Miracle-dz/UniFAR-FTUs huggingface dataset:
European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part I

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus‐based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono‐ or multisite involvement. Patients’ autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the ‘Cicatrising Conjunctivitis Assessment Tool’ and the Oral Disease Severity Score (ODSS). Patient‐reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course.
Differential degradation of RNA species by autophagy related pathways in Arabidopsis.

The plant vacuole recycles proteins and RNA delivered to it by autophagy. Here, we provide a comprehensive characterization of the plant vacuolar RNAome by isolating intact vacuoles from Arabidopsis plants, subsequent RNA purification and deep sequencing. In the vacuolar RNAomes, we detected ribosomal RNAs, and transfer RNAs, including those of chloroplast origin and small RNA types in addition. As autophagy is a main mechanism for the transport of RNA to the vacuole, atg5-1 mutants deficient in autophagy were included in our analysis. We observed severely reduced amounts of most chloroplast-derived RNA species in these mutants. By comparison with the cellular RNA composition, indications for the upregulation of alternative RNA breakdown pathways were obtained. By contrast, vacuolar RNA processing and composition in plants lacking vacuolar ribonuclease 2, involved in cellular RNA homeostasis, only showed minor alterations, possibly because of the presence of further so far unknown vacuolar RNase species. Among the small RNA types, we detected mature miRNAs in all vacuolar preparations but at much lower frequency in atg5-1, raising the possibility of a biological role for vacuolar miRNAs.
Multiple Kernel Clustering With Compressed Subspace Alignment

Multiple kernel clustering (MKC) has recently achieved remarkable progress in fusing multisource information to boost the clustering performance. However, the <inline-formula> <tex-math notation="LaTeX">$\mathcal {O}({n}^{2})$ </tex-math></inline-formula> memory consumption and <inline-formula> <tex-math notation="LaTeX">$\mathcal {O}({n}^{3})$ </tex-math></inline-formula> computational complexity prohibit these methods from being applied into median- or large-scale applications, where <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula> denotes the number of samples. To address these issues, we carefully redesign the formulation of subspace segmentation-based MKC, which reduces the memory and computational complexity to <inline-formula> <tex-math notation="LaTeX">$\mathcal {O}({n})$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$\mathcal {O}({n}^{2})$ </tex-math></inline-formula>, respectively. The proposed algorithm adopts a novel sampling strategy to enhance the performance and accelerate the speed of MKC. Specifically, we first mathematically model the sampling process and then learn it simultaneously during the procedure of information fusion. By this way, the generated anchor point set can better serve data reconstruction across different views, leading to improved discriminative capability of the reconstruction matrix and boosted clustering performance. Although the integrated sampling process makes the proposed algorithm less efficient than the linear complexity algorithms, the elaborate formulation makes our algorithm straightforward for parallelization. Through the acceleration of GPU and multicore techniques, our algorithm achieves superior performance against the compared state-of-the-art methods on six datasets with comparable time cost to the linear complexity algorithms.
The Danish HIV Birth Cohort (DHBC) - a nationwide, prospective cohort

Purpose The purpose of the Danish HIV Birth Cohort (DHBC) is to investigate the significance of HIV-1 infection in pregnancy and after delivery in women living with HIV (WLWH) in Denmark and their children, in the era of antiretroviral therapy and other interventions for treatment and prophylaxis. Participants All WLWH giving birth to one or more children in Denmark after 31 December 1999 are included, with consecutive ongoing enrolment, if they are living with HIV and pregnant, or if they are diagnosed with HIV in relation to pregnancy, delivery or shortly after delivery. Findings to date DHBC has been used to describe trends in the management of pregnancies in WLWH and their outcomes on a nationwide basis, mode of delivery and predictors of emergency caesarean section as well as risk factors during pregnancy in WLWH for birth-related complications compared with women from the general population (WGP). We have found that HIV-exposed, but uninfected (HEU) children born to WLWH had a lower median birth weight and gestational age and were at higher risk of intrauterine growth retardation than children born to WGP. We have investigated risk of in-hospital admission and use of antibiotics during the first 4 years of life among HEU children and showed that HEU children had an increased risk of overall hospital admission compared with a matched control group of unexposed children. Further, we compared anthropometric outcomes in children with a matched control group of children not exposed to HIV. Future plans To continuously investigate the significance of HIV infection and antiretroviral therapy in pregnancy and after delivery in WLWH in Denmark and their HEU children and compare these findings with children born to WGP.
Effects of interventions for social anxiety and shyness in school-aged children: A systematic review and meta-analysis

In school, shyness is associated with psychosocial difficulties and has negative impacts on children’s academic performance and wellbeing. Even though there are different strategies and interventions to help children deal with shyness, there is currently no comprehensive systematic review of available interventions. This systematic review and meta-analysis aim to identify interventions for shy children and to evaluate the effectiveness in reducing psychosocial difficulties and other impacts. The methodology and reporting were guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and checklist. A total of 4,864 studies were identified and 25 of these met the inclusion criteria. These studies employed interventions that were directed at school-aged children between six and twelve years of age and described both pre- and post-intervention measurement in target populations of at least five children. Most studies included an intervention undertaken in a school setting. The meta-analysis revealed interventions showing a large effect in reducing negative consequences of shyness, which is consistent with extant literature regarding shyness in school, suggesting school-age as an ideal developmental stage to target shyness. None of the interventions were delivered in a classroom setting, limiting the ability to make comparisons between in-class interventions and those delivered outside the classroom, but highlighting the effectiveness of interventions outside the classroom. The interventions were often conducted in group sessions, based at the school, and involved activities such as play, modelling and reinforcement and clinical methods such as social skills training, psychoeducation, and exposure. Traditionally, such methods have been confined to a clinic setting. The results of the current study show that, when such methods are used in a school-based setting and involve peers, the results can be effective in reducing negative effects of shyness. This is consistent with recommendations that interventions be age-appropriate, consider social development and utilise wide, school-based programs that address all students.
When research is me-search: How researchers’ motivation to pursue a topic affects laypeople’s trust in science

Research is often fueled by researchers’ scientific, but also their personal interests: Sometimes, researchers decide to pursue a specific research question because the answer to that question is idiosyncratically relevant for themselves: Such “me-search” may not only affect the quality of research, but also how it is perceived by the general public. In two studies (N = 621), we investigate the circumstances under which learning about a researcher’s “me-search” increases or decreases laypeople’s ascriptions of trustworthiness and credibility to the respective researcher. Results suggest that participants’ own preexisting attitudes towards the research topic moderate the effects of “me-search” substantially: When participants hold favorable attitudes towards the research topic (i.e., LGBTQ or veganism), “me-searchers” were perceived as more trustworthy and their research was perceived as more credible. This pattern was reversed when participants held unfavorable attitudes towards the research topic. Study 2 furthermore shows that trustworthiness and credibility perceptions generalize to evaluations of the entire field of research. Implications for future research and practice are discussed.
The KrasG12D;Trp53fl/fl murine model of undifferentiated pleomorphic sarcoma is macrophage dense, lymphocyte poor, and resistant to immune checkpoint blockade

Sarcomas are rare, difficult to treat, mesenchymal lineage tumours that affect children and adults. Immunologically-based therapies have improved outcomes for numerous adult cancers, however, these therapeutic strategies have been minimally effective in sarcoma so far. Clinically relevant, immunologically-competent, and transplantable pre-clinical sarcoma models are essential to advance sarcoma immunology research. Herein we show that Cre-mediated activation of KrasG12D, and deletion of Trp53, in the hindlimb muscles of C57Bl/6 mice results in the highly penetrant, rapid onset undifferentiated pleomorphic sarcomas (UPS), one of the most common human sarcoma subtypes. Cell lines derived from spontaneous UPS tumours can be reproducibly transplanted into the hindlimbs or lungs of naïve, immune competent syngeneic mice. Immunological characterization of both spontaneous and transplanted UPS tumours demonstrates an immunologically-‘quiescent’ microenvironment, characterized by a paucity of lymphocytes, limited spontaneous adaptive immune pathways, and dense macrophage infiltrates. Macrophages are the dominant immune population in both spontaneous and transplanted UPS tumours, although compared to spontaneous tumours, transplanted tumours demonstrate increased spontaneous lymphocytic infiltrates. The growth of transplanted UPS tumours is unaffected by host lymphocyte deficiency, and despite strong expression of PD-1 on tumour infiltrating lymphocytes, tumours are resistant to immunological checkpoint blockade. This spontaneous and transplantable immune competent UPS model will be an important experimental tool in the pre-clinical development and evaluation of novel immunotherapeutic approaches for immunologically cold soft tissue sarcomas.
Sperm-binding regions on bovine egg zona pellucida glycoprotein ZP4 studied in a solid supported form on plastic plate

The zona pellucida (ZP) is a transparent envelope that surrounds the mammalian oocyte and mediates species-selective sperm–oocyte interactions. The bovine ZP consists of the glycoproteins ZP2, ZP3, and ZP4. Sperm-binding mechanisms of the bovine ZP are not yet fully elucidated. In a previous report, we established the expression system of bovine ZP glycoproteins using Sf9 insect cells and found that the ZP3/ZP4 heterocomplex inhibits the binding of sperm to the ZP in a competitive inhibition assay, while ZP2, ZP3, ZP4, the ZP2/ZP3 complex, and the ZP2/ZP4 complex do not exhibit this activity. Here, we show that bovine sperm binds to plastic plates coated with ZP4 in the absence of ZP3. We made a series of ZP4 deletion mutants to study the sperm-binding sites. The N-terminal region, Lys-25 to Asp-136, and the middle region, Ser-290 to Lys-340, of ZP4 exhibit sperm-binding activity. These results suggest that among the three components of bovine ZP glycoproteins, ZP4 contains the major potential sperm-binding sites, and the formation of a multivalent complex is necessary for the sperm-binding activity of ZP4.
Antioxidative and Antimicrobial Activities of Castanopsis cuspidata var. sieboldii Extracts

This study was designed to investigate the possible utilization of Castanopsis cuspidata as a source of antiseptic agents. The leaves of C. cuspidata, extracted by 80% ethanol, were sequentially fractionated with n-hexane, dichloromethane, ethylacetate, and n-butanol. In order to effectively screen for a natural preservative agent, we first investigated the antioxidant activities such as DPPH radical scavenging capacity, superoxide radical scavenging capacity, and xanthine oxidase inhibitory activity of the C. cuspidata ethanol extracts and fraction. Using a screening system, we found that the ethylacetate fraction had the strongest antioxidant activity, which followed a dose-dependent manner. The antimicrobial activities were shown in the ethylacetate fraction of C. cuspidata. Among the five fractions, the ethylacetate fraction showed the highest antimicrobial activities against microorganisms tested, which were Bacillus sublitis, Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, Salmonella enteritidis and Salmonella typhimurium. In addition, leaf extracts of C. cuspidata could be suitable for the development of food preservatives.
Regulation and functional consequences of mGlu4 RNA editing

Metabotropic glutamate receptor 4 (mGlu4) is one of eight mGlu receptors within the Class C G protein-coupled receptor superfamily. mGlu4 is primarily localized to the presynaptic membrane of neurons where it functions as an auto and heteroreceptor controlling synaptic release of neurotransmitter. mGlu4 is implicated in numerous disorders and is a promising drug target; however, more remains to be understood about its regulation and pharmacology. Using high-throughput sequencing, we have validated and quantified an adenosine-to-inosine (A-to-I) RNA editing event that converts glutamine 124 to arginine in mGlu4; additionally, we have identified a rare but novel K129R site. Using an in vitro editing assay, we then validated the pre-mRNA duplex that allows for editing by ADAR enzymes and predicted its conservation across the mammalian species. Structural modeling of the mGlu4 protein predicts the Q124R substitution to occur in the B helix of the receptor that is critical for receptor dimerization and activation. Interestingly, editing of a receptor homodimer does not disrupt G protein activation in response to the endogenous agonist, glutamate. Using an assay designed to specifically measure heterodimer populations at the surface, however, we found that Q124R substitution decreased the propensity of mGlu4 to heterodimerize with mGlu2 and mGlu7. Our study is the first to extensively describe the extent and regulatory factors of RNA editing of mGlu4 mRNA transcripts. In addition, we have proposed a novel functional consequence of this editing event that provides insights regarding its effects in vivo and expands the regulatory capacity for mGlu receptors.
Multiparametric magnetic resonance imaging features of a canine glioblastoma model

Purpose To assess glioblastoma multiforme (GBM) formation with similar imaging characteristics to human GBM using multiparametric magnetic resonance imaging (MRI) in an orthotopic xenograft canine GBM model. Materials and methods The canine GBM cell line J3T1 was subcutaneously injected into 6-week-old female BALB/c nude mice to obtain tumour fragments. Tumour fragments were implanted into adult male mongrel dog brains through surgery. Multiparametric MRI was performed with conventional MRI, diffusion-weighted imaging, and dynamic susceptibility contrast-enhanced perfusion-weighted imaging at one week and two weeks after surgery in a total of 15 surgical success cases. The presence of tumour cells, the necrotic area fraction, and the microvessel density (MVD) of the tumour on the histologic specimen were assessed. Tumour volume, diffusion, and perfusion parameters were compared at each time point using Wilcoxon signed-rank tests, and the differences between tumour and normal parenchyma were compared using unpaired t-tests. Spearman correlation analysis was performed between the imaging and histologic parameters. Results All animals showed a peripheral enhancing lesion on MRI and confirmed the presence of a tumour through histologic analysis (92.3%). The normalized perfusion values did not show significant decreases through at least 2 weeks after the surgery (P > 0.05). There was greater cerebral blood volume and flow in the GBM than in the normal-appearing white matter (1.46 ± 0.25 vs. 1.13 ± 0.16 and 1.30 ± 0.22 vs. 1.02 ± 0.14; P < 0.001 and P < 0.001, respectively). The MVD in the histologic specimens was correlated with the cerebral blood volume in the GBM tissue (r = 0.850, P = 0.004). Conclusion Our results suggest that the canine GBM model showed perfusion imaging characteristics similar to those of humans, and it might have potential as a model to assess novel technical developments for GBM treatment.
Where does the money go to? Cost analysis of gynecological patients with a benign condition

Objectives The impact of benign gynecological conditions on life of women and on costs for the society is high. The purpose of this study is to gain knowledge and understanding of costs of the treatment of these disorders in order to be able to improve the clinical care processes, gain insight into feasible savings opportunities and to allocate funds wisely. Methods The healthcare processes of 311 women attending university or community hospitals in the Helsinki and Uusimaa Hospital District between June 2012 and August 2013 due to a benign gynecological condition were followed up for two years and treatment costs analysed. Results Total direct hospital costs averaged 689€ at six months and 2194€ at two years. The most expensive treatment was that of uterine fibroids in the short term and that of endometriosis and fibroids later on. Costs did not depend on hospital size. Surgical operations caused nearly half of hospital costs. Productivity loss caused biggest expenses outside of the hospital. LNG-IUD (levonorgestrel-releasing intrauterine device) accounted for the largest pharmaceutical costs for patients. Hospital treatment was associated with a reduced need for outpatient services during follow-up. Conclusions A majority of direct hospital costs arise over time. This stresses the need for prolonged healthcare management. To control costs, the need for repetitive doctors’ appointments, monitoring tests, and ward treatments should be carefully evaluated. Procedures not needing an operation theatre (for example hysteroscopy for polypectomy), should be done ambulatorily.
Ecology of the Anthropocene signals hope for consciously managing the planetary ecosystem

Significance Human populations so dominate the ecology of the planet that geologists are describing this as the Anthropocene, “the time of humans. ” Therefore, understanding the ecology of our time requires understanding our growth, which multiple models have sought to explain. Here we apply a unified model of ecology to understand and summarize historic and prehistoric human populations and provide predictions that concur with some of the more complicated current methods. They reveal that in our societies, and in those of our prehuman ancestors, changes involving cultural evolution have altered fundamental ecological mechanisms, producing three great ecological discontinuities that are successively related to tools, agriculture, and control of fertility. Understanding our ecological development thus far can help guide us into our future. Human populations have grown to such an extent that our species has become a dominant force on the planet, prompting geologists to begin applying the term Anthropocene to recognize the present moment. Many approaches seek to explain the past and future of human population growth, in the form of narratives and models. Some of the most influential models have parameters that cannot be precisely known but are estimated by expert opinion. Here we apply a unified model of ecology to provide a macroscale summary of the net effects of many microscale processes, using a minimal set of parameters that can be known. Our models match estimates of historic and prehistoric global human population numbers and provide predictions that correspond to some of the more complicated current models. In addition to fitting the data well they reveal that, amidst enormous complexity in our human and prehuman past, three key ecological discontinuities have occurred in turn: 1) becoming dominant competitors of large predators rather than their prey, 2) becoming mutualists with food species rather than acting as predators upon them, and 3) changing from a regime of uncontrolled population growth to one of controlled fertility instead. All three processes have been interlinked with cultural evolution and all three ushered in developments of the Anthropocene. Understanding the trajectories that have delivered us to this stage can help guide prudent paths into the future.
Geographical variations and factors associated with recent HIV testing prevalence in Ghana: spatial mapping and complex survey analyses of the 2014 demographic and health surveys

Objective To examine the factors associated with recent HIV testing and to develop an HIV testing prevalence surface map using spatial interpolation techniques to identify geographical areas with low and high HIV testing rates in Ghana. Design Secondary analysis of Demographic and Health Survey. Setting Rural and urban Ghana Participants The study sample comprised 9380 women and 3854 men of 15–49 years. Results We found that 13% of women and 6% of men of Ghana had tested for HIV in the past 12 months. For women, being within the age groups of 15–39 years, being currently married, attainment of post-secondary education, having only one sexual partner and dwelling in certain regions with reference to greater Accra (Volta, Eastern, Upper West and Upper East) were associated with a higher likelihood of HIV testing. For men, being older than 19 years, attainment of post-secondary education and dwelling in the Upper East region with reference to the greater Accra region were significantly associated with a higher likelihood of HIV testing. The surface map further revealed intra-regional level differences in HIV testing estimates. Conclusion Given the results, HIV testing must be expanded with equitable testing resource allocation that target areas within the regions in Ghana with low HIV testing prevalence. Men should be encouraged to be tested for HIV.