bluuebunny/crossref_metadata_2025 huggingface dataset:
News Audiences and News Habits
Authors: Møller Hartley Jannie
Published: August 2018

The focus of news-audience research has shifted from investigating news audiences of single platforms—such as newspapers, television, or radio news—to audiences in an inherently cross-media context; and from examining the audience as passive, choosing between content made available for them; to investigating what audiences do with the news more actively, often coined by the term “news engagement.”

News-audience studies can be divided into five approaches: (a) media-effect studies of news consumption, (b) studies of news-media use and motives, (c) cultural audience studies of news practices, (d) news audiences’ comprehension and recall of news, and (e) news engagement in the digital age.

Due to changes in the media landscape, both technological and commercial, traditional analytical models in news-audience research have been challenged. The final discussion addresses how a tendency to focus on reducing audiences to quantifiable aggregates in big-data research runs the risk of removing news-audience research from actual empirical audiences. Furthermore, news audience research has moved in the direction of studying those habits across platforms while being less concerned with the structural forces of the field of news consumption impacting the audiences’ sensemaking practices and orientations toward civic engagement.
Agency and Structure in Foreign Policy Analysis
Authors: Hayes Jarrod
Published: August 2018

For much of the history of the study of international relations, and of foreign policy as a distinctive subfield, scholars have debated the relative weight of agency and structure in shaping the course of international events. Often, the significance of agency versus structure depends on the scope of inquiry. Efforts to identify broad patterns of social interaction tend to play up the significance of structure, while studies of specific events bring agency to the fore. International relations theory is typically associated with the former, and foreign policy analysis (FPA) is more closely linked to the latter. That association suggests that the question of agency versus structure in international outcomes is settled in FPA in favor of agency. An assessment of the literature in FPA shows such a suggestion to be wide of the mark. Not only does FPA struggle with the question of agency versus structure that pervades the study of international relations generally, but also it wrestles with how to reconcile agency and structure in the context of psychological constraints on human cognition. Thus, rather than resolving the debate between agency and structure, the literature on FPA shows that it extends down to the level of individual policymakers. The debate over the role of agency and structure occupies two axes. The first is the engagement of FPA with broader debates over agency and structure in international relations scholarship. The second is the tension between agency and structure in FPA that emerges once psychology is incorporated into the analytical matrix. In both cases, the significance of structure in the actual analysis of foreign policy is far greater than common conception recognizes. This reality means that FPA represents the cutting edge for theoretical and analytical efforts to understand the relationship between structure and agency in international outcomes.
Statistical Mediation in Lifespan Developmental Analyses
Authors: Gonzalez Oscar , MacKinnon David P.
Published: August 2018

Lifespan developmental research studies how individuals change throughout their lifetime and how intraindividual or interindividual change leads to future outcomes. Lifespan researchers are interested in how developmental processes unfold and how specific developmental pathways lead to an outcome. Developmental processes have been previously studied using developmental cascade models, concepts of equifinality and multifinality, and developmental interventions. Statistical mediation analysis also provides a framework for studying developmental processes and developmental pathways by identifying intermediate variables, known as mediators, that transmit the effect between early exposures and future outcomes. The role of statistical mediation in lifespan developmental research is either to explain how the developmental process unfolds, or to identify mediators that researchers can target in interventions so that individuals change developmental pathways. The statistical mediation model is inherently causal, so the relations between the exposures, mediators, and outcomes have to be correctly specified, and ruling out alternative explanations for the relations is of upmost importance.

The statistical mediation model can be extended to deal with longitudinal data. For example, the autoregressive mediation model can represent change through time by examining lagged relations in multiwave datasets. On the other hand, the multilevel mediation model can deal with the clustering of repeated measures within individuals to study intraindividual and interindividual change. Finally, the latent growth curve mediation model can represent the variability of linear and nonlinear trajectories for individuals in the variables in the mediation model through time. As a result, developmental researchers have access to a range of models that could describe the theory of change they want to study. Researchers are encouraged to consider mechanisms of change and to formulate mediation hypotheses about lifespan development.
Gang Joining
Authors: Densley James A.
Published: August 2018

This article examines the who, what, where, when, why, and how of gang joining. The question of what youth join when they join gangs speaks to the contested nature of gang definitions and types and the consequences of gang membership, specifically heightened levels of offending and victimization. The type of gang and the obligations of membership influence the joining process. Where youth join gangs, namely, the neighborhood and social context, also impacts individual opportunities and preferences for joining. When youth join gangs is considered in a developmental sense, to include both adolescent and adult onset, in order to account for continuity and change in individual levels of immersion or “embeddedness” in gangs across the life course. Who joins gangs provides a profile of gang membership grounded in the well-documented risk factors for gang membership, but limited by problems of prediction. Why youth join gangs speaks to the push and pull factors for membership, the appeal of gangs, and the selective incentives they offer. Still, motivations for gang membership cannot fully explain selection into gangs, nor can general theories of crime that do not necessarily fit with general knowledge of gangs. How youth join gangs, for example, is more complicated than initiation rites. The mechanisms underlying the selection process can be understood through the lens of signaling theory, with implications for practice.
Andrew Jackson and US Foreign Relations
Authors: Opal J.M.
Published: August 2018

The foreign relations of the Jacksonian age reflected Andrew Jackson’s own sense of the American “nation” as long victimized by non-white enemies and weak politicians. His goal as president from 1829 to 1837 was to restore white Americans’ “sovereignty,” to empower them against other nations both within and beyond US territory. Three priorities emerged from this conviction.

First, Jackson was determined to deport the roughly 50,000 Creeks, Cherokees, Choctaws, Chickasaws, and Seminoles living in southern states and territories. He saw them as hostile nations who threatened American safety and checked American prosperity. Far from a domestic issue, Indian Removal was an imperial project that set the stage for later expansion over continental and oceanic frontiers.

Second and somewhat paradoxically, Jackson sought better relations with Great Britain. These were necessary because the British Empire was both the main threat to US expansion and the biggest market for slave-grown exports from former Indian lands. Anglo-American détente changed investment patterns and economic development throughout the Western Hemisphere, encouraging American leaders to appease London even when patriotic passions argued otherwise.

Third, Jackson wanted to open markets and secure property rights around the globe, by treaty if possible but by force when necessary. He called for a larger navy, pressed countries from France to Mexico for outstanding debts, and embraced retaliatory strikes on “savages” and “pirates” as far away as Sumatra. Indeed, the Jacksonian age brought a new American presence in the Pacific. By the mid-1840s the United States was the dominant power in the Hawaiian Islands and a growing force in China. The Mexican War that followed made the Union a two-ocean colossus—and pushed its regional tensions to the breaking point.
Pilgrimage in Buddhist Tibet
Authors: Donnelly Paul B.
Published: August 2018

The English word “pilgrimage” has been used to translate the Tibetan nekor or nejel, which means to circumambulate or to meet a sacred place, respectively. “Tibet” here refers not only to the modern Tibetan Autonomous Region but also to what has been called “Ethnographic Tibet.” This area includes the three provinces of Utsang, Kham, and Amdo, but also regions outside the modern political borders of China, such as Ladakh, Zangskar, Bhutan, Dolpo, and Mustang. The people across these regions share a common written language, largely similar social institutions and values, and a shared sense of historical connection. Though lesser known in the West than the doctrinal and meditative traditions of Tibet, pilgrimage has always been central to the religious lives of the people of the Tibetan cultural regions. In fact, while doctrine and meditation have been the purview of the elite monastic scholarly minority, pilgrimage has been far more pervasive and practiced by laypeople as well as the monastics for purposes both worldly and soteriological. Though religious elites or even ordinary Tibetans may describe pilgrimages in sophisticated Buddhist doctrinal terms, what they actually do is often as rooted in indigenous Tibetan conceptions of place and sacred power as it is in Buddhism.

The concept of sacred place preceded the introduction of Buddhism into Tibet, and sacred places have remained important to both adherents of the Bön religion and of Buddhism. Pilgrimage to holy mountains, lakes, caves, and “hidden lands” was, and remains, central to Bön practice. This fact is consistent with the Bönpos’ self-identification as the preservers of the indigenous religion of Tibet. Buddhists in Tibet visited and venerated these powerful places, either overwriting their pre-Buddhist understandings with Buddhist ones or allowing the autochthonous powers respect alongside Buddhist practice. One well-known myth describes the Buddhist taming of Tibet in terms of Buddhist masters subduing and pinning down a demoness identified with the land of Tibet itself. Once tamed, mountains, lakes, caves, and hidden lands became understood in terms of tantric Buddhist doctrine and practice. After the conquest of Tibet by the People’s Republic of China (PRC) in 1950, pilgrimage became difficult for many Tibetans. This remained the case until the liberalizations of the PRC in Tibet in the mid-1980s. This shift allowed Tibetans to resume the practice of pilgrimage and opened Tibet to Western scholars interested in the practice. Since the mid-1990s, scholarship on Tibetan pilgrimage has flourished, and some scholars have turned their attention to pilgrimage in the ethnographically Tibetan regions in Northern India.
Excavation and Exhibition of the Pre-Hispanic Cultures during the Porfiriato
Authors: Bueno Christina
Published: August 2018

In the late 19th century, Mexico’s ancient ruins captivated much of the world. European and American explorers trekked through what was often touted as an “American Egypt” in search of pre-Columbian artifacts to display in private collections and museums. Mexicans similarly hunted after the remains of the Indian past, as their country witnessed a heightened interest in the excavation and exhibition of ancient artifacts during the dictatorship of Porfirio Díaz, the period commonly known as the Porfiriato (1876–1910). The Díaz regime embraced the indigenous past in order to present Mexico as a nation with ancient and prestigious roots. It took control of pre-Hispanic relics and ruins through archaeology, a discipline that was thought to give Mexico the coveted aura of a scientific, cosmopolitan, and modern nation. The Díaz regime gave unprecedented support to the National Museum in Mexico City, the nation’s most important institution for the study and display of Indian antiquity. Museum scholars such as Francisco del Paso y Troncoso, Alfredo Chavero, and Antonio Peñafiel, worked on building and organizing the archaeology collection as the government intensified the process of accumulating artifacts in the capital. One of the central figures in this process was Leopoldo Batres, the head of the General Inspectorate of Archaeological Monuments of the Republic. Batres brought antiquities to the museum, helped organize the archaeology collection, and built the Gallery of Monoliths, the nation’s premier showcase of pre-Columbian relics. He also carried out excavations at ruins throughout the country and reconstructed several archaeological sites, including Xochicalco and Mitla. His most famous (and most controversial) work took place at Teotihuacán, where he rebuilt the Pyramid of the Sun, turning Teotihuacán into the nation’s first official archaeological site, a project made to coincide with the centennial celebration of Mexican independence in 1910.
The Jewish Patriarchate
Authors: Levine Lee I.
Published: August 2018

The Jewish Patriarch (Hebr. Nasi) was the leading Jewish communal official in the late Roman and early Byzantine Empires, in both Palestine and the Diaspora. The Patriarchate, which emerged around the turn of the 3rd century under the leadership of Rabbi Judah I, had the support of the Severan dynasty (193–235 ce). The testimony of Origen (Letter to Africanus 14), who lived in Caesarea c. 230, views the function of the “Jewish ethnarch” (another term for Patriarch) as that of a king, enjoying, inter alia, the power of capital punishment.

Non-Jewish sources from the 4th century attest that the Patriarch enjoyed extensive prestige and recognition. The Theodosian Code is particularly revealing in this regard. One decree, issued by the emperors Arcadius and Honorius in 397, spells out the dominance of the Patriarch in a wide range of synagogue affairs; he stood at the head of a network of officials, including archisynagogues, presbyters, and others—all of whom had privileges on a par with the Christian clergy. Together with other realms of Patriarchal authority noted in earlier rabbinic literature, such as making calendrical decisions, declaring public fast days, and issuing bans, the prominence of this office in Jewish communal and religious life had become quite pronounced at this time.

The Patriarchate’s disappearance around 425 ce (for reasons unknown) was the last vestige of a unifying public office for Jews living under Roman domination.
Origin and Development of Agriculture in New Guinea, Island Melanesia, and Polynesia
Authors: Denham Tim
Published: August 2018

Early agricultural and arboricultural practices in the Pacific are based on vegetative principles, namely, the asexual propagation and transplantation of plants. A vegetative orientation is reflected in the exploitation of underground storage organs (USOs) within Near Oceania, as well as Island Southeast Asia, during the Pleistocene. During the early Holocene, people in the New Guinea region (including Near Oceania) began to intensify the management of plant resources in different landscapes. The increased degree of plant management, as well as associated environmental transformation, is most clearly manifest in the agricultural chronology at Kuk Swamp in the highlands of Papua New Guinea. At Kuk, shifting cultivation was potentially practiced during the early Holocene, with mounded cultivation by c. 7000–6400 cal BP and ditched drainage of wetlands for cultivation by c. 4400–4000 cal BP. Comparable agricultural records are lacking for other regions of Near Oceania; lowland sites indicate a range of arboricultural practices focused on fruit- and nut-bearing trees during the Terminal Pleistocene and throughout the Holocene, as well as potentially sago during the late Holocene. By c. 4000–3000 cal BP, indigenous agricultural and arboricultural elements were integrated with new cultural traits from Southeast Asia, including domestic animals, pottery and potentially new varieties of traditional crops. From c. 3250 to 2800 cal BP, different elements of agricultural and arboricultural practices from lowland New Guinea and Island Melanesia were taken by Lapita pottery–bearing colonists into the western Pacific. A later period of agricultural expansion occurred around c. 1000–750 cal BP with the colonization of eastern Polynesia. Agricultural practices and crops were variably taken and adapted to different islands and island groups across the Pacific. Additional transformations to agriculture occurred with the Polynesian adoption of the sweet potato (Ipomoea batatas), a South American domesticate, as well as following protohistoric and historic encounters.
Drug Gene Budger (DGB): an application for ranking drugs to modulate a specific gene based on transcriptomic signatures
Authors: Wang Zichen , He Edward , Sani Kevin , Jagodnik Kathleen M , Silverstein Moshe C , Ma’ayan Avi
Published: August 2018

Mechanistic molecular studies in biomedical research often discover important genes that are aberrantly over- or under-expressed in disease. However, manipulating these genes in an attempt to improve the disease state is challenging. Herein, we reveal Drug Gene Budger (DGB), a web-based and mobile application developed to assist investigators in order to prioritize small molecules that are predicted to maximally influence the expression of their target gene of interest. With DGB, users can enter a gene symbol along with the wish to up-regulate or down-regulate its expression. The output of the application is a ranked list of small molecules that have been experimentally determined to produce the desired expression effect. The table includes log-transformed fold change, P-value and q-value for each small molecule, reporting the significance of differential expression as determined by the limma method. Relevant links are provided to further explore knowledge about the target gene, the small molecule and the source of evidence from which the relationship between the small molecule and the target gene was derived. The experimental data contained within DGB is compiled from signatures extracted from the LINCS L1000 dataset, the original Connectivity Map (CMap) dataset and the Gene Expression Omnibus (GEO). DGB also presents a specificity measure for a drug–gene connection based on the number of genes a drug modulates. DGB provides a useful preliminary technique for identifying small molecules that can target the expression of a single gene in human cells and tissues.

Availability and implementation

The application is freely available on the web at http://DGB.cloud and as a mobile phone application on iTunes https://itunes.apple.com/us/app/drug-gene-budger/id1243580241? mt=8 and Google Play https://play.google.com/store/apps/details? id=com.drgenebudger.

Supplementary information

Supplementary data are available at Bioinformatics online.
PhysiBoSS: a multi-scale agent-based modelling framework integrating physical dimension and cell signalling
Authors: Letort Gaelle , Montagud Arnau , Stoll Gautier , Heiland Randy , Barillot Emmanuel , Macklin Paul , Zinovyev Andrei , Calzone Laurence
Published: August 2018

Motivation

Due to the complexity and heterogeneity of multicellular biological systems, mathematical models that take into account cell signalling, cell population behaviour and the extracellular environment are particularly helpful. We present PhysiBoSS, an open source software which combines intracellular signalling using Boolean modelling (MaBoSS) and multicellular behaviour using agent-based modelling (PhysiCell).

Results

PhysiBoSS provides a flexible and computationally efficient framework to explore the effect of environmental and genetic alterations of individual cells at the population level, bridging the critical gap from single-cell genotype to single-cell phenotype and emergent multicellular behaviour. PhysiBoSS thus becomes very useful when studying heterogeneous population response to treatment, mutation effects, different modes of invasion or isomorphic morphogenesis events. To concretely illustrate a potential use of PhysiBoSS, we studied heterogeneous cell fate decisions in response to TNF treatment. We explored the effect of different treatments and the behaviour of several resistant mutants. We highlighted the importance of spatial information on the population dynamics by considering the effect of competition for resources like oxygen.

Availability and implementation

PhysiBoSS is freely available on GitHub (https://github.com/sysbio-curie/PhysiBoSS), with a Docker image (https://hub.docker.com/r/gletort/physiboss/). It is distributed as open source under the BSD 3-clause license.

Supplementary information

Supplementary data are available at Bioinformatics online.
ANNOgesic: a Swiss army knife for the RNA-seq based annotation of bacterial/archaeal genomes
Authors: Yu Sung-Huan , Vogel Jörg , Förstner Konrad U
Published: August 2018

To understand the gene regulation of an organism of interest, a comprehensive genome annotation is essential. While some features, such as coding sequences, can be computationally predicted with high accuracy based purely on the genomic sequence, others, such as promoter elements or noncoding RNAs, are harder to detect. RNA sequencing (RNA-seq) has proven to be an efficient method to identify these genomic features and to improve genome annotations. However, processing and integrating RNA-seq data in order to generate high-resolution annotations is challenging, time consuming, and requires numerous steps. We have constructed a powerful and modular tool called ANNOgesic that provides the required analyses and simplifies RNA-seq-based bacterial and archaeal genome annotation. It can integrate data from conventional RNA-seq and differential RNA-seq and predicts and annotates numerous features, including small noncoding RNAs, with high precision. The software is available under an open source license (ISCL) at https://pypi.org/project/ANNOgesic/.
Assessing Negative Response Bias in Competency to Stand Trial Evaluations
Authors: Rubenzer Steven J.
Published: August 2018

Assessing Negative Response Bias in Competency to Stand Trial Evaluations provides a comprehensive guide to assessing malingering, feigning, poor effort, and lack of cooperation in competency to stand trial (CST) examinations. It draws on both the author’s extensive experience as a CST examiner and the vast, dynamic professional literature from forensic psychology, clinical psychology, and neuropsychology on assessing response style. The assessment process is considered from beginning to report writing and testimony, with tips regarding interview strategies, fact patterns and behaviors suggestive of feigning, testing, and creative and ethical use of collateral data. Every major validity test used by CST examiners is thoroughly and critically reviewed, as are others that are promising and not yet widely adopted. This includes self-report inventories such as the MMPI-2, MMPI-2-RF, PAI, and SIMS; structured interviews like the SIRS, SIRS-2, and M-FAST; performance validity tests like the TOMM, VIP, 15 item Test, and WMT; and CST-specific tests like the ILK and ECST-R Atypical Presentation Scales. A complete chapter is devoted to means to summarize and combine data from different tests and sources, and another to special populations such as defendants who claim amnesia, are intellectually disabled, or are adolescents. Report writing and testimony considerations are discussed in detail, with implications for the assessment and practice. In Chapter 10, CST examiners’ practices, including preferences for tests and collateral sources, are reported along with the perceived prevalence of various invalid presentation styles. Finally, policy implications of feigning and suggestions for cost-effective practice are provided.
Pulmonary embolism
Authors: Katritsis Demosthenes G. , Gersh Bernard J. , Camm A. John
Published: August 2018

Venous thromboembolism denotes pulmonary embolism and deep venous thrombosis. This chapter addresses the diagnosis, acute therapy, and prophylaxis of pulmonary embolism.
Chronic Pain Self-Management Program for Low-Income Patients: Themes from a Qualitative Inquiry
Authors: Turner Barbara J , Rodriguez Natalia , Bobadilla Raudel , Hernandez Arthur E , Yin Zenong
Published: August 2018

Objective

To examine factors influencing initial engagement, ongoing participation, learned behaviors, and subjective functional outcomes after a trial of the Living Better Beyond Pain (LBBP) chronic pain self-management program.

Design

Qualitative study using the Grounded Theory approach.

Setting

Two 60-minute focus groups and phone interviews in May 2017.

Subjects

Focus groups with 18 participants who completed LBBP and six-month measures; telephone interviews with 17 participants who stopped attending.

Methods

Study coordinators randomly selected program completers for focus groups and conducted phone interviews with noncompleters. Inductive thematic analysis was used to identify patterns in semantic content with a recursive process applied to focus group transcripts and interview transcriptions to codify into themes. Themes were categorized according to the Theory of Planned Behavior.

Results

Focus group and telephone interview participants were primarily Hispanic and unemployed. Attitudes fostering participation in LBBP included dissatisfaction with the status quo, need to reduce pain medication, and lack of training and knowledge about chronic pain. Positive social norms from meeting others with chronic pain and support from the LBBP team encouraged attendance and adoption of behaviors. Transportation, pain, and competing activities were barriers, whereas adapting activities for the disabled was a facilitator. Maintaining behaviors and activities at home was challenging but ultimately rewarding due to improvement in daily function with less pain medication.

Conclusions

This qualitative study complements quantitative results showing clinically significant improvements in function after the LBBP program by adding practical insights into ways to increase participation and outcomes. Participants strongly endorsed the need for chronic pain self-management training.
Predicting Performance of First-Year Residents: Correlations Between Structured Interview, Licensure Exam, and Competency Scores in a Multi-Institutional Study
Authors: Marcus-Blank Brittany , Dahlke Jeffrey A. , Braman Jonathan P. , Borman-Shoap Emily , Tiryaki Ezgi , Chipman Jeffrey , Andrews John S. , Sackett Paul R. , Cullen Michael J.
Published: August 2018

Purpose

To determine whether scores on structured interview (SI) questions designed to measure noncognitive competencies in physicians (1) predict subsequent first-year resident performance on Accreditation Council for Graduate Medical Education (ACGME) milestones and (2) add incremental validity over United States Medical Licensing Examination (USMLE) Step 1 and Step 2 Clinical Knowledge scores in predicting performance.

Method

The authors developed 18 behavioral description questions to measure key noncognitive competencies (e.g., teamwork). In 2013–2015, 14 programs (13 residency, 1 fellowship) from 6 institutions used subsets of these questions in their selection processes. The authors conducted analyses to determine the validity of SI and USMLE scores in predicting first-year resident milestone performance in the ACGME’s core competency domains and overall.

Results

SI scores predicted midyear and year-end overall performance (r = 0.18 and 0.19, respectively, P < .05) and year-end performance on patient care, interpersonal and communication skills, and professionalism competencies (r = 0.23, r = 0.22, and r = 0.20, respectively, P < .05). SI scores contributed incremental validity over USMLE scores in predicting year-end performance on patient care (ΔR = 0.05), interpersonal and communication skills (ΔR = 0.09), and professionalism (ΔR = 0.09; all P < .05). USMLE scores contributed incremental validity over SI scores in predicting year-end performance overall and on patient care and medical knowledge.

Conclusions

SI scores predict first-year resident year-end performance in the interpersonal and communication skills, patient care, and professionalism competency domains. Future research should investigate whether SIs predict a range of clinically relevant outcomes.
Approaches to Teaching the Physical Exam to Preclerkship Medical Students: Results of a National Survey
Authors: Uchida Toshiko , Park Yoon Soo , Ovitsh Robin K. , Hojsak Joanne , Gowda Deepthiman , Farnan Jeanne M. , Boyle Mary , Blood Angela D. , Achike Francis I. , Silvestri Ronald C.
Published: August 2018

Purpose

To assess current approaches to teaching the physical exam to preclerkship students at U.S. medical schools.

Method

The Directors of Clinical Skills Courses developed a 49-question survey addressing the approach, pedagogical methods, and assessment methods of preclerkship physical exam curricula. The survey was administered to all 141 Liaison Committee on Medical Education–accredited U.S. medical schools in October 2015. Results were aggregated across schools, and survey weights were used to adjust for response rate and school size.

Results

One hundred six medical schools (75%) responded. Seventy-nine percent of schools (84) began teaching the physical exam within the first two months of medical school. Fifty-six percent of schools (59) employed both a “head-to-toe” comprehensive approach and a clinical reasoning approach. Twenty-three percent (24) taught a portion of the physical exam interprofessionally. Videos, online modules, and simulators were used widely, and 39% of schools (41) used bedside ultrasonography. Schools reported a median of 4 formative assessments and 3 summative assessments, with 16% of schools (17) using criterion-based standard-setting methods for physical exam assessments. Results did not vary significantly by school size.

Conclusions

There was wide variation in how medical schools taught the physical exam to preclerkship students. Common pedagogical approaches included early initiation of physical exam instruction, use of technology, and methods that support clinical reasoning and competency-based medical education. Approaches used by a minority of schools included interprofessional education, ultrasound, and criterion-based standard-setting methods for assessments. Opportunities abound for research into the optimal methods for teaching the physical exam.
Current Basal and Squamous Cell Skin Cancer Management
Authors: Mendez Bernardino M. , Thornton James F.
Published: August 2018

Learning Objectives:

After studying this article, the participant should be able to: 1. Characterize basal and squamous cell carcinomas as low or high risk based on size, location, histology, and clinical features. 2. Understand appropriate surgical margins in low- and high-risk lesions, and other management options, including Mohs micrographic surgery, electrodissection and curettage, topical agents, cryotherapy, photodynamic therapy, and radiation therapy. 3. Discuss adjuvant therapies for locally advanced and metastatic disease, including radiation therapy, chemotherapy, and targeted therapies such as hedgehog pathway inhibitors. 4. Educate patients on preventive measures such as skin examinations, sun protection, oral retinoids, and oral nicotinamide (vitamin B3). 5. Devise a reconstructive plan once clear oncologic margins are obtained.

With the growing incidence of basal and squamous cell carcinoma, there is an increasing demand for appropriate oncologic management and aesthetic reconstruction. The goal of this CME article is to provide a foundation of knowledge to accurately diagnose, stage, and treat nonmelanoma skin cancers. In addition, it provides the practicing plastic surgeon alternate tools for managing these skin lesions, including topical agents, destructive therapies, and radiation therapy. Lastly, reconstructive plans for selected soft-tissue defects are discussed.
Current Evidence in Cardiothoracic Imaging: Growing Evidence for Coronary Computed Tomography Angiography as a First-line Test in Stable Chest Pain
Authors: Maroules Christopher D. , Rajiah Prabhakar , Bhasin Mohit , Abbara Suhny
Published: August 2018

Coronary computed tomography angiography (CCTA) is a validated technique for the evaluation of patients with suspected coronary artery disease, showing high accuracy compared with invasive coronary angiography and high negative predictive value. CCTA is also well positioned as a first-line test for the evaluation of stable chest pain. This purpose of this review is to examine the evidence behind CCTA in the setting of stable chest pain, with attention to 5 key strengths of a CCTA-based approach: (1) effective gatekeeping to cardiac catheterization, (2) selective discrimination for revascularization and tailored medical therapy, (3) advanced risk stratification, (4) improvement in outcomes, and (5) support from multisociety guidelines. Given the expansion of CT technologies to include functional strategies for evaluating ischemia both with and without vasodilators, CCTA is poised to become the comprehensive examination for stable chest pain and anginal equivalent cardiopulmonary symptoms.
Effect of Navigation System on Removal of Foreign Bodies in Head and Neck Surgery
Authors: Ji Yefeng , Jiang Hongbing , Wan Linzhong , Yuan Hua
Published: August 2018

Foreign bodies retained in oral and maxillofacial regions include different types and properties. Road traffic accident is one of the major causes of the maxillofacial trauma. Foreign bodies can cause direct or indirect damage to the body, even life-threatening. It is a demanding procedure to detect the accurate position and implement surgical removal of the embedded fragments in the soft tissue in clinic.

Usually, foreign bodies are close to important structures such as the head and neck region with limited intraoperative visibility and anatomical intricacies. Therefore, the key to remove foreign bodies in head and neck surgery is precise localization and reasonable surgical approaches. The authors reported that the foreign bodies adjacent to large vessels in a case were successfully removed assisted by AccuNavi-A surgical navigation system.
Kidney Transplant Outcomes in Recipients With Cognitive Impairment: A National Registry and Prospective Cohort Study
Authors: Thomas Alvin G. , Ruck Jessica M. , Shaffer Ashton A. , Haugen Christine E. , Ying Hao , Warsame Fatima , Chu Nadia , Carlson Michelle C. , Gross Alden L. , Norman Silas P. , Segev Dorry L. , McAdams-DeMarco Mara
Published: August 2018

Background.

Cognitive impairment is common in patients with end-stage renal disease and is associated with poor outcomes on dialysis. We hypothesized that cognitive impairment might be associated with an increased risk of all-cause graft loss (ACGL) in kidney transplant (KT) recipients.

Methods.

Using the Modified Mini-Mental State (3MS) examination, we measured global cognitive function at KT hospital admission in a prospective, 2-center cohort of 864 KT candidates (August 2009 to July 2016). We estimated the association between pre-KT cognitive impairment and ACGL using Cox regression, adjusting for recipient, donor, and transplant factors.

Results.

In living donor KT (LDKT) recipients, the prevalence was 3.3% for mild impairment (60 ≤ 3MS < 80) and 3.3% for severe impairment (3MS < 60). In deceased donor KT (DDKT) recipients, the prevalence was 9.8% for mild impairment and 2.6% for severe impairment. The LDKT recipients with cognitive impairment had substantially higher ACGL risk than unimpaired recipients (5-year ACGL: 45.5% vs 10.6%; P < 0.01; adjusted hazard ratio [aHR] any impairment, 5.40 (95% confidence interval [CI], 1.78-16.34; P < 0.01); aHR severe impairment, 5.57 (95% CI, 1.29-24.00; P = 0.02). Similarly, DDKT recipients with severe impairment had higher ACGL risk than recipients without severe impairment (5-year ACGL, 53.0% vs 24.2%; P = 0.04); aHR severe impairment, 2.92 (95% CI, 1.13-7.50; P = 0.03).

Conclusions.

Given the elevated risk of ACGL among KT recipients with cognitive impairment observed in this 2-center cohort, research efforts should explore the mechanisms of graft loss and mortality associated with cognitive impairment and identify potential interventions to improve posttransplant survival.
Incorporation of doxorubicin in different polymer nanoparticles and their anti-cancer activity
Authors: Pieper S. , Onafuye H. , Mulac D. , Cinatl Jindrich , Wass Mark N. , Michaelis M. , Langer K.
Published: August 2018

Nanoparticles are under investigation as carrier systems for anti-cancer drugs. They have been shown to accumulate in cancer tissues through the enhanced permeability and retention (EPR) effect, to reduce toxicity to non-target tissues, and to protect drugs from preliminary inactivation. However, nanoparticle preparations are not commonly compared for their anti-cancer effects at the cellular level. Here, we prepared doxorubicin-loaded nanoparticles based on poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), and PEGylated PLGA (PLGA-PEG) by solvent displacement and emulsion diffusion approaches. The resulting nanoparticles covered a size range between 73 and 246 nm. PLGA-PEG nanoparticle preparation by solvent displacement resulted in the smallest nanoparticles. In PLGA nanoparticles, the drug load could be optimised using solvent displacement at pH7 reaching 53 µg doxorubicin/mg nanoparticle. In addition, these PLGA nanoparticles displayed sustained doxorubicin release kinetics compared to the more burst-like kinetics of the other preparations. In neuroblastoma cells, doxorubicin-loaded PLGA-PEG nanoparticles (presumably due to their small size) and PLGA nanoparticles prepared by solvent displacement at pH7 (presumably due to their high drug load and superior drug release kinetics) exerted the strongest anti-cancer effects. In conclusion, doxorubicin-loaded nanoparticles made by different methods from different materials displayed substantial discrepancies in their anti-cancer activity at the cellular level. Optimised preparation methods resulted in PLGA nanoparticles characterised by increased drug load, controlled drug release, and high anti-cancer efficacy. The design of drug-loaded nanoparticles with optimised anti-cancer activity at the cellular level is an important step in the development of improved nanoparticle preparations for anti-cancer therapy.
Exploration of inositol 1,4,5-trisphosphate (IP3) regulated dynamics of N-terminal domain of IP3 receptor reveals early phase molecular events during receptor activation
Authors: Chandran Aneesh , Chee Xavier , Prole David L. , Rahman Taufiq
Published: August 2018

Inositol 1, 4, 5-trisphosphate (IP3) binding at the N-terminus (NT) of IP3 receptor (IP3R) allosterically triggers the opening of a Ca2+-conducting pore located ~ 100 Å away from the IP3-binding core (IBC). However, the precise mechanism of IP3 binding and correlated domain dynamics in the NT that are central to the IP3R activation, remains unknown. Our all-atom molecular dynamics (MD) simulations recapitulate the characteristic twist motion of the suppresser domain (SD) and reveal correlated ‘clam closure’ dynamics of IBC with IP3-binding, complementing existing suggestions on IP3R activation mechanism. Our study further reveals the existence of inter-domain dynamic correlation in the NT and establishes the SD to be critical for the conformational dynamics of IBC. Also, a tripartite interaction involving Glu283-Arg54-Asp444 at the SD – IBC interface seemed critical for IP3R activation. Intriguingly, during the sub-microsecond long simulation, we observed Arg269 undergoing an SD-dependent flipping of hydrogen bonding between the first and fifth phosphate groups of IP3. This seems to play a major role in determining the IP3 binding affinity of IBC in the presence/absence of the SD. Our study thus provides atomistic details of early molecular events occurring within the NT during and following IP3 binding that lead to channel gating.
Evidence for minimal cardiogenic potential of Sca-1 positive cells in the adult mouse heart
Authors: Neidig Lauren E. , Weinberger Florian , Palpant Nathan J. , Mignone John , Martinson Amy M. , Sorensen Daniel W. , Bender Ingrid , Nemoto Natsumi , Reinecke Hans , Pabon Lil , Molkentin Jeffery D. , Murry Charles E. , van Berlo Jop H.
Published: August 2018

Background

Despite modern pharmacotherapy, heart failure remains a major medical burden. The heart has a limited regenerative capacity, and bolstering regeneration might represent new therapeutic approaches for heart failure patients. Various progenitor cells in the heart have been proposed to have cardiomyogenic properties, but this evidence is based mostly on cell culture and transplantation studies. One population of interest is characterized by the expression of Stem Cell Antigen-1 (Sca-1). Here we tested the hypothesis that Sca-1+cells are endogenous progenitors for cardiomyocytes in the adult heart.

Methods

We evaluated the innate cardiogenic potential of Sca-1+cellsin vivoby generating a novel mouse model to genetically lineage-trace the fate of Sca-1 expressing cells. This was accomplished by introducing a tamoxifen-inducible Cre-recombinase into the Sca-1 locus (Sca-1mCm/+). Crossing this mouse line to a Cre-dependent tdTomato reporter line allowed for genetic lineage-tracing of endogenous Sca-1+cells (Sca-1mCmR26tdTomato). The frequency of Sca-1+cardiomyocytes was quantified from dispersed cell preparations and confirmed by in situ histology.

Results

We validated the genetic lineage tracing mouse model in bone marrow and heart. Unlike previous publications suggesting significant cardiogenic potential, we found that less than 0.02% of cardiomyocytes per year were derived from Sca-1+cells in the adult heart under homeostatic conditions. At six months after myocardial infarction, we found less than 0.01% of cardiomyocytes were derived from Sca-1+cells.

Conclusion

Our results show that Sca-1+cells in the adult heart have minimal cardiogenic potential under homeostatic conditions or in response to myocardial infarction.
HIV-1 Protease Uses Bi-Specific S2/S2’ Subsites To Optimize Cleavage of Two Classes of Target Sites
Authors: Potempa Marc , Lee Sook-Kyung , KurtYilmaz Nese , Nalivaika Ellen A. , Rogers Amy , Spielvogel Ean , Carter Charles W. , Schiffer Celia A. , Swanstrom Ronald
Published: August 2018

Retroviral proteases (PR) have a unique specificity that allows cleavage of sites with or without a P1’ proline. A P1’ proline is required at the MA/CA cleavage site due to its role in a post-cleavage conformational change in the capsid protein. However, the HIV-1 PR prefers to have large hydrophobic amino acids flanking the scissile bond, suggesting PR recognizes two different classes of substrate sequences. We analyzed the cleavage rate of over 150 iterations of six different HIV-1 cleavage sites to explore rate determinants of cleavage. We found that cleavage rates are strongly influenced by the two amino acids flanking the amino acids at the scissile bond (P2-P1/P1’-P2’), with two complementary sets of rules. When P1’ is proline, the P2 side chain interacts with a polar region in the S2 subsite of the PR, while the P2’ amino acid interacts with a hydrophobic region of the S2’ subsite. When P1’ is not proline, the orientations of the P2 and P2’ side chains with respect to the scissile bond are reversed; P2 residues interact with a hydrophobic face of the S2 subsite while the P2’ amino acid usually engages hydrophilic amino acids in the S2’ subsite. These results reveal that the HIV-1 PR has evolved bi-functional S2 and S2’ subsites to accommodate the steric effects imposed by a P1’ proline on the orientation of P2 and P2’ substrate side chains. These results also suggest a new strategy for inhibitor design to engage the multiple specificities in these subsites.
Bayesian-estimated hierarchical HMMs enable robust analysis of single-molecule kinetic heterogeneity
Authors: Hon Jason , Gonzalez Ruben L.
Published: August 2018

Single-molecule kinetic experiments allow the reaction trajectories of individual biomolecules to be directly observed, eliminating the effects of population averaging and providing a powerful approach for elucidating the kinetic mechanisms of biomolecular processes. A major challenge to the analysis and interpretation of these experiments, however, is the kinetic heterogeneity that almost universally complicates the recorded single-molecule signal versus time trajectories (i.e., signal trajectories). Such heterogeneity manifests as changes and/or differences in the transition rates that are observed within individual signal trajectories or across a population of signal trajectories. Although characterizing kinetic heterogeneity can provide critical mechanistic information, there are currently no computational methods available that effectively and/or comprehensively enable such analysis. To address this gap, we have developed a computational algorithm and software program, hFRET, that uses the variational approximation for Bayesian inference to estimate the parameters of a hierarchical hidden Markov model, thereby enabling robust identification and characterization of kinetic heterogeneity. Using simulated signal trajectories, we demonstrate the ability of hFRET to accurately and precisely characterize kinetic heterogeneity. In addition, we use hFRET to analyze experimentally recorded signal trajectories reporting on the conformational dynamics of ribosomal pre-translocation (PRE) complexes. The results of our analyses demonstrate that PRE complexes exhibit kinetic heterogeneity, reveal the physical origins of this heterogeneity, and allow us to expand the current model of PRE complex dynamics. The methods described here can be applied to signal trajectories generated using any type of signal and can be easily extended to the analysis of signal trajectories exhibiting more complex kinetic behaviors. Moreover, variations of our approach can be easily developed to integrate kinetic data obtained from different experimental constructs and/or from molecular dynamics simulations of a biomolecule of interest. The hFRET source code, graphical user interface, and user manual can be downloaded as freeware at https://github.com/GonzalezBiophysicsLab/hFRET.