Miracle-dz/UniFAR-FTUs huggingface dataset:
The Equine Faecal Microbiota of Healthy Horses and Ponies in The Netherlands: Impact of Host and Environmental Factors

Simple Summary Several studies have described the bacterial composition in the intestines of horses, and several factors of influence have been detected. Variation in the results between studies, however, is substantial. Therefore, the current study aimed to study the bacterial composition in the faeces of healthy horses and ponies kept under standard housing and management condition in The Netherlands. Seventy-nine horses and ponies originating from two farms were included. Several factors, such as location, age, the season of sampling, horse type (horses vs. ponies) and pasture access significantly affected the bacterial composition. The current study provides important baseline information on variation in the bacterial composition in healthy horses and ponies under standard housing and management conditions. The aforementioned factors identified in this study to affect the bacterial population of the gut should be considered in future studies regarding the bacterial population of the equine gut. Abstract Several studies have described the faecal microbiota of horses and the factors that influence its composition, but the variation in results is substantial. This study aimed to investigate the microbiota composition in healthy equids in The Netherlands under standard housing and management conditions and to evaluate the effect of age, gender, horse type, diet, pasture access, the season of sampling and location on it. Spontaneously produced faecal samples were collected from the stall floor of 79 healthy horses and ponies at two farms. The validity of this sampling technique was evaluated in a small pilot study including five ponies showing that the microbiota composition of faecal samples collected up to 6 h after spontaneous defaecation was similar to that of the samples collected rectally. After DNA extraction, Illumina Miseq 16S rRNA sequencing was performed to determine microbiota composition. The effect of host and environmental factors on microbiota composition were determined using several techniques (NMDS, PERMANOVA, DESeq2). Bacteroidetes was the largest phylum found in the faecal microbiota (50.1%), followed by Firmicutes (28.4%). Alpha-diversity and richness decreased significantly with increasing age. Location, age, season, horse type and pasture access had a significant effect on beta-diversity. The current study provides important baseline information on variation in faecal microbiota in healthy horses and ponies under standard housing and management conditions. These results indicate that faecal microbiota composition is affected by several horse-related and environment-related factors, and these factors should be considered in future studies of the equine faecal microbiota.
Cutaneous and Vascular Deposits of 18F-NaF by PET/CT in the Follow-Up of Patients with Pseudoxanthoma Elasticum

Active microcalcification of elastic fibers is a hallmark of pseudoxanthoma elasticum and it can be measured with the assessment of deposition of 18F-NaF using a PET/CT scan at the skin and vascular levels. It is not known whether this deposition changes over time in absence of specific therapy. We repeated in two years a PET/CT scan using 18F-NaF as a radiopharmaceutical in patients with the disease and compared the deposition at skin and vessel. Furthermore, calcium score values at the vessel wall were also assessed. Main results indicate in the vessel walls that calcification progressed in each patient; by contrast, the active microcalcification, measured and target-to-background ratio showed reduced active deposition. By contrast, at skin levels (neck and axillae) the uptake of the pharmaceutical remains unchanged. In conclusion, because calcification in the arterial wall is not specific for pseudoxanthoma elasticum condition, the measurement of the deposition of 18F-NaF in the neck might be potentially used as a surrogate marker in future trials for the disease.
Polymeric Drug Delivery System Based on Pluronics for Cancer Treatment

Pluronic polymers (pluronics) are a unique class of synthetic triblock copolymers containing hydrophobic polypropylene oxide (PPO) and hydrophilic polyethylene oxide (PEO) arranged in the PEO-PPO-PEO manner. Due to their excellent biocompatibility and amphiphilic properties, pluronics are an ideal and promising biological material, which is widely used in drug delivery, disease diagnosis, and treatment, among other applications. Through self-assembly or in combination with other materials, pluronics can form nano carriers with different morphologies, representing a kind of multifunctional pharmaceutical excipients. In recent years, the utilization of pluronic-based multi-functional drug carriers in tumor treatment has become widespread, and various responsive drug carriers are designed according to the characteristics of the tumor microenvironment, resulting in major progress in tumor therapy. This review introduces the specific role of pluronic-based polymer drug delivery systems in tumor therapy, focusing on their physical and chemical properties as well as the design aspects of pluronic polymers. Finally, using newer literature reports, this review provides insights into the future potential and challenges posed by different pluronic-based polymer drug delivery systems in tumor therapy.
Discovery of Antivirals Using Phage Display

The latest coronavirus disease outbreak, COVID-19, has brought attention to viral infections which have posed serious health threats to humankind throughout history. The rapid global spread of COVID-19 is attributed to the increased human mobility of today’s world, yet the threat of viral infections to global public health is expected to increase continuously in part due to increasing human–animal interface. Development of antiviral agents is crucial to combat both existing and novel viral infections. Recently, there is a growing interest in peptide/protein-based drug molecules. Antibodies are becoming especially predominant in the drug market. Indeed, in a remarkably short period, four antibody therapeutics were authorized for emergency use in COVID-19 treatment in the US, Russia, and India as of November 2020. Phage display has been one of the most widely used screening methods for peptide/antibody drug discovery. Several phage display-derived biologics are already in the market, and the expiration of intellectual property rights of phage-display antibody discovery platforms suggests an increment in antibody drugs in the near future. This review summarizes the most common phage display libraries used in antiviral discovery, highlights the approaches employed to enhance the antiviral potency of selected peptides/antibody fragments, and finally provides a discussion about the present status of the developed antivirals in clinic.
Biomarkers for Diagnosis, Prognosis and Response to Immunotherapy in Melanoma

Simple Summary Cutaneous Melanoma is a form of skin cancer characterized by an elevated mutational load that favors high spread to distant organs and resistance to therapies. The identification of biomarkers, able to dissect normal and pathogenic biological processes and response to therapeutic intervention, is necessary to describe melanoma as accurately as possible, having a positive impact on early diagnosis, in turn selecting the best therapeutic option. Recently, a great number of new biomarkers were evaluated, in order to identify those patients who may have clinical benefit from a therapeutic choice, particularly for immunotherapy. At present, these new biomarkers wait to be validated before clinical use. Hence, the requirement to look at and periodically update the advances in this field. Abstract Cutaneous Melanoma classification is constantly looking for specific and sensitive biomarkers capable of having a positive effect on diagnosis, prognosis and risk assessment, eventually affecting clinical outcome. Classical morphological, immunohistochemical and the well-known BRAF and NRAS genetic biomarkers do not allow the correct categorization of patients, being melanoma conditioned by high genetic heterogeneity. At the same time, classic prognostic methods are unsatisfactory. Therefore, new advances in omics and high-throughput analytical techniques have enabled the identification of numerous possible biomarkers, but their potentiality needs to be validated and standardized in prospective studies. Melanoma is considered an immunogenic tumor, being the first form of cancer to take advantage of the clinical use of the immune-checkpoint blockers. However, as immunotherapy is effective only in a limited number of patients, biomarkers associated with different responses are essential to select the more promising therapeutic approach and maximize clinical benefits. In this review, we summarize the most utilized biomarkers for Cutaneous Melanoma diagnosis, focusing on new prognostic and predictive biomarkers mainly associated with immunotherapy.
Bioengineering Approaches to Improve In Vitro Performance of Prepubertal Lamb Oocytes

Juvenile in vitro embryo technology (JIVET) provides exciting opportunities in animal reproduction by reducing the generation intervals. Prepubertal oocytes are also relevant models for studies on oncofertility. However, current JIVET efficiency is still unpredictable, and further improvements are needed in order for it to be used on a large-scale level. This study applied bioengineering approaches to recreate: (1) the three-dimensional (3D) structure of the cumulus–oocyte complex (COC), by constructing—via bioprinting technologies—alginate-based microbeads (COC-microbeads) for 3D in vitro maturation (3D-IVM); (2) dynamic IVM conditions, by culturing the COC in a millifluidic bioreactor; and (3) an artificial follicular wall with basal membrane, by adding granulosa cells (GCs) and type I collagen (CI) during bioprinting. The results show that oocyte nuclear and cytoplasmic maturation, as well as blastocyst quality, were improved after 3D-IVM compared to 2D controls. The dynamic 3D-IVM did not enhance oocyte maturation, but it improved oocyte bioenergetics compared with static 3D-IVM. The computational model showed higher oxygen levels in the bioreactor with respect to the static well. Microbead enrichment with GCs and CI improved oocyte maturation and bioenergetics. In conclusion, this study demonstrated that bioengineering approaches that mimic the physiological follicle structure could be valuable tools to improve IVM and JIVET.
The TNFRSF13C H159Y Variant Is Associated with Severe COVID-19: A Retrospective Study of 500 Patients from Southern Italy

To identify host genetic determinants involved in humoral immunity and associated with the risk of developing severe COVID-19, we analyzed 500 SARS-CoV-2 positive subjects from Southern Italy. We examined the coding sequences of 10 common variable immunodeficiency-associated genes obtained by the whole-exome sequencing of 121 hospitalized patients. These 10 genes showed significant enrichment in predicted pathogenic point mutations in severe patients compared with the non-severe ones. Moreover, in the TNFRSF13C gene, the minor allele of the p.His159Tyr variant, which is known to increase NF-kB activation and B-cell production, was significantly more frequent in the 38 severe cases compared to both the 83 non-severe patients and the 375 asymptomatic subjects further genotyped. This finding identified a potential genetic risk factor of severe COVID-19 that not only may serve to unravel the mechanisms underlying the disease severity but, also, may contribute to build the rationale for individualized management based on B-cell therapy.
A Pan-Inhibitor for Protein Arginine Methyltransferase Family Enzymes

Protein arginine methyltransferases (PRMTs) play important roles in transcription, splicing, DNA damage repair, RNA biology, and cellular metabolism. Thus, PRMTs have been attractive targets for various diseases. In this study, we reported the design and synthesis of a potent pan-inhibitor for PRMTs that tethers a thioadenosine and various substituted guanidino groups through a propyl linker. Compound II757 exhibits a half-maximal inhibition concentration (IC50) value of 5 to 555 nM for eight tested PRMTs, with the highest inhibition for PRMT4 (IC50 = 5 nM). The kinetic study demonstrated that II757 competitively binds at the SAM binding site of PRMT1. Notably, II757 is selective for PRMTs over a panel of other methyltransferases, which can serve as a general probe for PRMTs and a lead for further optimization to increase the selectivity for individual PRMT.
Evaluating the Performance of Deep Eutectic Solvents for Use in Extractive Denitrification of Liquid Fuels by the Conductor-like Screening Model for Real Solvents

A total of 94 deep eutectic solvents (DESs) based on different combinations of salt cation, anion, hydrogen-bond donor (HBD) and salt:HBD molar ratio are screened via the conductor-like screening model for real solvents for potential use in the extractive denitrification of diesel. Five nonbasic and six basic nitrogen compounds were included in this study. The activity coefficient at infinite dilution, γ∞, of each nitrogen compound in the DESs was predicted; and the values are used to screen the DESs on the basis of selectivity, capacity, and performance index at infinite dilution (S∞, C∞, and PI). The extraction of nitrogen compounds using DES is driven by hydrogen-bonding interaction. It was found that nonbasic compounds report higher S∞ and C∞ than basic compounds. Ammonium-based DESs give higher S∞ but phosphonium-based DESs report higher C∞. DESs combined with Cl– anion give higher S∞, but those with Br– anion report higher C∞. DESs with alcohol- and amide-based HBDs give higher S∞ but HBDs with carb.
The Association between Vitamin D and Nonalcoholic Fatty Liver Disease Assessed by Controlled Attenuation Parameter

Background: An association between nonalcoholic fatty liver disease (NAFLD) and low vitamin D levels has been suggested. We investigated the relationship between vitamin D and NAFLD assessed by controlled attenuation parameter (CAP). Methods: We conducted a retrospective cohort study of apparently healthy subjects who underwent Fibroscan during health screening tests. NAFLD was diagnosed using CAP values. Results: Among the 1202 subjects (mean age 57.2 years, 60.6% male), 630 (52.4%) subjects had NAFLD with CAP ≥ 248 dB/m. Multivariable analysis was conducted after adjusting for metabolic risk factors including diabetes, hypertension, hypercholesterolemia, body mass index, high-density lipoprotein cholesterol, triglyceride and smoking. Higher vitamin D levels showed a lower risk of NAFLD compared to the lowest quartile of vitamin D in a dose-dependent manner (OR 0.68, 95% CI 0.47–1.00 in Q2 vs. Q1; OR 0.65, 95% CI 0.44–0.94 in Q3 vs. Q1; and OR 0.64, 95% CI 0.44–0.94 in Q4 vs. Q1). The highest quartile of vitamin D showed a decreased risk of a severe grade of steatosis (CAP ≥ 302 dB/m) compared to the lowest quartile (OR 0.52, 95% CI 0.31–0.87 in Q4 vs. Q1). Conclusions: Higher levels of serum vitamin D were associated with a decreased risk of CAP-defined NAFLD, compared to low levels of serum vitamin D. The association between NAFLD and vitamin D suggests that vitamin D may exert a protective role against NAFLD.
Nasal Methicillin-Resistant Staphylococcus aureus Colonization in Patients with Type 1 Diabetes in Taiwan

Nasal methicillin-resistant Staphylococcus aureus (MRSA) colonies are an essential reservoir of infection, especially for patients with diabetes. However, data on MRSA colonization in patients with type 1 diabetes are limited. We investigated the epidemiology of MRSA colonization in patients with type 1 diabetes. This prospective cross-sectional study was conducted in a medical center (Chang Gung Memorial Hospital) in Taiwan from 1 July to 31 December 2020. Nasal sampling and MRSA detection were performed. The molecular characteristics of MRSA isolates were tested, and factors associated with MRSA colonization were analyzed. We included 245 patients with type 1 diabetes; nasal MRSA colonization was identified in 13 (5.3%) patients. All isolates belonged to community-associated MRSA genetic strains; the most frequent strain was clonal complex 45 (53.8%), followed by ST59 (30.8%) (a local community strain). MRSA colonization was positively associated with age ≤ 10 years, body mass index < 18 kg/m2, and diabetes duration < 10 years; moreover, it was negatively associated with serum low-density lipoprotein cholesterol ≥ 100 mg/dL. No independent factor was reported. The nasal MRSA colonization rate in type 1 diabetes is approximately 5% in Taiwan. Most of these colonizing strains are community strains, namely clonal complex 45 and ST59.
Accuracy of a Machine-Learning Algorithm for Detecting and Classifying Choroidal Neovascularization on Spectral-Domain Optical Coherence Tomography

Background: To evaluate the performance of a machine-learning (ML) algorithm to detect and classify choroidal neovascularization (CNV), secondary to age-related macular degeneration (AMD) on spectral-domain optical coherence tomography (SD-OCT) images. Methods: Baseline fluorescein angiography (FA) and SD-OCT images from 1037 treatment-naive study eyes and 531 fellow eyes, without advanced AMD from the phase 3 HARBOR trial (NCT00891735), were used to develop, train, and cross-validate an ML pipeline combining deep-learning–based segmentation of SD-OCT B-scans and CNV classification, based on features derived from the segmentations, in a five-fold setting. FA classification of the CNV phenotypes from HARBOR was used for generating the ground truth for model development. SD-OCT scans from the phase 2 AVENUE trial (NCT02484690) were used to externally validate the ML model. Results: The ML algorithm discriminated CNV absence from CNV presence, with a very high accuracy (area under the receiver operating characteristic [AUROC] = 0.99), and classified occult versus predominantly classic CNV types, per FA assessment, with a high accuracy (AUROC = 0.91) on HARBOR SD-OCT images. Minimally classic CNV was discriminated with significantly lower performance. Occult and predominantly classic CNV types could be discriminated with AUROC = 0.88 on baseline SD-OCT images of 165 study eyes, with CNV from AVENUE. Conclusions: Our ML model was able to detect CNV presence and CNV subtypes on SD-OCT images with high accuracy in patients with neovascular AMD.
Miúda (Nopalea cochenillifera (L.) Salm-Dyck)—The Best Forage Cactus Genotype for Feeding Lactating Dairy Cows in Semiarid Regions

Simple Summary The usage of forage cactus is essential for the maintenance of livestock activity in semiarid regions as an alternative to conventional crops. Cactaceae have adaptive characteristics that ensure their development progress under drought conditions. Four genotypes of forage cactus (Gigante, Miúda, IPA Sertânia, and Orelha de Elefante Mexicana) were fed to lactating dairy cows and the diets were then evaluated based on animal performance, milk fatty acid profile, and microbial protein synthesis. Miúda forage cactus led to a higher nutrient intake and milk yield, as well as greater microbial protein synthesis. Higher saturated fatty acids were observed when the Gigante and IPA Sertânia forage cactus genotypes were fed to dairy cows. Orelha de Elefante Mexicana forage cactus caused lower milk yield along with protein yields and content; however, it improved the milk fatty acid profile by promoting a higher ratio of unsaturated to saturated fatty acids and desirable fatty acids. It is concluded that the Miúda forage cactus is the genotype most suitable for the diets of lactating dairy cows. Abstract This study aimed to investigate the effects on nutrient intake and digestibility, milk yield (MY) and composition, milk fatty acids profile, and microbial protein synthesis caused by feeding lactating dairy cows four different forage cactus genotypes. Eight Girolando cows (5/8 Holstein × 3/8 Gyr), weighing 490 ± 69.0 kg (means ± standard deviation), and producing 15.5 ± 1.0 kg/d of milk during pretrial were distributed to two contemporaneous 4 × 4 Latin squares. The cows were fed a total mixed ration composed of sorghum silage (385 g/kg of dry matter (DM)), concentrated mix (175 g/kg DM), and forage cactus (440 g/kg DM). The experimental treatments consisted of different cactus genotypes, such as Gigante cactus (GC), Miúda cactus (MC), IPA Sertânia cactus (SC), and Orelha de Elefante Mexicana cactus (OEMC). The feeding of MC provided a higher intake of DM, organic matter (OM), and total digestible nutrients, as well as higher MY, energy-corrected milk, and microbial protein synthesis in comparison with those resulting from the other genotypes tested. The GC promoted lower DM and OM, and the apparent digestibility of neutral detergent fiber. The cows fed with OEMC showed lower MY and milk protein yield and content, and higher unsaturated over saturated fatty acid ratio in milk. Miúda forage cactus increased nutrient intake, digestibility of DM and OM, and microbial synthesis without impairing the milk fatty acid profile.
What Can N-glycomics and N-glycoproteomics of Cerebrospinal Fluid Tell Us about Alzheimer Disease?

Proteomics—large-scale studies of proteins—has over the last decade gained an enormous interest for studies aimed at revealing proteins and pathways involved in disease. To fully understand biological and pathological processes it is crucial to also include post-translational modifications in the “omics”. To this end, glycomics (identification and quantification of glycans enzymatically or chemically released from proteins) and glycoproteomics (identification and quantification of peptides/proteins with the glycans still attached) is gaining interest. The study of protein glycosylation requires a workflow that involves an array of sample preparation and analysis steps that needs to be carefully considered. Herein, we briefly touch upon important steps such as sample preparation and preconcentration, glycan release, glycan derivatization and quantification and advances in mass spectrometry that today are the work-horse for glycomics and glycoproteomics studies. Several proteins related to Alzheimer disease pathogenesis have altered protein glycosylation, and recent glycomics studies have shown differences in cerebrospinal fluid as well as in brain tissue in Alzheimer disease as compared to controls. In this review, we discuss these techniques and how they have been used to shed light on Alzheimer disease and to find glycan biomarkers in cerebrospinal fluid.