Miracle-dz/UniFAR-FTUs huggingface dataset:
A Unified Framework for Generalized Low-Shot Medical Image Segmentation With Scarce Data

Medical image segmentation has achieved remarkable advancements using deep neural networks (DNNs). However, DNNs often need big amounts of data and annotations for training, both of which can be difficult and costly to obtain. In this work, we propose a unified framework for generalized low-shot (one- and few-shot) medical image segmentation based on distance metric learning (DML). Unlike most existing methods which only deal with the lack of annotations while assuming abundance of data, our framework works with extreme scarcity of both, which is ideal for rare diseases. Via DML, the framework learns a multimodal mixture representation for each category, and performs dense predictions based on cosine distances between the pixels’ deep embeddings and the category representations. The multimodal representations effectively utilize the inter-subject similarities and intraclass variations to overcome overfitting due to extremely limited data. In addition, we propose adaptive mixing coefficients for the multimodal mixture distributions to adaptively emphasize the modes better suited to the current input. The representations are implicitly embedded as weights of the fc layer, such that the cosine distances can be computed efficiently via forward propagation. In our experiments on brain MRI and abdominal CT datasets, the proposed framework achieves superior performances for low-shot segmentation towards standard DNN-based (3D U-Net) and classical registration-based (ANTs) methods, e.g., achieving mean Dice coefficients of 81%/69% for brain tissue/abdominal multi-organ segmentation using a single training sample, as compared to 52%/31% and 72%/35% by the U-Net and ANTs, respectively.
The Effect of Orally Supplemented Melatonin on Larval Performance and Skeletal Deformities in Farmed Gilthead Seabream (Sparus aurata)

The gilthead seabream larval rearing in continuous light is common in most Mediterranean hatcheries to stimulate larval length growth and increase food consumption. Several studies have shown that continuous light affects larval development and increases the prevalence of skeletal deformities. Melatonin is a crucial pineal neurohormone that displays daily secretion patterns, stimulates cell proliferation and embryonic development in Atlantic salmon and zebrafish, and improves osseointegration in mice and humans. However, no studies have examined the effects of orally supplemented melatonin on skeletal deformities in Sparus aurata larvae. We administered exogenous melatonin to gilthead seabream larvae via enriched rotifers and nauplii of Artemia. Exogenous melatonin induced bone deformities and stimulated parathyroid hormone-related protein-coding gene (PTHrP) mRNA expression. In addition to the melatonin-induced PTHrP high expression level, the recorded non coordinated function of skeletal muscle and bone during growth can be the fountainhead of bone deformities. Both myosin light chain 2 (mlc2) and bone gamma-carboxyglutamate protein-coding gene (bglap) expression levels were significantly affected by melatonin administration in an inverse dose–response manner during the exogenous melatonin administration. This is the first study to report the effect of inducing melatonin bone deformities on Sparus aurata larvae reared under ordinary hatchery conditions.
Chemical Profiling, Antioxidant, Cytotoxic Activities and Molecular Docking Simulation of Carrichtera annua DC. (Cruciferae)

Our investigation intended to analyze the chemical composition and the antioxidant activity of Carrichtera annua and to evaluate the antiproliferative effect of C. annua crude and phenolics extracts by MTT assay on a panel of cancerous and non-cancerous breast and liver cell lines. The total flavonoid and phenolic contents of C. annua were 47.3 ± 17.9 mg RE/g and 83.8 ± 5.3 mg respectively. C. annua extract exhibited remarkable antioxidant capacity (50.92 ± 5.64 mg GAE/g) in comparison with BHT (74.86 ± 3.92 mg GAE/g). Moreover, the extract exhibited promising reduction ability (1.17 mMol Fe+2/g) in comparison to the positive control (ascorbic acid with 2.75 ± 0.91) and it displayed some definite radical scavenging effect on DPPH (IC50 values of 211.9 ± 3.7 µg/mL). Chemical profiling of C. annua extract was achieved by LC-ESI-TOF-MS/MS analysis. Forty-nine hits mainly polyphenols were detected. Flavonoid fraction of C. annua was more active than the crude extract. It demonstrated selective cytotoxicity against the MCF-7 and HepG2 cells (IC50 = 13.04 and 19.3 µg/mL respectively), induced cell cycle arrest at pre-G1 and G2/M-phases and displayed apoptotic effect. Molecular docking studies supported our findings and revealed that kaempferol-3,7-O-bis-α-L-rhamnoside and kaempferol-3-rutinoside were the most active inhibitors of Bcl-2. Therefore, C. annua herb seems to be a promising candidate to further advance anticancer research. In extrapolation, the intake of C. annua phenolics might be adventitious for alleviating breast and liver malignancies and tumoral proliferation in humans.
Drug Survival of Biologic Therapy in Elderly Patients With Rheumatoid Arthritis Compared With Nonelderly Patients

Supplemental digital content is available in the text. Objective Although the proportion of elderly patients with rheumatoid arthritis (RA) is increasing, the persistency of biologic therapy in elderly patients requires additional investigation. This study evaluated the drug survival of biologic therapy and associated factors in elderly compared with nonelderly patients. Methods This longitudinal observational study included RA patients who were enrolled in the Korean College of Rheumatology Biologics Registry (NCT01965132, started from January 1, 2013) between 2013 and 2015. We compared the retention rate of biologic therapy between elderly (age ≥70 years) and nonelderly (age <70 years) patients, and investigated the causes and predictors of biologic withdrawal in both groups. Results Of 682 patients, 122 were aged 70 years or older. The retention rate of biologic therapy at 24 months was 57.8% and 46.5% in nonelderly and elderly patients, respectively (p = 0.027). Biologic withdrawal due to adverse events and inefficacy within 24 months was not significantly different between the 2 groups, although adverse events were more common in elderly patients (20.6% vs 12.8%, p = 0.360). Drug withdrawal due to patient refusal was more common in elderly patients (9.8% vs 1.8%, p < 0.001). In elderly patients, biologic withdrawal was associated with current smoking and older age at disease onset, whereas the use of tumor necrosis factor inhibitors, nonuse of methotrexate, and combination of corticosteroid were important in nonelderly patients. Conclusions Elderly RA patients are more likely to discontinue biologic agents within 24 months. To increase the retention rate of biologic therapy, rheumatologists should consider patient characteristics before and during biologic therapy.
Circulating MicroRNA Profiling Reveals Specific Subsignatures in Response to a Maximal Incremental Exercise Test.

ABSTRACT Fernández-Sanjurjo, M, Díaz-Martínez, ÁE, Díez-Robles, S, González-González, F, de Gonzalo-Calvo, D, Rabadán, M, Dávalos, A, Fernández-García, B, and Iglesias-Gutiérrez, E. Circulating microRNA profiling reveals specific subsignatures in response to a maximal incremental exercise test. J Strength Cond Res XX(X): 000-000, 2020-Circulating microRNAs (c-miRNAs) have been described as emergent regulators and biomarkers of exercise. The aim of this study was to analyze the c-miRNA response to a maximal incremental exercise test (MIET) and its relationship with markers of exercise response and adaptation. Two blood samples were collected from 9 male amateur runners (31-50 years), before (Pre) and after (Post) a MIET. The maximal oxygen uptake (V[Combining Dot Above]O2max), maximum heart rate (HRmax), and maximal aerobic speed (MAS) were recorded. Lactate and creatine kinase (CK) plasma concentrations were measured. A panel of 752 miRNAs was analyzed using standardized protocols and relative quantification to Pre. A total of 13 miRNAs were found significantly upregulated at Post. By focusing on the exercise markers that correlate with the expression of these miRNAs, they were clustered into different functional groups or subsignatures. Thus, miR-21-5p, miR-29b-3p, and miR-183-5p showed a strong correlation with HRmax and a validated target signature related to fatty acid metabolism. Furthermore, let-7c-5p, miR-340-5p, miR-425-3p, and miR-629-5p were significantly correlated with CK, and the most significantly enriched pathways for these subsignatures were the Hippo signaling pathway and signaling pathways regulating pluripotency of stem cells. Finally, Pre miR-106b-5p expression showed an inverse association with MAS and Post lactate concentration, which highlights its relevance as biomarker of training status and its predictive value for performance. No significant correlations were observed with V[Combining Dot Above]O2max. Our results define for the first time specific functional c-miRNA subsignatures, adding novel evidence about their potential regulatory role in exercise response.
Current Genetic Survey and Potential Gene-Targeting Therapeutics for Neuromuscular Diseases

Neuromuscular diseases (NMDs) belong to a class of functional impairments that cause dysfunctions of the motor neuron-muscle functional axis components. Inherited monogenic neuromuscular disorders encompass both muscular dystrophies and motor neuron diseases. Understanding of their causative genetic defects and pathological genetic mechanisms has led to the unprecedented clinical translation of genetic therapies. Challenged by a broad range of gene defect types, researchers have developed different approaches to tackle mutations by hijacking the cellular gene expression machinery to minimize the mutational damage and produce the functional target proteins. Such manipulations may be directed to any point of the gene expression axis, such as classical gene augmentation, modulating premature termination codon ribosomal bypass, splicing modification of pre-mRNA, etc. With the soar of the CRISPR-based gene editing systems, researchers now gravitate toward genome surgery in tackling NMDs by directly correcting the mutational defects at the genome level and expanding the scope of targetable NMDs. In this article, we will review the current development of gene therapy and focus on NMDs that are available in published reports, including Duchenne Muscular Dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked myotubular myopathy (XLMTM), Spinal Muscular Atrophy (SMA), and Limb-girdle muscular dystrophy Type 2C (LGMD2C).
Interaction Effect of the Mediterranean Diet and an Obesity Genetic Risk Score on Adiposity and Metabolic Syndrome in Adolescents: The HELENA Study

Obesity and metabolic syndrome (MetS) are worldwide major health challenges. The Mediterranean diet (MD) is associated with a better cardiometabolic profile, but these beneficial effects may be influenced by genetic variations, modulating the predisposition to obesity or MetS. The aim was to assess whether interaction effects occur between an obesity genetic risk score (obesity-GRS) and the MD on adiposity and MetS in European adolescents. Multiple linear regression models were used to assess the interaction effects of an obesity-GRS and the MD on adiposity and MetS and its components. Interaction effects between the MD on adiposity and MetS were observed in both sex groups (p < 0.05). However, those interaction effects were only expressed in a certain number of adolescents, when a limited number of risk alleles were present. Regarding adiposity, a total of 51.1% males and 98.7% females had lower body mass index (BMI) as a result of higher MD adherence. Concerning MetS, only 9.9% of males with higher MD adherence had lower MetS scores. However, the same effect was observed in 95.2% of females. In conclusion, obesity-related genotypes could modulate the relationship between MD adherence and adiposity and MetS in European adolescents; the interaction effect was higher in females than in males.
Radical Scavenging-Linked Anti-Adipogenic Activity of Aster scaber Ethanolic Extract and Its Bioactive Compound

Aster scaber is a wild vegetable cultivated in Korea and is known to contain phytochemicals with various biological activities. The potential antioxidant and anti-obesity effects of A. scaber and their mechanism are yet to be reported. We evaluated the total phenolic, flavonoid, and proanthocyanidin contents and oxygen radical absorbance capacity of A. scaber ethanolic extract (ASE), and analyzed the major phenolic compounds of ASE. Antioxidant activity was measured at the chemical level through 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power assay, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), and fluorescence recovery after photobleaching (FRAP) assay. In addition, it was measured in vitro through inhibition of Reactive oxygen species (ROS) production in 3T3-L1 adipocyte, and inhibition of lipid accumulation was also evaluated. ASE reduced the expression of enzymes involved in the production of ROS and increased the expression of antioxidant enzymes that reduce increased ROS levels. They also reduced the expression of adipogenesis transcription factors that regulate adipocyte differentiation in relation to ROS production, inhibited the expression of lipogenesis-related genes related to fat accumulation through AMP-activated protein kinase (AMPK) activity, and increased expression of lipolysis-related genes. Thus, ASE containing CGA (chlorogenic acid) inhibits ROS production in 3T3-L1 adipocytes, owing to its strong antioxidant activity, and inhibits lipid accumulation caused by oxidative stress. The extract can be used as a potential functional food material for reducing oxidative stress and obesity.
Extended capillary wave theory and the ellipsometric coefficient

The extended capillary wave theory (ECW) proposed by Robledo et al. and formulated in terms of the unknown direct correlation function C of the two-phase system with a planar interface between liquid and its vapor, is applied to our simulation data on the full inhomogeneous two-point correlation function H from which C is also obtained. The required projection, C(q), is shown and discussed. The coefficient of q4, the apparent bending coefficient, was inequivocally negative, in agreement with the view that the true bending coefficient may be absent in one-component interfaces. The ellipsometric coefficient diverged and its calculation still required an ultraviolet cutoff. It is thus demonstrated that ECW is but the first step and further terms, some discovered earlier, as well as mode–mode coupling, are required. These are discussed.
Acute Effects of Warming Up on Achilles Tendon Blood Flow and Stiffness

Abstract Pieters, D, Wezenbeek, E, De Ridder, R, Witvrouw, E, and Willems, T. Acute effects of warming up on Achilles tendon blood flow and stiffness. J Strength Cond Res 36(10): 2717–2724, 2022—The aim of this study was to investigate the acute effect of frequently used warm-up exercises on the Achilles tendon blood flow and stiffness. In doing so, we want to explore which exercises are suitable to properly prepare the athlete's Achilles tendon in withstanding high amounts of loading during sport activities. This knowledge could help sport physicians and physiotherapists when recommending warm-up exercises that are able to improve sport performance while reducing the injury susceptibility. Achilles tendon blood flow and stiffness measurements of 40 healthy subjects (20 men and 20 women) aged between 18 and 25 years were obtained before and immediately after 4 different warm-up exercises: running, plyometrics, eccentric heel drops, and static stretching. The effect of these warm-up exercises and possible covariates (sex, age, body mass index, rate of perceived exertion, and sports participation) on the Achilles tendon blood flow and stiffness was investigated with linear mixed models. The level of significance was set at α = 0.05. The results of this study showed a significant increase in Achilles tendon blood flow and stiffness after 10 minutes of running (p < 0.001 and p < 0.001) and plyometrics (p < 0.001 and p = 0.039). Static stretching and eccentric exercises elicited no significant changes. From these results, it could be suggested that warm-up exercises should be intensive enough to properly prepare the Achilles tendon for subsequent sport activities. When looking at Achilles tendon blood flow and stiffness, we advise the incorporation of highly intensive exercises such as running and plyometrics within warm-up programs.
Assessment of Internalin A Gene Sequences and Cell Adhesion and Invasion Capacity of Listeria monocytogenes Strains Isolated from Foods of Animal and Related Origins.

Listeria monocytogenes is a foodborne pathogen of global relevance that causes outbreaks and sporadic cases of listeriosis, acquired through the consumption of contaminated products, including milk or meat products and ready-to-eat meat products subjected to intensive handling. The objective of the present study was to classify L. monocytogenes isolated from various food-related sources in the Federal District of Brazil and surrounding areas to sequence internalin A (inlA) genes from these isolates and assess their adhesion and invasion capacity using Caco-2 cells. In addition, 15 were classified as group I, 3 as group II, and 7 classified as group IV. Premature stop codons (PMSCs) at the nucleotide position 976 (GAA→TAA) of the inlA gene were identified in 5 of the 25 isolates. Adhesion and invasion tests in Caco-2 cells showed that all the isolates were capable of adhesion and cellular invasion, with isolates containing PMSCs exhibiting on average higher invasion capacity than those without PMSCs (p = 0.041) and a median of adhesion very distinctive from those without stop codons. These results are the first report of PMSCs in the inlA gene of L. monocytogenes from the Federal District of Brazil and Brazil.
Ligand-Binding-Site Refinement to Generate Reliable Holo Protein Structure Conformations from Apo Structures

The first important step in a structure-based virtual screening is the judicious selection of a receptor protein. In cases where the holo protein receptor structure is unavailable, significant reduction in virtual screening performance has been reported. In this work, we present a robust method to generate reliable holo protein structure conformations from apo structures using molecular dynamics (MD) simulation with restraints derived from holo structure binding-site templates. We perform benchmark tests on two different datasets: 40 structures from a directory of useful decoy-enhanced (DUD-E) and 84 structures from the Gunasekaran dataset. Our results show successful refinement of apo binding-site structures toward holo conformations in 82% of the test cases. In addition, virtual screening performance of 40 DUD-E structures is significantly improved using our MD-refined structures as receptors with an average enrichment factor (EF), an EF1% value of 6.2 compared to apo structures with 3.5. Docking of native ligands to the refined structures shows an average ligand root mean square deviation (RMSD) of 1.97 Å (DUD-E dataset and Gunasekaran dataset) relative to ligands in the holo crystal structures, which is comparable to the self-docking (i.e., docking of the native ligand back to its crystal structure receptor) average, 1.34 Å (DUD-E dataset) and 1.36 Å (Gunasekaran dataset). On the other hand, docking to the apo structures yields an average ligand RMSD of 3.65 Å (DUD-E) and 2.90 Å (Gunasekaran). These results indicate that our method is robust and can be useful to improve virtual screening performance of apo structures.
Dynamics of Fecal Microbiota with and without Invasive Cervical Cancer and Its Application in Early Diagnosis

Simple Summary The fecal microbiome has been suggested to be linked to invasive cervical cancer (ICC). Considering that ICC is common in women, it is important to identify bacterial signatures from fecal microbiota that contribute in classifying cervical cancer. Although previous studies have suggested possible biomarkers based on fecal microbiota, limited information exists in terms of the diagnostic ability using gut microbiota-derived signatures for detecting early ICC. The purpose of this study was to investigate the potential association between early ICC and fecal microbiota and to examine whether fecal microbiota-derived markers can be utilized as a non-invasive tool to diagnose early ICC using machine learning (ML) techniques. Further studies to incorporate quantitative and qualitative characterization of identified individual bacterial genus and validate our model in larger cohorts are imperative in terms of causality for the association between cervical cancer and microbes. Abstract The fecal microbiota is being increasingly implicated in the diagnosis of various diseases. However, evidence on changes in the fecal microbiota in invasive cervical cancer (ICC) remains scarce. Here, we aimed to investigate the fecal microbiota of our cohorts, develop a diagnostic model for predicting early ICC, and identify potential fecal microbiota-derived biomarkers using amplicon sequencing data. We obtained fecal samples from 29 healthy women (HC) and 17 women with clinically confirmed early ICC (CAN). Although Shannon’s diversity index was not reached at statistical significance, the Chao1 and Observed operational taxonomic units (OTUs) in fecal microbiota was significantly different between CAN and HC group. Furthermore, there were significant differences in the taxonomic profiles between HC and CAN; Prevotella was significantly more abundant in the CAN group and Clostridium in the HC group. Linear discriminant analysis effect size (LEfSe) analysis was applied to validate the taxonomic differences at the genus level. Furthermore, we identified a set of seven bacterial genera that were used to construct a machine learning (ML)-based classifier model to distinguish CAN from patients with HC. The model had high diagnostic utility (area under the curve [AUC] = 0.913) for predicting early ICC. Our study provides an initial step toward exploring the fecal microbiota and helps clinicians diagnose.
Dynamical Mechanism of Chemical Mechanical Polishing Analyzed to Correct Preston’s Empirical Model

The dynamical mechanism of chemical mechanical polishing (CMP) is described. The relationships between removal rate and CMP parameters were evaluated by directly measuring the frictional force acting on a wafer under actual CMP conditions. According to the evaluation using various types of slurries, we devised a new relationship to replace Preston's empirical equation by taking into account the dynamic frictional coefficient and the polishing efficiency. The quantitative analysis revealed that the removal rate was proportional to frictional force rather than down force, and the dynamic frictional coefficient and the polishing efficiency remain constant by the change of the down force. The change of removal rate by the sliding speed is varied depending on the kind of slurries. The polishing efficiency tends to be degraded by the increase of the sliding speed, while the dynamic frictional coefficient can either increase or decrease depending on the slurries. This suggests that the CMP mechanism changes by the sliding speed.