Miracle-dz/UniFAR-FTUs huggingface dataset:
Peripheral Nerve Activation Evokes Machine-Learnable Signals in the Dorsal Column Nuclei

The brainstem dorsal column nuclei (DCN) are essential to inform the brain of tactile and proprioceptive events experienced by the body. However, little is known about how ascending somatosensory information is represented in the DCN. Our objective was to investigate the usefulness of high-frequency (HF) and low-frequency (LF) DCN signal features (SFs) in predicting the nerve from which signals were evoked. We also aimed to explore the robustness of DCN SFs and map their relative information content across the brainstem surface. DCN surface potentials were recorded from urethane-anesthetized Wistar rats during sural and peroneal nerve electrical stimulation. Five salient SFs were extracted from each recording electrode of a seven-electrode array. We used a machine learning approach to quantify and rank information content contained within DCN surface-potential signals following peripheral nerve activation. Machine-learning of SF and electrode position combinations was quantified to determine a hierarchy of information importance for resolving the peripheral origin of nerve activation. A supervised back-propagation artificial neural network (ANN) could predict the nerve from which a response was evoked with up to 96.8 ± 0.8% accuracy. Guided by feature-learnability, we maintained high prediction accuracy after reducing ANN algorithm inputs from 35 (5 SFs from 7 electrodes) to 6 (4 SFs from one electrode and 2 SFs from a second electrode). When the number of input features were reduced, the best performing input combinations included HF and LF features. Feature-learnability also revealed that signals recorded from the same midline electrode can be accurately classified when evoked from bilateral nerve pairs, suggesting DCN surface activity asymmetry. Here we demonstrate a novel method for mapping the information content of signal patterns across the DCN surface and show that DCN SFs are robust across a population. Finally, we also show that the DCN is functionally asymmetrically organized, which challenges our current understanding of somatotopic symmetry across the midline at sub-cortical levels.
Exploiting digital evidence artefacts: finding and joining digital dots

As digital evidence becomes increasingly significant to criminal investigations, so does the importance of adopting the most effective approach to examining it. An ineffective examination can result in evidence not being identified. Even if evidence is noted, connections may not be made between the disparate values. This thesis proposes a new classification system to gauge, select and compare digital evidence from a variety of sources. It performs this using a type of model called an ontology. This is used to map the potential location of evidence on digital devices applying a code to each piece that is identified. The codes are then used for selection of the artefacts that are most appropriate to enquiries based on the investigative Who, What, When, Where, How and Why questions. Any evidence with the same code can be compared. In applying this ontology it is demonstrated how investigations are made more effective, and the reliability of any recovered evidence can be more easily understood.
The Role of microRNAs in Ovarian Granulosa Cells in Health and Disease

The granulosa cell (GC) is a critical somatic component of the ovary. It is essential for follicle development by supporting the developing oocyte, proliferating and producing sex steroids and disparate growth factors. Knowledge of the GC's function in normal ovarian development and function, and reproductive disorders, such as polycystic ovary syndrome (PCOS) and premature ovarian failure (POF), is largely acquired through clinical studies and preclinical animal models. Recently, microRNAs have been recognized to play important regulatory roles in GC pathophysiology. Here, we examine the recent findings on the role of miRNAs in the GC, including four related signaling pathways (Transforming growth factor-β pathway, Follicle-stimulating hormones pathway, hormone-related miRNAs, Apoptosis-related pathways) and relevant diseases. Therefore, miRNAs appear to be important regulators of GC function in both physiological and pathological conditions. We suggest that targeting specific microRNAs is a potential therapeutic option for treating ovary-related diseases, such as PCOS, POF, and GCT.
Extensive Ethnic Variation and Linkage Disequilibrium at the FCGR2/3 Locus: Different Genetic Associations Revealed in Kawasaki Disease

The human Fc-gamma receptors (FcγRs) link adaptive and innate immunity by binding immunoglobulin G (IgG). All human low-affinity FcγRs are encoded by the FCGR2/3 locus containing functional single nucleotide polymorphisms (SNPs) and gene copy number variants. This locus is notoriously difficult to genotype and high-throughput methods commonly used focus on only a few SNPs. We performed multiplex ligation-dependent probe amplification for all relevant genetic variations at the FCGR2/3 locus in >4,000 individuals to define linkage disequilibrium (LD) and allele frequencies in different populations. Strong LD and extensive ethnic variation in allele frequencies was found across the locus. LD was strongest for the FCGR2C-ORF haplotype (rs759550223+rs76277413), which leads to expression of FcγRIIc. In Europeans, the FCGR2C-ORF haplotype showed strong LD with, among others, rs201218628 (FCGR2A-Q27W, r2 = 0.63). LD between these two variants was weaker (r2 = 0.17) in Africans, whereas the FCGR2C-ORF haplotype was nearly absent in Asians (minor allele frequency <0.005%). The FCGR2C-ORF haplotype and rs1801274 (FCGR2A-H131R) were in weak LD (r2 = 0.08) in Europeans. We evaluated the importance of ethnic variation and LD in Kawasaki Disease (KD), an acute vasculitis in children with increased incidence in Asians. An association of rs1801274 with KD was previously shown in ethnically diverse genome-wide association studies. Now, we show in 1,028 European KD patients that the FCGR2C-ORF haplotype, although nearly absent in Asians, was more strongly associated with susceptibility to KD than rs1801274 in Europeans. Our data illustrate the importance of interpreting findings of association studies concerning the FCGR2/3 locus with knowledge of LD and ethnic variation.
Hapln2 in Neurological Diseases and Its Potential as Therapeutic Target

Hyaluronan and proteoglycan link protein 2 (Hapln2) is important for the binding of chondroitin sulfate proteoglycans to hyaluronan. Hapln2 deficiency leads to the abnormal expression of extracellular matrix (ECM) proteins and dysfunctional neuronal conductivity, demonstrating the vital role of Hapln2 in these processes. Studies have revealed that Hapln2 promotes the aggregation of α-synuclein, thereby contributing to neurodegeneration in Parkinson’s disease (PD), and it was recently suggested to be in intracellular neurofibrillary tangles (NFTs). Additionally, the expression levels of Hapln2 showed lower in the anterior temporal lobes of individuals with schizophrenia than those of healthy subjects. Together, these studies implicate the involvement of Hapln2 in the pathological processes of neurological diseases. A better understanding of the function of Hapln2 in the central nervous system (CNS) will provide new insights into the molecular mechanisms of these diseases and help to establish promising therapeutic strategies. Herein, we review the recent progress in defining the role of Hapln2 in brain physiology and pathology.
A Case Study of Two Rodent-Borne Viruses: Not Always the Same Old Suspects

Two Old World rodents, the house mouse (Mus musculus) and the Norway rat (Rattus norvegicus) have been introduced into and established populations on every Continent save Antarctica. With their travels they have carried various human pathogens. Two viruses- Lymphocytic choriomeningitis virus (LCMV; genus Arenavirus with mice) and Seoul virus (SEOV; genus Hantavirus with rats) - can cause chronic infections within their respective rodent hosts resulting in persistent or life-long sporadic shedding of virus through secreta and excreta. Although the prevalence of infection within their wild rodent hosts can exceed 25% among mice infected with LCMV and 50% among rats infected with SEOV, acute human disease resulting from direct transmission from wild rodents are rarely reported even though both species live in close coexistence with humans. However, the usual ‘classic’ zoonotic cycle of transmission from wild rodent reservoirs to humans now includes multiple unusual/unexpected routes. The largest described outbreaks of human disease caused by these viruses are linked to pet rodents. SEOV outbreaks are linked to fancy rats kept as pets, and, a novel reservoir host, the Golden hamster, has supplanted the house mouse as major source of LCMV infection. Following LCMV, and to a lesser extent SEOV, outbreaks associated lab animals, have led to 100’s of cases of LCMV among owners of pet hamsters. LCMV infections in research settings have also been traced to mouse-derived cell cultures and nude mice. Additionally, LCMV is now a recognized source of severe congenital disease and is the unexpected source of severe and often fatal disease among solid organ recipients. Although the extensive usual and unusual routes of LCMV infection are exceptional there are many parallels with SEOV emergence.
Human sFLT1 Leads to Severe Changes in Placental Differentiation and Vascularization in a Transgenic hsFLT1/rtTA FGR Mouse Model

The anti-angiogenic soluble fms-like tyrosine kinase 1 (sFLT1) is one of the candidates in the progression of preeclampsia, often associated with fetal growth restriction (FGR). Therapeutic agents against preeclampsia with/without FGR, as well as adequate transgenic sFLT1 mouse models for testing such agents, are still missing. Much is known about sFLT1–mediated endothelial dysfunction in several tissues; however, the influence of sFLT1 on placental and fetal development is currently unknown. We hypothesize that sFLT1 is involved in the progression of FGR by influencing placental differentiation and vascularization and is a prime candidate for interventional strategies. Therefore, we generated transgenic inducible human sFLT1/reverse tetracycline-controlled transactivator (hsFLT1/rtTA) mice, in which hsFLT1 is ubiquitously overexpressed during pregnancy in dams and according to the genetics in hsFLT1/rtTA homozygous and heterozygous fetuses. Induction of hsFLT1 led to elevated hsFLT1 levels in the serum of dams and on mRNA level in all placentas and hetero-/homozygous fetuses, resulting in FGR in all fetuses at term. The strongest effects in respect to FGR were observed in the hsFLT1/rtTA homozygous fetuses, which exhibited the highest hsFLT1 levels. Only fetal hsFLT1 expression led to impaired placental morphology characterized by reduced placental efficiency, enlarged maternal sinusoids, reduced fetal capillaries, and impaired labyrinthine differentiation, associated with increased apoptosis. Besides impaired placental vascularization, the expression of several transporter systems, such as glucose transporter 1 and 3 (Glut-1; Glut-3); amino acid transporters, solute carrier family 38, member one and two (Slc38a1; Slc38a2); and most severely the fatty acid translocase Cd36 and fatty acid binding protein 3 (Fabp3) was reduced upon hsFLT1 expression, associated with an accumulation of phospholipids in the maternal serum. Moreover, the Vegf pathway showed alterations, resulting in reduced Vegf, Vegfb, and Plgf protein levels and increased Bad and Caspase 9 mRNA levels. We suggest that hsFLT1 exerts an inhibitory influence on placental vascularization by reducing Vegf signaling, which leads to apoptosis in fetal vessels, impairing placental differentiation, and the nutrient exchange function of the labyrinth. These effects were more pronounced when both the dam and the fetus expressed hsFLT1 and ultimately result in FGR and resemble the preeclamptic phenotype in humans.
Arginine Vasotocin and Cortisol Co-regulate Vasotocinergic, Isotocinergic, Stress, and Thyroid Pathways in the Gilthead Sea Bream (Sparus aurata)

In teleosts, a complex interaction between several endocrine axes modulates physiological functions related to metabolism, stress, and osmoregulation. Although many studies in fish underline the interconnection between the hypothalamic–pituitary–interrenal (HPI) and hypothalamic–pituitary–thyroid (HPT) endocrine axes, their relationship with the vasotocinergic and isotocinergic systems remains unknown. The aim of the present study is therefore to shed light on the potential cross-regulations between HPT, HPI, and the vasotocinergic and isotocinergic axes in gilthead sea bream (Sparus aurata) at hypothalamic, hypophyseal, and plasma levels. Sea breams were administered with intraperitoneal slow-release implants containing different doses of vasotocin (the active peptide in vasotocinergic system) or cortisol (the last component of HPI axis). Plasma osmolality was higher in active neuropeptides vasotocin (Avt)-treated fish, indicating an osmoregulatory function of this hormone. Low concentrations of Avt increased hypothalamic arginine vasotocin precursor (avt) mRNA levels and increased Avt storage in the pituitary. Avt treatment down-regulated hypothalamic arginine vasotocin receptor v1a-type (avtrv1a), suggesting a negative paracrine co-regulation of the HPI axis due to the close location of avtrv1a and adrenocorticotropin hormone (Acth) cells in the anterior pituitary. Furthermore, the up-regulation observed in arginine vasotocin receptor v2-type (avtrv2) suggests their involvement in metabolic and cortisol-related pathways in the hypothalamus. The decrease in isotocin (It) pituitary storage and the up-regulation of it receptor, observed in the Avt-treated group, reinforce the idea of an interconnection between the vasotocinergic and isotocinergic systems. Cortisol and Avt administration each inhibited the HPI axis, down-regulating crh gene expression in the absence of variations in corticotropin releasing hormone binding protein (crhbp). Finally, both hormonal treatments activated the HPT axis via up-regulation of trh and down-regulation of thrb. Our results provide evidence for strong interactions among the Avt/It, HPI, and HPT axes of marine teleosts, particularly at the hypothalamic level.
Genomics of Flower Identity in Grapevine (Vitis vinifera L.)

The identity of the four characteristic whorls of typical eudicots, namely, sepals, petals, stamens, and carpels, is specified by the overlapping action of homeotic genes, whose single and combined contributions have been described in detail in the so-called ABCDE model. Continuous species-specific refinements and translations resulted in this model providing the basis for understanding the genetic and molecular mechanisms of flower development in model organisms, such as Arabidopsis thaliana and other main plant species. Although grapevine (Vitis vinifera L.) represents an extremely important cultivated fruit crop globally, studies related to the genetic determinism of flower development are still rare, probably because of the limited interest in sexual reproduction in a plant that is predominantly propagated asexually. Nonetheless, several studies have identified and functionally characterized some ABCDE orthologs in grapevine. The present study is intended to provide a comprehensive screenshot of the transcriptional behavior of 18 representative grapevine ABCDE genes encoding MADS-box transcription factors in a developmental kinetic process, from preanthesis to the postfertilization stage and in different flower organs, namely, the calyx, calyptra, anthers, filaments, ovary, and embryos. The transcript levels found were compared with the proposed model for Arabidopsis to evaluate their biological consistency. With a few exceptions, the results confirmed the expression pattern expected based on the Arabidopsis data.
The effect of dietary supplementation on brain-derived neurotrophic factor and cognitive functioning in Alzheimer's dementia

Background and Aim: The objective of the present study was to investigate the effect of an aloe polymannose multinutrient complex (APMC) on pro brain-derived neurotrophic factor (BDNF) and mature BDNF in persons with moderate to severe Alzheimer's dementia. Methods: A 12-month open-label trial was utilized to evaluate the effect of the APMC on proBDNF and BDNF and their relationship to cognitive functioning. Thirty-four adults were enrolled and consumed 4 teaspoons/day of APMC for 12 months. Subjects were assessed at baseline and twelve months follow-up for proBDNF and BDNF and with a neuropsychological battery to measure cognitive functioning. Cognitive functioning was correlated with proBDNF and BDNF. Results: Few adverse effects were reported. While proBDNF (baseline M = 6,108.9, SD = 854.9 and 12 months M = 5,799.2, SD = 573.4; p = 0.57) and BDNF (baseline M = 5,673.8, SD = 3,342.3 and 12 months M = 6,312.9, SD = 2,830.9; p = 0.29) did not significantly change, the correlations between the ADAS-cog total score and BDNF (r = -0.53, p = 0.04) and BDNF/proBDNF ratio (r = -0.58, p = 0.05) became statistically significant after 12 months of dietary supplementation. Other correlations were noted for various cognitive functioning assessments and BDNF and/or BDNF/proBDNF ratio at both baseline and 12 months. Conclusions: These findings suggest that the relationship between cognitive functioning and BDNF and BDNF/proBDNF ratio improved in response to consumption of a dietary supplement in persons with Alzheimer's dementia, which is consistent with our previous findings on cognitive functioning. Relevance for patients: Overall, our results showed modest improvements in clinical outcomes for a disease that otherwise has no standard conventional approach to treatment with proven efficacy.
Recent developments in genetics and medically-assisted reproduction: from research to clinical applications

Abstract Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively-parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.
An Empirical Study of Messaging Passing Concurrency in Go Projects

Go is a popular programming language renowned for its good support for system programming and its channel-based message passing concurrency mechanism. These strengths have made it the language of choice of many platform software such as Docker and Kubernetes. In this paper, we analyse 865 Go projects from GitHub in order to understand how message passing concurrency is used in publicly available code. Our results include the following findings: (1) message passing primitives are used frequently and intensively, (2) concurrency-related features are generally clustered in specific parts of a Go project, (3) most projects use synchronous communication channels over asynchronous ones, and (4) most Go projects use simple concurrent thread topologies, which are however currently unsupported by existing static verification frameworks.
Cutaneous Bowen’s Disease: an Analysis of 182 Cases according To Age, Sex, and Anatomical Site from an Italian Center

Bowen’s disease (BD), also known as squamous cell carcinoma in situ, is a type of non-melanocytic intraepidermal malignancy characterised by a slowly enlarging erythematous to pink, scaly patch or plaque with irregular and well-demarcated borders. These lesions are usually persistent and progressive; it has been estimated that in general population around 3% to 5% of Bowen’s disease transform into invasive squamous cell carcinoma. This report describes our experience with cutaneous BD and assesses the differences found about age, sex and anatomical site. Bowen’s disease was seen more frequently in male patients rather than in female patients in contrast to what confirmed in literature - this difference is probably because being head-neck an exposed region, patients are more easily induced to autoexam and to consult the dermatologist.
Fast-track pneumonia pathway focusing on early progressive mobilisation: a clinical feasibility study

Pneumonia and lower respiratory tract infection are the most common reasons for acute hospital admission in Denmark [1], with an incidence of 3.1 cases per 1000 inhabitants [2]. Various European studies report a substantial mortality rate of 5–15% among admitted patients following pneumonia. Pneumonia affects people of all ages across all sociodemographic profiles, with greater risk in frail, older individuals [3]. Often, patients are characterised by multiple comorbidities, low levels of function, reduced energy intake, cognitive impairment and depression [4]. In addition, acutely admitted elderly patients are exposed to prolonged bedrest and immobilisation, causing further physical deterioration [5]. Interdisciplinary efforts should be organised into a fast-track concept to enhance mobilisation within the clinical environment and post-discharge to reduce hospital length of stay and increase survival in pneumonia http://ow.ly/tu0s30nKLrE