bluuebunny/crossref_metadata_2025 huggingface dataset:
Informellt tvång mot patienter
Authors: Pelto-Pirri Veikko , Hylén Ulrika , Kjellin Lars
Published: December 2020

Det har gjorts relativt omfattande forskning om formellt tvång mot patienter i psykiatrin, dvs. tvång som regleras av lagstiftningen. Däremot finns det inte lika mycket forskning om informellt tvång, speciellt inte ur ett personalperspektiv. Denna studie har utgått från tidigare forskning där man identifierat fem former av tvång i psykiatrin som personal använder; övertalning, utnyttjande av den personliga relationen, belöning, hot och formellt tvång. Syftet var att få personalens reflektioner över formerna för, och användningen av, informellt tvång gentemot patienter.  

Vi genomförde fyra fokusgruppsintervjuer med kuratorer, psykologer och läkare där syftet var att skapa ett reflekterande samtal om informellt tvång. Dessa intervjuer analyserades med kvalitativ innehållsanalys. 

Förutom de fem tidigare identifierade former av tvång i psykiatrin fann vi även tre andra former; att lura patienten, uppfostrande attityd samt användning av regler och rutiner. Deltagare beskrev även tvång från andra intressenter som anhöriga och andra myndigheter. När det gäller övriga reflektioner tolkades dessa som professionalitet och tvång, där deltagarna betonade betydelsen av personalens förhållningssätt till patienter, tydlig kommunikation, en individanpassad vård samt fungerande samarbete och samverkan.  

Enligt deltagarna i studien användes informellt tvång ofta samtidigt som det fanns en tveksamhet till det. Det var främst hur man som personal bör utnyttja den personliga relationen till patienten samt hur patienten uppfattade informellt tvång där deltagarna hade väldigt skilda uppfattningar. De rapporterade svårigheter i att hantera det informella tvånget som anhöriga och andra myndigheter använder gentemot psykiatrins patienter eftersom det kunde hota patienternas återhämtning. En slutsats är att informellt tvång inte enbart bör ses från ett juridiskt och kliniskt perspektiv utan att också att viktiga etiska aspekter kring informellt tvång bör uppmärksammas.
Role of Phosphorylated Gonadotropin-Regulated Testicular RNA Helicase (GRTH/DDX25) in the Regulation of Germ Cell Specific mRNAs in Chromatoid Bodies During Spermatogenesis
Authors: Anbazhagan Rajakumar , Kavarthapu Raghuveer , Coon Steven L. , Dufau Maria L.
Published: December 2020

GRTH/DDX25 is a member of the DEAD-box family of RNA helicases that play an essential role in spermatogenesis. GRTH knock-in (KI) mice with the human mutant GRTH gene (R242H) show loss of the phospho-species from cytoplasm with preservation of the non-phospho form in the cytoplasm and nucleus. GRTH KI mice are sterile and lack elongated spermatids and spermatozoa, with spermatogenic arrest at step 8 of round spermatids which contain chromatoid body (CB) markedly reduced in size. We observed an absence of phospho-GRTH in CB of GRTH KI mice. RNA-Seq analysis of mRNA isolated from CB revealed that 1,421 genes show differential abundance, of which 947 genes showed a decrease in abundance and 474 genes showed an increase in abundance in GRTH KI mice. The transcripts related to spermatid development, differentiation, and chromatin remodeling (Tnp1/2,Prm1/2/3,Spem1/2,Tssk 2/3/6,Grth,tAce, andUpf2) were reduced, and the transcripts encoding for factors involved in RNA transport, regulation, and surveillance and transcriptional and translational regulation (Eef1a1, Ppp1cc,Pabpc1,Ybx3,Tent5b,H2al1m,Dctn2, andDync1h1) were increased in the CB of KI mice and were further validated by qPCR. In the round spermatids of wild-type mice, mRNAs ofTnp2,Prm2, andGrthwere abundantly co-localized with MVH protein in the CB, while in GRTH KI mice these were minimally present. In addition, GRTH binding toTnp1/2,Prm1/2,Grth, andTssk6mRNAs was found to be markedly decreased in KI. These results demonstrate the importance of phospho-GRTH in the maintenance of the structure of CB and its role in the storage and stability of germ cell-specific mRNAs during spermiogenesis.
PECAM1 Combines With CXCR4 to Trigger Inflammatory Cell Infiltration and Pulpitis Progression Through Activating the NF-κB Signaling Pathway
Authors: Liu Yonghong , Zhang Zhiyong , Li Wenjing , Tian Songbo
Published: December 2020

Pulpitis is a frequent bacterially driven inflammation featured with the local accumulation of inflammatory products in human dental pulps. A GEO dataset GSE16134 comprising data of inflamed dental pulp tissues was used for bioinformatics analyses. A protein-protein interaction (PPI) analysis suggested that chemokine receptor 4 (CXCR4) owned a high correlation with platelet endothelial cell adhesion molecule-1 (PECAM1). A rat model with pulpitis was established, and lipopolysaccharide (LPS)-induced human dental pulp fibroblasts (HDPFs) were used for in vitro experiments. Then, high expression of PECAM1 and CXCR4 was validated in the inflamed dental pulp tissues in rats and in LPS-induced HDPFs. Either downregulation of PECAM1 or CXCR4 suppressed inflammatory cell infiltration in inflamed tissues as well as the inflammation and apoptosis of HDPFs. A transcription factor myocyte-enhancer factor 2 (MEF2C) was predicted and validated as a positive regulator of either PECAM1 or CXCR4, which activated the NF-κB signaling pathway and promoted pulpitis progression. To sum up, this study suggested that MEF2C transcriptionally activates PECAM1 and CXCR4 to activate the B-cell and NF-κB signaling pathways, leading to inflammatory cell infiltration and pulpitis progression.
The Downregulation of c19orf12 Negatively Affects Neuronal and Musculature Development in Zebrafish Embryos
Authors: Mignani Luca , Zizioli Daniela , Borsani Giuseppe , Monti Eugenio , Finazzi Dario
Published: December 2020

Mitochondrial membrane Protein Associated Neurodegeneration (MPAN) is a rare genetic disorder due to mutations inC19orf12gene. In most cases, the disorder is transmitted as an autosomal recessive trait and the main clinical features are progressive spastic para/tetraparesis, dystonia, motor axonal neuropathy, parkinsonisms, psychiatric symptoms, and optic atrophy. Besides iron accumulation in the globus pallidus and substantia nigra, the neuropathology shows features also observed in Parkinson’s Disease brains, such as α-synuclein-positive Lewy bodies and hyperphosphorylated tau. Mutations in the gene have been found in other neurodegenerative disorders, including PD, hereditary spastic paraplegia, pallido-pyramidal syndrome, and amyotrophic lateral sclerosis. The biological function ofC19orf12gene is poorly defined. In humans, it codes for two protein isoforms: the longer one is present in mitochondria, endoplasmic reticulum, and contact regions between mitochondria and ER. Mutations in the gene appear to be linked to defects in mitochondrial activity, lipid metabolism and autophagy/mitophagy. To increase the available tools for the investigation of MPAN pathogenesis, we generated a new animal model in zebrafish embryos. The zebrafish genome contains four co-orthologs of humanC19orf12. One of them, located on chromosome 18, is expressed at higher levels at early stages of development. We downregulated its expression by microinjecting embryos with a specific ATG-blocking morpholino, and we analyzed embryonal development. Most embryos showed morphological defects such as unsettled brain morphology, with smaller head and eyes, reduced yolk extension, tilted and thinner tail. The severity of the defects progressively increased and all injected embryos died within 7 days post fertilization. Appropriate controls confirmed the specificity of the observed phenotype. Changes in the expression and distribution of neural markers documented a defective neuronal development, particularly evident in the eyes, the optic tectum, the midbrain-hindbrain boundary; Rohon Beard and dorsal root ganglia neurons were also affected. Phalloidin staining evidenced a significant perturbation of musculature formation that was associated with defective locomotor behavior. These data are consistent with the clinical features of MPAN and support the validity of the model to investigate the pathogenesis of the disease and evaluate molecules with potential therapeutic effect.
The Role of Complement in Myocardial Infarction Reperfusion Injury: An Underappreciated Therapeutic Target
Authors: Vogel Carl-Wilhelm
Published: December 2020

This article reviews the pathogenetic role of the complement system in myocardial infarction reperfusion injury. The complement activation pathways involved in myocardial tissue injury are identified, as are the complement-derived effector molecules. The results of past anti-complement therapies are reviewed; as the more recent therapeutic concept of complement depletion with humanized CVF described.
Mediating Food Sovereign Voices in Documentary Media
Authors: Khan Sabiha Ahmad
Published: December 2020

The aims of food sovereignty need to be underscored to counteract the prevalence of food insecurity media discourse during the COVID-19 pandemic. La Via Campesina's inclusion of interacting with others in their definition of food sovereignty helps sustain food autonomy through shared food practices among populations deemed to be at risk. Key to sustaining autonomy is a revision of how food sovereign voices are mediated in documentary media. Documentary media often claim to amplify the voices of the powerless, a move that rings of the same type of paternalism that often marks food insecurity discourse. Drawing from currents in rhetorical studies, film studies, and studies in food communication, as well as my own documentary work, I argue that voice inheres in that which grates against a neoliberal understanding of food systems and the representational modes that operate within that sphere. Developing a documentary approach that navigates the modalities of mainstream food systems discourse while underscoring long-standing interactions of marginalized people around food is key to mediating food sovereign voices across cultures, generations, and palates.
Loss, Doubt, and Betrayal: Strands of Vaccination Skepticism on Three Facebook Pages Involved in the Controversy Over Human Papillomavirus (HPV) Vaccination
Authors: Agergaard Torben Esbo , Nielsen Kristian H.
Published: December 2020

This study conducted a discourse analysis of posts, comments, and contextual material on three Danish Facebook Pages, all established because of social groups' skepticism of human papillomavirus (HPV) vaccination. The researchers of this study accessed most administrator posts and visitors' comments, and pursued additional information through links provided on the Pages, supplementary media coverage, and available knowledge about the development of the controversy over HPV vaccination in Denmark. Using the discourse analysis framework, discourses of loss, doubt, and betrayal were identified. Associating important existential, propositional, and value assumptions affiliated with HPV vaccination, these three interconnected discourses embody important strands of vaccination skepticism. The loss discourse emerged from the personal stories about losing one's mobility or quality of life, which then mobilized expressions of sympathy and a genuine wish that things would improve. The doubt discourse was affiliated with posts and comments questioning the evidence behind HPV vaccination. Administrators and visitors doubted the information provided by the health authorities for many reasons. Some were skeptical of the epistemic value of studies showing HPV vaccination to be safe, and others simply did not trust the health authorities for sound medical advice. Finally, the betrayal discourse underlying the HPV vaccination skepticism was connected to statements that accused the health authorities of betraying all those who have experienced personal loss in relation to HPV vaccination. This discourse established a difference between “us” and “them.” The “we” indicated all those afflicted by suspected adverse events, and all those taking a critical stance on HPV vaccination. The “they” were all those in favor of HPV vaccination, particularly the health authorities, pharmaceutical companies, and the Danish Cancer Society. Based on the study findings, it can be concluded that HPV vaccination skepticism is mediated through discourses that are personal, epistemological, social, or political, and value-laden in nature. Dealing with one of these dimensions alone, for example treating HPV vaccination skepticism as an information deficit or as a partisan issue, may risk missing the point entirely.
The Case for Pragmatic Evidence-Based Higher Education: A Useful Way Forward?
Authors: Newton Philip M. , Da Silva Ana , Berry Sam
Published: December 2020

Arguments for and against the idea of evidence-based education have occupied the academic literature for decades. Those arguing in favor plead for greater rigor and clarity to determine “what works.” Those arguing against protest that education is a complex, social endeavor and that for epistemological, theoretical and political reasons it is not possible to state, with any useful degree of generalizable certainty, “what works.” While academics argue, policy and practice in Higher Education are beset with problems. Ineffective methods such as “Learning Styles” persist. Teaching quality and teacher performance are measured using subjective and potentially biased feedback. University educators have limited access to professional development, particularly for practical teaching skills. There is a huge volume of higher education research, but it is disconnected from educational practice. Change is needed. We propose a pragmatic model of Evidence-Based Higher Education, empowering educators and others to make judgements about the application of the most useful evidence, in a particular context, including pragmatic considerations of cost and other resources. Implications of the model include a need to emphasize pragmatic approaches to research in higher education, delivering results that are more obviously useful, and a pragmatic focus on practical teaching skills for the development of educators in Higher Education.
Topography and Traits Modulate Tree Performance and Drought Response in a Tropical Forest
Authors: Schwartz Naomi B. , Feng Xiaohui , Muscarella Robert , Swenson Nathan G. , Umaña María Natalia , Zimmerman Jess K. , Uriarte María
Published: December 2020

Predicting drought responses of individual trees in tropical forests remains challenging, in part because trees experience drought differently depending on their position in spatially heterogeneous environments. Specifically, topography and the competitive environment can influence the severity of water stress experienced by individual trees, leading to individual-level variation in drought impacts. A drought in 2015 in Puerto Rico provided the opportunity to assess how drought response varies with topography and neighborhood crowding in a tropical forest. In this study, we integrated 3 years of annual census data from the El Yunque Chronosequence plots with measurements of functional traits and LiDAR-derived metrics of microsite topography. We fit hierarchical Bayesian models to examine how drought, microtopography, and neighborhood crowding influence individual tree growth and survival, and the role functional traits play in mediating species’ responses to these drivers. We found that while growth was lower during the drought year, drought had no effect on survival, suggesting that these forests are fairly resilient to a single-year drought. However, growth response to drought, as well as average growth and survival, varied with topography: tree growth in valley-like microsites was more negatively affected by drought, and survival was lower on steeper slopes while growth was higher in valleys. Neighborhood crowding reduced growth and increased survival, but these effects did not vary between drought/non-drought years. Functional traits provided some insight into mechanisms by which drought and topography affected growth and survival. For example, trees with high specific leaf area grew more slowly on steeper slopes, and high wood density trees were less sensitive to drought. However, the relationships between functional traits and response to drought and topography were weak overall. Species sorting across microtopography may drive observed relationships between average performance, drought response, and topography. Our results suggest that understanding species’ responses to drought requires consideration of the microenvironments in which they grow. Complex interactions between regional climate, topography, and traits underlie individual and species variation in drought response.
A Comprehensive Analysis of cis-Acting RNA Elements in the SARS-CoV-2 Genome by a Bioinformatics Approach
Authors: Ahmed Firoz , Sharma Monika , Al-Ghamdi Abdulsalam Abdullah , Al-Yami Sultan Muhammad , Al-Salami Abdulaziz Musa , Refai Mohammed Y. , Warsi Mohiuddin Khan , Howladar Saad M. , Baeshen Mohammed N.
Published: December 2020

The emergence of a new coronavirus (CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for severe respiratory disease in humans termed coronavirus disease of 2019 (COVID-19), became a new global threat for health and the economy. The SARS-CoV-2 genome is about a 29,800-nucleotide-long plus-strand RNA that can form functionally important secondary and higher-order structures called cis-acting RNA elements. These elements can interact with viral proteins, host proteins, or other RNAs and be involved in regulating translation and replication processes of the viral genome and encapsidation of the virus. However, the cis-acting RNA elements and their biological roles in SARS-CoV-2 as well as their comparative analysis in the closely related viral genome have not been well explored, which is very important to understand the molecular mechanism of viral infection and pathogenies. In this study, we used a bioinformatics approach to identify the cis-acting RNA elements in the SARS-CoV-2 genome. Initially, we aligned the full genomic sequence of six different CoVs, and a phylogenetic analysis was performed to understand their evolutionary relationship. Next, we predicted the cis-acting RNA elements in the SARS-CoV-2 genome using the structRNAfinder tool. Then, we annotated the location of these cis-acting RNA elements in different genomic regions of SARS-CoV-2. After that, we analyzed the sequence conservation patterns of each cis-acting RNA element among the six CoVs. Finally, the presence of cis-acting RNA elements across different CoV genomes and their comparative analysis was performed. Our study identified 12 important cis-acting RNA elements in the SARS-CoV-2 genome; among them, Corona_FSE, Corona_pk3, and s2m are highly conserved across most of the studied CoVs, and Thr_leader, MAT2A_D, and MS2 are uniquely present in SARS-CoV-2. These RNA structure elements can be involved in viral translation, replication, and encapsidation and, therefore, can be potential targets for better treatment of COVID-19. It is imperative to further characterize these cis-acting RNA elements experimentally for a better mechanistic understanding of SARS-CoV-2 infection and therapeutic intervention.
Mechanistic Modeling of Gene Regulation and Metabolism Identifies Potential Targets for Hepatocellular Carcinoma
Authors: Sun Renliang , Xu Yizhou , Zhang Hang , Yang Qiangzhen , Wang Ke , Shi Yongyong , Wang Zhuo
Published: December 2020

Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and has long been among the top three cancers that cause the most deaths worldwide. Therapeutic options for HCC are limited due to the pronounced tumor heterogeneity. Thus, there is a critical need to study HCC from a systems point of view to discover effective therapeutic targets, such as through the systematic study of disease perturbation in both regulation and metabolism using a unified model. Such integration makes sense for cancers as it links one of the dominant physiological features of cancers (growth, which is driven by metabolic networks) with the primary available omics data source, transcriptomics (which is systematically integrated with metabolism through the regulatory-metabolic network model). Here, we developed an integrated transcriptional regulatory-metabolic model for HCC molecular stratification and the prediction of potential therapeutic targets. To predict transcription factors (TFs) and target genes affecting tumorigenesis, we used two algorithms to reconstruct the genome-scale transcriptional regulatory networks for HCC and normal liver tissue. which were then integrated with corresponding constraint-based metabolic models. Five key TFs affecting cancer cell growth were identified. They included the regulator CREB3L3, which has been associated with poor prognosis. Comprehensive personalized metabolic analysis based on models generated from data of liver HCC in The Cancer Genome Atlas revealed 18 genes essential for tumorigenesis in all three subtypes of patients stratified based on the non-negative matrix factorization method and two other genes (ACADSB and CMPK1) that have been strongly correlated with lower overall survival subtype. Among these 20 genes, 11 are targeted by approved drugs for cancers or cancer-related diseases, and six other genes have corresponding drugs being evaluated experimentally or investigationally. The remaining three genes represent potential targets. We also validated the stratification and prognosis results by an independent dataset of HCC cohort samples (LIRI-JP) from the International Cancer Genome Consortium database. In addition, microRNAs targeting key TFs and genes were also involved in established cancer-related pathways. Taken together, the multi-scale regulatory-metabolic model provided a new approach to assess key mechanisms of HCC cell proliferation in the context of systems and suggested potential targets.
Immunomodulation Induced During Interferon-α Therapy Impairs the Anti-HBV Immune Response Through CD24+CD38hi B Cells
Authors: Fu Binqing , Wang Dongyao , Shen Xiaokun , Guo Chuang , Liu Yanyan , Ye Ying , Sun Rui , Li Jiabin , Tian Zhigang , Wei Haiming
Published: December 2020

Type I interferon is widely used for antiviral therapy, yet has yielded disappointing results toward chronic HBV infection. Here we identify that PEG-IFNα-2b therapy toward persistent infection in humans is a double-edged sword of both immunostimulation and immunomodulation. Our studies of this randomised trial showed persistent PEG-IFNα-2b therapy induced large number of CD24+CD38hi B cells and launched a CD24+CD38hi B cells centered immunosuppressive response, including downregulating functions of T cells and NK cells. Patients with low induced CD24+CD38hi B cells have achieved an improved therapeutic effect. Specifically, using the anti-CD24 antibody to deplete CD24+CD38hi B cells without harming other B cell subsets suggest a promising strategy to improve the therapeutic effects. Our findings show that PEG-IFNα-2b therapy toward persistent infection constitutes an immunomodulation effect, and strategies to identifying the molecular basis for the antiviral versus immunomodulatory effects of PEG-IFNα-2b to selectively manipulate these opposing activities provide an opportunity to ameliorate anti-virus immunity and control viral infection.
Hemoglobin Genotypes Modulate Inflammatory Response to Plasmodium Infection
Authors: Harp Keri Oxendine , Botchway Felix , Dei-Adomakoh Yvonne , Wilson Michael D. , Hood Joshua L. , Adjei Andrew A. , Stiles Jonathan K. , Driss Adel
Published: December 2020

In 2018, 228 million cases and 405,000 malaria-associated deaths were reported worldwide with a majority being in Africa. A wide range of factors, including parasitemia, host immunity, inflammatory responses to infection, and host hemoglobin genotype, mediate the severity of malaria. Among the hemoglobinopathies, hemoglobin S (HbS) is caused by a single amino acid substitution of Glutamic Acid replaced by Valine at the sixth position of the beta-globin chain (E6V). Hemoglobin C (HbC) on the other hand, involves a single amino acid substitution of Glutamic Acid by a Lysine (E6K), which has received the most attention. These substitutions alter the stability of Hb leading to wide-ranging hematological disorders. The homozygous state of hemoglobin S (HbSS) results in sickle cell anemia (SCA) whereas the heterozygous state (HbAS) results in sickle cell trait (SCT). Both mutations are reported to mediate the reduction in the severity and fatality of Plasmodium falciparum malaria. The mechanism underlying this protection is poorly understood. Since both malaria and sickle cell disease (SCD) are associated with the destruction of erythrocytes and widespread systemic inflammation, identifying which inflammatory factor(s) mediate susceptibility of individuals with different hemoglobin genotypes toPlasmodiuminfection could result in the discovery of new predictive markers and interventions against malaria or SCD severity. We hypothesized that hemoglobin genotypes modulate the inflammatory response toPlasmodiuminfection. We conducted a cross-sectional study in Ghana, West Africa, between 2014 and 2019 to ascertain the relationships between blood inflammatory cytokines,Plasmodiuminfection, and hemoglobin genotype. A total of 923 volunteers were enrolled in the study. A total of 74, age and sex-matched subjects were identified with various genotypes including HbAS, HbAC, HbSS, HbSC, HbCC, or HbAA. Complete blood counts and serum inflammatory cytokine expression levels were assessed. The results indicate that differential expression of CXCL10, TNF-α, CCL2, IL-8, and IL-6 were tightly linked to hemoglobin genotype and severity ofPlasmodiuminfection and that these cytokine levels may be predictive for susceptibility to severe malaria or SCD severity.
HCoV- and SARS-CoV-2 Cross-Reactive T Cells in CVID Patients
Authors: Steiner Sophie , Sotzny Franziska , Bauer Sandra , Na Il-Kang , Schmueck-Henneresse Michael , Corman Victor M. , Schwarz Tatjana , Drosten Christian , Wendering Désirée J. , Behrends Uta , Volk Hans-Dieter , Scheibenbogen Carmen , Hanitsch Leif G.
Published: December 2020

The inability of patients with CVID to mount specific antibody responses to pathogens has raised concerns on the risk and severity of SARS-CoV-2 infection, but there might be a role for protective T cells in these patients. SARS-CoV-2 reactive T cells have been reported for SARS-CoV-2 unexposed healthy individuals. Until now, there is no data on T cell immunity to SARS-CoV-2 infection in CVID. This study aimed to evaluate reactive T cells to human endemic corona viruses (HCoV) and to study pre-existing SARS-CoV-2 reactive T cells in unexposed CVID patients. We evaluated SARS-CoV-2- and HCoV-229E and –OC43 reactive T cells in response to seven peptide pools, including spike and nucleocapsid (NCAP) proteins, in 11 unexposed CVID, 12 unexposed and 11 post COVID-19 healthy controls (HC). We further characterized reactive T cells by IFNγ, TNFα and IL-2 profiles. SARS-CoV-2 spike-reactive CD4+ T cells were detected in 7 of 11 unexposed CVID patients, albeit with fewer multifunctional (IFNγ/TNFα/IL-2) cells than unexposed HC. CVID patients had no SARS-CoV-2 NCAP reactive CD4+ T cells and less reactive CD8+ cells compared to unexposed HC. We observed a correlation between T cell reactivity against spike of SARS-CoV-2 and HCoVs in unexposed, but not post COVID-19 HC, suggesting cross-reactivity. T cell responses in post COVID-19 HC could be distinguished from unexposed HC by higher frequencies of triple-positive NCAP reactive CD4+ T cells. Taken together, SARS-CoV-2 reactive T cells are detectable in unexposed CVID patients albeit with lower recognition frequencies and polyfunctional potential. Frequencies of triple-functional reactive CD4+ cells might provide a marker to distinguish HCoV cross-reactive from SARS-CoV-2 specific T cell responses. Our data provides evidence, that anti-viral T cell immunity is not relevantly impaired in most CVID patients.
De Novo Donor Specific Antibody and Long-Term Outcome After Liver Transplantation: A Systematic Review and Meta-Analysis
Authors: Beyzaei Zahra , Geramizadeh Bita , Bagheri Zahra , Karimzadeh Sara , Shojazadeh Alireza
Published: December 2020

Background

The impact of de novo anti-HLA donor-specific alloantibodies (DSA) which develop after long-term liver transplantation (LT) remains controversial and unclear. The aim of this study was to investigate the role of de novo DSAs on the outcome in LT.

Methods

We did a systematic review and meta-analysis of observational studies published until Dec 31, 2019, that reported de novo DSA outcome data (≥1 year of follow-up) after liver transplant. A literature search in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus and Web of Science Core Collection databases was performed.

Results

Of 5,325 studies identified, 15 fulfilled our inclusion criteria. The studies which reported 2016 liver transplant recipients with de novo DSAs showed an increased complication risk, i.e. graft loss and chronic rejection (OR 3.61; 95% CI 1.94–6.71, P < 0.001; I2 58.19%), and allograft rejection alone (OR 6.43; 95% CI: 3.17–13.04; P < 0.001; I2 49.77%); they were compared to patients without de novo DSAs. The association between de novo DSAs and overall outcome failure was consistent across all subgroups and sensitivity analysis.

Conclusions

Our study suggested that de novo DSAs had a significant deleterious impact on the liver transplant risk of rejection. The routine detection of de novo DSAs may be beneficial as noninvasive biomarker-guided risk stratification.
Microplastic Consumption and Its Effect on Respiration Rate and Motility of Calanus helgolandicus From the Marmara Sea
Authors: Isinibilir Melek , Svetlichny Leonid , Mykitchak Taras , Türkeri Ezgi E. , Eryalçın Kamil Mert , Doğan Onur , Can Gülşah , Yüksel Esin , Kideys Ahmet E.
Published: December 2020

Consumption rates of polystyrene microplastics (beads of 6, 12, and 26 μm diameter) and their effects on energy metabolism and motor activity of the copepodCalanus helgolandicusliving in the Marmara Sea were investigated. All sizes of microplastic particles were actively consumed and excreted via fecal pellets, however, copepods displayed a significant preference for beads sized 6 μm. In a mixture of algae and microplastics beads of 6 μm, microplastics consumption rates linearly (r2= 0.78,n= 154) increased 800 times from 50.8 ± 17.3 to 8,612 ± 5,972 beads ind–1day–1with an increase in bead concentration from 10 to 44,000 beads ml–1. The total and basal metabolic rates as well as time spent swimming forC. helgolandicus, decreased 1.7, 1.8 and about 3-fold, respectively after 7–8 days exposure to microplastic treatments, which was similar to the metabolism and activity of starving animals in filtered water. In copepods consuming microplastics, all vital parameters decreased on the first day of exposure, indicating either accelerated starvation, probably due to increased losses of energy and biological matter in the formation of fecal pellets and/or traumatic/toxic effects of the polystyrene beads on the copepods. Our data from laboratory experiments indicate that the presence of large concentrations of microplastics in water, even when mixed with algae, lowered energy metabolism levels ofC. helgolandicus.
A Portable Cruising Speed Net: Expanding Global Collection of Sea Surface Plankton Data
Authors: von Ammon Ulla , Jeffs Andrew , Zaiko Anastasija , van der Reis Aimee , Goodwin Deb , Beckley Lynnath E. , Malpot Emmanuel , Pochon Xavier
Published: December 2020

Plankton are central to planetary ecology, generating 50% of Earth’s atmospheric oxygen and forming the largest system of interconnected life at the base of the marine food chain. Yet, current oceanographic models aimed at predicting global climate change lack high-resolution biological data, emphasizing the need for innovative approaches to collect plankton biodiversity and distribution data over larger spatial, temporal, and taxonomic scales. The significant number of boats, ranging from small sailing yachts to large commercial vessels, that ply the world’s oceans every day could help scientists collect thousands of valuable plankton samples. Traditional Plankton Nets (TPN) are not suited to the speed of a recreational craft cruising in the high seas (i.e., at speeds >2 knots). We developed and validated the efficiency of a lightweight, easily deployable Cruising Speed Net (CSN) that enables the collection of ocean surface micro- and mesoplankton at speeds up to 5 knots. Field testing was conducted during two distinct research cruises along coastal and oceanic latitudinal gradients (SSV Robert C. Seamans in New Zealand and RV Investigator in the south-east Indian Ocean). DNA metabarcoding performed on the collected plankton samples showed the TPN and CSN yielded identical sequence-based diversity at low speed, with the CSN also effective at higher speed for characterizing latitudinal distribution of plankton communities. The CSN represents a valuable new tool for expanding the global collection of plankton data.
Optimization of the Spatial Configuration of Local Defects in Phononic Crystals for High Q Cavity
Authors: Reyes Delfino , Martínez David , Mayorga Miguel , Heo Hyeonu , Walker Ezekiel , Neogi Arup
Published: December 2020

Defects can be introduced within a 2-D periodic lattice to realize phononic cavities or phononic crystal (PnC) waveguides at the ultrasonic frequency range. The arrangement of these defects within a PnC lattice results in the modification of the Q factor of the cavity or the waveguide. In this work, cavity defects within a PnC formed using cylindrical stainless steel scatterers in water have been modified to control the propagation and Q factor of acoustic waveguides realized through defect channels. The defect channel–based waveguides within the PnC were configured horizontally, vertically, and diagonally along the direction of the propagation of the acoustic waves. Numerical simulations supported by experimental demonstration indicate that the defect-based waveguide’s Q factor is improved by over 15 times for the diagonal configuration compared to the horizontal configuration. It also increases due to an increase in the scatterers’ radius, which was varied from 0.7 to 0.95 mm.
Development and Use of Gene Therapy Orphan Drugs—Ethical Needs for a Broader Cooperation Between the Pharmaceutical Industry and Society
Authors: Kerpel-Fronius Sandor , Baroutsou Varvara , Becker Sander , Carlesi Roberto , Collia Luis , Franke-Bray Brigitte , Kleist Peter , Kurihara Chieko , Laranjeira Luis Filipe , Matsuyama Kotone , Naseem Shehla , Schenk Johanna , Silva Honorio
Published: December 2020

Gene therapy orphan medicinal products constitute a unique group of new drugs which in case of hereditary diseases are usually administered only once at an early age, in the hope to provide sufficient gene product to last for the entire life of the patients. The combination of an exceptionally large single payment and the life-long clinical follow-up needed for understanding the long-term benefits and safety of gene therapy, represent new types of scientific, financial, social and ethical challenges for the pharmaceutical industry, regulators and society. With special consideration of the uniqueness and importance of gene therapy, the authors propose a three points plan for a close cooperation between the pharmaceutical industry and society to develop orphan gene therapy. (1) In fully transparent health technology negotiations a close and long-lasting, contractually fixed cooperation should be established between the manufacturers and local health-care stakeholders for sharing the medical and scientific benefits, the financial risks as well as the burdens of the post-authorization clinical and regulatory development. (2) The parties should agree on a fair, locally affordable drug price without the usually very high premium price calculated to compensate for the low number of patients. In case of high manufacturing costs, the companies should offer prolonged, 15–20 years long payment by installment with risk-sharing, especially considering that the late outcome of the treatment is unknown. Society should assist scientifically and financially organizing a specific patient registry, treatment in specialized hospitals and adequate long-term follow-up of patients, the coordinated management of financial transactions related to the risk sharing program. (3) The post-authorization treatment and prolonged observation of additional new cases coordinated by society should provide real world data needed for the modern complex regulatory evaluation of gene therapy products by the competent authorities. We assume that fair sharing of the benefits and risks as well as a well-organized cooperation of society with the industry in collecting real world evidence might result in better drug evaluation and improved accessibility due to lower prices. The outlined concept might support gene therapy more efficiently than the presently requested outstandingly high prices.
Comparison of Clinical Features in HLA-B27 Positive and Negative Patients With Axial Spondyloarthritis: Results From a Cohort of 4,131 Patients
Authors: Zhang Shangzhu , Wang Yanhong , Peng Linyi , Su Jinmei , Zeng Xiaofeng , Li Mengtao , Wu Zhenbiao , Xu Jian , Yang Min , Wu Lijun , Zhao Cheng , Duan Xinwang , Li Qin , Zhu Jing , Fan Wenqiang
Published: December 2020

Objective: The aim of our study was to assess the influence of the HLA-B27 status on axial spondyloarthritis (axSpA) in the largest cohort in China.

Methods: An observational, cross-sectional, and analytic study of axSpA patients from the China axSpA database was performed. Demographic and clinical data were compared in terms of the HLA-B27 status. Univariate and multivariate analyses were performed to identify variables related to HLA-B27 presence.

Results: We enrolled 4,131 patients in this study; of those, 36,95 (89.4%) were HLA-B27 positive. In the multivariate analysis, male gender (p < 0.001), younger age (p < 0.001), a disease duration of more than 3 years (p < 0.001), a family history of SpA (p < 0.001), uveitis (p < 0.001), ASDAS-CRP (p < 0.001), and biologic treatment (p < 0.001) were the main variables that were independently related to HLA-B27 presence, whereas a diagnosis delay time >36 months (p < 0.001) and psoriasis (p < 0.001) were independently related to HLA-B27 absence.

Conclusion: In Chinese axial SpA patients, presence of HLA-B27 is associated with the male sex, younger age, longer disease duration, greater family aggregation, and higher frequency of uveitis; absence of HLA-B27 is associated with longer diagnosis delay time and higher frequency of psoriasis.
Singularities of Pyogenic Streptococcal Biofilms – From Formation to Health Implication
Authors: Alves-Barroco Cinthia , Paquete-Ferreira João , Santos-Silva Teresa , Fernandes Alexandra R.
Published: December 2020

Biofilms are generally defined as communities of cells involved in a self-produced extracellular matrix adhered to a surface. In biofilms, the bacteria are less sensitive to host defense mechanisms and antimicrobial agents, due to multiple strategies, that involve modulation of gene expression, controlled metabolic rate, intercellular communication, composition, and 3D architecture of the extracellular matrix. These factors play a key role in streptococci pathogenesis, contributing to therapy failure and promoting persistent infections. The species of the pyogenic group together with Streptococcus pneumoniae are the major pathogens belonging the genus Streptococcus, and its biofilm growth has been investigated, but insights in the genetic origin of biofilm formation are limited. This review summarizes pyogenic streptococci biofilms with details on constitution, formation, and virulence factors associated with formation.
Chemically Induced Models of Parkinson’s Disease: History and Perspectives for the Involvement of Ferroptosis
Authors: Wen Shuheng , Aki Toshihiko , Unuma Kana , Uemura Koichi
Published: December 2020

Ferroptosis is a newly discovered form of necrotic cell death characterized by its dependency on iron and lipid peroxidation. Ferroptosis has attracted much attention recently in the area of neurodegeneration since the involvement of ferroptosis in Parkinson’s disease (PD), a major neurodegenerative disease, has been indicated using animal models. Although PD is associated with both genetic and environmental factors, sporadic forms of PD account for more than 90% of total PD. Following the importance of environmental factors, various neurotoxins are used as chemical inducers of PD both in vivo and in vitro. In contrast to other neurodegenerative diseases such as Alzheimer’s and Huntington’s diseases (AD and HD), many of the characteristics of PD can be reproduced in vivo by the use of specific neurotoxins. Given the indication of ferroptosis in PD pathology, several studies have been conducted to examine whether ferroptosis plays role in the loss of dopaminergic neurons in PD. However, there are still few reports showing an authentic form of ferroptosis in neuronal cells during exposure to the neurotoxins used as PD inducers. In this review article, we summarize the history of the uses of chemicals to create PD models in vivo and in vitro. Besides, we also survey recent reports examining the possible involvement of ferroptosis in chemical models of PD.
Rupture Risk Assessment for Cerebral Aneurysm Using Interpretable Machine Learning on Multidimensional Data
Authors: Ou Chubin , Liu Jiahui , Qian Yi , Chong Winston , Zhang Xin , Liu Wenchao , Su Hengxian , Zhang Nan , Zhang Jianbo , Duan Chuan-Zhi , He Xuying
Published: December 2020

Background: Assessment of cerebral aneurysm rupture risk is an important task, but it remains challenging. Recent works applying machine learning to rupture risk evaluation presented positive results. Yet they were based on limited aspects of data, and lack of interpretability may limit their use in clinical setting. We aimed to develop interpretable machine learning models on multidimensional data for aneurysm rupture risk assessment.

Methods: Three hundred seventy-four aneurysms were included in the study. Demographic, medical history, lifestyle behaviors, lipid profile, and morphologies were collected for each patient. Prediction models were derived using machine learning methods (support vector machine, artificial neural network, and XGBoost) and conventional logistic regression. The derived models were compared with the PHASES score method. The Shapley Additive Explanations (SHAP) analysis was applied to improve the interpretability of the best machine learning model and reveal the reasoning behind the predictions made by the model.

Results: The best machine learning model (XGBoost) achieved an area under the receiver operating characteristic curve of 0.882 [95% confidence interval (CI) = 0.838–0.927], significantly better than the logistic regression model (0.779; 95% CI = 0.729–0.829; P = 0.002) and the PHASES score method (0.758; 95% CI = 0.713–0.800; P = 0.001). Location, size ratio, and triglyceride level were the three most important features in predicting rupture. Two typical cases were analyzed to demonstrate the interpretability of the model.

Conclusions: This study demonstrated the potential of using machine learning for aneurysm rupture risk assessment. Machine learning models performed better than conventional statistical model and the PHASES score method. The SHAP analysis can improve the interpretability of machine learning models and facilitate their use in a clinical setting.
Outcome Measures in Clinical Trials of Patients With Myasthenia Gravis
Authors: Thomsen Jan Lykke Scheel , Andersen Henning
Published: December 2020

Myasthenia gravis (MG) is a heterogeneous disorder whose clinical presentation ranges from mild ocular deficits to severe widespread weakness. This variance poses a challenge when quantifying clinical deficits. Deficits and symptoms are quantified using standardized clinical scales and questionnaires which are often used as outcome measures. The past decades have seen the development of several validated outcome measures in MG, which are used in clinical trials to obtain regulatory approval. In recent years, emphasis has moved from objective assessments to patient-reported outcomes. Despite a growing body of literature on the validity of the MG-specific outcome measures, several unresolved factors remain. As several novel therapeutics are currently in clinical development, knowledge about capabilities and limitations of outcome measures is needed. In the present paper, we describe the most widely used clinical classifications and scales in MG. We highlight the choice of outcome measures in published and ongoing trials, and we denote whether trial efficacy was reached on these outcomes. We discuss advantages and limitations of the individual scales, and discuss some of the unresolved factors relating to outcome assessments in MG.
Repeatability and Reproducibility of in-vivo Brain Temperature Measurements
Authors: Sharma Ayushe A. , Nenert Rodolphe , Mueller Christina , Maudsley Andrew A. , Younger Jarred W. , Szaflarski Jerzy P.
Published: December 2020

Background: Magnetic resonance spectroscopic imaging (MRSI) is a neuroimaging technique that may be useful for non-invasive mapping of brain temperature (i.e., thermometry) over a large brain volume. To date, intra-subject reproducibility of MRSI-based brain temperature (MRSI-t) has not been investigated. The objective of this repeated measures MRSI-t study was to establish intra-subject reproducibility and repeatability of brain temperature, as well as typical brain temperature range.

Methods: Healthy participants aged 23–46 years (N = 18; 7 females) were scanned at two time points ~12-weeks apart. Volumetric MRSI data were processed by reconstructing metabolite and water images using parametric spectral analysis. Brain temperature was derived using the frequency difference between water and creatine (TCRE) for 47 regions of interest (ROIs) delineated by the modified Automated Anatomical Labeling (AAL) atlas. Reproducibility was measured using the coefficient of variation for repeated measures (COVrep), and repeatability was determined using the standard error of measurement (SEM). For each region, the upper and lower bounds of Minimal Detectable Change (MDC) were established to characterize the typical range of TCRE values.

Results: The mean global brain temperature over all subjects was 37.2°C with spatial variations across ROIs. There was a significant main effect for time [F(1, 1,591) = 37.0, p < 0.0001] and for brain region [F(46, 1,591) = 2.66, p < 0.0001]. The time*brain region interaction was not significant [F(46, 1,591) = 0.80, p = 0.83]. Participants' TCRE was stable for each ROI across both time points, with ROIs' COVrep ranging from 0.81 to 3.08% (mean COVrep = 1.92%); majority of ROIs had a COVrep <2.0%.

Conclusions: Brain temperature measurements were highly consistent between both time points, indicating high reproducibility and repeatability of MRSI-t. MRSI-t may be a promising diagnostic, prognostic, and therapeutic tool for non-invasively monitoring brain temperature changes in health and disease. However, further studies of healthy participants with larger sample size(s) and numerous repeated acquisitions are imperative for establishing a reference range of typical brain TCRE, as well as the threshold above which TCRE is likely pathological.