bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of currents, waves, and biofilms on motion and surface contacts by tubeworm larvae swimming above or below surfaces
Authors: Koehl MAR , Perotti E , Sischo D , Hata T , Hadfield MG
Published: January 2022

Larvae of many benthic marine invertebrates swim more slowly than the ambient water flow that carries them past surfaces where they might settle. Competent larvae of the tubeworm Hydroides elegans, abundant early colonists in warm-water fouling communities, were used to determine if active behavior by microscopic larvae carried in flowing water can affect their contacts with surfaces representing early stages of fouling community succession (clean flat surface, flat biofilm, biofilm on worm tubes). We studied larvae in waves and in the unidirectional flow used in earlier studies of larval settlement, and near surfaces above them (like those where fouling organisms recruit) or below them. We videotaped larval motion near surfaces in a small flume in which we mimicked fine-scale flow measured near surfaces in harbors. Swimming larvae within millimeters of surfaces moved up and down while being carried by horizontal flow, enhancing their contact rates with surfaces above and below them compared with dead larvae passively carried by the current. After contact, live larvae ‘bounced’ along the surface, sampling it many times per distance they were carried by the current, whereas dead larvae did not. Thus, active behaviors of larvae of H. elegans, which must touch a biofilmed surface to be stimulated to attach and metamorphose, enhance their contact with and exploration of surfaces in flowing water. These behaviors are effective in unidirectional flow and waves, for surfaces above or below larvae, and for smooth or rough surfaces, all of which are conditions that the larvae of fouling-community animals encounter in harbors.
Intento de suicidio
Authors:   Instituto Nacional de Salud
Published: January 2022

​El suicidio es considerado un problema de salud pública grave y creciente a nivel mundial. Según la Organización Mundial de la Salud (OMS), por cada muerte por suicidio se registran 20 intentos. La OMS afirma que las tasas de suicidio han aumentado un 60% en los últimos 50 años y ese incremento ha sido más marcado entre los jóvenes, al punto de convertirlos en la actualidad en el grupo de mayor riesgo en un tercio de los países del mundo. El suicidio a nivel mundial se encuentra entre las tres primeras causas de muerte en las personas de 15 a 44 años, teniendo un alto impacto en términos de años potenciales de vida perdidos.
Lesiones de causa externa
Authors:   Instituto Nacional de Salud
Published: January 2022

Son definidas como el daño o lesión en una persona en forma intencional o de manera no intencional. Esta lesión o daño puede originarse por un traumatismo, envenenamiento, agresión, accidentes, etc. puede ser mortal (lesión fatal) o no conducir a la muerte (lesión no fatal)
The Medical Press and its Public
Authors: Frampton Sally
Published: January 2022

This chapter examines the wide range of medical periodicals that were available in the nineteenth century. It argues that, as well as promoting professional cohesiveness, medical periodicals of the era were also significant in facilitating laypeople’s engagement with and contributions to medical knowledge, public health and politics. Particular attention is paid to three genres of medical journalism: the professional press, journals devoted to non-orthodox, alternative medicine practices like homeopathy and mesmerism, and medical and health journals which actively sought to include the public in their audience, the latter of which found increasing popularity in the last three decades of the century. These categories are neither neat nor entirely discrete; indeed, by examining them together this chapter evinces their continuous entanglement with one another.
Literature and Consolation
Authors: Pieters Jürgen
Published: January 2022

By focusing on a number of significant moments in the interlocking histories of the book’s two central concepts – literature and consolation – this study articulates the premises that underlie the assumption that literary writings can bring comfort. What is it in these texts that provides this special experience? How does literature help us to understand what consolation means and the effects it can have on individual readers?
The intersecting ideas of literature and consolation, from Homer, Dante, Shakespeare and Flaubert through to Roland Barthes, Denise Riley and Julian Barnes, guide today’s readers on how literature provides examples, food for thought and good companionship in times of grief and pain. Taking its cue from the rich history of consolatory thinking, the book shows how writers from different times have explored the potential of their writing to offer solace. The result of these explorations, this book argues, has shaped the history of Western literature decisively.
Fashion on the Red Carpet
Authors: Lundén Elizabeth Castaldo
Published: January 2022

The Academy Awards’ red-carpet is the most prominent fashion show in media culture. This book investigates the historical liaison between Hollywood and fashion institutions to describe how public relations campaigns and the media articulated fashion discourses around the Oscars throughout history. It argues that the fashion industry’s business model of celebrity endorsement and renowned designers as branded labels is based on the triangulation done by Hollywood studios, department stores, and American garment manufacturers during the interwar era. Departing from archival sources, and tracing discourses of fashion, stardom, and celebrity around Hollywood and the Oscars, this study unravels this phenomenon’s cultural, political and economic impact, explaining how the Academy Awards’ red-carpet became a marquee for the global endorsement of high-end fashion brands.
The book addresses globalisation as a central topic to frame the red-carpet phenomenon, linking the fashion and media industries throughout the 20th Century. It points at the postwar as a historical turning point that consolidated the position of the United States as a veritable behemoth exporter of popular culture, depicting the American lifestyle as synonymous with wealth and comfort to further the global expansion of consumer culture. The book identifies power shift towards television, the emergence of celebrity culture, the post-war reactivation of transatlantic trade, the growth of fashion journalism, and the increasing circulation of designer names in the media as a series of converging factors that led to the institutionalisation of the red-carpet parade as a fashion event in its own right.
The Auditory Setting
Authors: Chattopadhyay Budhaditya
Published: January 2022

The Auditory Setting introduces and investigates how narrative and a sense of place are constructed in film and media arts through the reproduction and mediation of site-specific environmental sounds, or ‘ambience’. Although this sonic backdrop acts as the acoustically mediated space where a story or event can take place, there has been little academic study of sound’s undervalued role in cinematic setting and its production. The aim of this book is to question classical assumptions about sound in film and media arts (e.g., image-based relationships) and shift the focus towards the site and its sonic environment, whose presence is often carefully constructed in a film or media artwork’s diegetic world as a vital narrative strategy. The emphasis on site in the book enables an informed investigation of an essentially anthropogenic process of the sonic environment’s mediation and (re)production. Sonic environments are inhabited, experienced, exploited and transformed every day, their corporeality augmented by human agency in mediated forms. The human agency of sonic environments is crucial to unwrap in order to understand cultural expectations from the audiovisual media; greater awareness is required of narration, depiction, communication and artistic production approaches and affordances harnessed through media technologies. Drawing on theories of narrative, diegesis, mimesis and presence, and following a varied number of relevant audio-visual works, this book is a ground-breaking exploration of human agency in mediating environmental sounds and the nature of the sonic experience in the Anthropocene.
Gold Rush Societies and Migrant Networks in the Tasman World
Authors: Davy Daniel
Published: January 2022

This book creatively explores the gold rushes in the Tasman World through an examination of the Otago gold rushes. It adopts a new methodology to reveal how transnational connections and local social and natural environments shaped colonial identities. The first monograph-length study on the Otago gold rushes and their place in the histories of British and Irish migration, it further increases our understanding of the British World by grounding transnational networks in the local ecologies, geologies and weather patterns which shaped local social structures and profoundly affected migrants' relationships to loved ones in Britain, Ireland and elsewhere. In doing so, Gold Rush Societies evolves as neither a local nor a transnational history but one which blends the two into a single study and offers fresh perspectives on each in the process.
Dissent After Disruption
Authors: Mallon Ryan
Published: January 2022

A history of post-Disruption Scottish Presbyterian dissent and its religious, political and social influence.
The Disruption of the Church of Scotland was one of the most important events in Victorian Britain and had a profound and lasting impact on Scottish religion, politics and society. This book provides the first detailed account of the two major non-established Presbyterian denominations in the two decades after 1843, which together accounted for roughly half of Scotland’s churchgoers: the Free Church, formed by those who left the Established Church at the Disruption, and the United Presbyterian Church, a consolidation of the various secessions of the previous century.
Ryan Mallon explores how the relationship between these churches developed from the bitter feuds over the church-state connection prior to the Disruption to co-operation in the major ecclesiastical, political, and social matters of the day, paving the way to negotiations for merger commencing in 1863. The period between 1843 and 1863 redefined conceptions of what it meant to be Presbyterian and Scottish. By examining a key transitional period in Scottish history, this monograph charts how definitions of Presbyterianism, the Kirk, and dissent evolved as Scotland’s national religion slowly moved from the divisions of the previous century towards eventual reunion in 1929.
New Ecological Realisms
Authors: Kaup Monika
Published: January 2022

What is the singular reality of humanistic objects of study? New Ecological Realism argues that our contemporary moment after the exhaustion of postmodernism presents an unprecedented opportunity to pursue this question. It proposes that the answer is found in a new concept of the real that hinges on, instead of denying, context, organization and form. New Ecological Realism showcases a context-based concept of the real, arguing that new realisms of complex and embedded wholes, actor-networks, and ecologies, rather than old realisms of isolated parts and things, represent the most promising escape from the impasses of constructivism and positivism.
To achieve this, this study devotes equal attention to literature and theory. By pairing post-apocalyptic novels by Margaret Atwood, José Saramago, Octavia Butler, and Cormac McCarthy with new realist theories, this study shows that, just as new realist theories can illuminate post-apocalyptic fiction, post-apocalyptic fiction also embeds new theories of the real. Reassessing the recent revival of interest in ontology in contemporary theory, this study brings together four contemporary theories that formulate context-based realisms: Bruno Latour’s actor-network theory; Chilean neurophenomenologists Humberto Maturana and Francisco Varela’s theories of autopoiesis and enactivism; German philosopher Markus Gabriel’s new ontology of fields of sense; French philosopher Jean-Luc Marion’s phenomenology of givenness and American philosopher Alphonso Lingis’s writings on passionate identification. Their shared emphasis on interconnectedness over individuation has gone unnoticed because these theories have never been considered together before.
WORLD ACHIEVEMENTS AND INNOVATIVE TECHNOLOGIES IN MODERN TOURISM AND HOTEL RESTAURANT BUSINESS
Authors: Opanaschuk Yuriy , Kolisnychenko Tеtiana , Verhun Antonina
Published: January 2022

The purpose of the article – find out and summarize the practical experience
of using innovative technologies in the hotel and restaurant and tourism business.
The research methodology consists in the application of methods of analysis,
synthesis, comparison, generalization, forecasting, as well as in the use of systemic and activity-based approaches.
The scientific novelty lies in the fact that this article presents modern product
innovations, technological innovations in the development of transport infrastructure, accommodation facilities for the premium segment and tourism innovations
in different regions of the world.
Conclusions. As a result of the study, it was found that innovations in the
tourist infrastructure contribute to a change in the structure of demand and the
volume of tourist flow, to attract funds to the country, create opportunities to
increase the attractiveness of a tourist destination.
Keywords: innovations, innovative activity, product innovations, technological
innovations, transport infrastructure, hotel infrastructure.
(University) Management after Valuation Studies: Carving a practice between the offended native, the anxious scholar, and the useless practitioner
Authors: Ossandón José
Published: January 2022

This text introduces this issues’ symposium: “A correspondence on (University) Management after Valuation Studies”. The text has two parts. The first introduces the dilemma, the question of whether valuation studies could, besides studying valuation in practice, inform better practices of valuation, and the method of the correspondence, to use situations in which researchers of valuation are also practitioners, namely, the management of quality in higher education, as the starting point to think the correspondence’s problem. In the second part, the author reflects on his own experience in a situation of valuation at work, and proposes three different personae for the student of valuation: the offended native, the anxious scholar, and the useless practitioner.
Human Umbilical Cord Mesenchymal Stem Cells Improve Locomotor Function in Parkinson’s Disease Mouse Model Through Regulating Intestinal Microorganisms
Authors: Sun Zhengqin , Gu Ping , Xu Hongjun , Zhao Wei , Zhou Yongjie , Zhou Luyang , Zhang Zhongxia , Wang Wenting , Han Rui , Chai Xiqing , An Shengjun
Published: January 2022

Parkinson’s disease (PD) is a progressive neurological disorder characterized by loss of neurons that synthesize dopamine, and subsequent impaired movement. Umbilical cord mesenchymal stem cells (UC-MSCs) exerted neuroprotection effects in a rodent model of PD. However, the mechanism underlying UC-MSC-generated neuroprotection was not fully elucidated. In the present study, we found that intranasal administration of UC-MSCs significantly alleviated locomotor deficits and rescued dopaminergic neurons by inhibiting neuroinflammation in a PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, a toxic agent which selectively destroys nigrostriatal neurons but does not affect dopaminergic neurons elsewhere). Furthermore, UC-MSC treatment altered gut microbiota composition characterized by decreased phylum Proteobacteria, class Gammaproteobacteria, family Enterobacteriaceae, and genus Escherichia-Shigella. In addition, the neurotransmitter dopamine in the striatum and 5-hydroxytryptamine in the colon were also modulated by UC-MSCs. Meanwhile, UC-MSCs significantly maintained intestinal goblet cells, which secrete mucus as a mechanical barrier against pathogens. Furthermore, UC-MSCs alleviate the level of TNF-α and IL-6 as well as the conversion of NF-κB expression in the colon, indicating that inflammatory responses were blocked by UC-MSCs. PICRUSt showed that some pathways including bacterial invasion of epithelial cells, fluorobenzoate degradation, and pathogenic Escherichia coli infection were significantly reversed by UC-MSCs. These data suggest that the beneficial effects were detected following UC-MSC intranasal transplantation in MPTP-treated mice. There is a possible neuroprotective role of UC-MSCs in MPTP-induced PD mice by cross talk between the brain and gut.
Prognosis and Immunotherapy Response With a Novel Golgi Apparatus Signature-Based Formula in Lung Adenocarcinoma
Authors: Jiang Yupeng , Ouyang Wenhao , Zhang Chenzi , Yu Yunfang , Yao Herui
Published: January 2022

The Golgi apparatus (GA) is a cellular organelle that participates in the packaging, modification, and transport of proteins and lipids from the endoplasmic reticulum to be further fabricated before being presented to other cellular components. Recent studies have demonstrated that GA facilitates numerous cellular processes in cancer development. Therefore, this study aimed to establish a novel lung adenocarcinoma (LUAD) risk evaluation model based on GA gene signatures. In this study, we used TCGA-LUAD (n = 500) as the training cohort and GSE50081 (n = 127), GSE68465 (442), and GSE72094 (398) as the validation cohorts. Two immunotherapy datasets (GSE135222 and GSE126044) were also obtained from a previous study. Based on machine algorithms and bioinformatics methods, a GA gene-related risk score (GARS) was established. We found that the GARS independently predicted the prognosis of LUAD patients and remained effective across stages IA to IIIA. Then, we identified that the GARS was highly correlated with mutations in P53 and TTN. Further, this study identified that GARS is related to multiple immune microenvironmental characteristics. Furthermore, we investigated GSE135222 and GSE126044 and found that a lower GARS may be indicative of an improved therapeutic effect of PD-1/PD-L1 therapy. We also found that high GARS may lead to a better response to multiple anticancer drugs. Finally, we established a nomogram to better guide clinical application. To our knowledge, this is the first study to demonstrate a novel GA signature-based risk score formula to predict clinical prognosis and guide the treatment of LUAD patients.
Impact of PBP4 Alterations on β-Lactam Resistance and Ceftobiprole Non-Susceptibility Among Enterococcus faecalis Clinical Isolates
Authors: Lazzaro Lorenzo M. , Cassisi Marta , Stefani Stefania , Campanile Floriana
Published: January 2022

Penicillin-resistance among Enterococcus faecalis clinical isolates has been recently associated with overexpression or aminoacidic substitutions in low-affinity PBP4. Ceftobiprole (BPR), a new-generation cephalosporin, is a therapeutic option against E. faecalis. Here, we present evidence that pbp4 gene sequence alterations may influence the expression level of the gene and ceftobiprole binding to PBP4 in E. faecalis clinical isolates showing remarkable MDR-phenotypes, and how this could interfere with BPR in vitro antibacterial and bactericidal activity. Seven E. faecalis strains from bloodstream infections were analyzed for their antibiotic and β-lactam resistance. BPR bactericidal activity was assessed by time-kill analysis; pbp4 genes were sequenced and pbp4 relative expression levels of transcription were performed by RT-qPCR. Five penicillin-resistant ampicillin-susceptible (PRAS) isolates were detected, 4 of which were also BPR non-susceptible (BPR-NS). In the time-kill experiments, BPR exposure resulted in a potent bactericidal activity (3-5 log10 reduction) at the different concentrations tested. pbp4 gene sequence analysis revealed some mutations that may account for the changes in PBP4 affinity and MIC increase in the 4 BPR-NS strains (MICs 4-16 mg/L): the deletion of an adenine (delA) in the promoter region in all PRAS/BPR-NS strains; 12 different amino acid substitutions, 7 of which were next to the PBP catalytic-sites. The most significant were: T418A, located 6 amino acids (aa) upstream of the catalytic-serine included in the 424STFK427motif I; L475Q, 7 aa upstream of the 482SDN484motif II; V606A and the novel Y605H, 13/14 aa upstream of the 619KTGT622motif III. Taken together, our data showed that elevated BPR MICs were attributable to increased transcription of pbp4 - associated with a single upstream adenine deletion and PBP4 alterations in the catalytic-site motifs – which might interfere with the formation of the BPR/PBP4 complex. pbp4 molecular alterations may account for the changes in PBP4 affinity and MIC increase, without affecting BPR cidal activity. Indeed, our in vitro dynamic analysis by time-kill assays showed that BPR exerted a bactericidal activity against E. faecalis clinical isolates, despite their MDR phenotypes.
Initial Validation for the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS) Hebrew Battery in Adolescents and Young Adults With Typical Development
Authors: Fussman Shanie , Mashal Nira
Published: January 2022

Currently there is no validated battery to assess pragmatic abilities in Hebrew. The use of such battery has great importance, as it may provide norms to the assessment of impaired pragmatic skills across several populations, such as ASD, schizophrenia, specific learning disorders and intellectual disabilities. In order to validate the battery, the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS) was translated to Hebrew. The APACS battery was previously validated and found high reliability and validity for ages 19–89 years. The battery includes six tasks, focusing on two main domains: pragmatic production and pragmatic comprehension. The assessment of pragmatic production will be conducted by the use of interview and description tasks, whereas pragmatic comprehension will be assessed by narratives, two figurative language, and humor tasks. The translated battery, APACS-Heb is currently the most comprehensive and the first validated battery for pragmatic tests in Hebrew. Forty Hebrew-speaking adolescents ages 16–20 participated in the study. All participants performed screening tests assessing vocabulary, Theory of Mind and social responsiveness. In addition, the validity and test-retest reliability of APACS-Heb were assessed. Furthermore, the effect of vocabulary, Theory of Mind and social responsiveness on performance was evaluated. High internal consistency, content validity and test-retest reliability was found for most APACS-Heb tasks and all composite scores. Furthermore, an effect of age and gender was found for most tasks with females outperformed males. In addition, a contribution of Theory of Mind to pragmatic production, pragmatic comprehension and APACS total scores was found. Lastly, a factor analysis revealed two factors, in which the first factor correlates with most tasks, and the second factor correlates only to humor. The results thus suggest that humor is a separate skill among the other pragmatic skills. In conclusion, normative data was collected for the APACS-Heb battery, and it was found that it is a valid and reliable measure of pragmatic skills. Since APACS is a comprehensive battery assessing the various aspects of figurative language, it can identify the specific deficits in figurative language and therefore may pinpoint the appropriate intervention program for each individual.
Molecular Mechanisms of Cardiac Injury Associated With Myocardial SARS-CoV-2 Infection
Authors: Liu Xianfang , Lou Longquan , Zhou Lei
Published: January 2022

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world. The development of cardiac injury is a common condition in patients with COVID-19, but the pathogenesis remains unclear. The RNA-Seq dataset (GSE150392) comparing expression profiling of mock human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and SARS-CoV-2-infected hiPSC-CMs was obtained from Gene Expression Omnibus (GEO). We identified 1,554 differentially expressed genes (DEGs) based on GSE150392. Gene set enrichment analysis (GSEA), Gene ontology (GO) analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that immune-inflammatory responses were activated by SARS-CoV-2, while muscle contraction, cellular respiration, and cell cycle of hiPSC-CMs were inhibited. A total of 15 hub genes were identified according to protein–protein interaction (PPI), among which 11 upregulated genes were mainly involved in cytokine activation related to the excessive inflammatory response. Moreover, we identified potential drugs based on these hub genes. In conclusion, SARS-CoV-2 infection of cardiomyocytes caused a strong defensive response, leading to excessive immune inflammation, cell hypoxia, functional contractility reduction, and apoptosis, ultimately resulting in myocardial injury.
Scaffold-Free Tubular Engineered Heart Tissue From Human Induced Pluripotent Stem Cells Using Bio-3D Printing Technology in vivo
Authors: Kawai Yujiro , Tohyama Shugo , Arai Kenichi , Tamura Tadashi , Soma Yusuke , Fukuda Keiichi , Shimizu Hideyuki , Nakayama Koichi , Kobayashi Eiji
Published: January 2022

Engineered heart tissues (EHTs) that are fabricated using human induced pluripotent stem cells (hiPSCs) have been considered as potential cardiac tissue substitutes in case of heart failure. In the present study, we have created hiPSC-derived cardiac organoids (hiPSC-COs) comprised of hiPSC-derived cardiomyocytes, human umbilical vein endothelial cells, and human fibroblasts. To produce a beating conduit for patients suffering from congenital heart diseases, we constructed scaffold-free tubular EHTs (T-EHTs) using hiPSC-COs and bio-3D printing with needle arrays. The bio-3D printed T-EHTs were cut open and transplanted around the abdominal aorta as well as the inferior vena cava (IVC) of NOG mice. The transplanted T-EHTs were covered with the omentum, and the abdomen was closed after completion of the procedure. Additionally, to compare the functionality of hiPSC-COs with that of T-EHTs, we transplanted the former around the aorta and IVC as well as injecting them into the subcutaneous tissue on the back of the mice. After 1 m of the transplantation procedures, we observed the beating of the T-EHTs in the mice. In histological analysis, the T-EHTs showed clear striation of the myocardium and vascularization compared to hiPSC-COs transplanted around the aorta or in subcutaneous tissue. Based on these results, bio-3D-printed T-EHTs exhibited a better maturation in vivo as compared to the hiPSC-COs. Therefore, these beating T-EHTs may form conduits for congenital heart disease patients, and T-EHT transplantation can form a treatment option in such cases.
Different Rates of Bioprosthetic Aortic Valve Failure With Perimount™ and Trifecta™ Bioprostheses
Authors: Lange Rüdiger , Alalawi Zahra , Voss Stephanie , Boehm Johannes , Krane Markus , Vitanova Keti
Published: January 2022

Objectives

The use of bioprostheses in surgical aortic valve replacement (SAVR) has increased in younger patients. Comparative analysis of different types of bioprostheses is lacking. We aimed to compare two proprietary bioprostheses with different designs, i.e., internally and externally mounted leaflets, focusing on the long-term durability and survival.

Methods

We conducted a large single-center retrospective analysis of all consecutive patients who underwent SAVR with either Perimount™ or Trifecta™ bioprostheses between 2001 and 2019. The patient groups were further subdivided by age <65 and >65. Endpoints of the study were all-cause mortality and reoperation due to bioprosthetic valve failure (BVF).

Results

Selection criteria resulted in a total sample of 5,053 patients; 2,630 received a Perimount prosthesis (internally mounted leaflets) and 2,423 received a Trifecta prosthesis (externally mounted leaflets). The mean age at surgery was similar (69 ± 11 y, PM, and 68 ± 10 y, TF, p = 0.9), as was estimated survival at 8 years (76.1 ± 1.3%, PM, and 63.7 ± 1.9% TF; p=0.133). Patients in the Trifecta group had a significantly higher cumulative reoperation rate at 8 years compared to those in the Perimount group (16.9 ± 1.9% vs. 3.8 ± 0.4%; p < 0.01). This difference persisted across age groups (<65 y, 13.3% TF vs. 8.6% PM; >65 y, 12% TF vs. 7% PM).

Conclusion

Bioprostheses for SAVR with externally mounted leaflets (Trifecta) showed significantly higher long-term reoperation rates compared to those with internally mounted leaflets (Perimount), regardless of the patient's age at SAVR. Survival was similar with both bioprostheses.
Evaluating the Impact of a Comprehensive Canadian Science-Art Residency Program on the Participating Scientist, Artist and the Public
Authors: Lau Catherine , Barriault Chantal , Krolik Julia
Published: January 2022

Science-art residencies can provide opportunities for insightful cross-disciplinary collaborations, science communication, and engagement with the general public. Currently, there are few formal ways for artists and scientists to collaborate in Canada, and even fewer publications on how these experiences can impact learning in informal settings. Art the Science (a Canadian non-profit organization facilitating cross-disciplinary relationships between artists and scientists) piloted a comprehensive multiphase science-art residency program. Phase 1 informed the artist’s work through a full-time experience in a scientific laboratory at an academic institution, Phase 2 showcased the artist’s final artwork, Between the Sand at an off-campus local community event, and Phase 3 published an interactive online version of the work for global exhibition. Residency evaluation in each phase was conducted through the use of qualitative and quantitative methods, including interviews, concept mapping, video diaries, and surveys. The artist, scientist and lab members gained new perspectives and inspiration about their respective fields. The artist was able to incorporate theories and processes from the research group into their artistic practice. On the other hand, the scientist saw renewed enthusiasm and curiosity within their research lab, and the lab members reported new ways of thinking about how to communicate their research. Both exhibitions proved to be engaging informal learning experiences for 66.2% of survey participants, and revealed several major learning themes. Despite promoting both events as artwork exhibitions, 79.2% of survey participants considered Between the Sand as both an artwork and a science communication product suggesting that science-based art may have the potential to communicate science, even when it is not presented as a science communication effort. Public responses revealed that public perception of funding is not skewed to either discipline and instead seems to call upon both science and arts grants to fund such interdisciplinary initiatives. Providing comprehensive artist residencies in science labs may have a valuable impact on everyone involved: the artist, the research group, and the public.
Brown Adipose Tissue Rescues Bone Loss Induced by Cold Exposure
Authors: Du Jingke , He Zihao , Xu Mingming , Qu Xinhua , Cui Junqi , Zhang Shuangyan , Zhang Shuhong , Li Hanjun , Yu Zhifeng
Published: January 2022

Cold temperature activates the sympathetic nervous system (SNS) to induce bone loss by altering bone remodeling. Brown adipose tissue (BAT) is influenced by the SNS in cold environments. Many studies have confirmed a positive relationship between BAT volume and bone mass, but the influence and mechanism of BAT on bone in vivo and in vitro is still unknown. Two-month-old C57/BL6j male mice were exposed to cold temperature (4°C) to induce BAT generation. BAT volume, bone remodeling and microstructure were assessed after 1 day, 14 days and 28 days of cold exposure. CTX-1, P1NP and IL-6 levels were detected in the serum by ELISA. To determine the effect of BAT on osteoclasts and osteoblasts in vitro, brown adipocyte conditional medium (BAT CM) was collected and added to the differentiation medium of bone marrow-derived macrophages (BMMs) and bone marrow mesenchymal stem cells (BMSCs). Micro-CT results showed that the bone volume fraction (BV/TV, %) significantly decreased after 14 days of exposure to cold temperature but recovered after 28 days. Double labeling and TRAP staining in vivo showed that bone remodeling was altered during cold exposure. BAT volume enlarged after 14 days of cold stimulation, and IL-6 increased. BAT CM promoted BMSC mineralization by increasing osteocalcin (Ocn), RUNX family transcription factor 2 (Runx2) and alkaline phosphatase (Alp) expression, while bone absorption was inhibited by BAT CM. In conclusion, restoration of bone volume after cold exposure may be attributed to enlarged BAT. BAT has a beneficial effect on bone mass by facilitating osteogenesis and suppressing osteoclastogenesis.
Yearly Height Gain Is Dependent on the Truly Received Dose of Growth Hormone and the Duration of Periods of Poor Adherence: Practical Lessons From the French Easypod™ Connect Multicenter Observational Study
Authors: Coutant Régis , Nicolino Marc , Cammas Benoit , de Buyst Valérie , Tauber Maïthé , Hamel Jean-François
Published: January 2022

Objective

To study the impact of the true mean daily dose and the true mean number of injections per week on the yearly height gain in short children treated with recombinant human growth hormone (rhGH).

Design and Methods

220 children from the French Easypod™ Connect Observational Study (ECOS) used the Easypod™ electronic device to record rhGH injections. The mean daily rhGH dose (the sum of the doses truly received divided by the number of days) and mean number of injections per week (the number of injections truly performed divided by the number of weeks) were calculated. Linear mixed models were used to study the impact of short (3-month) and long (1-year) variations in rhGH administration on the yearly height change [as a standard deviation score (SDS)], with time on treatment as a covariate. For each patient, several periods of 3 or 12 months were considered and designated as poorly adherence or fully adherence. We studied the impact of each of period on the height change.

Results

At treatment initiation, the mean ± SD age was 9.8 ± 3.7 years (females: 47%, prepubertal: 86%) and the mean height was -2.28 ± 0.92 SDS. The mean treatment duration was 3.2 ± 1.1 years (685.2 patient years). 122 patients were GH-deficient, 79 were small for gestational age, and 19 had Turner syndrome. When treatment was computed over 12-month periods, receiving a mean daily dose <0.03 mg/kg.d was associated with a 20% lower mean yearly height gain SDS when<3 injections/week were received (vs.>5 injections/week), whereas maintaining a mean daily dose >0.03 mg/kg.d with<3 injections/week was not associated with a lower yearly height gain SDS (vs.>5 injections/week). For 3-month periods, changes in the daily rhGH dose or the number of injections per week over such short period did not influence the yearly height gain SDS.

Conclusion

The 12-month treatment model showed that when poor adherence leads to a low true daily GH dose, the yearly height gain is low. The 3-month treatment model showed that poor adherence for short periods (<3 months) had no impact on the height SDS.
Systematic Analysis of Expression and Prognostic Values of Lysyl Oxidase Family in Gastric Cancer
Authors: Wang Li , Cao Shan , Zhai Rujun , Zhao Yang , Song Guodong
Published: January 2022

Background: Gastric cancer (GC) remains the fifth most commonly diagnosed malignancy worldwide, with a poor prognosis. The lysyl oxidase (LOX) family, a type of secreted copper-dependent amine oxidases, is comprised of LOX and four LOX-like (LOXL) 1–4 isoforms and has been reported to be dysregulated in a number of different type cancers. However, the diverse expression patterns and prognostic values of LOX family in GC have yet to be systematically analyzed.

Methods: ONCOMINE, GEPIA, UALCAN, Kaplan–Meier Plotter, LOGpc, cBioPortal, GeneMANIA and Metascape databases were utilized in this study to analyze the expression, prognostic values, mutations and functional networks of LOX family in GC.

Results: The mRNA expression levels of LOX, LOXL1 and LOXL2 were significantly higher in GC, the expression level of LOXL3 was contrary in different databases, while the expression level of LOXL4 made no difference; the expression levels of LOX, LOXL1 and LOXL3 were higher in stages 2–4 than that of normal tissues and stage 1, while the mRNA level of LOXL2 in stage 1–4 was higher than normal tissues; patients with high expression of LOX and LOXL 2-4 had poor OS; the genes correlated with LOX and LOXL2 were enriched in extracellular matrix organization, vasculature development and skeletal system development.

Conclusion: Our results indicated that the LOX family, especially LOX and LOXL2, might play an important role in GC oncogenesis, and they may become biomarkers for predicting tumor prognosis and potential targets for tumor therapy.
Shared Genetic Architecture and Causal Relationship Between Asthma and Cardiovascular Diseases: A Large-Scale Cross-Trait Analysis
Authors: Zhou Yi , Liang Zhi-Sheng , Jin Yinzi , Ding Jiayuan , Huang Tao , Moore Jason H. , Zheng Zhi-Jie , Huang Jie
Published: January 2022

Background: Accumulating evidence has suggested that there is a positive association between asthma and cardiovascular diseases (CVDs), implying a common architecture between them. However, the shared genetic architecture and causality of asthma and CVDs remain unclear.

Methods: Based on the genome-wide association study (GWAS) summary statistics of recently published studies, our study examined the genetic correlation, shared genetic variants, and causal relationship between asthma (N = 127,669) and CVDs (N = 86,995–521,612). Statistical methods included high-definition likelihood (HDL), cross-trait meta-analyses of large-scale GWAS, transcriptome-wide association studies (TWAS), and Mendelian randomization (MR).

Results: First, we observed a significant genetic correlation between asthma and heart failure (HF) (Rg = 0.278, P = 5 × 10−4). Through cross-trait analyses, we identified a total of 145 shared loci between asthma and HF. Fifteen novel loci were not previously reported for association with either asthma or HF. Second, we mapped these 145 loci to a total of 99 genes whose expressions are enriched in a broad spectrum of tissues, including the seminal vesicle, tonsil, appendix, spleen, skin, lymph nodes, breast, cervix and uterus, skeletal muscle, small intestine, lung, prostate, cardiac muscle, and liver. TWAS analysis identified five significant genes shared between asthma and HF in tissues from the hemic and immune system, digestive system, integumentary system, and nervous system. GSDMA, GSDMB, and ORMDL3 are statistically independent genetic effects from all shared TWAS genes between asthma and HF. Third, through MR analysis, genetic liability to asthma was significantly associated with heart failure at the Bonferroni-corrected significance level. The odds ratio (OR) is 1.07 [95% confidence interval (CI): 1.03–1.12; p = 1.31 × 10−3] per one-unit increase in loge odds of asthma.

Conclusion: These findings provide strong evidence of genetic correlations and causal relationship between asthma and HF, suggesting a shared genetic architecture for these two diseases.
Genetic Alteration, Prognostic and Immunological Role of Acyl-CoA Synthetase Long-Chain Family Member 4 in a Pan-Cancer Analysis
Authors: Yu Yongsheng , Sun Xuepu , Chen Fei , Liu Miao
Published: January 2022

Acyl-CoA Synthetase long-chain family member 4 (ACSL4) is a member of acyl-CoA synthetase protein long-chain family, which is associated with amino acid synthesis, lipid synthesis and lipid peroxidation dependent iron death. However, the role of ACSL4 in generalized carcinoma remains unclear. We aim to analyze the expression and prognostic value of ACSL4 in pan-cancer, and further explore the correlation between ACSL4 and immune infiltration. Through ONCOMINE, TIMER (Tumor Immune Estimation Resource), GEPIA (Gene expression Profiling Interactive), UALCAN and HPA, ACSL4 expression patterns of in pan-cancer were analyzed. The prognostic value of ACSL4 was analyzed using PrognoScan and Kaplan-Meier Plotter databases. Furthermore, gene variation and epigenetic modification of ACSL4 were analyzed by cBioPortal and GSCA databases. Meanwhile, GEPIA and TIMER databases applied to evaluate the relationship between ACSL4 expression and immune infiltration. These results indicate that ACSL4 expression is down-regulated and associated with prognosis in most tumors. In general, lower ACSL4 expression shows more beneficial prognosis. The most common genetic alteration of ACSL4 is point mutation. ACSL4 is negatively correlated with DNA methylation levels in most cancers. ACSL4 mutations or hypomethylation are associated with poor prognosis. In addition, ACSL4 is positively correlated with immune infiltration in cancers. ACSL4 and immune infiltration are strongly associated with prognosis in BRCA (Breast invasive carcinoma) and SKCM (Skin Cutaneous Melanoma). ACSL4 mutation caused significant changes of immune infiltration in UCEC (Uterine Corpus Endometrial Carcinoma) and SARC (Sarcoma). ACSL4 may be a promising prognostic biomarker for pan-cancer and is closely associated with immune infiltration in the tumor microenvironment.
Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy
Authors: Mohamed Hager , Gurrola Theodore , Berman Rachel , Collins Mackenzie , Sariyer Ilker K. , Nonnemacher Michael R. , Wigdahl Brian
Published: January 2022

Globally, human immunodeficiency virus type 1 (HIV-1) infection is a major health burden for which successful therapeutic options are still being investigated. Challenges facing current drugs that are part of the established life-long antiretroviral therapy (ART) include toxicity, development of drug resistant HIV-1 strains, the cost of treatment, and the inability to eradicate the provirus from infected cells. For these reasons, novel anti-HIV-1 therapeutics that can prevent or eliminate disease progression including the onset of the acquired immunodeficiency syndrome (AIDS) are needed. While development of HIV-1 vaccination has also been challenging, recent advancements demonstrate that infection of HIV-1-susceptible cells can be prevented in individuals living with HIV-1, by targeting C-C chemokine receptor type 5 (CCR5). CCR5 serves many functions in the human immune response and is a co-receptor utilized by HIV-1 for entry into immune cells. Therapeutics targeting CCR5 generally involve gene editing techniques including CRISPR, CCR5 blockade using antibodies or antagonists, or combinations of both. Here we review the efficacy of these approaches and discuss the potential of their use in the clinic as novel ART-independent therapies for HIV-1 infection.
The Dual Role of CCR5 in the Course of Influenza Infection: Exploring Treatment Opportunities
Authors: Ferrero Maximiliano Ruben , Tavares Luciana Pádua , Garcia Cristiana Couto
Published: January 2022

Influenza is one of the most relevant respiratory viruses to human health causing annual epidemics, and recurrent pandemics. Influenza disease is principally associated with inappropriate activation of the immune response. Chemokine receptor 5 (CCR5) and its cognate chemokines CCL3, CCL4 and CCL5 are rapidly induced upon influenza infection, contributing to leukocyte recruitment into the airways and a consequent effective antiviral response. Here we discuss the existing evidence for CCR5 role in the host immune responses to influenza virus. Complete absence of CCR5 in mice revealed the receptor’s role in coping with influenza via the recruitment of early memory CD8+ T cells, B cell activation and later recruitment of activated CD4+ T cells. Moreover, CCR5 contributes to inflammatory resolution by enhancing alveolar macrophages survival and reprogramming macrophages to pro-resolving phenotypes. In contrast, CCR5 activation is associated with excessive recruitment of neutrophils, inflammatory monocytes, and NK cells in models of severe influenza pneumonia. The available data suggests that, while CCL5 can play a protective role in influenza infection, CCL3 may contribute to an overwhelming inflammatory process that can harm the lung tissue. In humans, the gene encoding CCR5 might contain a 32-base pair deletion, resulting in a truncated protein. While discordant data in literature regarding this CCR5 mutation and influenza severity, the association of CCR5delta32 and HIV resistance fostered the development of different CCR5 inhibitors, now being tested in lung inflammation therapy. The potential use of CCR5 inhibitors to modulate the inflammatory response in severe human influenza infections is to be addressed.
Case Report: Eosinophilic Esophagitis in a Patient With a Novel STAT1 Gain-of-Function Pathogenic Variant
Authors: Scott Ori , Sharfe Nigel , Dadi Harjit , Vong Linda , Garkaby Jenny , Abrego Fuentes Laura , Willett Pachul Jessica , Nelles Sandra , Nahum Amit , Roifman Chaim M.
Published: January 2022

Background

STAT1 gain-of-function (GOF) is a primary immune dysregulatory disorder marked by wide infectious predisposition (most notably chronic mucocutaneous Candidiasis), autoimmunity, vascular disease and malignant predisposition. While atopic features have been described in some STAT1 GOF patients, they are not considered a predominant feature of the disease. Additionally, while eosinophilic gastrointestinal infiltration has been reported in some cases, this has always been described in the context of pre-existing oropharyngeal and/or esophageal Candidiasis.

Clinical cases

Herein, we report 3 members of a multi-generational family diagnosed with STAT1 GOF caused by a novel mutation in the N-terminal domain, c.194A>C (p.D65A). The proband presented initially with a long-standing history of treatment-refractory eosinophilic esophagitis (EoE) without preceding gastrointestinal tract fungal infections, and her mother was diagnosed with esophagitis as well.

Conclusion

EoE has been previously associated with alterations to STAT6 and STAT3 signaling pathways. The current report expands the possible association between JAK/STAT-related disorders and EoE, suggesting that EoE could be a primary disease manifestation of STAT1 GOF, even in the absence of oropharyngeal and/or esophageal Candidiasis.
Alu RNA Structural Features Modulate Immune Cell Activation and A-to-I Editing of Alu RNAs Is Diminished in Human Inflammatory Bowel Disease
Authors: Aune Thomas M. , Tossberg John T. , Heinrich Rachel M. , Porter Krislyn P. , Crooke Philip S.
Published: January 2022

Alu retrotransposons belong to the class of short interspersed nuclear elements (SINEs). Alu RNA is abundant in cells and its repetitive structure forms double-stranded RNAs (dsRNA) that activate dsRNA sensors and trigger innate immune responses with significant pathological consequences. Mechanisms to prevent innate immune activation include deamination of adenosines to inosines in dsRNAs, referred to as A-to-I editing, degradation of Alu RNAs by endoribonucleases, and sequestration of Alu RNAs by RNA binding proteins. We have previously demonstrated that widespread loss of Alu RNA A-to-I editing is associated with diverse human diseases including viral (COVID-19, influenza) and autoimmune diseases (multiple sclerosis). Here we demonstrate loss of A-to-I editing in leukocytes is also associated with inflammatory bowel diseases. Our structure-function analysis demonstrates that ability to activate innate immune responses resides in the left arm of Alu RNA, requires a 5’-PPP, RIG-I is the major Alu dsRNA sensor, and A-to-I editing disrupts both structure and function. Further, edited Alu RNAs inhibit activity of unedited Alu RNAs. Altering Alu RNA nucleotide sequence increases biological activity. Two classes of Alu RNAs exist, one class stimulates both IRF and NF-kB transcriptional activity and a second class only stimulates IRF transcriptional activity. Thus, Alu RNAs play important roles in human disease but may also have therapeutic potential.