bluuebunny/crossref_metadata_2025 huggingface dataset:
Classroom Discussions
Authors: Murphy P. Karen , Firetto Carla M. , Lloyd Gwendolyn M. , Wei Liwei , Baszczewski Sara E.
Published: March 2020

Classroom discussions are a common pedagogical approach that involve verbal exchanges of information between teachers and students. Given their importance to teaching and learning, classroom discussions have been the focus of extensive curricular mandates and, to a lesser extent, research over the last several decades. In traditional classroom discussions, the teacher tends to be situated at the center of the discussion. This type of discussion model is commonly referred to as a transmissionary model, where the teacher transmits knowledge and understandings and often leads the discussion by posing factual questions and responding to students’ answers by giving evaluative feedback. However, productive classroom discussions are better characterized by a dialogic model with students at the center of the discussion. When students are encouraged to ask thoughtful questions, give reflective responses, and challenge each other using reasoned arguments within classroom discussions, they are more likely to become builders and owners of their knowledge. Indeed, productive classroom discussions tend to ignite students’ engagement, thinking, and understanding of knowledge across academic content areas. When adopting a dialogic model, classroom discussions can advance students’ learning by promoting their basic and high-level comprehension of literary text, reasoning, and argumentation during mathematical sense-making, scientific reasoning, and model building and even second-language proficiency and communicative competence. While the overarching aim of classroom discussions is to enhance student learning across content areas (e.g., language arts, mathematics, science, or second-language learning), the various roles that teachers assume in each of the content areas may have different emphases that align with various content learning expectations. Optimizing classroom discussions requires specific considerations of the content-focused goal, teacher knowledge of content and discourse orchestration, student instruction on classroom talk, and context of content learning. Importantly, the potential and promise of productive classroom discussions can be realized by supporting teachers’ content-specific discussion practices through sustained professional development and by supporting students through explicit instruction about discussion.
Congo in the Americas and Brazil
Authors: Souza Marina
Published: March 2020

In the late 15th century, the coast of West-Central Africa was integrated into Atlantic trading circuits due to the actions of Portuguese navigators and traders, supported by the Crown and followed by the Dutch, French, and English. Thousands of people were enslaved through Congolese routes and sold several times until they reached the Americas, where they were put to work in agriculture, artisanal activities, cargo transportation, mining, and domestic and urban services, among many others. The enslaved Central Africans, for three centuries brought to the Caribbean and the Americas, and especially to Brazil, established new communities and cultural manifestations from the knowledge and sensibilities that they brought from their societies of origin.

The Congo has been present in the Americas in many ways. One of these was the election of a Congo king, celebrated with festive processions, in which the royal couple and their court paraded through the streets and attended dances with special choreographies set to African musical rhythms. These celebrations articulated and consolidated black identities and existed in various parts of the Americas and the Caribbean. In Brazil, they have been a tradition since colonial times and still go on today, referred to as congadas. Such festivities project an abstract idea of primordial motherland onto the memory of a mythic Congo, annually updated in festive rites that celebrate a Catholic African king and affirm black identities in Brazilian society.
Women in Somalia
Authors: Aidid Safia
Published: March 2020

Although Somali women have played a dynamic and important role in the making of Somalia’s history, their histories have been obscured by archival limitations and androcentric scholarship. Women in traditional Somali society—pastoralists, agriculturalists, and urbanites alike—were central to their communities for their reproductive and productive labor. They embodied social capital, as the practice of exogamous marriage that brought them to other communities also created important reciprocal relations between different kinship groups. Although a deeply patriarchal culture defined their life roles primarily as wives and mothers, Somali women used that very culture and the indigenous resources available to them to exercise agency, negotiate their positions, and carve out their own spaces. The advent of colonial rule, which partitioned the Somali peninsula between Britain, France, Italy, and the Ethiopian empire, drastically altered women’s lives. It fused traditional patriarchal relations with European ones, codified tradition and flexible communal identities, treated women as dependents of their male relatives, and created opportunities for men in education and employment that were not available to women. Though Somali women were at the forefront of the anticolonial struggle, the male elite who inherited the state after independence excluded women from the political sphere. Women’s rights took on a prominent role in the military dictatorship of General Mohamed Siad Barre, yet the repression and state violence that characterized his rule affected women acutely. The civil war that followed the disintegration of the Somali state has similarly affected women intimately. In addition to the gendered experience of violence, the increasingly conservative nature of Somali society has resulted in the loss of many gains made for women’s rights after independence. From precolonial society to colonial rule, dictatorship, and civil war, Somali women have exhibited the resilience, agency, and fortitude to make the most of their circumstances.
Girlhood in Africa
Authors: Bellows-Blakely Sarah
Published: March 2020

There is no singular or universal experience of girlhood in Africa. Conceptions of childhood, youth, generation, gender, and sexuality have differed across the continent and around the world over time. Since the 19th century, varying understandings of African girlhood have been deeply connected to the growth of racist hierarchies of human societies, the European colonization of Africa, African nationalisms, transnational feminist movements, and crises in capitalism. Case studies of two areas concerning African girlhood—female circumcision and the emergence of the girls’ rights movement—show how politicized girlhood in Africa has been. These two topics provide a distinct vantage point from which to understand far-reaching political processes and how these processes have uniquely played out in and through debates over girls’ bodies.
The Many Lives of Nelson Mandela
Authors: Lodge Tom
Published: March 2020

Biographical portrayals of Mandela have been strongly influenced by his own self-representations, beginning with his trial testimonies in 1962 and 1964. Authorized narratives about his life that were consolidated during the 1990s reflected Mandela’s political priorities at that time. In the unitary subject that these stories project—in the “unchanging man” whose story they told—their protagonist is a patrician-born aristocrat whose values and codes of behavior are shaped by his upbringing in the culture of a royal court. In important respects, though, this understanding of Mandela is at odds with earlier treatments of his life for which he had been a willing collaborator. Several of the biographical interpretations written in the early 21st-century draw upon archival evidence and prompt serious revisions of established or conventional understandings of Mandela’s life, particularly in terms of the validity of biographical investigations that emphasize consistency and order. Questions persist in the early 21st century as to whether Mandela’s experiences as a political prisoner and his role in constitutional negotiations will be subjected to such archive-based research, and whether the final stages of his public life will undergo an assessment.
Financial Inclusion and Human Development
Authors: Martinez Peria Maria Soledad , Shin Mu Yang
Published: March 2020

The link between financial inclusion and human development is examined here. Using cross-country data, the behavior of variables that try to capture these concepts is examined and preliminary evidence of a positive association is offered. However, because establishing a causal relationship with macro-data is difficult, a thorough review of the literature on the impact of financial inclusion, focusing on micro-studies that can better address identification is conducted. The literature generally distinguishes between different dimensions of financial inclusion: access to credit, access to bank branches, and access to saving instruments (i.e., accounts). Despite promising results from a first wave of studies, the impact of expanding access to credit seems limited at best, with little evidence of transformative effects on human development outcomes. While there is more promising evidence on the impact of expanding access to bank branches and formal saving instruments, studies show that some interventions such as one-time account opening subsidies are unlikely to have a sizable impact on social and economic outcomes. Instead well-designed interventions catering to individuals’ specific needs in different contexts seem to be required to realize the full potential of formal financial services to enrich human lives.
Global House Prices: Trends and Cycles
Authors: Ahir Hites , Loungani Prakash
Published: March 2020

On average across countries, house prices have been on an upward trend over the past 50 years, following a 100-year period over which there was no long-term increase. The rising trend in prices reflects a demand boost due to greater availability of housing finance running up against supply constraints, as land has increasingly become a fixed factor for many reasons. The entire 150-year period has been marked by boom and bust cycles around the trend. These also reflect episodes of demand momentum—due to cheap finance or reasonable or unreasonable expectations of higher incomes—meeting a sluggish supply response. Policy options to manage boom–bust cycles, given the significant costs to the economy from house price busts, are discussed.
Language as Social Action
Authors: Cavanaugh Jillian R.
Published: March 2020

Linguistic anthropology is the study of language as social action. Linguistic anthropologists study how people use language, and how, in using language, people are also defining and displaying who they are, enacting their membership in particular groups, and bringing various types of truths into being. Language, then, is a set of practices that people engage in every day in numerous forms, which helps to define their positions in their families, communities, workplaces, schools, and even nation-states. How one speaks is not only who one is—it is what one does. This is possible because language is multifunctional, that is, it works in many different ways to connect people, convey meanings and feelings, move people to action, and define who they are. The major functions of language are the referential function, the emotive function, the conative function, the poetic function, the phatic function, the metalinguistic function, and the indexical function, which often overlap when people use language and are shaped by language ideologies, that is, the beliefs and attitudes that shape speakers’ relationships to their own and others’ languages, mediating between the social practice of language and the socioeconomic, historical, and political structures within which it occurs. Language use is part of what makes humans human, and as anthropologists, focused on how humans live and make sense of each other and the world, language should always be part of what anthropologists attend to and investigate.
The Popular Assembly of the Peoples of Oaxaca (APPO)
Authors: Estrada Saavedra Marco
Published: March 2020

The summer and fall of 2006 saw a violent, protracted conflict in Oaxaca, Mexico between the state government and the Popular Assembly of the Peoples of Oaxaca (Asamblea Popular de los Pueblos de Oaxaca, APPO). What began as a contentious labor negotiation between the local government and the teachers’ union soon developed into a popular protest and mobilization throughout the state, especially in the Valles Centrales region, home to the state capital. The governor’s repressive actions against critics and opponents of his administration led the APPO members to a consensus demanding his removal. The result was a government in paralysis, with none of the three constitutional branches able to exercise their normal authority or carry out their activities. The APPO achieved territorial control by the following means: with the erection of hundreds of barricades throughout the capital to protect it from sneak attacks by irregular units of the state police; with its occupation, operation, and diffusion of public and private media outlets; with a permanent mobilization of its members; and with the construction of a popular government, the Oaxaca Commune, to manage public affairs and services. This experience of popular autonomy involved the dismantling of the local system of domination and also of the authoritarian, clientelist, patrimonialist, and patriarchal relationships within the organizations of the APPO itself. It ended in violent repression.
Gilberto Freyre and the Politics of Culture, 1930–1980
Authors: Pallares-Burke Maria Lúcia
Published: March 2020

Although his views on the subject were changeable and difficult to define, Gilberto Freyre was interested in politics from his youth onwards. He had a brief political career as assistant to the Governor of Pernambuco (1926–1930) and as a deputy in the Constituent Assembly (1946–1950), where he spoke for the North East. He had what he called a “quasi-political” career as a journalist for most of his long life and he was also a cultural manager who founded or supported institutions that spread the ideas he believed in. More importantly, his central interests and ideas had political implications. He was accused of “Bolshevism” for his emphasis on the African element in Brazilian culture. His regionalism embodied a protest against centralization and standardization. His lifelong interest in architecture included a concern with housing for the poor that was hygienic and environmentally friendly, and also with the conservation of colonial buildings to serve as an inspiration for a Brazilian style of modern architecture. As a scholar, Freyre supported what he called the “tropicalization” of the social sciences, freeing them from generalizations based simply on European and North American experience. His view of Brazil in terms of culture instead of race implied that the government should be concerned with the health and education of the poor rather than with “whitening” the country by encouraging immigration from Europe. His idea that mixture was the core of Brazilian identity was taken up by governments from Vargas to Lula, while his idea of “Luso-Tropicalism,” claiming that the Portuguese were more flexible and benevolent colonizers than other nations, was used as a defense against critics of colonialism by the Salazar regime.
The Concheros Dance in Mexico City
Authors: Rostas Susanna
Published: March 2020

In the middle decades of the 20th century, groups of Concheros dancing in public places began to attract academic attention. However, a much wider interest in their activities developed in the run-up to the celebrations for the so-called “discovery” of the Americas in 1992, when they were invited to participate in some of the commemorative events. Their dance tradition, one among many in Mexico, is often assumed to have been created either in the 1820s after Mexico gained its independence from Spain or more recently after the Mexican Revolution in 1910. Both were periods when central Mexico became more aware of the Aztec past and interested in reviving aspects of it, and the Concheros’ circle dances were thought to have been part of that revindication—an invented tradition. However, their history has more complex roots than this. The predominant myth claims that the dance began in the Bajio region in the 16th century, an area that had not been dominated by the Aztecs. Counter to that, however, are the beliefs that many began to advocate as the movement of Mexicanidad (or Mexicayotl) flourished during the late 20th century, which has led to the eponymous Mexica challenging many of the Concheros’ beliefs and practices.
César Moscoso Carrasco and Malaria Eradication in Bolivia
Authors: Pacino Nicole L.
Published: March 2020

César Moscoso Carrasco (1904–1966), a central figure in Bolivia’s mid-20th-century public health system, wanted to liberate Bolivia from malaria. In a career that spanned three decades, he came close to achieving this goal, but ultimately did not live to see successful eradication. Moscoso was one of the first Bolivian public health specialists in malariology, and was recognized by the World Health Organization for his contributions to the field in 1963. At all stages of his career, he fortuitously aligned himself with the individual or organization that could help him accomplish his professional ambitions and his mission of eradicating malaria in Bolivia. He was the founder and director of the National Anti-Malaria Service in 1929, where he made a name for himself working to halt the spread of malaria in Mizque, in the Cochabamba region. In the 1940s, he secured a position with the Rockefeller Foundation, where he had access to resources beyond the scope of the Bolivian government and an international network of public health specialists. Finally, in the 1950s, he headed the newly formed National Service for Malaria Eradication, which was a Bolivian government initiative supported by international organizations, such as the World Health Organization and the Pan-American Sanitary Bureau. In the 1950s and 1960s, he came the closest to achieving his goal. Unfortunately, he died the same way he lived: fighting a disease, possibly malaria, which he contracted on a visit to Ceylon as a malaria expert and consultant.

Moscoso’s life is a window into many aspects of Bolivia’s 20th-century history. First, his life story illustrates both the potential and limitations of the Bolivian healthcare system. Indeed, Moscoso often had to work with international or binational organizations to accomplish the work that he saw as necessary and important. Second, his career shows how political changes in Bolivia impacted healthcare. Since his career spans the Chaco War of 1932–1935, the politically tumultuous 1940s, and the 1952 National Revolution, it provides a personal account of how these events changed healthcare in Bolivia. His story demonstrates the hardships that Bolivian doctors faced as they worked to improve their healthcare system, including low pay, few resources, and little respect from their foreign colleagues.
Morphology in Northwest Caucasian Languages
Authors: Lander Yury
Published: March 2020

The five languages of the Northwest Caucasian family (also known as West Caucasian or Abkhaz-Adyghe), namely West Circassian, Kabardian, Ubykh, Abkhaz, and Abaza, are remarkable for their high degree of polysynthesis. This manifests itself in complex words that bear a lot of information on arguments and the characteristics of a situation, and which presumably can be constructed in the course of speech. Content words usually consist of several morphological zones within which certain permutations of morphemes are possible. Both prefixes and suffixes occur, with some morphemes being capable of appearing either as a prefix or a suffix, depending on the form. The predicate shows ergative-based cross-reference of core arguments and indirect objects introduced by applicatives, extensive use of the causative (including double causativization), highly developed means of expressing locational semantics within the predicate, and intricate tense-modality-aspect and polarity systems. Although classical noun-to-verb incorporation does not occur, there are constructions akin to incorporation, especially in the nominal domain. Nouns constitute a subclass of a broad class of predicates (both morphologically and syntactically) and hence may take the basic predicate morphology. At the same time, they form word-like nominal complexes with their attributes, and show specific head-marking possessive morphology (in West Circassian even distinguishing alienable and inalienable possession). Definiteness/specificity is regularly expressed either by articles (in Abkhaz, Abaza and Ubykh) or by the presence/absence of core case marking (in West Circassian and Kabardian). Morphemes demonstrate features that are not typical of morphemes in Standard Average European languages, including a high degree of autonomy reflected in affix order variation, widespread morphological recursion, occasional reduplication and even the ability to attach to complex syntactic constituents.
Beak coloration of starling (Sturnus unicolor) males depends on the length of their throat feathers
Authors: Azcárate-García Manuel , Ruiz-Rodríguez Magdalena , Ruiz-Castellano Cristina , Díaz-Lora Silvia , Tomás Gustavo , Martín-Vivaldi Manuel , Soler Juan José
Published: March 2020

Within the context of complex sexual signaling, most research has focused on exploring the associations between several signals and/or their relationships with different proxies of individual quality. However, very few studies have focused on checking whether the expression of one signal is conditioned by the expression of the others. Here, by experimentally shortening the throat feathers of male spotless starlings (Sturnus unicolor), we evaluated the influence of this trait on the color expression of the beak base. In addition, we tested the relationship between these two sexually dimorphic characters with traits indicating individual qualities, such as body condition and color reflectance at the wavelength related to carotenes in the tip of the beak. Our results show that the coloration of the beak base in males, but not in females, is positively related to body condition and to the length of ornamental throat feathers. Moreover, the experimental shortening of throat feathers in males had a negative effect on the blue chroma intensity of their beak base 1 year after manipulation. These results support for the first time a causal link between the expression of two sexually dimorphic characters, which is essential to understand their functionality in a multiple signaling framework.
GenMap: ultra-fast computation of genome mappability
Authors: Pockrandt Christopher , Alzamel Mai , Iliopoulos Costas S , Reinert Knut
Published: March 2020

Motivation

Computing the uniqueness of k-mers for each position of a genome while allowing for up to e mismatches is computationally challenging. However, it is crucial for many biological applications such as the design of guide RNA for CRISPR experiments. More formally, the uniqueness or (k, e)-mappability can be described for every position as the reciprocal value of how often this k-mer occurs approximately in the genome, i.e. with up to e mismatches.

Results

We present a fast method GenMap to compute the (k, e)-mappability. We extend the mappability algorithm, such that it can also be computed across multiple genomes where a k-mer occurrence is only counted once per genome. This allows for the computation of marker sequences or finding candidates for probe design by identifying approximate k-mers that are unique to a genome or that are present in all genomes. GenMap supports different formats such as binary output, wig and bed files as well as csv files to export the location of all approximate k-mers for each genomic position.

Availability and implementation

GenMap can be installed via bioconda. Binaries and C++ source code are available on https://github.com/cpockrandt/genmap.
ADFinder: accurate detection of programmed DNA elimination using NGS high-throughput sequencing data
Authors: Zheng Weibo , Chen Jing , Doak Thomas G , Song Weibo , Yan Ying
Published: March 2020

Motivation

Programmed DNA elimination (PDE) plays a crucial role in the transitions between germline and somatic genomes in diverse organisms ranging from unicellular ciliates to multicellular nematodes. However, software specific for the detection of DNA splicing events is scarce. In this paper, we describe Accurate Deletion Finder (ADFinder), an efficient detector of PDEs using high-throughput sequencing data. ADFinder can predict PDEs with relatively low sequencing coverage, detect multiple alternative splicing forms in the same genomic location and calculate the frequency for each splicing event. This software will facilitate research of PDEs and all down-stream analyses.

Results

By analyzing genome-wide DNA splicing events in two micronuclear genomes of Oxytricha trifallax and Tetrahymena thermophila, we prove that ADFinder is effective in predicting large scale PDEs.

Availability and implementation

The source codes and manual of ADFinder are available in our GitHub website: https://github.com/weibozheng/ADFinder.

Supplementary information

Supplementary data are available at Bioinformatics online.
Joint learning dimension reduction and clustering of single-cell RNA-sequencing data
Authors: Wu Wenming , Ma Xiaoke
Published: March 2020

Motivation

Single-cell RNA-sequencing (scRNA-seq) profiles transcriptome of individual cells, which enables the discovery of cell types or subtypes by using unsupervised clustering. Current algorithms perform dimension reduction before cell clustering because of noises, high-dimensionality and linear inseparability of scRNA-seq data. However, independence of dimension reduction and clustering fails to fully characterize patterns in data, resulting in an undesirable performance.

Results

In this study, we propose a flexible and accurate algorithm for scRNA-seq data by jointly learning dimension reduction and cell clustering (aka DRjCC), where dimension reduction is performed by projected matrix decomposition and cell type clustering by non-negative matrix factorization. We first formulate joint learning of dimension reduction and cell clustering into a constrained optimization problem and then derive the optimization rules. The advantage of DRjCC is that feature selection in dimension reduction is guided by cell clustering, significantly improving the performance of cell type discovery. Eleven scRNA-seq datasets are adopted to validate the performance of algorithms, where the number of single cells varies from 49 to 68 579 with the number of cell types ranging from 3 to 14. The experimental results demonstrate that DRjCC significantly outperforms 13 state-of-the-art methods in terms of various measurements on cell type clustering (on average 17.44% by improvement). Furthermore, DRjCC is efficient and robust across different scRNA-seq datasets from various tissues. The proposed model and methods provide an effective strategy to analyze scRNA-seq data.

Availability and implementation

The software is coded using matlab, and is free available for academic https://github.com/xkmaxidian/DRjCC.

Supplementary information

Supplementary data are available at Bioinformatics online.
Palmprint for Individual’s Personality Behavior Analysis
Authors: Prasad Shitala , Chai Tingting
Published: March 2020

Palmprint is an important key player in biometric family and also informs some extra basic personality details of an individual. In this paper, we utilize these extra information and designed an automated mobile vision (MV) system to extract principal lines from human palm and analyze them for behavioral significances. Hence, the main concern of this paper is to come up with a simple yet powerful low-level MV solution to extract the complex challenging features from palmprint. In the proposed system, the computational tasks are offloaded to a dedicated palmistry server and efficiently minimizes the energy consumption of mobile device after performing some preliminary computational low-level tasks. The implementation is divided into four major phases: (i) hand-image acquisition and pre-processing, (ii) region-of-interest extraction from the palm images, (iii) post-processing to extract principal lines and (iv) features computation for behavior analysis. The basic palmistry uses line lengths, angles, curves and branches to identify a person’s behavior. The exhaustive experiments show that the proposed system achieves an average accuracy of 96%, 92% and 84% for heart, life and head line detection and personality prediction, respectively. Finally, mapping the extracted results with the original palmprint is augmented back to the use for better visualization.
Impact of low health literacy on healthcare utilization in individuals with cardiovascular disease, chronic obstructive pulmonary disease, diabetes and mental disorders. A Danish population-based 4-year follow-up study
Authors: Friis Karina , Pedersen Marie Hauge , Aaby Anna , Lasgaard Mathias , Maindal Helle Terkildsen
Published: March 2020

Background

Previous research from the USA has shown that low health literacy is associated with higher hospitalization rates and higher rates of emergency service use. However, studies in a European context using more comprehensive health literacy definitions are lacking. The aim was to study the impact of low health literacy on healthcare utilization in a Danish context.

Methods

In this prospective cohort study, baseline survey data from 2013 were derived from a large Danish health and morbidity survey and merged with individual-level longitudinal register data for a 4-year follow-up period. The study included people in the general population (n = 29 473) and subgroups of people with four different chronic conditions: cardiovascular disease (CVD) (n = 2389), chronic obstructive pulmonary disease (COPD) (n = 1214), diabetes (n = 1685) and mental disorders (n = 1577).

Results

In the general population, low health literacy predicted slightly more visits to the general practitioner and admissions to hospital and longer hospitalization periods at 4 years of follow-up, whereas low health literacy did not predict planned outpatient visits or emergency room visits. In people with CVD, low health literacy predicted more days with emergency room visits. In people with mental disorders, difficulties in actively engaging with healthcare providers were associated with a higher number of hospital admission days. No significant association between health literacy and healthcare utilization was found for diabetes or COPD.

Conclusions

Even though Denmark has a universal healthcare system the level of health literacy affects healthcare use in the general population and in people with CVD and mental disorders.
Systemic therapy in an RNA toxicity mouse model with an antisense oligonucleotide therapy targeting a non-CUG sequence within the DMPK 3′UTR RNA
Authors: Yadava Ramesh S , Yu Qing , Mandal Mahua , Rigo Frank , Bennett C Frank , Mahadevan Mani S
Published: March 2020

Myotonic dystrophy type 1 (DM1), the most common adult muscular dystrophy, is an autosomal dominant disorder caused by an expansion of a (CTG)n tract within the 3′ untranslated region (3′UTR) of the dystrophia myotonica protein kinase (DMPK) gene. Mutant DMPK mRNAs are toxic, present in nuclear RNA foci and correlated with a plethora of RNA splicing defects. Cardinal features of DM1 are myotonia and cardiac conduction abnormalities. Using transgenic mice, we have demonstrated that expression of the mutant DMPK 3′UTR is sufficient to elicit these features of DM1. Here, using these mice, we present a study of systemic treatment with an antisense oligonucleotide (ASO) (ISIS 486178) targeted to a non-CUG sequence within the 3′UTR of DMPK. RNA foci and DMPK 3′UTR mRNA levels were reduced in both the heart and skeletal muscles. This correlated with improvements in several splicing defects in skeletal and cardiac muscles. The treatment reduced myotonia and this correlated with increased Clcn1 expression. Furthermore, functional testing showed improvements in treadmill running. Of note, we demonstrate that the ASO treatment reversed the cardiac conduction abnormalities, and this correlated with restoration of Gja5 (connexin 40) expression in the heart. This is the first time that an ASO targeting a non-CUG sequence within the DMPK 3′UTR has demonstrated benefit on the key DM1 phenotypes of myotonia and cardiac conduction defects. Our data also shows for the first time that ASOs may be a viable option for treating cardiac pathology in DM1.
Resolution of Inflammation and Gut Repair in IBD: Translational Steps Towards Complete Mucosal Healing
Authors: Ho Gwo-tzer , Cartwright Jennifer A , Thompson Emily J , Bain Calum C , Rossi Adriano G
Published: March 2020

Despite significant recent therapeutic advances, complete mucosal healing remains a difficult treatment target for many patients with inflammatory bowel diseases (IBD) to achieve. Our review focuses on the translational concept of promoting resolution of inflammation and repair as a necessary adjunctive step to reach this goal. We explore the roles of inflammatory cell apoptosis and efferocytosis to promote resolution, the new knowledge of gut monocyte-macrophage populations and their secreted prorepair mediators, and the processes of gut epithelial repair and regeneration to bridge this gap. We discuss the need and rationale for this vision and the tangible steps toward integrating proresolution therapies in IBD.
A close look at the contingencies of founders’ effect on venture performance
Authors: Grilli Luca , Jensen Paul H , Murtinu Samuele , Park Haemin Dennis
Published: March 2020

Studies show that founders’ industry-specific experience is beneficial to venture performance. However, we know little on the contingencies associated with such an effect. Using a panel dataset of 338 Italian high-tech ventures, we find that founders’ industry-specific experience positively affects venture performance. However, changes in the top management team (TMT) during the initial phases of the venture’s life weaken the positive relationship between founders’ industry-specific experience and venture performance, whereas founders’ functional heterogeneity does not. We further find evidence of substitution effects between founders’ human and social capital affecting venture performance, such that the effect of founders’ industry-specific experience on venture performance is attenuated when a subset of founders had common background prior to founding their venture.
Myectomy versus alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy
Authors: Afanasyev Alexander V , Bogachev-Prokophiev Alexander V , Kashtanov Maxim G , Astapov Dmitriy A , Zalesov Anton S , Budagaev Sergei A , Sharifulin Ravil M , Idov Eduard M , Zheleznev Sergei I
Published: March 2020

OBJECTIVES

There is very little evidence comparing the safety and efficacy of alcohol septal ablation versus septal myectomy for a septal reduction in patients with hypertrophic obstructive cardiomyopathy. This study aimed to compare the immediate and long-term outcomes of these procedures.

METHODS

Following propensity score matching, we retrospectively analysed outcomes in 105 patients who underwent myectomy and 105 who underwent septal ablation between 2011 and 2017 at 2 reference centres.

RESULTS

The mean age was 51.9 ± 14.3 and 52.2 ± 14.3 years in the myectomy and ablation groups, respectively (P = 0.855), and postoperative left ventricular outflow tract gradients were 13 (10–19) mmHg vs 16 (12–26) mmHg; P = 0.025. The 1-year prevalence of the New York Heart Association class III–IV was higher in the ablation group (none vs 6.4%; P = 0.041). The 5-year overall survival rate [96.8% (86.3–99.3) after myectomy and 93.5% (85.9–97.1) after ablation; P = 0.103] and cumulative incidence of sudden cardiac death [0% and 1.9% (0.5–7.5), respectively P = 0.797] did not differ between the groups. The cumulative reoperation rate within 5 years was lower after myectomy than after ablation [2.0% (0.5–7.6) vs 14.6% (8.6–24.1); P = 0.003]. Ablation was associated with a higher reoperation risk (subdistributional hazard ratio = 5.9; 95% confidence interval 1.3–26.3, P = 0.020). At follow-up, left ventricular outflow tract gradient [16 (11–20) vs 23 (15–59) mmHg; P < 0.001] and prevalence of 2+ mitral regurgitation (1.1% vs 10.6%; P = 0.016) were lower after myectomy than after ablation.

CONCLUSIONS

Both procedures improved functional capacity; however, myectomy better-resolved classes III–IV of heart failure. Septal ablation was associated with higher reoperation rates. Myectomy demonstrated benefits in gradient relief and mitral regurgitation elimination. The results suggest that decreasing rates of myectomy procedures need to be investigated and reconsidered.
A Critical Analysis of the Literature on Time-to-Antibiotics in Suspected Sepsis
Authors: Weinberger Jeremy , Rhee Chanu , Klompas Michael
Published: March 2020

The Surviving Sepsis Campaign recommends immediate antibiotics for all patients with suspected sepsis and septic shock, ideally within 1 hour of recognition. Immediate antibiotic treatment is lifesaving for some patients, but a substantial fraction of patients initially diagnosed with sepsis have noninfectious conditions. Aggressive time-to-antibiotic targets risk promoting antibiotic overuse and antibiotic-associated harms for this subset of the population. An accurate understanding of the precise relationship between time-to-antibiotics and mortality for patients with possible sepsis is therefore critical to finding the best balance between assuring immediate antibiotics for those patients who truly need them versus allowing clinicians some time for rapid investigation to minimize the risk of overtreatment and antibiotic-associated harms for patients who are not infected. More than 30 papers have been published assessing the relationship between time-to-antibiotics and outcomes, almost all of which are observational cohort studies. Most report significant associations but all have important limitations. Key limitations include focusing just on the sickest subset of patients (only patients requiring intensive care and/or patients with septic shock), blending together mortality estimates from patients with very long intervals until antibiotics with patients with shorter intervals and reporting a single blended (and thus inflated) estimate for the average increase in mortality associated with each hour until antibiotics, and failure to control for large potential confounders including patients’ presenting signs and symptoms and granular measures of comorbidities and severity of illness. In this study, we elaborate on these potential sources of bias and try to distill a better understanding of what the true relationship between time-to-antibiotics and mortality may be for patients with suspected sepsis or septic shock.
Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure
Authors: Eyal Nir , Lipsitch Marc , Smith Peter G
Published: March 2020

Controlled human challenge trials of SARS-CoV-2 vaccine candidates could accelerate the testing and potential rollout of efficacious vaccines. By replacing conventional phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly. Obviously, challenging volunteers with this live virus risks inducing severe disease and possibly even death. However, we argue that such studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related mortality and morbidity. Volunteers in such studies could autonomously authorize the risks to themselves, and their net risk could be acceptable if participants comprise healthy young adults, who are at relatively low risk of serious disease following natural infection, if they have a high baseline risk of natural infection, and if during the trial they receive frequent monitoring and, following any infection, the best available care.
Inclusion, Diversity, Access, and Equity (IDA&E) Roadmap: Infectious Diseases Society of America’s Commitment to the Future
Authors: Desruisseaux Mahalia S , Tan Tina Q
Published: March 2020

This article identifies the major elements of the strategic road map for the Infectious Diseases Society of America’s (IDSA) Inclusion, Diversity, Access, and Equity (IDA&E) initiative and discusses the long-term goals and the proposed steps needed to achieve these goals.
Structure, dynamics and function of the evolutionarily changing biliverdin reductase B family
Authors: Duff Michael R , Redzic Jasmina S , Ryan Lucas P , Paukovich Natasia , Zhao Rui , Nix Jay C , Pitts Todd M , Agarwal Pratul , Eisenmesser Elan Zohar
Published: March 2020

Biliverdin reductase B (BLVRB) family members are general flavin reductases critical in maintaining cellular redox with recent findings revealing that BLVRB alone can dictate cellular fate. However, as opposed to most enzymes, the BLVRB family remains enigmatic with an evolutionarily changing active site and unknown structural and functional consequences. Here, we applied a multi-faceted approach that combines X-ray crystallography, NMR and kinetics methods to elucidate the structural and functional basis of the evolutionarily changing BLVRB active site. Using a panel of three BLVRB isoforms (human, lemur and hyrax) and multiple human BLVRB mutants, our studies reveal a novel evolutionary mechanism where coenzyme ‘clamps’ formed by arginine side chains at two co-evolving positions within the active site serve to slow coenzyme release (Positions 14 and 78). We find that coenzyme release is further slowed by the weaker binding substrate, resulting in relatively slow turnover numbers. However, different BLVRB active sites imposed by either evolution or mutagenesis exhibit a surprising inverse relationship between coenzyme release and substrate turnover that is independent of the faster chemical step of hydride transfer also measured here. Collectively, our studies have elucidated the role of the evolutionarily changing BLVRB active site that serves to modulate coenzyme release and has revealed that coenzyme release is coupled to substrate turnover.
Concordance between treatment recommendations provided by IBM Watson for Oncology and a multidisciplinary tumor board for breast cancer in China
Authors: Zhao Xiaoyao , Zhang Yinbin , Ma Xingcong , Chen Yinxi , Xi Junfeng , Yin Xiaoran , Kang Huafeng , Guan Haitao , Dai Zijun , Liu Di , Zhao Fang , Sun Chu , Li Zongfang , Zhang Shuqun
Published: March 2020

Objective

Watson for Oncology (WFO), an artificial intelligence from IBM Corporation, can provide a treatment plan by analyzing patient’s disease characteristics. The present study was performed to examine the concordance between treatment recommendations proposed by WFO and the multidisciplinary tumor board at our center. The aim was to explore the feasibility of using WFO for breast cancer cases in China and to ascertain the ways to make WFO more suitable for Chinese patients with breast cancer.

Methods

Data from 302 breast cancer patients treated at the Second Affiliated Hospital of Xi’an Jiaotong University between October 2016 and February 2018 was retrieved and retrospectively analyzed by WFO. The recommendations were divided into ‘recommended’, ‘considered’ and ‘not recommended’ groups. Results were considered concordant when oncologists’ recommendations were categorized as ‘recommended’ or ‘for consideration’ by WFO.

Results

The concordance rate of 200 subjects with postoperative adjuvant therapy was 77%. However, the rate was 27.5% in the remaining 102 cases with metastatic disease receiving either first-line or no treatment. Further analysis demonstrated that inconsistencies were mainly due to different choices of chemotherapy regimens. Subgroup study indicates that tumor stage, receptor status and age also had influences at the concordance rate.

Conclusion

The results of this study suggest that WFO is a promising artificial intelligence system for the treatment of breast cancer. These findings can also serve as a reference framework for the inclusion of artificial intelligence in the ongoing medical reform in China.
Diagnostic Yield of Initial and Consecutive Blood Cultures in Children With Cancer and Febrile Neutropenia
Authors: Haeusler Gabrielle M , De Abreu Lourenco Richard , Clark Hannah , Thursky Karin A , Slavin Monica A , Babl Franz E , Mechinaud Francoise , Alvaro Frank , Clark Julia , Padhye Bhavna , Phillips Marianne , Super Leanne , Tapp Heather , Walwyn Thomas , Ziegler David , Phillips Robert , Worth Leon J
Published: March 2020

Background

The timing and necessity of repeated blood cultures (BCs) in children with cancer and febrile neutropenia (FN) are unknown. We evaluated the diagnostic yield of BCs collected pre- and post-empiric FN antibiotics.

Methods

Data collected prospectively from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study were used. Diagnostic yield was calculated as the number of FN episodes with a true bloodstream infection (BSI) detected divided by the number of FN episodes that had a BC taken.

Results

A BSI was identified in 13% of 858 FN episodes. The diagnostic yield of pre-antibiotic BCs was higher than of post-antibiotic cultures (12.3% vs 4.4%, P < .001). Two-thirds of the post-antibiotic BSIs were associated with a new episode of fever or clinical instability, and only 2 new BSIs were identified after 48 hours of empiric antibiotics and persistent fever. A contaminated BC was identified more frequently in post-antibiotic cultures.

Conclusions

In the absence of new fever or clinical instability, BCs beyond 48 hours of persistent fever have limited yield. Opportunity exists to optimize BC collection in this population and reduce the burden of unnecessary tests on patients, healthcare workers, and hospitals.
Incidental finding of adenocarcinoma in a gallbladder lumen with no wall involvement
Authors: Pinheiro Rodrigo Nascimento , Fontoura Renata P , Rodrigues Letícia L P , Netto José Donato S , Sarmento Bruno José Q
Published: March 2020

Gallbladder cancer (GBC) is a rare disease characterized by its aggressiveness. Resection with free tumour margins is the sole curative treatment and, in incidental findings, surgical reapproach is recommended for segmentectomy IVb and V or wedge resection of the gallbladder fossa and lymphadenectomy. Here we report a case of gallbladder adenocarcinoma as an incidental finding in a fragment in its lumen with no wall involvement evidentiated. The patient was reoperated for resection of the gallbladder bed with hepatic hilum and cystic duct lymphadenectomy, later evidentiated as free of residual disease. The normality of the bile ducts evidenced by imaging studies, in addition to signs of chronic cholecystitis corroborate to GBC diagnosis. We suspect that the fragment was detached gallbladder polypoid neoplastic lesion. Despite the lack of clinical manifestations, the fast surgical interventions and the histopathological analysis of the material was probably a prognostic determinant for the patient.