bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canine semen cryoconservation: Emerging data over the last 20 years
Authors: Bencharif Djemil , Dordas‐Perpinya Marta 
Published: February 2020

AbstractCanine semen cryoconservation was used since 1969, and this process is still nowadays in progress. This review aims to have an overview of two factors leading to a successful freezing–thawing semen. The success and efficiency of freezing process can be measured by the post‐thawing sperm mobility. The first factor is the best extender used as a cryoprotectant to have a similar osmolarity and pH compared to the seminal plasma to enable sperm survival. Historically, chicken egg yolk was used since 1940, but due to microbial risks and to the presence of granules (which interfere with counting dead spermatozoa and inhibits a spermatozoal respiration), despite these disadvantages, egg yolk is considered an excellent cryoprotectant for sperm of different animal species. The low‐density lipoproteins (LDL), contained in EY, when used at a concentration of 6% in a freezing medium associated with 20 mM of glutamine, show a mobility up to 54.5%, which is the best combination found. However, the sperm protection mechanism by LDL during freezing–thawing process only begins to be decrypted. But extraction protocols of LDL are not efficient for an industrial use. Therefore, egg yolk plasma is used within liquid or lyophilized state, and offering similar efficiency as the 6% LDL middle. The equilibration step, in which the diluted sperm is placed for a variable period of time at a temperature of +4°C, before freezing it. The studies show that 6 hr is the optimal duration for the canine sperm equilibration. The future of canine sperm cryopreservation is expected in liposome use and synthetic substances, which mimics LDL role.
Development of tumour peptide vaccines: From universalization to personalization
Authors: Ma Minjun , Liu Jingwen , Jin Shenghang , Wang Lan 
Published: February 2020

AbstractIn recent years, relying on the human immune system to kill tumour cells has become an effective means of cancer treatment. The development of peptide vaccines, which not only break the immune tolerance of a tumour but also attack malignant cells via specific antitumour immunity, has received increased attention in tumour immunization therapy due to their safety and easy preparation. The use of large‐scale sequencing technology enables the continuous discovery of new tumour antigens. With improved accuracy of epitope prediction by computer simulation and the usage of a tetramer assay, cytotoxic lymphocyte epitopes can be screened and identified more easily. Transmembrane peptide and nanoparticle technologies promote more effective intake and delivery of antigens. Consequently, considerable evolution from universal to personalized peptide vaccines has taken place, and such vaccines induce an efficient and specific immune response targeting tumour neoantigens. Recently, genomic analysis and bioinformatics approaches have greatly facilitated the breakthrough of personalized peptide vaccines targeting neoantigens, resulting in a renewed interest in this field. Further, the combination of tumour peptide vaccines with checkpoint blockades may improve patient outcomes. In this review, we discuss the development of tumour peptide vaccines and the new technological progress, from universalization to personalization, to highlight the substantial promise of tumour peptide vaccines in clinical cancer immunotherapy.
National Politics, Neighborly Politics: How Trump’s Election Impacted a Black and White Detroit Community
Authors: Cornelissen Sharon 
Published: February 2020

Most research on right‐wing populism has tried to explain the rise of populist movements and parties. While some have studied how neighborhood contexts and histories shape voting patterns, few have examined what happens locally after votes are cast. This article draws on three years of ethnographic research while the author lived in Brightmoor, a majority black, minority white poor depopulated Detroit neighborhood, to show how Trump’s politics shaped local expressions and experiences of racism. First, I show how white Trump supporters expressed distinct approaches to xenophobic ethnonationalism and racial politics. Trump’s surge empowered many to broadcast anti‐immigrant sentiments, while they continued to put interactional and discursive work into not being seen as racist. Many also applied a “Trump lens” to local interactions and geographies and rendered minorities salient under Trump politics hypervisible. Second, I show how black residents equated xenophobic ethnonationalism with antiblack racism: seeing through pro‐Trump whites’ attempts to separate these. Some also applied a new “Trump lens” to interactions and geographies, using the category of Trump voter and a sense of the voting map to anticipate and make sense of racist interactions. This article offers new insights into the local impacts of a national surge in right‐wing populism.
Evaluating social investment in disability policy
Authors: Reinders Folmer Christopher P. , Mascini Peter , Van der Veen Romke J. 
Published: February 2020

AbstractDisability policy in European countries is displaying a shift towards social investment: increasing human capital and access to the labour market. The reasoning that underlies this transition is that disabled persons would benefit from mainstream employment, but are impeded in traditional policy by deficiencies in labour supply and demand. However, the shift towards more activating policies in many countries is accompanied by a decline in social protection. It is unclear whether social investment may effectively promote the employment chances of disabled persons within this context. The present research examines this question through a quantitative, cross‐sectional, multilevel analysis on microdata from 22 EU countries. Our findings suggest greater activation to predict lower employment chances, while reducing passive support shows mixed effects. Conversely, measures for facilitation in daily life predict greater employment chances, as do measures for sheltered work. These findings raise questions over the value of social investment for disabled persons—and underline the need to overcome broader barriers in the labour market and in society.
Mathematical, Artistic and Literary Traces in Reason/Heart (Razón/Co‐razón) Transitions
Authors: Zalamea Fernando 
Published: February 2020

AbstractThis article studies some mathematical concepts which may be ramified in cultural environments, particularly in music and literature. The notions of definability (What may we capture with language, what escapes us?), representation (Which archetypes may be projected onto the world, which types arise from such projections?) and categoricity (Which unitary concepts govern the multiplicity of languages and images?) are narrowly linked with the essential issue of the trans, perhaps the crucial problem of our fleeting times.
A survey of work‐related musculoskeletal disorders associated with performing laparoscopic veterinary surgery
Authors: Jones Andrew R. E. 
Published: February 2020

AbstractObjectiveTo assess the prevalence of work‐related musculoskeletal disorders (WRMD) associated with laparoscopy in veterinary surgery.Study designCross‐sectional survey.Sample populationVeterinary surgeons who perform laparoscopy.MethodsResponses were collected with data regarding laparoscopic activities and experience as well as whether the respondents experienced pain as a result of laparoscopy and, if so, additional information on this topic. Variables associated with the risk of experiencing pain were determined by using χ2 tests and odds ratios (OR).ResultsThere were 149 respondents, an estimated 6% response proportion. Forty percent experienced pain that they attributed to the use of laparoscopic instruments during or after laparoscopic surgery. Surgeons who perform laparoscopic surgery frequently (at least monthly) were more likely to experience pain as a result of laparoscopic surgery compared with those who perform laparoscopic surgery infrequently (OR 2.25; 95% confidence interval 1.07‐4.75; P = .033). Pain during or after laparoscopic surgery was most often experienced in the neck (81%), back (77%), and shoulders (75%), with 90% of respondents reporting that surgery exacerbated their pain. Fifty‐four percent of respondents experienced the pain at home, 64% had taken painkillers for the pain, and 46% had sought other treatment for the pain such as physiotherapy, chiropractic treatment, or seeing a doctor.ConclusionLaparoscopic surgery was a potential source of pain in a proportion of surgeons. Surgeons who frequently perform laparoscopic surgery were more likely to experience a WRMD.Clinical significanceWork‐related musculoskeletal disorders may occur as a result of performing laparoscopic surgery.
Length of maternal schooling and children’s risk of malaria infection: evidence from a natural experiment in Uganda
Authors: Masuda Kazuya 
Published: February 2020

IntroductionAn estimated 216 million cases of malaria occurred worldwide every year. Cross-sectional studies have reported negative association between maternal education and child malaria risks; however, no randomised trial or quasi-experimental study using a natural experiment has confirmed a causal relationship between these two factors. I used the free primary education reform in Uganda to assess the causal effects of maternal schooling on children’s risk of malaria infection.MethodsMalaria biomarkers of children aged <5 years were collected from the 2009 and 2014 Uganda Malaria Indicator Surveys (n=5316). In 1997, the government eliminated tuition requirements in primary schools, which increased the educational attainment of the affected cohorts. Using exposure to the reform as an instrumental variable, I used a two-stage least squares approach to estimate the causal effects of maternal year of education on the probability that a child would contract malaria at the time of the survey. I also evaluated the cost-effectiveness of primary schooling as a malaria control intervention.ResultsOne extra year of maternal education reduced children’s risk of malaria infection by 7.5 percentage points (p=0.057) from baseline (34.9%). The length of maternal education was also positively associated with insecticide-treated bednet usage by their children. The results were robust to a variety of sensitivity tests. Primary schooling for women was a cost-effective intervention to reduce children’s malaria infection.ConclusionImproving access to primary education could be a cost-effective measure to reduce malaria prevalence among children of educated mothers aged <5 years in malaria-endemic countries.
Lessons from a multidisciplinary partnership involving women parliamentarians to address the overuse of caesarean section in Italy
Authors: Montilla Pilar , Merzagora Francesca , Scolaro Elisa , Requejo Jennifer , Ricciardi Walter , Meli Elena , Bazzi Adriana , Vittori Giorgio , Bustreo Flavia , Boldi Rosanna , Rizzoti Maria , Merialdi Mario , Betran Ana Pilar 
Published: February 2020

The increase of caesarean sections (CS) represents a global concern. Interventions tested to reduce unnecessary caesareans have shown limited success to date, partly because they have focused on medical perspectives or on single faceted interventions targeting only one group of stakeholders. Limited attention has been given to examining multidisciplinary and advocacy activities that could reduce unnecessary CS by raising awareness and engaging the media, advocacy groups, healthcare professionals and politicians. In 2009 in Italy, the national CS rate was the highest in Europe and momentum was building for action.
This case study includes a description of the activities conducted in Italy during 2009–2012 by a partnership that included the non-governmental organisation Osservatorio Nazionale sulla Salute della Donna, a bipartisan group of Italian women parliamentarians and the WHO. The objectives were to generate awareness about the increase and overuse of CS in Italy, to foster political actions to reverse this trend, to engage with the media and journalists and to better understand women’s birth preferences and needs.
A reduction of the CS rate has been observed in Italy following the activities of the initiative from 38.4% in 2009 to 34.2% in 2015 according to the Ministry of Health. Although we cannot infer a casual association between the Partnership and the CS decrease, it did contribute to political momentum and specific actions that should, in theory, have contributed to this reduction. These include the engagement of women parliamentarians for policy change, improved understanding of the local drivers of increases of CS including women’s needs and preferences, raising awareness and working with the media to convey appropriate information and an inclusive strategy giving the opportunity to local stakeholders to make their voices heard.
This partnership initiative illustrates a model for generating dialogue, reflection and action in countries showing signs of readiness to address escalating CS.
Reanalysis of Alzheimer’s brain sequencing data reveals absence of purported HHV6A and HHV7
Authors: Chorlton Samuel D. 
Published: February 2020

Readhead et al. recently reported in Neuron the detection and association of human herpesviruses 6A (HHV6A) and 7 (HHV7) with Alzheimer’s disease by shotgun sequencing. I was skeptical of the specificity of their modified Viromescan bioinformatics method and subsequent analysis for numerous reasons. Using their supplementary data, the prevalence of variola virus, the etiological agent of the eradicated disease smallpox, can be calculated at 97.5% of their Mount Sinai Brain Bank dataset. Reanalysis of Readhead et al.’s data using highly sensitive and specific alternative methods finds no HHV7 reads in their samples; HHV6A reads were found in only 2 out of their top 15 samples sorted by reported HHV6A abundance. Finally, recreation of Readhead et al.’s modified Viromescan method identifies reasons for its low specificity.
The 2020 Alonzo Church award for outstanding contributions to logic and computation
Authors: Murawski Andrzej 
Published: February 2020

An annual award, called the Alonzo Church Award for Outstanding Contributions to Logic and Computation, was established in 2015 by the ACM Special Interest Group for Logic and Computation (SIGLOG), the European Association for Theoretical Computer Science (EATCS), the European Association for Computer Science Logic (EACSL), and the Kurt Gödel Society (KGS). The award is for an outstanding contribution represented by a paper or by a small group of papers published within the past 25 years. This time span allows the lasting impact and depth of the contribution to have been established. The award can be given to an individual, or to a group of individuals who have collaborated on the research. For the rules governing this award, see: https://siglog.acm.org/alonzo-church-award-for-outstanding-contributions-to-logic-and-computation-2020/, https://www.eatcs.org/index.php/church-award/, and https://eacsl.org/.
The 2019 Alonzo Church Award was given jointly to Murdoch J. Gabbay and Andrew M. Pitts for their ground-breaking work introducing the theory of nominal representations, see: http://siglog.org/winners-of-the-2019-alonzo-church-award/. Previous awardees are listed at https://www.eatcs.org/index.php/church-award/.
Signaling through the interleukin-4 and interleukin-13 receptor complexes regulates cholangiocyte TMEM16A expression and biliary secretion
Authors: Dutta Amal K. , Boggs Kristy , Khimji Al-karim , Getachew Yonas , Wang Youxue , Kresge Charles , Rockey Don C. , Feranchak Andrew P. 
Published: February 2020

TMEM16A is a Ca2+-activated Cl−channel in the apical membrane of biliary epithelial cells, known as cholangiocytes, which contributes importantly to ductular bile formation. Whereas cholangiocyte TMEM16A activity is regulated by extracellular ATP-binding membrane purinergic receptors, channel expression is regulated by interleukin-4 (IL-4) through an unknown mechanism. Therefore, the aim of the present study was to identify the signaling pathways involved in TMEM16A expression and cholangiocyte secretion. Studies were performed in polarized normal rat cholangiocyte monolayers, human Mz-Cha-1 biliary cells, and cholangiocytes isolated from murine liver tissue. The results demonstrate that all the biliary models expressed the IL-4Rα/IL-13Rα1 receptor complex. Incubation of cholangiocytes with either IL-13 or IL-4 increased the expression of TMEM16A protein, which was associated with an increase in the magnitude of Ca2+-activated Cl−currents in response to ATP in single cells and the short-circuit current response in polarized monolayers. The IL-4- and IL-13-mediated increase in TMEM16A expression was also associated with an increase in STAT6 phosphorylation. Specific inhibition of JAK-3 inhibited the increase in TMEM16A expression and the IL-4-mediated increase in ATP-stimulated currents, whereas inhibition of STAT6 inhibited both IL-4- and IL-13-mediated increases in TMEM16A expression and ATP-stimulated secretion. These studies demonstrate that the cytokines IL-13 and IL-4 regulate the expression and function of biliary TMEM16A channels through a signaling pathway involving STAT6. Identification of this regulatory pathway provides new insight into biliary secretion and suggests new targets to enhance bile formation in the treatment of cholestatic liver disorders.NEW & NOTEWORTHY The Ca2+-activated Cl−channel transmembrane member 16A (TMEM16A) has emerged as an important regulator of biliary secretion and hence, ductular bile formation. The present studies represent the initial description of the regulation of TMEM16A expression in biliary epithelium. Identification of this regulatory pathway involving the IL-4 and IL-13 receptor complex and JAK-3 and STAT-6 signaling provides new insight into biliary secretion and suggests new therapeutic targets to enhance bile formation in the treatment of cholestatic liver disorders.
A Sox2:miR-486-5p Axis Regulates Survival of GBM Cells by Inhibiting Tumor Suppressor Networks
Authors: Lopez-Bertoni Hernando , Kotchetkov Ivan S. , Mihelson Nicole , Lal Bachchu , Rui Yuan , Ames Heather , Lugo-Fagundo Maria , Guerrero-Cazares Hugo , Quiñones-Hinojosa Alfredo , Green Jordan J. , Laterra John 
Published: February 2020

Abstract

Glioblastoma multiforme (GBM) and other solid malignancies are heterogeneous and contain subpopulations of tumor cells that exhibit stem-like features. Our recent findings point to a dedifferentiation mechanism by which reprogramming transcription factors Oct4 and Sox2 drive the stem-like phenotype in glioblastoma, in part, by differentially regulating subsets of miRNAs. Currently, the molecular mechanisms by which reprogramming transcription factors and miRNAs coordinate cancer stem cell tumor-propagating capacity are unclear. In this study, we identified miR-486-5p as a Sox2-induced miRNA that targets the tumor suppressor genes PTEN and FoxO1 and regulates the GBM stem-like cells. miR-486-5p associated with the GBM stem cell phenotype and Sox2 expression and was directly induced by Sox2 in glioma cell lines and patient-derived neurospheres. Forced expression of miR-486-5p enhanced the self-renewal capacity of GBM neurospheres, and inhibition of endogenous miR-486-5p activated PTEN and FoxO1 and induced cell death by upregulating proapoptotic protein BIM via a PTEN-dependent mechanism. Furthermore, delivery of miR-486-5p antagomirs to preestablished orthotopic GBM neurosphere-derived xenografts using advanced nanoparticle formulations reduced tumor sizes in vivo and enhanced the cytotoxic response to ionizing radiation. These results define a previously unrecognized and therapeutically targetable Sox2:miR-486-5p axis that enhances the survival of GBM stem cells by repressing tumor suppressor pathways.

Significance:
This study identifies a novel axis that links core transcriptional drivers of cancer cell stemness to miR-486-5p–dependent modulation of tumor suppressor genes that feeds back to regulate glioma stem cell survival.
FGF Trapping Inhibits Multiple Myeloma Growth through c-Myc Degradation–Induced Mitochondrial Oxidative Stress
Authors: Ronca Roberto , Ghedini Gaia C. , Maccarinelli Federica , Sacco Antonio , Locatelli Silvia L. , Foglio Eleonora , Taranto Sara , Grillo Elisabetta , Matarazzo Sara , Castelli Riccardo , Paganini Giuseppe , Desantis Vanessa , Cattane Nadia , Cattaneo Annamaria , Mor Marco , Carlo-Stella Carmelo , Belotti Angelo , Roccaro Aldo M. , Presta Marco , Giacomini Arianna 
Published: February 2020

Abstract

Multiple myeloma, the second most common hematologic malignancy, frequently relapses because of chemotherapeutic resistance. Fibroblast growth factors (FGF) act as proangiogenic and mitogenic cytokines in multiple myeloma. Here, we demonstrate that the autocrine FGF/FGFR axis is essential for multiple myeloma cell survival and progression by protecting multiple myeloma cells from oxidative stress–induced apoptosis. In keeping with the hypothesis that the intracellular redox status can be a target for cancer therapy, FGF/FGFR blockade by FGF trapping or tyrosine kinase inhibitor impaired the growth and dissemination of multiple myeloma cells by inducing mitochondrial oxidative stress, DNA damage, and apoptotic cell death that were prevented by the antioxidant vitamin E or mitochondrial catalase overexpression. In addition, mitochondrial oxidative stress occurred as a consequence of proteasomal degradation of the c-Myc oncoprotein that led to glutathione depletion. Accordingly, expression of a proteasome-nondegradable c-Myc protein mutant was sufficient to avoid glutathione depletion and rescue the proapoptotic effects due to FGF blockade. These findings were confirmed on bortezomib-resistant multiple myeloma cells as well as on bone marrow–derived primary multiple myeloma cells from newly diagnosed and relapsed/refractory patients, including plasma cells bearing the t(4;14) translocation obtained from patients with high-risk multiple myeloma. Altogether, these findings dissect the mechanism by which the FGF/FGFR system plays a nonredundant role in multiple myeloma cell survival and disease progression, and indicate that FGF targeting may represent a therapeutic approach for patients with multiple myeloma with poor prognosis and advanced disease stage.

Significance:
This study provides new insights into the mechanisms by which FGF antagonists promote multiple myeloma cell death.
Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors
Authors: Hankey William , Chen Zhong , Wang Qianben 
Published: February 2020

Abstract
The androgen receptor (AR) is a critical therapeutic target in prostate cancer that responds to antagonists in primary disease, but inevitably becomes reactivated, signaling onset of the lethal castration-resistant prostate cancer (CRPC) stage. Epigenomic investigation of the chromatin environment and interacting partners required for AR transcriptional activity has uncovered three pioneer factors that open up chromatin and facilitate AR-driven transcriptional programs. FOXA1, HOXB13, and GATA2 are required for normal AR transcription in prostate epithelial development and for oncogenic AR transcription during prostate carcinogenesis. AR signaling is dependent upon these three pioneer factors both before and after the clinical transition from treatable androgen-dependent disease to untreatable CRPC. Agents targeting their respective DNA binding or downstream chromatin-remodeling events have shown promise in preclinical studies of CRPC. AR-independent functions of FOXA1, HOXB13, and GATA2 are emerging as well. While all three pioneer factors exert effects that promote carcinogenesis, some of their functions may inhibit certain stages of prostate cancer progression. In all, these pioneer factors represent some of the most promising potential therapeutic targets to emerge thus far from the study of the prostate cancer epigenome.