bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the complexity of demand-side determinants on vaccine uptake in sub-Saharan Africa
Authors: van Heemskerken Phylisha G , Decouttere Catherine J , Broekhuizen Henk , Vandaele Nico J 
Published: November 2021

Abstract
Routine vaccination annually prevents millions of deaths worldwide but is underutilized in sub-Saharan Africa (SSA). The complexity of socio-cultural factors impacting vaccine uptake is not well understood. Hence, this paper aims to review the socio-cultural determinants of vaccine uptake and visualize their interrelationships. We conducted a literature search using Pubmed and Embase databases, including articles published from 2000 to 2019 describing socio-cultural demand-side determinants for vaccine uptake. Using the Andersen and Newman Framework of Health Services Utilization, demand-side determinants were categorized as predisposing, enabling or need factors. A qualitative system dynamics approach was employed to visualize how these factors and their dynamic interrelationships influence vaccine uptake. This visualization, by means of a causal-loop diagram (CLD), was mostly based on a qualitative input, with the majority being statements of the authors. These statements were abstracted from the papers found in the review. Quantification was done by counting direct (statistical) associations between each determinant and ‘timely and full routine immunization coverage’. A total of 90 articles, primarily from Nigeria (n = 23), Ethiopia (n = 17) and Kenya (n = 11), met the inclusion criteria. We find that maternal autonomy and the perceived benefits caregivers attach to vaccination and exert their influences on many other factors through several feedback loops, thereby influencing timely and full routine immunization coverage. Utilization of health services (supply-related) and access to information (demand-related) were considered as high-potential leverage points. Quantification has shown that maternal autonomy and perceived benefit have an unclear evidence base. Future research should focus on these key players as they play a central role in multiple complex pathways, through which they could influence the uptake of vaccines in SSA.
Mitochondrial genome-wide analysis of nuclear DNA methylation quantitative trait loci
Authors: Laaksonen Jaakko , Mishra Pashupati P , Seppälä Ilkka , Raitoharju Emma , Marttila Saara , Mononen Nina , Lyytikäinen Leo-Pekka , Kleber Marcus E , Delgado Graciela E , Lepistö Maija , Almusa Henrikki , Ellonen Pekka , Lorkowski Stefan , März Winfried , Hutri-Kähönen Nina , Raitakari Olli , Kähönen Mika , Salonen Jukka T , Lehtimäki Terho 
Published: November 2021

AbstractMitochondria have a complex communication network with the surrounding cell and can alter nuclear DNA methylation (DNAm). Variation in the mitochondrial DNA (mtDNA) has also been linked to differential DNAm. Genome-wide association studies have identified numerous DNAm quantitative trait loci, but these studies have not examined the mitochondrial genome. Herein, we quantified nuclear DNAm from blood and conducted a mitochondrial genome-wide association study of DNAm, with an additional emphasis on sex- and prediabetes-specific heterogeneity. We used the Young Finns Study (n = 926) with sequenced mtDNA genotypes as a discovery sample and sought replication in the Ludwigshafen Risk and Cardiovascular Health study (n = 2317). We identified numerous significant associations in the discovery phase (P &lt; 10−9), but they were not replicated when accounting for multiple testing. In total, 27 associations were nominally replicated with a P &lt; 0.05. The replication analysis presented no evidence of sex- or prediabetes-specific heterogeneity. The 27 associations were included in a joint meta-analysis of the two cohorts, and 19 DNAm sites associated with mtDNA variants, while four other sites showed haplogroup associations. An expression quantitative trait methylation analysis was performed for the identified DNAm sites, pinpointing two statistically significant associations. This study provides evidence of a mitochondrial genetic control of nuclear DNAm with little evidence found for sex- and prediabetes-specific effects. The lack of a comparable mtDNA data set for replication is a limitation in our study and further studies are needed to validate our results.
A rare case of abdominal wall necrotizing fasciitis caused by Actinomyces europaeus—a novel pathogen
Authors: Allen Neill , James Georgina , Jain Yogesh 
Published: November 2021

Abstract
Actinomyces europaeus is a sub-species of actinomyces first isolated in humans in 1997. It is commensal bacteria found within the genitourinary and gastrointestinal tract. Although it is known to cause soft tissue infection and has been known to cause abscesses, it has never been identified as the primary pathogen in a case of necrotizing fasciitis. We present the case of a 59-year-old man with recurrent groin infections, poorly controlled Type 2 diabetes and obesity who developed necrotizing fasciitis of his lower abdominal wall secondary to Actinomyces europaeus. We discuss the clinical course and the value of early identification of the pathogen and specialist microbiologist advice.
A Novel Technique for Securing a Bolster For Skin Grafting after Extensive Vulvar Resection
Authors: Fei Y. Frances , Welch Kathryn C. , Haefner Hope K. 
Published: November 2021

Summary:
Patients with stage III hidradenitis suppurativa of the vulva and adjacent areas, unresponsive to other therapies, may require extensive surgeries. These include excision of diseased areas on the buttocks, vulva, groins, and abdomen, followed by delayed skin grafting. Negative pressure wound therapy has been used over grafts, but it can be difficult to maintain a seal when extensive areas have been resected. We present a novel technique to bolster skin grafts for optimal success. A total vulvectomy and resection of the buttocks, groins, and abdomen are first performed for stage III HS, incorporating all diseased tissue. Negative pressure wound therapy is applied and changed on postoperative day 3–4. On postoperative day 7, split-thickness skin grafts are applied. The skin grafts are covered by Adaptic gauze (3M Company, Minn.), cotton, and a layer of Reston foam (3M Company, St. Paul, Minn.) which is cut to fit the size of the wound. Ostomy skin barriers (Hollister Incorporated, Libertyville, Ill.) are placed on the skin surrounding the excised areas. Pediatric Foley catheters are then placed through the ostomy skin barriers and tied together to prevent movement of the bolster. The use of ostomy skin barriers and pediatric Foley catheters to secure bolsters has not previously been described. We demonstrate a well-tolerated technique, using common surgical supplies, to provide consistent uniform pressure over the graft site. This technique also allows for easy bedside dressing change(s) when indicated.
Psychedelic medicines for mood disorders: current evidence and clinical considerations
Authors: Sarris Jerome , Pinzon Rubiano Diego , Day Kimberley , Galvão-Coelho Nicole L. , Perkins Daniel 
Published: November 2021

Purpose of review
Despite advances in treatment modalities for mood disorders over recent decades, further therapeutic options are still required. Increased research is occurring, with the pursuit of psychedelic-based pharmacotherapies for a range of mood disorders and other conditions.

Recent findings
Serotonergic psychedelics have been found to modulate brain networks underlying various psychiatric disorders, as well promoting neurogenesis and neuroplasticity. Randomized placebo-controlled trials have found psilocybin with psychological support effective at treating depression, including treatment-resistant depression; with emergent research also signalling N,N-dimethyltryptamine/ayahuasca also as a potential option for the treatment of depression. Lysergic acid diethylamide has been found to have anxiolytic effects, whereas 3,4-methylenedioxymethamphetamine (MDMA) has been used effectively to treat post-traumatic stress disorder (PTSD), with Phase III clinical trial evidence. Microdosing of psychedelics is a growing phenomenon that has shown benefits in some preclinical data; however, a recent self-directed controlled trial reported no evidence of improved mood.

Summary
Current research with medicinal psychedelics, usually as an adjunct to psychotherapy, has shown encouraging results in treating mood disorders. However, there are challenges regarding blinding and sample sizes remain small, and there have been no definitive Phase III studies (aside from MDMA for PTSD). Further work exploring novel formulations, interface with pharmacogenomics and the microbiome, and inflammatory pathways can be advised.
Interacting host modifier systems control Wolbachia-induced cytoplasmic incompatibility in a haplodiploid mite
Authors: Wybouw Nicky , Mortier Frederik , Bonte Dries 
Published: November 2021

AbstractMany reproductive parasites such as Wolbachia spread within host populations by inducing cytoplasmic incompatibility (CI). CI occurs when parasite-modified sperm fertilizes uninfected eggs. In haplodiploid hosts, CI can lead to different phenotypes depending on whether the fertilized eggs die or develop into males. Genetic conflict theories predict the evolution of host modulation of CI, which in turn strongly influences the stability of reproductive parasitism. Yet, despite the ubiquity of CI-inducing parasites in nature, there is no conclusive evidence for strong intraspecific host modulation of CI strength and phenotype. Here, we tested for intraspecific host modulation of Wolbachia-induced CI in haplodiploid Tetranychus spider mites. Using a single CI-inducing Wolbachia variant and mitochondrion, a Tetranychus urticae nuclear panel was created that consisted of infected and cured near-isogenic lines. We performed a highly replicated age-synchronized full diallel cross comprised of incompatible and compatible control crosses. We uncovered host modifier systems that strongly suppress CI strength when carried by infected T. urticae males. Interspecific crosses showed that the male modifier systems suppress CI strength across species boundaries. We also observed a continuum of CI phenotypes in our crosses and identified strong intraspecific female modulation of CI phenotype when paired with a specific male genotype. Crosses established a recessive genetic basis for the maternal effect and were consistent with polygenic Mendelian inheritance. Our findings identify spermatogenesis as an important target of selection for host suppression of CI strength and underscore the importance of maternal genetic effects for the CI phenotype. Both mechanisms interacted with the genotype of the mating partner, revealing that intraspecific host modulation of CI strength and phenotype is underpinned by complex genetic architectures.
A Landmark-based Common Coordinate Framework for Spatial Transcriptomics Data
Authors: Andersson Alma , Andrusivová Žaneta , Czarnewski Paulo , Li Xiaofei , Sundström Erik , Lundeberg Joakim 
Published: November 2021

1AbstractThe increasing amount of spatial transcriptomics data prompts for means to amalgamate observations from distinct experiments, especially attractive is to cast quantities from different sources into a common coordinate frame-work (CCF) to relate signals across space. We here present a method that enables transfer of information from multiple samples to a reference representing a CCF, and show its utility by analyzing an assortment of real and synthetic data sets.
networkGWAS: A network-based approach to discover genetic associations
Authors: Muzio Giulia , O’Bray Leslie , Meng-Papaxanthos Laetitia , Klatt Juliane , Borgwardt Karsten 
Published: November 2021

AbstractWhile the search for associations between genetic markers and complex traits has led to the discovery of tens of thousands of trait-related genetic variants, the vast majority of these only explain a small fraction of observed phenotypic variation. One possible strategy to detect stronger associations is to aggregate the effects of several genetic markers and to test entire genes, pathways or (sub)networks of genes for association to a phenotype. The latter, network-based genome-wide association studies, in particular suffers from a vast search space and an inherent multiple testing problem. As a consequence, current approaches are either based on greedy feature selection, thereby risking that they miss relevant associations, or neglect doing a multiple testing correction, which can lead to an abundance of false positive findings.To address the shortcomings of current approaches of network-based genome-wide association studies, we proposenetworkGWAS, a computationally efficient and statistically sound approach to network-based genome-wide association studies using mixed models and neighborhood aggregation. It allows for population structure correction and for well-calibratedp-values, which are obtained through circular and degree-preserving network permutation schemes.networkGWASsuccessfully detects known associations on semi-simulated common variants fromA. thalianaand on simulated rare variants fromH. sapiens, as well as neighborhoods of genes involved in stress-related biological processes on a stress-induced phenotype fromS. cerevisiae. It thereby enables the systematic combination of gene-based genome-wide association studies with biological network information.Availabilityhttps://github.com/BorgwardtLab/networkGWAS.gitContactgiulia.muzio@bsse.ethz.ch,karsten.borgwardt@bsse.ethz.ch
The chromatin-regulating CoREST complex is animal specific and essential for development in the cnidarian Nematostella vectensis
Authors: Gahan James M , Hernandez-Valladares Maria , Rentzsch Fabian 
Published: November 2021

AbstractChromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Many individual chromatin modifiers, however, predate the evolution of animal multicellularity and how they became integrated into the regulatory networks underlying development is unclear. Here we show that CoREST is an animal-specific protein that assembles a conserved, vertebrate-like histone-modifying complex including Lsd1 and HDAC1/2 in the sea anemone Nematostella vectensis. We further show that NvCoREST expression overlaps fully with that of NvLsd1 throughout development. NvCoREST mutants, generated using CRISPR-Cas9, reveal essential roles during development and for the differentiation of cnidocytes, thereby phenocopying NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach. Together, this shows that the evolution of CoREST allowed the formation of a chromatin-modifying complex that was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.
Risky choice: probability weighting explains Independence Axiom violations in monkeys
Authors: Ferrari-Toniolo Simone , Seak Leo Chi U , Schultz Wolfram 
Published: November 2021

AbstractExpected Utility Theory (EUT) provides axioms for maximizing utility in risky choice. The Independence Axiom (IA) is its most demanding axiom: preferences between two options should not change when altering both options equally by mixing them with a common gamble. We tested common consequence (CC) and common ratio (CR) violations of the IA over several months in thousands of stochastic choices using a large variety of binary option sets. Three monkeys showed consistently few outrightPreference Reversals(8%) but substantial gradedPreference Changes(46%) between the initial preferred gamble and the corresponding altered gamble. Linear Discriminant Analysis (LDA) indicated that gamble probabilities predicted mostPreference Changesin CC (72%) and CR (88%) tests. The Akaike Information Criterion indicated that probability weighting within Cumulative Prospect Theory (CPT) explained choices better than models using Expected Value (EV) or EUT. Fitting by utility and probability weighting functions of CPT resulted in nonlinear and non-parallel indifference curves (IC) in the Marschak-Machina triangle and suggested IA non-compliance of models using EV or EUT. Indeed, CPT models predictedPreference Changesbetter than EV and EUT models. Indifference points in out-of-sample tests were closer to CPT-estimated ICs than EV and EUT ICs. Finally, while the few outrightPreference Reversalsmay reflect the long experience of our monkeys, their more gradedPreference Changescorresponded to those reported for humans. In benefitting from the wide testing possibilities in monkeys, our stringent axiomatic tests contribute critical information about risky decision-making and serve as basis for investigating neuronal decision mechanisms.
Congenital Zika virus infection impairs corpus callosum development
Authors: Christoff Raissa R. , Quintanilha Jefferson H. , Ferreira Raiane O. , Ferreira Jessica C. C. G. , Guimarães Daniel M. , Valério-Gomes Bruna , Higa Luiza M. , Rossi Átila D. , Vasconcelos Janaina M. , Vianez João L.S.G. , Bellio Maria , Tanuri Amilcar , Lent Roberto , Garcez Patricia P. 
Published: November 2021

AbstractCongenital Zika Syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryosin uterowith a Brazilian ZIKV isolate and found that they are born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction of PH3+ cells, intermediate progenitor cells and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV infected cultures show a reduction of callosal axon length. GFAP labelling showed thatin uteroinfection compromises glial cells responsible for midline axon guidance. The RNA-Seq data from infected brains identified downregulation of axon guidance and axonogenesis related genes. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis but also axon guidance and growth across the midline.Summary StatementZika virus infection during development impairs the formation of corpus callosum by disturbing axon guidance and growth of callosal neurons.
MiR-144 regulates adipogenesis by mediating formation of C/EBPα-FoxO1 protein complex
Authors: Lin Weimin , Wen Xianyu , Li Xuexin , Chen Lei , Wei Wei , Zhang Lifan , Chen Jie 
Published: November 2021

AbstractExcessive adipogenesis caused obesity, which was a serious risk of health and led to a series of diseases, including type II diabetes (T2D) for example. Adipocyte as the basic unit of adipose tissue has emerged as one of significant target of the treatment of obesity-related metabolic syndromes by revealed its adipogenic molecular mechanism. MicroRNAs (miRNAs) have been demonstrated involving adipogenesis, and played a crucial role in the competitive endogenous RNA (ceRNA) effect. Besides that, C/EBPα as a crucial adipogenic regulator still lacked epigenetic explanation during pre-adipocyte adipogenesis. In this study, we first verified FoxO1 was one of the ceRNA of C/EBPα. They co-regulated adipogenesis through formed a protein complex that directly bound to its promoter to activate AdipoQ, and AdipoQ (Adiponectin) was a negative adipocytokines that suppressed adipogenesis, which played an important role in retaining adipogensis balance. Moreover, an adipose tissue specific enriched miRNA, miR-144 was the key regulator of the ceRNA effect between C/EBPα and FoxO1, which mediated the C/EBPα-FoxO1 complex formation, thus altered AdipoQ, furthermore regulated pre-adipocyte adipogenesis. This research will provide a new supplementary idea of the C/EBPα epigenetic role in pre-adipocyte adipogenesis.
Structural brain connectivity predicts acute pain after mild traumatic brain injury
Authors: Branco Paulo , Bosak Noam , Bielefeld Jannis , Cong Olivia , Granovsky Yelena , Kahn Itamar , Yarnitsky David , Apkarian A. Vania 
Published: November 2021

AbstractMild traumatic brain injury, mTBI, is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute post-injury pain is important since it is a strong predictor of long-term outcomes. In this study, we imaged the brains of 172 patients with mTBI, following a motorized vehicle collision and used a machine learning approach to extract white matter structural and resting state fMRI functional connectivity measures to predict acute pain. Stronger white matter tracts within the sensorimotor, thalamic-cortical, and default-mode systems predicted 20% of the variance in pain severity within 72 hours of the injury. This result generalized in two independent groups: 39 mTBI patients and 13 mTBI patients without whiplash symptoms. White matter measures collected at 6-months after the collision still predicted mTBI pain at that timepoint (n = 36). These white-matter connections were associated with two nociceptive psychophysical outcomes tested at a remote body site – namely conditioned pain modulation and magnitude of suprathreshold pain–, and with pain sensitivity questionnaire scores. Our validated findings demonstrate a stable white-matter network, the properties of which determine a significant amount of pain experienced after acute injury, pinpointing a circuitry engaged in the transformation and amplification of nociceptive inputs to pain perception.
Pangenome evolution in environmentally transmitted symbionts of deep-sea mussels is governed by vertical inheritance
Authors: Picazo Devani Romero , Werner Almut , Dagan Tal , Kupczok Anne 
Published: November 2021

AbstractMicrobial pangenomes vary across species; their size and structure are determined by genetic diversity within the population and by gene loss and horizontal gene transfer (HGT). Many bacteria are associated with eukaryotic hosts where the host colonization dynamics may impact bacterial genome evolution. Host-associated lifestyle has been recognized as a barrier to HGT in parentally transmitted bacteria. However, pangenome evolution of environmentally acquired symbionts remains understudied, often due to limitations in symbiont cultivation. Using high-resolution metagenomics, here we study pangenome evolution of two co-occurring endosymbionts inhabiting Bathymodiolus brooksi mussels from a single cold seep. The symbionts, sulfur-oxidizing (SOX) and methane-oxidizing (MOX) gamma-proteobacteria, are environmentally acquired at an early developmental stage and individual mussels may harbor multiple strains of each species. We found differences in the accessory gene content of both symbionts across individual mussels, which are reflected by differences in symbiont strain composition. Compared to core genes, accessory genes are enriched in functions involved in genome integrity. We found no evidence for recent horizontal gene transfer between both symbionts. A comparison between the symbiont pangenomes revealed that the MOX population is less diverged and contains fewer accessory genes, supporting that the MOX association with B. brooksi is more recent than that of SOX. Our results show that the pangenomes of both symbionts evolved mainly by vertical inheritance. We conclude that environmentally transmitted symbionts that associate with individual hosts over their lifetime show features of narrow symbioses, where the frequency of HGT is constrained.