Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors Differentiating the Antioxidant Activity of Macular Xanthophylls in the Human Eye Retina

Macular xanthophylls, which are absorbed from the human diet, accumulate in high concentrations in the human retina, where they efficiently protect against oxidative stress that may lead to retinal damage. In addition, macular xanthophylls are uniquely spatially distributed in the retina. The zeaxanthin concentration (including the lutein metabolite meso-zeaxanthin) is ~9-fold greater than lutein concentration in the central fovea. These numbers do not correlate at all with the dietary intake of xanthophylls, for which there is a dietary zeaxanthin-to-lutein molar ratio of 1:12 to 1:5. The unique spatial distributions of macular xanthophylls—lutein, zeaxanthin, and meso-zeaxanthin—in the retina, which developed during evolution, maximize the protection of the retina provided by these xanthophylls. We will correlate the differences in the spatial distributions of macular xanthophylls with their different antioxidant activities in the retina. Can the major protective function of macular xanthophylls in the retina, namely antioxidant actions, explain their evolutionarily determined, unique spatial distributions? In this review, we will address this question.
Reverse Scan Conversion and Efficient Deep Learning Network Architecture for Ultrasound Imaging on a Mobile Device

Point-of-care ultrasound (POCUS), realized by recent developments in portable ultrasound imaging systems for prompt diagnosis and treatment, has become a major tool in accidents or emergencies. Concomitantly, the number of untrained/unskilled staff not familiar with the operation of the ultrasound system for diagnosis is increasing. By providing an imaging guide to assist clinical decisions and support diagnosis, the risk brought by inexperienced users can be managed. Recently, deep learning has been employed to guide users in ultrasound scanning and diagnosis. However, in a cloud-based ultrasonic artificial intelligence system, the use of POCUS is limited due to information security, network integrity, and significant energy consumption. To address this, we propose (1) a structure that simultaneously provides ultrasound imaging and a mobile device-based ultrasound image guide using deep learning, and (2) a reverse scan conversion (RSC) method for building an ultrasound training dataset to increase the accuracy of the deep learning model. Experimental results show that the proposed structure can achieve ultrasound imaging and deep learning simultaneously at a maximum rate of 42.9 frames per second, and that the RSC method improves the image classification accuracy by more than 3%.
A Retrospective Case Study into the Effect of Hoof Lesions on the Lying Behaviour of Holstein–Friesian in a Loose-Housed System

Simple Summary Lameness is a substantial welfare and economic problem in production animals. It can alter indicators of welfare such as lying time. Lying down is very important for cows, and they are highly motivated to perform this behaviour for 12 h or more per day. Conversely, cows that lie down too much or are uncomfortable standing may miss an opportunity to feed or drink if there is competition from sound (non-lame) cows. This study monitored different lesions that cause lameness in cattle through the use of accelerometers. The lesions included sole ulcers, sole haemorrhage, white line disease, interdigital hyperplasia and phelgmon, and digital dermatitis. Leg-based activity monitors that track the cows’ lying behaviour and mobility were used. From these data, it was found that cows with lesions on the foot spent longer lying down than those with no lesions, and cows with lesions in the soft tissue spent less time lying down than those with foot lesions. Trimming the cows’ feet altered the lying times of the cows with foot lesions and returned them closer to those of cows with no lesions. Abstract The association between hoof lesions and lying behaviour was assessed on a Holstein–Friesian dairy farm in England. Twenty-nine cows were included in the study. Cows with claw horn disruption lesions (CHDL, n = 8), soft tissue lesions (STL, n = 6), and no lesions (NL, n = 15) were assessed. Data were collected on parity, days in milk (DIM), and mobility scores. Cows were trimmed and treated, and lesions were recorded by a professional foot trimmer. Lying behaviour was assessed before and after claw trimming. The milking herd (n = 96) prevalence of lameness was 32.3%. Mobility was scored using the Agriculture and Horticulture Development Board (AHDB) Mobility Scoring system. Mobility scores were significantly different across lesions groups (p = 0.022). CHDL cows had a mean mobility score of 2.0 ± 0.9 (mean ± SD), STL were scored 1.2 ± 1.3, and NL cows were 0.9 ± 0.7. CHDL were associated with longer lying times (15.00 ± 1.04 h/d; p = 0.0006) and shorter standing times (9.68 ± 2.38 h/d; p = 0.0351) compared with NL lying times (11.77 ± 1.67 h/d) and standing times (12.21 ± 1.67 h/d). STL cows spent significantly less time lying (11.30 ± 2.44; p = 0.0013) than CHDL but not NL cows. No significant differences were found with any of the other lying behaviours. After trimming, CHDL cows spent significantly less time lying down than before trimming (13.66 ± 0.98; p = 0.0125). Cows with NL spent significantly more time lying down (12.57 ± 1.90; p = 0.0398) and had a shorter minimum lying bout duration (0.17 ± 0.09; p = 0.0236) after trimming. In conclusion, lying behaviour in dairy cattle was impacted by type of hoof lesions and hoof trimming.
Inhibition of Autophagy at Different Stages by ATG5 Knockdown and Chloroquine Supplementation Enhances Consistent Human Disc Cellular Apoptosis and Senescence Induction rather than Extracellular Matrix Catabolism

The intervertebral disc is the largest avascular organ. Autophagy is an important cell survival mechanism by self-digestion and recycling damaged components under stress, primarily nutrient deprivation. Resident cells would utilize autophagy to cope with the harsh disc environment. Our objective was to elucidate the roles of human disc cellular autophagy. In human disc cells, serum deprivation and pro-inflammatory interleukin-1β (IL-1β) stimulation increased autophagy marker microtubule-associated protein 1 light chain 3 (LC3)-II and decreased autophagy substrate p62/sequestosome 1 (p62/SQSTM1), indicating enhanced autophagy. Then, RNA interference (RNAi) of autophagy-related gene 5 (ATG5), essential for autophagy, showed decreases in ATG5 protein (26.8%–27.4%, p < 0.0001), which suppressed early-stage autophagy with decreased LC3-II and increased p62/SQSTM1. Cell viability was maintained by ATG5 RNAi in serum-supplemented media (95.5%, p = 0.28) but reduced in serum-free media (80.4%, p = 0.0013) with IL-1β (69.9%, p = 0.0008). Moreover, ATG5 RNAi accelerated IL-1β-induced changes in apoptosis and senescence. Meanwhile, ATG5 RNAi unaffected IL-1β-induced catabolic matrix metalloproteinase release, down-regulated anabolic gene expression, and mitogen-activated protein kinase pathway activation. Lysosomotropic chloroquine supplementation presented late-stage autophagy inhibition with apoptosis and senescence induction, while catabolic enzyme production was modest. Disc-tissue analysis detected age-related changes in ATG5, LC3-II, and p62/SQSTM1. In summary, autophagy protects against human disc cellular apoptosis and senescence rather than extracellular matrix catabolism.
Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update

Fibromyalgia is a syndrome characterized by chronic and widespread musculoskeletal pain, often accompanied by other symptoms, such as fatigue, intestinal disorders and alterations in sleep and mood. It is estimated that two to eight percent of the world population is affected by fibromyalgia. From a medical point of view, this pathology still presents inexplicable aspects. It is known that fibromyalgia is caused by a central sensitization phenomenon characterized by the dysfunction of neuro-circuits, which involves the perception, transmission and processing of afferent nociceptive stimuli, with the prevalent manifestation of pain at the level of the locomotor system. In recent years, the pathogenesis of fibromyalgia has also been linked to other factors, such as inflammatory, immune, endocrine, genetic and psychosocial factors. A rheumatologist typically makes a diagnosis of fibromyalgia when the patient describes a history of pain spreading in all quadrants of the body for at least three months and when pain is caused by digital pressure in at least 11 out of 18 allogenic points, called tender points. Fibromyalgia does not involve organic damage, and several diagnostic approaches have been developed in recent years, including the analysis of genetic, epigenetic and serological biomarkers. Symptoms often begin after physical or emotional trauma, but in many cases, there appears to be no obvious trigger. Women are more prone to developing the disease than men. Unfortunately, the conventional medical therapies that target this pathology produce limited benefits. They remain largely pharmacological in nature and tend to treat the symptomatic aspects of various disorders reported by the patient. The statistics, however, highlight the fact that 90% of people with fibromyalgia also turn to complementary medicine to manage their symptoms.
Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis

Simple Summary The epithelial to mesenchymal transition (EMT) is a well-documented process in the study of cancer metastases. The cytoskeleton is an intricate network involved in various cellular activities and impacts cell shape, division, trafficking, and motility. However, several functions and activities of the cytoskeleton, which plays a pivotal role in EMT, are not fully understood. This review aims to provide significant insights into the cytoskeleton’s physiological functions and the crucial role in the EMT process. Our review focuses on the participation of actin filaments, intermediate filaments, and microtubules in promoting EMT and their influence on cancer metastasis. We have also highlighted potential therapeutic targets associated with EMT activation for clinical intervention. A better understanding of multi-drug resistance (MDR) mechanisms in cancer cells with the cytoskeleton could accelerate the discovery of new therapies for aggressive cancer. Abstract In cancer cells, a vital cellular process during metastasis is the transformation of epithelial cells towards motile mesenchymal cells called the epithelial to mesenchymal transition (EMT). The cytoskeleton is an active network of three intracellular filaments: actin cytoskeleton, microtubules, and intermediate filaments. These filaments play a central role in the structural design and cell behavior and are necessary for EMT. During EMT, epithelial cells undergo a cellular transformation as manifested by cell elongation, migration, and invasion, coordinated by actin cytoskeleton reorganization. The actin cytoskeleton is an extremely dynamic structure, controlled by a balance of assembly and disassembly of actin filaments. Actin-binding proteins regulate the process of actin polymerization and depolymerization. Microtubule reorganization also plays an important role in cell migration and polarization. Intermediate filaments are rearranged, switching to a vimentin-rich network, and this protein is used as a marker for a mesenchymal cell. Hence, targeting EMT by regulating the activities of their key components may be a potential solution to metastasis. This review summarizes the research done on the physiological functions of the cytoskeleton, its role in the EMT process, and its effect on multidrug-resistant (MDR) cancer cells—highlight some future perspectives in cancer therapy by targeting cytoskeleton.
Recent Advances of Interventional Endoscopic Retrograde Cholangiopancreatography and Endoscopic Ultrasound for Patients with Surgically Altered Anatomy

Endoscopic retrograde cholangiopancreatography (ERCP) is considered to be the gold standard for diagnosis and interventions in biliopancreatic diseases. However, ERCP in patients with surgically altered anatomy (SAA) appears to be more difficult compared to cases with normal anatomy. Since the production of a balloon enteroscope (BE) for small intestine disorders, BE had also been used for biliopancreatic diseases in patients with SAA. Since the development of BE-assisted ERCP, the outcomes of procedures, such as stone extraction or drainage, have been reported as favorable. Recently, an interventional endoscopic ultrasound (EUS), such as EUS-guided biliary drainage (EUS-BD), has been developed and is available mainly for patients with difficult cases of ERCP. It is a good option for patients with SAA. The effectiveness of interventional EUS for patients with SAA has been reported. Both BE-assisted ERCP and interventional EUS have advantages and disadvantages. The choice of procedure should be individualized to the patient’s condition or the expertise of the endoscopists. The aim of this review article is to discuss recent advances in interventional ERCP and EUS for patients with SAA.
Clinical Impact of the Time in Therapeutic Range on Early Hospital Readmission in Patients with Acute Heart Failure Treated with Oral Anticoagulation in Internal Medicine

Background and objectives: Patients with heart failure (HF) often present with non-valvular atrial fibrillation and require oral anticoagulation with coumarin anticoagulants such as acenocoumarol. The objective of this study was to evaluate the relationship between time in therapeutic range (TTR) and the risk of early readmission. Materials and Methods: A retrospective descriptive study was carried out on hospitalized patients with a diagnosis of HF between 2014 and 2018 who had adverse effects due to oral anticoagulation with acenocoumarol (underdosing, overdosing, or hemorrhage). Clinical, analytical, therapeutic, and prognostic variables were collected. TTR is defined as the duration of time in which the patient’s International Normalized Ratio (INR) values were within a desired range. Early readmission was defined as readmission within 30 days after hospital discharge. Patients were divided into two groups depending on whether or not they had a TTR less than 60% (TTR < 60%) over the 6 months prior to the adverse event. Results: In the cohort of 304 patients, the mean age was 82 years, 59.9% of the patients were female, and 54.6% had a TTR < 60%. Patients with TTR < 60% had a higher HAS-BLED score (4.04 vs. 2.59; p < 0.001) and INR (6 vs. 5.31; p < 0.05) but lower hemoglobin (11.67 vs. 12.22 g/dL; p < 0.05). TTR < 60% was associated with early readmission after multivariate analysis (OR: 2.05 (CI 95%: 1.16–3.61)). They also had a higher percentage of hemorrhagic events and in-hospital mortality but without reaching statistical significance. Conclusions: Patients with HF and adverse events due to acenocoumarol often have poor INR control, which is independently associated with a higher risk of early readmission.
CRISPR-Induced Expression of N-Terminally Truncated Dicer in Mouse Cells

RNA interference (RNAi) designates sequence-specific mRNA degradation mediated by small RNAs generated from long double-stranded RNA (dsRNA) by RNase III Dicer. RNAi appears inactive in mammalian cells except for mouse oocytes, where high RNAi activity exists because of an N-terminally truncated Dicer isoform, denoted DicerO. DicerO processes dsRNA into small RNAs more efficiently than the full-length Dicer expressed in somatic cells. DicerO is expressed from an oocyte-specific promoter of retrotransposon origin, which is silenced in other cell types. In this work, we evaluated CRISPR-based strategies for epigenetic targeting of the endogenous Dicer gene to restore DicerO expression and, consequently, RNAi. We show that reactivation of DicerO expression can be achieved in mouse embryonic stem cells, but it is not sufficient to establish a robust canonical RNAi response.
Relationship between Sensory Alterations and Repetitive Behaviours in Children with Autism Spectrum Disorders: A Parents’ Questionnaire Based Study

The relationship between sensory profile and repetitive behaviours in autism spectrum disorder (ASD) has long been known. However, there is no consensus on the type of relationship that exists between them. This monocentric retrospective–prospective observational study aimed (a) to detect a clinical correlation between the severity of repetitive behaviours and the alterations of sensory profile in a sample of 50 children diagnosed with ASD; (b) to evaluate how different patterns of stereotypies and sensory alterations correlate with each other and with the main clinical–instrumental variables in the same sample. We enrolled 29 children in the retrospective phase of the study and 21 in the prospective phase. The Repetitive Behaviour Scale-Revised (RBS-R) and the Short Sensory Profile (SSP) were administered to the caregivers, and clinical–instrumental data were collected. SSP and RBS-R total scores directly correlated with a high significance rate. Among the subscales, the strongest correlations involved “Visual/Auditory Sensitivity”, related to “Stereotyped Behaviour” and “Sameness Behaviour”. “Under-Responsive/Seeks Sensation” related to “Stereotyped Behaviour”. Sex and intellectual disability significantly influenced both the stereotypies and the sensory alterations of the examined population. In conclusion, this study provides new insights into the relationship between sensory alterations and repetitive behaviours in ASD children by using direct medical observation and parent observation.
Proteomic Analysis Identifies Potential Markers for Chicken Primary Follicle Development

Simple Summary Our study presents a comprehensive approach elaborating the mechanism of primary follicle development in the chicken. The identified differentially expressed proteins of small and developing primary follicles (SPFs and DPFs) could be used as potential markers in chicken primary follicle development. The DEPs have their functional involvement in different processes including glycolysis, pyruvate metabolism, amino acid synthesis, and oocyte meiosis. The Anxa2, Pdia3, and Capzb have a connotation in primary follicle development. These findings were validated by real-time quantitative PCR and provided a basis for the exploration of DEPs as suitable makers related to the primary follicle development in chicken. Abstract Follicles’ development in chicken imparts a major impact on egg production. To enhance the egg-laying efficiency, comprehensive knowledge of different phases of follicular development is a prerequisite. Therefore, we used the tandem mass tag (TMT) based proteomic approach to find the genes involved in the primary follicular development of chicken. The primary follicles were divided into two groups—small primary follicles (81–150 μm) and developed primary follicles (300–500 μm). Differential expression analysis (fold change > 1.2, p-value < 0.05) revealed a total of 70 differentially expressed proteins (DEPs), of which 38 were upregulated and 32 were downregulated. Gene ontology (GO) enrichment analysis disclosed that DEPs were intricate with cellular protein localization, the establishment of protein localization, and nucleoside phosphate-binding activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway indicated the involvement of DEPs in different metabolic pathways such as glycolysis, pyruvate metabolism, galactose metabolism, and fructose and mannose metabolism. The current proteomic analysis suggested suitable markers such as Anxa2, Pdia3, and Capzb, which may serve as a potential role for primary follicle development. The present study provides the first insight into the proteome dynamics of primary follicle development and would play a potential role for further studies in chicken to improve egg productivity.
On Time Scales of Intrinsic Oscillations in the Climate System

Proxy temperature data records featuring local time series, regional averages from areas all around the globe, as well as global averages, are analyzed using the Slow Feature Analysis (SFA) method. As explained in the paper, SFA is much more effective than the traditional Fourier analysis in identifying slow-varying (low-frequency) signals in data sets of a limited length. We find the existence of a striking gap from ~1000 to about ~20,000 years, which separates intrinsic climatic oscillations with periods ranging from ~60 years to ~1000 years, from the longer time-scale periodicities (20,000 year+) involving external forcing associated with Milankovitch cycles. The absence of natural oscillations with periods within the gap is consistent with cumulative evidence based on past data analyses, as well as with earlier theoretical and modeling studies.
Sadness and Other Health Complaints among Swedish Adolescents: A Cross-Sectional Study

Health complaints are increasing among adolescents and are recognized as a global public health issue. Health complaints are an indicator for subjective ill-being, but little is known about the relationship between sadness and other health complaints. The aim of this study was to investigate sadness and other health complaints among Swedish adolescents. A survey with a cross-sectional design was completed by adolescents (n = 1489, 15–17 years old) in the south of Sweden. A logistic regression analysis was used to analyze the relationship between sadness and other health complaints. The result show that sadness and other health complaints were common among adolescents, and sadness was related to health complaints (headache (OR: 1.58), sleeping difficulties (OR: 2.00), reduced appetite (OR: 1.43), tension (OR: 2.44), and concentration difficulties (OR: 2.75)). When adolescents express sadness or other health complaints it is important to reflect on what these complaints are an expression of, and take into account the body as physical and psychological intertwined. This might entail person-centered support that hopefully leads to an improvement in adolescents’ well-being. Future research that profoundly highlights adolescents’ existential health is needed.