Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment of a novel experimental model for muscle‐invasive bladder cancer using a dog bladder cancer organoid culture

In human and dogs, bladder cancer (BC) is the most common neoplasm affecting the urinary tract. Dog BC resembles human muscle‐invasive BC in histopathological characteristics and gene expression profiles, and could be an important research model for this disease. Cancer patient‐derived organoid culture can recapitulate organ structures and maintains the gene expression profiles of original tumor tissues. In a previous study, we generated dog prostate cancer organoids using urine samples, however dog BC organoids had never been produced. Therefore we aimed to generate dog BC organoids using urine samples and check their histopathological characteristics, drug sensitivity, and gene expression profiles. Organoids from individual BC dogs were successfully generated, expressed urothelial cell markers (CK7, CK20, and UPK3A) and exhibited tumorigenesis in vivo. In a cell viability assay, the response to combined treatment with a range of anticancer drugs (cisplatin, vinblastine, gemcitabine or piroxicam) was markedly different in each BC organoid. In RNA‐sequencing analysis, expression levels of basal cell markers (CK5 and DSG3) and several novel genes (MMP28, CTSE, CNN3, TFPI2, COL17A1, and AGPAT4) were upregulated in BC organoids compared with normal bladder tissues or two‐dimensional (2D) BC cell lines. These established dog BC organoids might be a useful tool, not only to determine suitable chemotherapy for BC diseased dogs but also to identify novel biomarkers in human muscle‐invasive BC. In the present study, for the 1st time, dog BC organoids were generated and several specifically upregulated organoid genes were identified. Our data suggest that dog BC organoids might become a new tool to provide fresh insights into both dog BC therapy and diagnostic biomarkers.
Genetic diversity and linkage disequilibrium using SNP (KASP) and AFLP markers in a worldwide durum wheat (Triticum turgidum L. var durum) collection

The aim of this work was to analyze the genetic diversity and linkage disequilibrium in a collection of 168 durum wheat accessions (Triticum turgidum L. var. durum) of different origins. Our collection was mainly composed of released and unreleased Argentinian germplasm, with additional genotypes from Italy, Chile, France, CIMMYT, Cyprus, USA and WANA region. To this end, the entire collection was characterized with 85 Single Nucleotide Polymorphism (SNP) markers obtained by Kompetitive Allele Specific PCR (KASP), giving a heterozygosity (He) mean value of 0.183 and a coefficient of genetic differentiation (Gst) value of 0.139. A subset of 119 accessions was characterized with six Amplified Fragment Length Polymorphism (AFLP) primer combinations. A total of 181 polymorphic markers (125 AFLP and 56 SNP) amplified across this subset revealed He measures of 0.352 and 0.182, respectively. Of these, 134 were selected to estimate the genome-wide linkage disequilibrium obtaining low significant values (r2 = 0.11) in the subset, indicating its suitability for future genome-wide association studies (GWAS). The structure analysis conducted in the entire collection with SNP detected two subpopulations. However, the structure analysis conducted with AFLP markers in the subset of 119 accessions proved to have greater degree of resolution and detect six subpopulations. The information provided by both marker types was complementary and showed a strong association between old Argentinian and Italian germplasm and a contribution of CIMMYT germplasm to modern Argentinian, Chilean and Cypriot accessions. The influence of Mediterranean germplasm, mainly from Italy, on part of the modern Argentinian cultivars or breeding lines was also clearly evidenced. Although our analysis yields conclusive results and useful information for association mapping studies, further analyses are needed to refine the number of subpopulations present in the germplasm collection analyzed.
Diurnal Variation of Markers for Cholesterol Synthesis, Cholesterol Absorption, and Bile Acid Synthesis: A Systematic Review and the Bispebjerg Study of Diurnal Variations

Human studies have shown diurnal rhythms of cholesterol and bile acid synthesis, but a better understanding of the role of the circadian system in cholesterol homeostasis is needed for the development of targeted interventions to improve metabolic health. Therefore, we performed a systematic literature search on the diurnal rhythms of cholesterol synthesis and absorption markers and of bile acid synthesis markers. We also examined the diurnal rhythms of the cholesterol synthesis markers lathosterol and desmosterol, and of the cholesterol absorption markers cholestanol, campesterol, and sitosterol in serum samples from the Bispebjerg study. These samples were collected every three hours over a 24-h period in healthy males (n = 24) who consumed low-fat meals. The systematic search identified sixteen papers that had examined the diurnal rhythms of the cholesterol synthesis markers lathosterol (n = 3), mevalonate (n = 9), squalene (n = 2), or the bile acid synthesis marker 7α-hydroxy-4-cholesten-3-one (C4) (n = 4). Results showed that lathosterol, mevalonate, and squalene had a diurnal rhythm with nocturnal peaks, while C4 had a diurnal rhythm with daytime peaks. Furthermore, cosinor analyses of the serum samples showed a significant diurnal rhythm for lathosterol (cosinor p < 0.001), but not for desmosterol, campesterol, sitosterol, and cholestanol (cosinor p > 0.05). In conclusion, cholesterol synthesis and bile acid synthesis have a diurnal rhythm, though no evidence for a diurnal rhythm of cholesterol absorption was found under highly standardised conditions. More work is needed to further explore the influence of external factors on the diurnal rhythms regulating cholesterol homeostasis.
Learning outcomes from corpus consultation

Large corpora have been hailed as a veritable “revolution” in kuhnian terms for the field of language teaching (e.g. McCarthy, 2008: 564), certainly insofar as they have influenced syllabus design, testing, and even materials. However, the effects may remain largely invisible downstream to teachers and learners, especially if they remain passive consumers of upstream work. Certainly, as Carter (1998: 64) pointed out a decade ago, there is no necessary reason why corpus description (what to teach) should translate into classroom practice (how to teach). However, it is possible for learners to explore corpora themselves, either directly via a concordancer, or mediated by other software or materials, in what has come to be known as data-driven learning or DDL (Johns, 1990). DDL represents a fairly “radical” approach (Johns, 1988: 20-22), and remains generally confined to the university research environment despite efforts by many researchers to undertake a “corpus mission” (Römer, 2009: 92) to introduce DDL to a wider teaching community. One frequently-cited problem could be the type of information available: in particular, there is very little in the way of ‘off-the-peg’ materials, or indeed any texts geared towards end-users, teachers and learners alike (see, for example, Boulton, in press a). Furthermore, there may be literally hundreds of academic papers discussing applications of corpora in language learning and teaching, but, it is routinely alleged, very few that attempt any empirical evaluation of the approach. It is commonplace for articles in many disciplines to call for more empirical research, but this seems to be particularly the case for DDL. Among many others, one could cite Johansson (2009: 42) who has recently insisted that:
Effects of the Sex Ratio and Socioeconomic Deprivation on Male Mortality

We explored relationships between male mortality and the sex ratio. (We tested relationships across 142 societies and in longitudinal data from Scotland. A male-biased sex ratio was associated with reduced mortality by intentional self-harm across 142 societies. This was replicated in longitudinal Scottish data, and men were less likely to die by suicide and assault when there were more men in the population only when levels of unemployment were low. We argue that this is consistent with a theoretical model in which men increase investment in relationships and offspring as “competition” under a male-biased sex ratio, and that the conflicting results of previous work may stem from divergent effects of the sex ratio on mortality depending upon relative deprivation.
Discovery of high affinity, pan-allelic, and pan-mammalian reactive antibodies against the myeloid checkpoint receptor SIRPα

ABSTRACT Targeting the CD47-signal-regulatory protein α (SIRPα) pathway represents a novel therapeutic approach to enhance anti-cancer immunity by promoting both innate and adaptive immune responses. Unlike CD47, which is expressed ubiquitously, SIRPα expression is mainly restricted to myeloid cells and neurons. Therefore, compared to CD47-targeted therapies, targeting SIRPα may result in differential safety and efficacy profiles, potentially enabling lower effective doses and improved pharmacokinetics and pharmacodynamics. The development of effective SIRPα antagonists is restricted by polymorphisms within the CD47-binding domain of SIRPα, necessitating pan-allele reactive anti-SIRPα antibodies for therapeutic intervention in diverse patient populations. We immunized wild-type and human antibody transgenic chickens with a multi-allele and multi-species SIRPα regimen in order to discover pan-allelic and pan-mammalian reactive anti-SIRPα antibodies suitable for clinical translation. A total of 200 antibodies were isolated and screened for SIRPα reactivity from which approximately 70 antibodies with diverse SIRPα binding profiles, sequence families, and epitopes were selected for further characterization. A subset of anti-SIRPα antibodies bound to both human SIRPα v1 and v2 alleles with high affinity ranging from low nanomolar to picomolar, potently antagonized the CD47/SIRPα interaction, and potentiated macrophage-mediated antibody-dependent cellular phagocytosis in vitro. X-ray crystal structures of five anti-SIRPα antigen-binding fragments, each with unique epitopes, in complex with SIRPα (PDB codes 6NMV, 6NMU, 6NMT, 6NMS, and 6NMR) are reported. Furthermore, some of the anti-SIRPα antibodies cross-react with cynomolgus SIRPα and various mouse SIRPα alleles (BALB/c, NOD, BL/6), which can facilitate preclinical to clinical development. These properties provide an attractive rationale to advance the development of these anti-SIRPα antibodies as a novel therapy for advanced malignancies. Abbreviations: ADCC: antibody-dependent cellular cytotoxicity; ADCP: antibody-dependent cellular phagocytosis; CFSE: carboxyfluorescein succinimidyl ester; Fab: fragment antigen binding; Fc: fragment crystallizable; FcγR: Fcγ receptor; Ig: immunoglobulin; IND: investigational new drug; MDM⊘: monocyte-derived macrophage; NOD: non-obese diabetic; scFv: single chain fragment variable; SCID: severe combined immunodeficiency; SIRP: signal-regulatory protein
Pattern of Renal Diseases and the Need for Establishment of Renal Biopsy Registry in Saudi Arabia

Renal disease is a common medical problem in Saudi Arabia. Varieties of renal lesions if not treated properly or not discovered early will lead to a chronic kidney disease. Identifying the types of renal lesions can help in identifying the high-risk patients and appropriate treatment can be provided. Glomerulonephritis (GN) is considered one of the leading causes of end-stage renal disease in Saudi Arabia. The prevalence of different renal lesions were identified by different reports; however, these reports showed inconsistency. One important reason for such differences is related to the lack of unified methods in diagnosing and processing renal tissues and to the fact that different reports were reported by different pathologists. In addition, the differences in the reported results may reflect patient selection biases for renal biopsy or to the different policies and protocols adopted by different nephrologists. This is a prospective, multicenter study that involves different patients from different institutes and from different regions in Saudi Arabia to delineate the pattern of renal diseases based on renal biopsies. Four hundred and five cases were selected and studied over two years. This preliminary report shows that the most common primary renal lesion in Saudi Arabia is focal segmental glomerulosclerosis in 24.1%, followed by IgA nephropathy (15.2%), mesangioproliferative non-IgA, (13.2%), and membranoproliferative GN (12.4%). Lupus nephritis was the most common cause of secondary GN in 66% of the secondary causes.
Internal carotid and vertebral arteries diameters and their interrelationships to sex and left/right side.

The available anatomical data about diameters of inflow vessels to the circle of Willis (COW) reflect various diagnostic and imaging methods used, sample sizes, levels of measurements, and lack of possible specific ethnic, regional or genetic data. Additionally, the data are often without distinctions about left- right or sex. Therefore, using CT angiography (CTA) we investigated diameters of internal carotid (ICA) and vertebral (VA) arteries in 70 adult persons (28 - 75 years) of both sexes (34 males and 36 females), at predefined cervical parts of ICA (2 cm above carotid bifurcation) and of VA (5 mm before VA penetrated the dura). Sex differences were expressed as highly significant larger diameters of left VA (LVA) in males (3.49 mm) than in females (3.00 mm), and as significantly larger diameters of right VA (RVA) in males (3.20 mm) than in females (2.82 mm), as well as of right ICA (RICA) diameters in males (5.04 mm) than in females (4.56 mm), but without such difference for left ICA (LICA) between males (4.82 mm) and females (4.60 mm). Intrasex (in males or in females) left- right differences of ICA and VA diameters were not significant. Significant positive correlations were found in females between RICA and RVA, and in males between RICA and LICA. Calculated mean sum of ipsilateral diameters of right arteries (RAA= RICA + RVA) was in males 8.25 mm, in females 7.38 mm, and of left arteries (LAA= LICA + LVA) was in males 8.31, and in females 7.60 mm, without statistically significant difference between right (RAA) and left arteries (LAA), neither in males, nor in females. Statistically highly significant larger sums of diameters were in males than in females for both, right (RAA) and left (LAA) arteries. Our findings, as the first data about diameters of ICA and VA systematically obtained by CTA in the population of western Balkans, suggest that in the studies of these diameters is absolutely necessary to analyze separately the data for sex, and to use defined standard levels.
Empirical or microbiologically-guided systemic antimicrobials as adjuncts to non-surgical periodontal therapy? a systematic review.

BACKGROUND It is unclear if patients with specific subgingival microbiological profiles benefit more from adjunctive systemic antibiotics. AIMS To answer the question: 'What is the clinical benefit in periodontitis patients taking adjunctive systemic antimicrobials to non-surgical therapy, depending on pre-treatment detection of periodontopathogenic bacteria? ' MATERIALS AND METHODS A search was conducted in 4 electronic databases for randomised controlled trials reporting clinical outcomes following adjunctive antibiotic therapy for patients divided by baseline microbiological profiles. RESULTS The initial search resulted in 643 papers, reduced to 5 after screening and author contact. Four of these studies were suitable for a fixed effects two-stage individual participant data meta-analysis adjusted for baseline data. Collectively, adjunctive Amoxicillin and Metronidazole yielded superior clinical results (measured as reduction of PPDs) compared to placebo. No significant differences were detected for the effect of adjunctive antibiotics by detection of A. actinomycetemcomitans on PPDs ≥ 5 mm (WMD=1.16, 95% CI[-5.37, 7.68], I2 =37.8%) or other clinical outcomes. All included studies had low risk of bias. CONCLUSION There is no evidence to suggest that baseline detection of periodontopathogenic bacteria should be used as criterion for prescribing adjunctive antibiotics, although only limited information on microbial data and specific antimicrobials were available for analysis.
Research on an On-Chip MEMS Based Safety and Arming Device with a Mechanical Encryption System

The design and characterization of microelectromechanical systems (MEMS) based on-chip SAD (Safety and Arming Device) are proposed. An encryption system has been integrated into the device to enhance its reliability during the electromagnetic interference. The conversion between safe status and arm status is reversible due to the bidirectional actuation design of the slider and pawl on the SOI (Silicon on Insulator) chip, being driven by the chevron electrothermal actuators. The width of each tooth on the slider, which contains coding information, is different from that of its adjacent neighbor. Additionally, the different teeth width, respectively 32 μm, 82 μm, requiring different decoding displacement of 100 μm and 150 μm, corresponds to the different decoding voltage of 13.5 V and 14.8 V. The travel range of interrupter in the SAD will only be limited by the chip dimension and be able to cover the motion of ±1 mm in the present research, due to the capability of motion retention. Finally, the SAD is integrated with a copper azide exploding chip to measure the average velocity of the titanium flyer for the application feasibility validation.
Directional optical coherence tomography reveals melanin concentration-dependent scattering properties of retinal pigment epithelium

Abstract. Optical coherence tomography (OCT) is a powerful tool in ophthalmology that provides in vivo morphology of the retinal layers and their light scattering properties. The directional (angular) reflectivity of the retinal layers was investigated with focus on the scattering from retinal pigment epithelium (RPE). The directional scattering of the RPE was studied in three mice strains with three distinct melanin concentrations: albino (BALB/c), agouti (129S1/SvlmJ), and strongly pigmented (C57BL/6J). The backscattering signal strength was measured with a directional OCT system in which the pupil entry position of the narrow OCT beam can be varied across the dilated pupil of the eyes of the mice. The directional reflectivity of other retinal melanin-free layers, including the internal and external limiting membranes, and Bruch’s membrane (albinos) were also measured and compared between the strains. The intensity of light backscattered from these layers was found highly sensitive to the angle of illumination, whereas the inner/outer segment (IS/OS) junctions showed a reduced sensitivity. The reflections from the RPE are largely insensitive in highly pigmented mice. The differences in directional scattering between strains shows that directionality decreases with an increase in melanin concentrations in RPE, suggesting increasing contribution of Mie scattering by melanosomes.
Self-reported motivations for offending by autistic sexual offenders

Autism spectrum disorder is a neurodevelopmental disorder estimated to have elevated prevalence in forensic populations (approximately 4.5%). It has been suggested that offenders with autism spectrum disorder engage more frequently in crimes against the person and sexual offences than other types of offences such as property, driving and drug offences. To date little is empirically known about the reasons why autistic individuals engage in sexual offences, yet understanding the motivation(s) for offending are key to developing and implementing effective interventions to help reduce both initial offending and also re-offending. In this study, semi-structured interviews were conducted with nine autistic sexual offenders in prisons and probation services across England and Wales. Thematic analyses revealed five main themes (social difficulties, misunderstanding, sex and relationship deficits, inadequate control and disequilibrium). Analyses indicated that social skills difficulties, lack of perspective/weak central coherence, misunderstanding the seriousness of their behaviours and a lack of appropriate relationships were the main reasons for offending reported by this group of autistic sexual offenders. Findings highlight a need to develop sex and relationship education interventions which are tailored to the needs of autistic individuals, to address both their reported reasons for offending and their reported lack of sexual knowledge and awareness.
Visual and Thermal Image Processing for Facial Specific Landmark Detection to Infer Emotions in a Child-Robot Interaction

Child-Robot Interaction (CRI) has become increasingly addressed in research and applications. This work proposes a system for emotion recognition in children, recording facial images by both visual (RGB—red, green and blue) and Infrared Thermal Imaging (IRTI) cameras. For this purpose, the Viola-Jones algorithm is used on color images to detect facial regions of interest (ROIs), which are transferred to the thermal camera plane by multiplying a homography matrix obtained through the calibration process of the camera system. As a novelty, we propose to compute the error probability for each ROI located over thermal images, using a reference frame manually marked by a trained expert, in order to choose that ROI better placed according to the expert criteria. Then, this selected ROI is used to relocate the other ROIs, increasing the concordance with respect to the reference manual annotations. Afterwards, other methods for feature extraction, dimensionality reduction through Principal Component Analysis (PCA) and pattern classification by Linear Discriminant Analysis (LDA) are applied to infer emotions. The results show that our approach for ROI locations may track facial landmarks with significant low errors with respect to the traditional Viola-Jones algorithm. These ROIs have shown to be relevant for recognition of five emotions, specifically disgust, fear, happiness, sadness, and surprise, with our recognition system based on PCA and LDA achieving mean accuracy (ACC) and Kappa values of 85.75% and 81.84%, respectively. As a second stage, the proposed recognition system was trained with a dataset of thermal images, collected on 28 typically developing children, in order to infer one of five basic emotions (disgust, fear, happiness, sadness, and surprise) during a child-robot interaction. The results show that our system can be integrated to a social robot to infer child emotions during a child-robot interaction.
Impulsivity and Cognitive Flexibility as Neuropsychological Markers for Suicidality: A Multi-Modal Investigation Among Military Veterans with Alcohol Use Disorder and PTSD

Objective: To examine relations between self-report and behavioral measures of impulsivity and cognitive flexibility with suicidal ideation and self-harm and suicide attempt history. Methods: Eighty-seven military veterans who met DSM-5 diagnostic criteria for alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) were evaluated for current suicidal ideation and self-harm, suicide attempt history, impulsivity, and cognitive flexibility. Results: Higher levels of self-reported impulsivity were associated with greater suicidal ideation and self-harm and lower behavioral inhibition was associated with greater likelihood of endorsing a suicide attempt. Conclusion: Use of multi-modal assessment of impulsivity and cognitive flexibility may aid in suicide screening and intervention among vulnerable and high-risk populations.