared rats was significantly impaired. They concluded that these results provide candidates for behavioral biomarkers of isolation rearing during physical injury, i.e. reduced immediate mPFC gene expression and hyperactivity. They suggested that a biomarker such as IEGs might aid in demarcating patients with resilient and adaptive responses to physical illness from those with maladaptive responses
Models of Mental Health Training for Non-Psychiatric Physicians
Authors: Strain James J.
Published: March 2018

Teaching models for mental health training for non-psychiatric physicians have been extant for many years. Several are unstructured and have no intent for the trainee to receive a standard curriculum, or gain experience with a set of competencies in regard to knowledge, skills, or attitudes. Two recent models are currently employed that may enhance the learning of the non-psychiatric physician: The collaborative care model and the medical model. These are examined in detail with explanations of how they can be introduced into the medical setting. The diagnosis and management of depression in the medical setting is examined.
A Video Atlas of Neuromuscular Disorders
Authors: Shaibani Aziz
Published: March 2018

This online title is the first real cases video atlas of neuromuscular disorders. It contains close to 300 video cases taken directly from a real neuromuscular clinic, illustrating a myriad of disorders and shedding light on their diagnosis and treatment, as well as providing updates about many of them. It provides an invaluable approach that should benefit anyone interested in neuromuscular disorders which comprise more than 50% of presenting disease to general neurologists and even to general practitioners. Some rare diseases are also described, giving an opportunity for future diagnosis of these conditions in patients, despite the rarity of the condition and its infrequent presentation in clinic.
Tongue Signs
Authors: Shaibani Aziz
Published: March 2018

The tongue is heavily innervated and plays a central role in articulation, swallowing, and tasting. Unilateral weakness is usually well tolerated. Intermittent weakness of the tongue is highly indicative of myasthenia gravis (MG), while progressive weakness and atrophy is typical for amyotrophic lateral sclerosis (ALS). Tongue weakness without atrophy or fasciculations is a sign of upper motor neuron (UMN) or cerebellar involvement. Lingual dysarthria should be differentiated from other types of dysarthria. Tongue tremor is common and may be confused with fasciculation. Inspection of the tongue while resting in the mouth is more telling than a contracted and protruded tongue for the presence of fsciculations. Direct needle examination of the tongue is painful and is rarely needed.
Dysarthria
Authors: Shaibani Aziz
Published: March 2018

Slurring of speech is usually noticed by family members or friends before patients know it. It is usually associated with swallowing difficulty due to dual function of the tongue and frequent involvement of the tongue and pharyngeal muscles together. Dysphagia usually precedes dysarthria in myasthenia gravis (MG) and follows it in amyotrophic lateral sclerosis (ALS). In advanced cases, anarthria becomes a total communication barrier and other means of communications should be established. Cerebellar dysarthria is characterized by being irregular. Dysphonia should be differentiated from dysarthria. This chapter describes features and presentations of different types of dysarthria.
Weakness of the Neck Muscles
Authors: Shaibani Aziz
Published: March 2018

The neck is furnished by tens of muscles for flexion, extension, lateral bending, and rotation. It carries a 10-pound head for at least two-thirds of every day. These muscles are under delicate central control, and they are subject to different central and peripheral malfunctions. Differential involvement of the neck flexors’ Vs extensors helps with the diagnosis of various neuromuscular disorders. Weakness of the cervical extensors leads to head drop, a troubling condition that is caused by many neuromuscular disorders. Movement disorders such as cervical dystonia and Parkinson disease lead to head drop, causing confusion with neuromuscular causes such as myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS). Head protrusion of the elderly (camptocormia) is a different entity.