Miracle-dz/UniFAR-FTUs huggingface dataset:
Mandible Segmentation of Dental CBCT Scans Affected by Metal Artifacts Using Coarse-to-Fine Learning Model

Accurate segmentation of the mandible from cone-beam computed tomography (CBCT) scans is an important step for building a personalized 3D digital mandible model for maxillofacial surgery and orthodontic treatment planning because of the low radiation dose and short scanning duration. CBCT images, however, exhibit lower contrast and higher levels of noise and artifacts due to extremely low radiation in comparison with the conventional computed tomography (CT), which makes automatic mandible segmentation from CBCT data challenging. In this work, we propose a novel coarse-to-fine segmentation framework based on 3D convolutional neural network and recurrent SegUnet for mandible segmentation in CBCT scans. Specifically, the mandible segmentation is decomposed into two stages: localization of the mandible-like region by rough segmentation and further accurate segmentation of the mandible details. The method was evaluated using a dental CBCT dataset. In addition, we evaluated the proposed method and compared it with state-of-the-art methods in two CT datasets. The experiments indicate that the proposed algorithm can provide more accurate and robust segmentation results for different imaging techniques in comparison with the state-of-the-art models with respect to these three datasets.
Association of Trimethylamine N-Oxide (TMAO) with the Clinical Severity of Hidradenitis Suppurativa (Acne Inversa)

In this case-control, cross-sectional, observational study, we evaluated circulating trimethylamine n-oxide (TMAO) levels, a gut-derived metabolite associated with inflammation and cardiometabolic risk, in patients with hidradenitis suppurativa (HS), a highly disabling inflammatory skin disease associated with an elevated prevalence of comorbidities, especially cardiovascular and metabolic diseases. In this study, we enrolled 35 naive-treatment patients with HS and 35 controls, matched for sex, age, and body mass index (BMI). HS Sartorius score was 49.0 (33.0–75.0), while according to the Harley system 12 and 23 patients presented grade 1 and grade 2 severity, respectively. HS patients had a lower adherence to the Mediterranean diet (MD) (p = 0.002), lower phase angle (PhA) (p < 0.001), and higher circulating TMAO levels (p < 0.001) than the control group. HS patients with grade 2 rather than grade 1 of Harley grade severity showed a higher BMI (p = 0.007), waist circumference (p = 0.016), total energy intake (p = 0.005), and lower PhA (p < 0.001) and adherence to the MD (p = 0.003). Of interest, patients with Hurley grade 2 of severity exhibited higher circulating TMAO levels (p < 0.001) compared to grade 1. Circulating TMAO levels showed a positive correlation with HS Sartorius score even after adjustment for confounding covariates, including BMI, waist circumference, adherence to the MD, total energy intake, and PhA (r = 0.570, p = 0.001). Using a linear regression model, circulating TMAO levels and PhA were the main predictors of the clinical severity of HS.
Improved Models of Human Endometrial Organoids Based on Hydrogels from Decellularized Endometrium

Organoids are three-dimensional (3D) multicellular tissue models that mimic their corresponding in vivo tissue. Successful efforts have derived organoids from primary tissues such as intestine, liver, and pancreas. For human uterine endometrium, the recent generation of 3D structures from primary endometrial cells is inspiring new studies of this important tissue using precise preclinical models. To improve on these 3D models, we decellularized pig endometrium containing tissue-specific extracellular matrix and generated a hydrogel (EndoECM). Next, we derived three lines of human endometrial organoids and cultured them in optimal and suboptimal culture expansion media with or without EndoECM (0.01 mg/mL) as a soluble additive. We characterized the resultant organoids to verify their epithelial origin, long-term chromosomal stability, and stemness properties. Lastly, we determined their proliferation potential under different culture conditions using proliferation rates and immunohistochemical methods. Our results demonstrate the importance of a bioactive environment for the maintenance and proliferation of human endometrial organoids.
CRISPR-Mediated Endogenous Activation of Fibroin Heavy Chain Gene Triggers Cellular Stress Responses in Bombyx mori Embryonic Cells

Simple Summary Based on a CRISPRa approach, activating endogenous fibroin heavy chain (FibH) gene expression in Bombyx mori embryonic (BmE) cells, which was driven by a combination of the dCas9-VPR (a tripartite activator, composed of VP64, p65, and Rta) and the sgRNA targeting to the promoter of FibH gene, was performed for investigating the biological roles of FibH in the development of silk gland cells. The activation of the endogenous FibH gene lead to up-regulation of cellular stress responses-related genes, which suggested a significant positive correlation between activated FibH gene expression and cellular stress responses. Moreover, the present findings might provide a potential model for studying the cellular stress responses caused by silk secretion disorder and lay a foundation for the understanding of silk gland development in silk-spinning insects. Abstract The silkworm Bombyx mori is an economically important insect, as it is the main producer of silk. Fibroin heavy chain (FibH) gene, encoding the core component of silk protein, is specifically and highly expressed in silk gland cells but not in the other cells. Although the silkworm FibH gene has been well studied in transcriptional regulation, its biological functions in the development of silk gland cells remain elusive. In this study, we constructed a CRISPRa system to activate the endogenous transcription of FibH in Bombyx mori embryonic (BmE) cells, and the mRNA expression of FibH was successfully activated. In addition, we found that FibH expression was increased to a maximum at 60 h after transient transfection of sgRNA/dCas9-VPR at a molar ratio of 9:1. The qRT-PCR analysis showed that the expression levels of cellular stress response-related genes were significantly up-regulated along with activated FibH gene. Moreover, the lyso-tracker red and monodansylcadaverine (MDC) staining assays revealed an apparent appearance of autophagy in FibH-activated BmE cells. Therefore, we conclude that the activation of FibH gene leads to up-regulation of cellular stress responses-related genes in BmE cells, which is essential for understanding silk gland development and the fibroin secretion process in B. mori.
Synthesis of Caffeoyl-Prolyl-Histidyl-Xaa Derivatives and Evaluation of Their Activities and Stability upon Long-Term Storage

Antioxidants play a critical role in the treatment of degenerative diseases and delaying the aging of dermal tissue. Caffeic acid (CA) is a representative example of the antioxidants found in plants. However, CA is unsuitable for long-term storage because of its poor stability under ambient conditions. Caffeoyl-Pro-His-NH2 (CA-Pro-His-NH2, CA-PH) exhibits the highest antioxidant activity, free radical scavenging and lipid peroxidation inhibition activity among the histidine-containing CA-conjugated dipeptides reported to date. The addition of short peptides to CA, such as Pro-His, is assumed to synergistically enhance its antioxidative activity. In this study, several caffeoyl-prolyl-histidyl-Xaa-NH2 derivatives were synthesized and their antioxidative activities evaluated. CA-Pro-His-Asn-NH2 showed enhanced antioxidative activity and higher structural stability than CA-PH, even after long-term storage. CA-Pro-His-Asn-NH2 was stable for 3 months, its stability being evaluated by observing the changes in its NMR spectra. Moreover, the solid-phase synthetic strategy used to prepare these CA-Pro-His-Xaa-NH2 derivatives was optimized for large-scale production. We envision that CA-Pro-His-Xaa-NH2 derivatives can be used as potent dermal therapeutic agents and useful cosmetic ingredients.
Mitogenomics and Evolutionary History of Rodent Whipworms (Trichuris spp.) Originating from Three Biogeographic Regions

Trichuris spp. is a widespread nematode which parasitizes a wide range of mammalian hosts including rodents, the most diverse mammalian order. However, genetic data on rodent whipworms are still scarce, with only one published whole genome (Trichuris muris) despite an increasing demand for whole genome data. We sequenced the whipworm mitogenomes from seven rodent hosts belonging to three biogeographic regions (Palearctic, Afrotropical, and Indomalayan), including three previously described species: Trichuris cossoni, Trichuris arvicolae, and Trichuris mastomysi. We assembled and annotated two complete and five almost complete mitogenomes (lacking only the long non-coding region) and performed comparative genomic and phylogenetic analyses. All the mitogenomes are circular, have the same organisation, and consist of 13 protein-coding, 2 rRNA, and 22 tRNA genes. The phylogenetic analysis supports geographical clustering of whipworm species and indicates that T. mastomysi found in Eastern Africa is able to infect multiple closely related rodent hosts. Our results are informative for species delimitation based on mitochondrial markers and could be further used in studies on phylogeny, phylogeography, and population genetics of rodent whipworms
Economic Analysis of Offering Different Herbage Allowances to Dairy Cows Fed a Partial Mixed Ration

Simple Summary In south-eastern Australia, most dairy cows consume grazed pasture, cereal grain fed in the dairy and hay in the paddock. Previous research has shown that feeding supplements to grazing cows as a well-formulated mixed ration can increase feed intake, milk production and profit. This previous work was conducted under a limited herbage allowance to represent the conditions of drought or a high stocking rate. Two subsequent animal experiments were performed, one in early lactation and the other in late lactation, where the herbage allowance was varied from low to high and used to investigate the economics of partial mixed ration (PMR) feeding. We found that offering a medium allowance (25 and 20 kg DM/cow per day in early and late lactation, respectively) resulted in higher profit (total milk income minus feed costs) than a low herbage allowance (15 and 12 kg DM/cow per day in early and late lactation). No additional profit was obtained by further increasing the herbage allowance from medium to high (40 and 32 kg DM/cow per day in early and late lactation). These findings will assist farmers to manage their PMR systems in a profitable way. Abstract The economics of grazing dairy cows offered a range of herbage allowances and fed supplements as a partial mixed ration (PMR) were examined where profit was defined as the margin between total milk income and the cost of pasture plus PMR supplement. The analysis made use of milk production and feed intake data from two dairy cow nutrition experiments, one in early lactation and the other in late lactation. In early lactation and at a PMR intake of 6 kg DM/cow per day, the profit from the cows with access to a medium herbage allowance (25 kg DM/cow per day) was AUD 1.40/cow per day higher than that for cows on a low allowance (15 kg DM/cow per day). At a higher PMR intake of 14 kg DM/cow per day, the profit from the cows on a medium herbage allowance was AUD 0.45/cow per day higher than the cows on a low allowance; there was no additional profit from increasing the herbage allowance from medium to high (40 kg DM/cow per day). In late lactation, the profit from the cows fed a PMR with a medium herbage allowance (20 kg DM/cow per day) was only higher than the cows on a low allowance (12 kg DM/cow per day) when the PMR intake was between 6 and 12 kg DM/cow per day. There was also a difference of AUD +0.50/cow per day between the PMR with medium and high herbage allowance (32 kg DM/cow per day). It was concluded that farmers who feed a PMR to dairy cows should offer at least a medium herbage allowance to optimize profit. While feeding additional PMR increases milk production and profit, further gains would be available by offering a higher herbage allowance. These findings provide an estimate of the net benefits of different herbage allowances when feeding a PMR and will enable farmers to manage their feeding systems more profitably.
Analysis of Features of Alzheimer’s Disease: Detection of Early Stage from Functional Brain Changes in Magnetic Resonance Images Using a Finetuned ResNet18 Network

One of the first signs of Alzheimer’s disease (AD) is mild cognitive impairment (MCI), in which there are small variants of brain changes among the intermediate stages. Although there has been an increase in research into the diagnosis of AD in its early levels of developments lately, brain changes, and their complexity for functional magnetic resonance imaging (fMRI), makes early detection of AD difficult. This paper proposes a deep learning-based method that can predict MCI, early MCI (EMCI), late MCI (LMCI), and AD. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) fMRI dataset consisting of 138 subjects was used for evaluation. The finetuned ResNet18 network achieved a classification accuracy of 99.99%, 99.95%, and 99.95% on EMCI vs. AD, LMCI vs. AD, and MCI vs. EMCI classification scenarios, respectively. The proposed model performed better than other known models in terms of accuracy, sensitivity, and specificity.
Thiolated-Polymer-Based Nanoparticles as an Avant-Garde Approach for Anticancer Therapies—Reviewing Thiomers from Chitosan and Hyaluronic Acid

Thiomers (or thiolated polymers) have broken through as avant-garde approaches in anticancer therapy. Their distinguished reactivity and properties, closely linked to their final applications, justify the extensive research conducted on their preparation and use as smart drug-delivery systems (DDSs). Multiple studies have demonstrated that thiomer-rich nanoformulations can overcome major drawbacks found when administering diverse active pharmaceutical ingredients (APIs), especially in cancer therapy. This work focuses on providing a complete and concise review of the synthetic tools available to thiolate cationic and anionic polymers, in particular chitosan (CTS) and hyaluronic acid (HA), respectively, drawing attention to the most successful procedures. Their chemical reactivity and most relevant properties regarding their use in anticancer formulations are also discussed. In addition, a variety of NP formation procedures are outlined, as well as their use in cancer therapy, particularly for taxanes and siRNA. It is expected that the current work could clarify the main synthetic strategies available, with their scope and drawbacks, as well as provide some insight into thiomer chemistry. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of cancer.
The Assessment of Agrobiological and Disease Resistance Traits of Grapevine Hybrid Populations (Vitis vinifera L. × Muscadinia rotundifolia Michx.) in the Climatic Conditions of Crimea

The Crimean autochthonous grape varieties are unique by their origin and serve as a valuable source for breeding new cultivars with increased salt and frost resistance, as well as high-quality berries. However, they suffer from fungal pathogens, as the dry and hot summer months contribute to the epiphytotic course of diseases. An increase in the resistance of Crimean grape varieties is currently achieved through interspecific hybridization. In this study, we describe the genetic and agrobiological diversity of three hybrid populations obtained using the Vitis interspecific hybrid ‘Magarach 31-77-10′ as a female parent and Muscadinia rotundifolia × Vitis vinifera BC5 hybrid plants as male parents. The hybrid nature of the populations was assessed using RADseq high-throughput genotyping. We discovered 12,734 SNPs, which were common to all three hybrid populations. We also proved with the SSR markers that the strong powdery and downy mildew resistance of the paternal genotypes is determined by the dominant Run1/Rpv1 locus inherited from M. rotundifolia. As a result, the disease development score (R, %) for both mildew diseases in the female parent ‘Magarach 31-77-10’ was three times higher than in male parents 2000-305-143 and 2000-305-163 over two years of phytopathological assessment. The highest values of yield-contributing traits (average bunch weight ~197 g and 1.3 kg as yield per plant) were detected in the population 4-11 (♀M. No. 31-77-10 × 2000-305-163). Despite the epiphytotic development of PM, the spread of oidium to the vegetative organs of hybrids 4-11 did not exceed 20%. Some hybrid genotypes with high productivity and resistance to pathogens were selected for further assessment as promising candidates for new varieties.
Recent Advances in Antifouling Materials for Surface Plasmon Resonance Biosensing in Clinical Diagnostics and Food Safety

Strategies to develop antifouling surface coatings are crucial for surface plasmon resonance (SPR) sensing in many analytical application fields, such as detecting human disease biomarkers for clinical diagnostics and monitoring foodborne pathogens and toxins involved in food quality control. In this review, firstly, we provide a brief discussion with considerations about the importance of adopting appropriate antifouling materials for achieving excellent performances in biosensing for food safety and clinical diagnosis. Secondly, a non-exhaustive landscape of polymeric layers is given in the context of surface modification and the mechanism of fouling resistance. Finally, we present an overview of some selected developments in SPR sensing, emphasizing applications of antifouling materials and progress to overcome the challenges related to the detection of targets in complex matrices relevant for diagnosis and food biosensing.
Data-Driven Fault Diagnosis for Electric Drives: A Review

The need to manufacture more competitive equipment, together with the emergence of the digital technologies from the so-called Industry 4.0, have changed many paradigms of the industrial sector. Presently, the trend has shifted to massively acquire operational data, which can be processed to extract really valuable information with the help of Machine Learning or Deep Learning techniques. As a result, classical Condition Monitoring methodologies, such as model- and signal-based ones are being overcome by data-driven approaches. Therefore, the current paper provides a review of these data-driven active supervision strategies implemented in electric drives for fault detection and diagnosis (FDD). Hence, first, an overview of the main FDD methods is presented. Then, some basic guidelines to implement the Machine Learning workflow on which most data-driven strategies are based, are explained. In addition, finally, the review of scientific articles related to the topic is provided, together with a discussion which tries to identify the main research gaps and opportunities.
Active Ratio Test (ART) as a Novel Diagnostic for Ovarian Cancer

Background: Despite substantial effort, there remains a lack of biomarker-based, clinically relevant testing for the accurate, non-invasive diagnostic or prognostic profiling of epithelial ovarian cancers (EOC). Our previous work demonstrated that whilst the inflammatory marker C-X-C motif chemokine ligand 10 (CXCL10) has prognostic relevance in ovarian cancer, its use is complicated by the presence of multiple, N-terminally modified variants, mediated by several enzymes including Dipeptidyl Peptidase 4 (DPP4). Methods: In this study, we provide the first evidence for the “Active Ratio Test” (ART) as a novel method to measure biologically relevant CXCL10 proteoforms in clinical samples. Results: In a cohort of 275 patients, ART accurately differentiated patients with malignant EOCs from those with benign gynaecological conditions (AUC 0.8617) and significantly out-performed CA125 alone. Moreover, ART combined with the measurement of CA125 and DPP4 significantly increased prognostic performance (AUC 0.9511; sensitivity 90.0%; specificity 91.7%; Cohen’s d > 1) for EOC detection. Conclusion: Our data demonstrate that ART provides a useful method to accurately discriminate between patients with benign versus malignant EOC, and highlights their relevance to ovarian cancer diagnosis. This marker combination may also be applicable in broader screening applications, to identify or discriminate benign from malignant disease in asymptomatic women.
Biosensors Coupled with Signal Amplification Technology for the Detection of Pathogenic Bacteria: A Review

Foodborne disease caused by foodborne pathogens is a very important issue in food safety. Therefore, the rapid screening and sensitive detection of foodborne pathogens is of great significance for ensuring food safety. At present, many research works have reported the application of biosensors and signal amplification technologies to achieve the rapid and sensitive detection of pathogenic bacteria. Thus, this review summarized the use of biosensors coupled with signal amplification technology for the detection of pathogenic bacteria, including (1) the development, concept, and principle of biosensors; (2) types of biosensors, such as electrochemical biosensors, optical biosensors, microfluidic biosensors, and so on; and (3) different kinds of signal amplification technologies applied in biosensors, such as enzyme catalysis, nucleic acid chain reaction, biotin-streptavidin, click chemistry, cascade reaction, nanomaterials, and so on. In addition, the challenges and future trends for pathogenic bacteria based on biosensor and signal amplification technology were also discussed and summarized.
Riluzole Administration to Rats with Levodopa-Induced Dyskinesia Leads to Loss of DNA Methylation in Neuronal Genes

Dyskinesias are characterized by abnormal repetitive involuntary movements due to dysfunctional neuronal activity. Although levodopa-induced dyskinesia, characterized by tic-like abnormal involuntary movements, has no clinical treatment for Parkinson’s disease patients, animal studies indicate that Riluzole, which interferes with glutamatergic neurotransmission, can improve the phenotype. The rat model of Levodopa-Induced Dyskinesia is a unilateral lesion with 6-hydroxydopamine in the medial forebrain bundle, followed by the repeated administration of levodopa. The molecular pathomechanism of Levodopa-Induced Dyskinesia is still not deciphered; however, the implication of epigenetic mechanisms was suggested. In this study, we investigated the striatum for DNA methylation alterations under chronic levodopa treatment with or without co-treatment with Riluzole. Our data show that the lesioned and contralateral striata have nearly identical DNA methylation profiles. Chronic levodopa and levodopa + Riluzole treatments led to DNA methylation loss, particularly outside of promoters, in gene bodies and CpG poor regions. We observed that several genes involved in the Levodopa-Induced Dyskinesia underwent methylation changes. Furthermore, the Riluzole co-treatment, which improved the phenotype, pinpointed specific methylation targets, with a more than 20% methylation difference relative to levodopa treatment alone. These findings indicate potential new druggable targets for Levodopa-Induced Dyskinesia.