Miracle-dz/UniFAR-FTUs huggingface dataset:
A Methodology for Automatised Outlier Detection in High-Dimensional Datasets: An Application to Euro Area Banks’ Supervisory Data

Outlier detection in high-dimensional datasets poses new challenges that have not been investigated in the literature. In this paper, we present an integrated methodology for the identification of outliers which is suitable for datasets with higher number of variables than observations. Our method aims to utilise the entire relevant information present in a dataset to detect outliers in an automatized way, a feature that renders the method suitable for application in large dimensional datasets. Our proposed five-step procedure for regression outlier detection entails a robust selection stage of the most explicative variables, the estimation of a robust regression model based on the selected variables, and a criterion to identify outliers based on robust measures of the residuals' dispersion. The proposed procedure deals also with data redundancy and missing observations which may inhibit the statistical processing of the data due to the ill-conditioning of the covariance matrix. The method is validated in a simulation study and an application to actual supervisory data on banks’ total assets. JEL Classification: C18, C81, G21
Clinical features and prognosis of canine megaesophagus in Japan

Megaesophagus (ME) is a common esophageal disease in dogs and the prognosis is generally poor, especially with aspiration pneumonia (AP). We retrospectively investigated the clinical features and prognosis of canine ME in Japan. Twenty-eight dogs were included in this study, with the Miniature Dachshund breed being significantly overrepresented (odds ratio: 4.33). Most cases (21 of 28) were diagnosed as idiopathic ME and Myasthenia gravis was the most common cause of secondary ME. The overall median survival time (MST) was not reached and the 3-month survival rate was 85.7%. Ten dogs were diagnosed with AP, at least once during the study period, and the MST of ME dogs with AP was 114 days. The survival time overall and even with AP, was notably more prolonged compared to the previous studies. We hypothesized that treatment for canine ME could prolong the survival time, even in those with both ME and AP.
Long term follow-up of a family with GUCY2D dominant cone dystrophy.

AIM To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms (ERGs) and occipital pattern reversal visual evoked potentials were recorded. RESULTS Two members of the same family (father and son) were identified to have the heterozygous R838C mutation in the GUCY2D gene. The father presented at the age of 45 with bilateral bull's eye maculopathy and temporal disc pallor. Over 13y of serial follow up visits, the bull's eye maculopathy progressed gradually into macular atrophy. Electrophysiological tests were significantly degraded suggesting poor macular function. Spectral-domain optical coherence tomography (SD-OCT) scans showed progressive loss and disruption of the ellipsoid layer at the foveal level. His son presented at the age of 16 with bilateral granular retinal pigment epithelial changes in both maculae. Electrophysiological testing was initially borderline normal but has gradually deteriorated to show reduced cone ERGs and macula function. SD-OCT demonstrated gradual macular thinning and atrophy bilaterally. Unlike his father, there was no disruption of the ellipsoid layer. CONCLUSION Both family members exhibited gradual changes in their fundi, electrophysiological testing and multimodal imaging. Changes were milder than those observed in other mutations of the same gene.
Return to Sport Activity After Meniscal Allograft Transplantation: At What Level and at What Cost? A Systematic Review and Meta-analysis

Context: Meniscal injuries are common among both sport- and non–sport-related injuries, with over 1.7 million meniscal surgeries performed worldwide every year. As meniscal surgeries become more common, so does meniscal allograft transplantation (MAT). However, little is known about the outcomes of MAT in active patients who desire to go back to preinjury activities. Objective: The purpose of this systematic review and meta-analysis was to evaluate return to sport, clinical outcome, and complications after MAT in sport-active patients. Data Sources: A systematic search of MEDLINE, EMBASE, and CINAHL electronic databases was performed on February 25, 2018. Study Selection: Studies of level 1 through 4 evidence looking at MAT in physically active patients with reported return to activity outcomes and at least 2-year follow-up were included. Study Design: Systematic review and meta-analysis. Level of Evidence: Level 4. Data Extraction: Details of sport-related outcomes and reoperations were extracted and pooled in a meta-analysis. Results: Nine studies were included in this systematic review. A majority (77%) of athletes and physically active patients were able to return to sport after MAT; two-thirds were able to perform at preinjury levels. Graft-related reoperations were reported in 13% of patients, while the joint replacement rate with partial or total knee prosthesis was 1.2%. Conclusion: Physical activity after MAT appears possible, especially for low-impact sports. However, because of the limited number of studies, their low quality, and the short-term follow-up, the participation recommendation for high-impact and strenuous activities should be considered with caution until high-quality evidence of long-term safety becomes available.
Expression Changes of Structural Protein Genes May Be Related to Adaptive Skin Characteristics Specific to Humans

Abstract Human skin is morphologically and physiologically different from the skin of other primates. However, the genetic causes underlying human-specific skin characteristics remain unclear. Here, we quantitatively demonstrate that the epidermis and dermis of human skin are significantly thicker than those of three Old World monkey species. In addition, we indicate that the topography of the epidermal basement membrane zone shows a rete ridge in humans but is flat in the Old World monkey species examined. Subsequently, we comprehensively compared gene expression levels between human and nonhuman great ape skin using next-generation cDNA sequencing (RNA-Seq). We identified four structural protein genes associated with the epidermal basement membrane zone or elastic fibers in the dermis (COL18A1, LAMB2, CD151, and BGN) that were expressed significantly greater in humans than in nonhuman great apes, suggesting that these differences may be related to the rete ridge and rich elastic fibers present in human skin. The rete ridge may enhance the strength of adhesion between the epidermis and dermis in skin. This ridge, along with a thick epidermis and rich elastic fibers might contribute to the physical strength of human skin with a low amount of hair. To estimate transcriptional regulatory regions for COL18A1, LAMB2, CD151, and BGN, we examined conserved noncoding regions with histone modifications that can activate transcription in skin cells. Human-specific substitutions in these regions, especially those located in binding sites of transcription factors which function in skin, may alter the gene expression patterns and give rise to the human-specific adaptive skin characteristics.
Community-based occupational therapy in Norway: Content, dilemmas, and priorities

Abstract Background: Profound changes in municipal health services, are calling for new models for community-based occupational therapy services. Objective: The aim of the study is to explore how Norwegian occupational therapists position themselves in relation to the tasks delivered. Method: Focus group interviews were conducted with ten community-based occupational therapists. Systematic text condensation was then used in the data analysis. Results: Norwegian occupational therapists description of professional practices can be constructed into four ideal types; being ‘the all-rounder’, ‘the provider of assistive device’, ‘the fire extinguisher’, or ‘the innovator’. The ideal types can help us understand more of the content and dilemmas that community-based occupational therapists encountered in their daily practice, and the priorities they make during these encounters. Conclusions and Significance: Community-based occupational therapists positioned themselves in different ways, and some of these positions were considered to be more favourable than others. The therapists struggled between ‘traditional’ occupational therapy tasks and new ways of delivering occupational therapy services. The study reveals similarities and differences between rural and urban occupational therapy practice. The ideal types can help community-based therapists to reflect on their own practice and empower them to be more in keeping with the OT’s objectives and preferences.
Vitamin E: Regulatory role on gene and protein expression and metabolomics profiles

Results from microarray analyzes have shown that both vitamin E deficiency and supplementation have a significant impact on the gene expression of various tissues and cells. Genes that were modulated by vitamin E supplementation were different depending on the tissue, which suggested that changes in gene expression are reflective of tissue function and the tissue‐specific regulation of vitamin E. In addition, the magnitude of gene expression and types of genes whose expression was altered were differentially affected by the vitamin E forms used for intervention. Metabolite analyzes have provided better understanding of the vitamin E metabolic pathway and have established evidence for the regulation of energy, lipid, and glucose metabolism by vitamin E. However, there are a limited number of studies that have applied advanced genomics, proteomics, and metabolomics technologies to investigate vitamin E's biological functions and mechanisms of action. In this review, the effects of vitamin E on gene and protein expression investigated by microarray, transcriptome, and proteomics analysis are discussed. © 2019 IUBMB Life, 71(4):442–455, 2019
Pre‐optimisation of patients undergoing emergency laparotomy: a review of best practice

Although the concept of pre‐operative optimisation is traditionally applied to elective surgery, there is ample opportunity to apply similar principles to patients undergoing emergency laparotomy. The key challenge is achieving meaningful improvements in a patient's condition without introducing delays to time‐sensitive surgery, which may be required in a matter of hours. Optimisation can be considered in two parts: that of the patient's condition; and that of the care pathway. Optimising the patient's condition is less about improving long‐term pathology, and more about correcting physiological derangement, such as electrolyte and fluid balance, blood loss, prompt treatment of sepsis, and ensuring appropriate continuation of medication in the peri‐operative period. Optimising the care pathway involves ensuring that the system is designed to deliver reliably the appropriate interventions, such as prompt antibiotics, and access to computed tomography scanning and the operating theatre with minimal delay.
Novel Dexterous Robotic Finger Concept with Controlled Stiffness

This paper introduces a novel robotic finger concept for variable impedance grasping in unstructured tasks. The novel robotic finger combines three key features: minimal actuation, variable mechanical compliance and full manipulability. This combination of features allows for a minimal component design, while reducing control complexity and still providing required dexterity and grasping capabilities. The conceptual properties (such as variable compliance) are studied in a port-Hamiltonian framework.
DCAF1 (VprBP): emerging physiological roles for a unique dual-service E3 ubiquitin ligase substrate receptor

Cullin-RING ligases (CRLs) comprise a large group of modular eukaryotic E3 ubiquitin ligases. Within this family, the CRL4 ligase (consisting of the Cullin4 [CUL4] scaffold protein, the Rbx1 RING finger domain protein, the damaged DNA binding protein 1 [DDB1], and one of many DDB1-associated substrate receptor proteins) has been intensively studied in recent years due to its involvement in regulating various cellular processes, its role in cancer development and progression, and its subversion by viral accessory proteins. Initially discovered as a target for hijacking by the human immunodeficiency virus accessory protein r, the normal targets and function of the CRL4 substrate receptor protein DDB1-Cul4 associated factor 1 (DCAF1; also known as VprBP) had remained elusive, but newer studies have begun to shed light on these questions. Here, we review recent progress in understanding the diverse physiological roles of this DCAF1 in supporting various general and cell type-specific cellular processes in its context with the CRL4 E3 ligase, as well as another HECT-type E3 ligase with which DCAF1 also associates, called EDD/UBR5. We also discuss emerging questions and areas of future study to uncover the dynamic roles of DCAF1 in normal physiology.
The Contribution of Alcohol Dehydrogenase 3 to the Development of Alcoholic Osteoporosis in Mice.

BACKGROUND Alcohol dehydrogenase 3 (ADH3) plays major roles not only in alcohol metabolism but also in nitric oxide metabolism as S-nitrosoglutathione reductase (GSNOR). ADH3/GSNOR regulates both adipogenesis and osteogenesis through the denitrosylation of peroxisome proliferator-activated receptor γ. The current study investigated the contribution of ADH3 to the development of alcoholic osteoporosis in chronic alcohol consumption (CAC). METHODS Nine-week-old male mice of different ADH genotypes [wild-type (WT) and Adh3-/-] were administered a 10% ethanol solution for 12 months. The femurs were evaluated by histochemical staining and computed tomography-based bone densitometry. The mRNA levels of ADH3 were evaluated in the WT mice by reverse transcription-quantitative polymerase chain reaction. RESULTS The Adh3-/- control mice exhibited increased activities of both osteoblasts and osteoclasts and lower bone masses than the WT control mice. CAC exhibited no remarkable change in osteoblastic and osteoclastic activities, but decreased bone masses were observed in WT mice despite an increase in the mRNA levels of ADH3. Conversely, bone masses in the Adh3-/- control mice were not reduced after CAC. CONCLUSIONS The Adh3-/- control mice exhibited a high turnover of osteoporosis since osteoclastogenesis dominated osteoblastogenesis; however, bone resorption was not enhanced after CAC. In comparison, CAC lead to alcoholic osteoporosis in WT mice, accompanied by increased mRNA levels of ADH3. Hence, ADH3 can prevent osteoporosis development in normal ADH genotypes with no alcohol ingestion. However, ADH3 contributes to the development of alcoholic osteoporosis under CAC by participating in alcohol metabolism, increasing metabolic toxicity, and lowering GSNO reducing activity.
AUDIENCE INTERACTIVE PERFORMANCE IN "THE LAST MAN TO DIE"

The Last Man to Die is an ongoing interactive performance project by Last Man to Die, a cross artform group consisting of actor, Hanna Cormick, visual artist, Benjamin Forster and percussionist, Charles Martin. One of the goals of this project is to allow the audience to “play” with our system and enjoy unexpected and unguarded responses. This paper explains technical and artistic aspects of our open-ended performance, designed to meet this goal, and our focussed method of interaction with the audience, QR codes printed on their tickets. 1. THE PERFORMANCE
Breast Cancer Stem Cells: Understanding and Opportunities for Therapeutics

Cancer stem cells (CSCs) are defined as rare immortal cell population within a tumor that can self-renew and give rise to several different cell types that establish the tumor and contribute to cancer therapy resistance. CSC follows asymmetric cell division that generates un-identical cell types during embryogenesis which ultimately helps these cells to maintain the homeostasis. The CSCs contribute to the development of tumor heterogeneity that is recognized by the existence of the diverse cell population within the tumor which poses a serious challenge for diagnosis and therapy. Breast cancer is one of the most heterogeneous tumors due to the high degree of diversity between and within tumors and a leading cause of cancer-related deaths in the women worldwide. Breast cancer stem cells (BCSCs) have been implicated in therapy resistance that significantly influences the overall clinical outcome of the breast cancer. The BCSCs phenotypes of tumors found to be unresponsive to chemotherapy and paclitaxel treatment. Interestingly these drugs induce the BCSCs phenotype in breast cancer cells in vitro. In addition, BCSCs escape chemotherapy and promote drug resistance by accumulate mutation, and accelerate self-renewal process after drug delivery[1]. Moreover, enhanced expression of CD44+/CD24-, a CSC marker were detected in primary tumors after chemotherapy[2]. Further, resistance to endocrine therapy was associated with elevated BCSCs[3]. In addition, the BCSCs were demonstrated to be resistance to radiotherapy in animal model[4]. Altogether, this evidence suggests that BCSC promotes therapy resistance, thus targeting this cancer cell population can be an effective therapeutic strategy for breast cancer treatment. The BCSC demonstrated resistant to conventional therapies attributed to elevated membrane transport, ROS scavengBreast Cancer Stem Cells: Understanding and Opportunities for Therapeutics
BBS4 is required for intraflagellar transport coordination and basal body number in mammalian olfactory cilia

ABSTRACT Bardet–Beidl syndrome (BBS) manifests from genetic mutations encoding for one or more BBS proteins. BBS4 loss impacts olfactory ciliation and odor detection, yet the cellular mechanisms remain unclear. Here, we report that Bbs4-/− mice exhibit shorter and fewer olfactory sensory neuron (OSN) cilia despite retaining odorant receptor localization. Within Bbs4−/− OSN cilia, we observed asynchronous rates of IFT-A/B particle movements, indicating miscoordination in IFT complex trafficking. Within the OSN dendritic knob, the basal bodies are dynamic, with incorporation of ectopically expressed centrin-2 and γ-tubulin occurring after nascent ciliogenesis. Importantly, BBS4 loss results in the reduction of basal body numbers separate from cilia loss. Adenoviral expression of BBS4 restored OSN cilia lengths and was sufficient to re-establish odor detection, but failed to rescue ciliary and basal body numbers. Our results yield a model for the plurality of BBS4 functions in OSNs that includes intraciliary and periciliary roles that can explain the loss of cilia and penetrance of ciliopathy phenotypes in olfactory neurons. Highlighted Article: Bbs4−/− mice exhibited reduced olfactory sensory neuron cilia length/number and basal body number, as well as miscoordination of intraflagellar transport. Ectopic re-expression of BBS4 lengthened cilia, which alone was sufficient to rescue olfactory function.
Docosahexaenoic acid is both a product of and a precursor to tetracosahexaenoic acid in the rat[S]

Tetracosahexaeoic acid (THA; 24:6n-3) is thought to be the immediate precursor of DHA in rodents; however, the relationship between THA and DHA metabolism has not been assessed in vivo. Here, we infused unesterified 2H5-THA and 13C22-DHA, at a steady state, into two groups of male Long-Evans rats and determined the synthesis-secretion kinetics, including daily synthesis-secretion rates of all 20-24 carbon n-3 PUFAs. We determined that the synthesis-secretion coefficient (a measure of the capacity to synthesize a given fatty acid) for the synthesis of DHA from plasma unesterified THA to be 134-fold higher than for THA from DHA. However, when considering the significantly higher endogenous plasma unesterified DHA pool, the daily synthesis-secretion rates were only 7-fold higher for DHA synthesis from THA (96.3 ± 31.3 nmol/d) compared with that for THA synthesis from DHA (11.4 ± 4.1 nmol/d). Furthermore, plasma unesterified THA was converted to DHA and secreted into the plasma at a 2.5-fold faster rate than remaining as THA itself (26.2 ± 6.3 nmol/d), supporting THA’s primary role as a precursor to DHA. In conclusion, using a 3 h infusion model in rats, we demonstrate for the first time in vivo that DHA is both a product and a precursor to THA.
Closed loop small bowel obstruction due to paracaecal internal herniation: a lesson in rarity

A 40-year-old man presented to the emergency department of our tertiary hospital with acute abdominal pain since 1 day, which responded to conservative measures initially. On further investigation and abdominal CT, he was diagnosed with closed loop small bowel obstruction with an encapsulated lesion with small bowel loops within, in the right iliac fossa, which was initially missed. On exploration, the patient had a sac in the right iliac fossa (paracaecal incarcerated internal hernia) with distended bowel loops within, the sac was excised after reduction of the contents. Postoperative recovery was uneventful.
Prevalence of antibodies against BKPyV subtype I and IV in kidney transplant recipients and in the general Czech population

Active infection with BK polyomavirus (BKPyV) may cause serious complications in transplantation settings. Recently, the level of BKPyV IgG seroreactivity in graft donors has been shown to predict viremia and BKPyV‐associated nephropathy in kidney transplant (KTx) recipients. Pretransplantation testing of the donor and recipient BKPyV serostatus could, therefore, identify patients at high risk. For the development of serological immunoassays, antibody response to the predominant BKPyV subtypes (BKPyV‐I and BKPyV‐IV) was studied using virus‐like particle (VLP)‐based enzyme‐linked immunosorbent assay (ELISA). VLPs made from the capsid protein, VP1, derived from BKPyV‐I and BKPyV‐IV subtypes were produced using a baculovirus expression system and used as antigens. The tests were used for IgG antibody determination in 50 KTx recipients and 111 healthy blood donors. While 87% of samples reacted with mixed BKPyV‐I and BKPyV‐IV antigens, only 49% of samples were reactive in both ELISA tests when using BKPyV‐I or BKPyV‐IV antigens separately. Twenty‐seven percent of healthy blood donors and 26% of KTx recipients were reactive only with BKPyV‐I, while 9% and 20% were reactive only with BKPyV‐IV, respectively. To determine the specificities of the antigens, selected seropositive samples were retested after preadsorption with soluble BKPyV‐I, BKPyV‐IV, or JC polyomavirus antigens. The experiments confirmed that recombinant VP1 VLP‐based ELISAs predominantly detected BKPyV type‐specific antibodies. The results imply that anti‐BKPyV antibody ELISA tests should contain a mixture of subtype‐specific VLP‐based antigens instead of antigen derived from the most prevalent BKPyV‐I subtype. The tests can be used for serological surveys of BKPyV infection and improved KTx patient management.