Miracle-dz/UniFAR-FTUs huggingface dataset:
Contractile Activity of Myotubes Derived from Human Induced Pluripotent Stem Cells: A Model of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a genetic disorder that results from deficiency of the dystrophin protein. In recent years, DMD pathological models have been created using induced pluripotent stem (iPS) cells derived from DMD patients. In addition, gene therapy using CRISPR-Cas9 technology to repair the dystrophin gene has been proposed as a new treatment method for DMD. However, it is not known whether the contractile function of myotubes derived from gene-repaired iPS cells can be restored. We therefore investigated the maturation of myotubes in electrical pulse stimulation culture and examined the effect of gene repair by observing the contractile behaviour of myotubes. The contraction activity of myotubes derived from dystrophin-gene repaired iPS cells was improved by electrical pulse stimulation culture. The iPS cell method used in this study for evaluating muscle contractile activity is a useful technique for analysing the mechanism of hereditary muscular disease pathogenesis and for evaluating the efficacy of new drugs and gene therapy.
Live Biosensors for Ultrahigh-Throughput Screening of Antimicrobial Activity against Gram-Negative Bacteria

Gram-negative pathogens represent an urgent threat due to their intrinsic and acquired antibiotic resistance. Many recent drug candidates display prominent antimicrobial activity against Gram-positive bacteria being inefficient against Gram-negative pathogens. Ultrahigh-throughput, microfluidics-based screening techniques represent a new paradigm for deep profiling of antibacterial activity and antibiotic discovery. A key stage of this technology is based on single-cell cocultivation of microbiome biodiversity together with reporter fluorescent pathogen in emulsion, followed by the selection of reporter-free droplets using fluorescence-activated cell sorting. Here, a panel of reporter strains of Gram-negative bacteria Escherichia coli was developed to provide live biosensors for precise monitoring of antimicrobial activity. We optimized cell morphology, fluorescent protein, and selected the most efficient promoters for stable, homogeneous, high-level production of green fluorescent protein (GFP) in E. coli. Two alternative strategies based on highly efficient constitutive promoter pJ23119 or T7 promoter leakage enabled sensitive fluorescent detection of bacterial growth and killing. The developed live biosensors were applied for isolating potent E. coli-killing Paenibacillus polymyxa P4 strain by the ultrahigh-throughput screening of soil microbiome. The multi-omics approach revealed antibiotic colistin (polymyxin E) and its biosynthetic gene cluster, mediating antibiotic activity. Live biosensors may be efficiently implemented for antibiotic/probiotic discovery, environmental monitoring, and synthetic biology.
Risk Factors of Forced Take-Off in Dairy Cows Milked Three Times per Day in A Rotary Milking Parlor: A Case Control Study

Simple Summary To remain competitive on the global market in the presence of shrinking profit margins, dairy producers continuously seek to increase the efficiency of their operations. One way to increase the operating efficiency in rotary milking parlors is to enhance the rotational speed of the platform. However, increasing the rotational speed reduces the maximum milking duration that is possible during a single rotation. This can increase the number of cows that have not finished milking and milk remaining in the mammary gland if the milking unit is removed early by means of a forced take-off, a practice that is typical for dairy herds in North America and some European countries. To provide a means for monitoring these cows, we described a protocol for the identification of cows that repeatedly are subjected to a forced take-off (RFTO) at the end of milking. Using this protocol, we then investigated cow characteristics that were associated with RFTO. The associations found suggested that the developed protocol could serve as a useful tool to identify cows at risk of RFTO. Through modification of the case definition, dairy producers will be able to adjust their monitoring protocol according to their individual farm-goals. Abstract The aims of the research were to: (1) describe a protocol for the identification of cows that are subjected repeatedly to a forced retraction event at the end of milking; (2) study risk factors of repeated forced take-off (RFTO); and (3) assess the average milk flow rate at which the forced retraction event occurred. In a retrospective study, we collected milk flow data over a 1-week period from a 4300-cow dairy with a rotary milking parlor and a thrice-daily milking schedule. We identified 109 cases of RFTO and 2467 controls. A multivariable logistic regression model revealed associations of parity, stage of lactation, average daily milk production, and milking speed with RFTO. Cows in parity 3 or greater, animals ≤100 days in milk, high-producing animals, and cows with low milking speed had higher odds of RFTO. The average (least squares means (95% CI)) milk flow rates at the time of removal of the milking unit were 2.1 (2.0–2.1) kg/min in milking observations that were terminated with the forced retract and 1.5 (1.4–1.5) kg/min when milking units were removed with the automatic cluster remover. Future research to better understand the effect of RFTO on milk production, udder health, and animal well-being is warranted.
Analysis of Codon Usage Patterns of Six Sequenced Brachypodium distachyon Lines Reveals a Declining CG Skew of the CDSs from the 5′-ends to the 3′-ends

Brachypodium distachyon, a new monocotyledonous model plant, has received wide attention in biological research due to its small genome and numerous genetic resources. Codon usage bias is an important feature of genes and genomes, and it can be used in transgenic and evolutionary studies. In this study, the nucleotide compositions and patterns of codon usage bias were calculated using Codon W. Additionally, an ENC plot, Parity rule 2 and correspondence analyses were used to explore the major factors influencing codon usage bias patterns. The numbers of hydrogen bonds and skews were used to analyze the GC trend in the 5′-ends of the coding sequences. The results showed that minor differences in the codon usage bias patterns were revealed by the ENC plot, Parity rule 2 and correspondence analyses. The analyses of the CG-skew and the number of hydrogen bonds showed a declining trend in the number of cytosines at the 5′-ends of the CDSs (from the 5′-ends to the 3′-ends), indicating that GC may play a major role in codon usage bias. In addition, our results laid a foundation for the study of codon usage bias patterns in Brachypodium genus and suggested that the GC plays a major role in determining these patterns.
Activity of Two Antimicrobial Peptides against Enterococcus faecalis in a Model of Biofilm-Mediated Endodontic Infection

Enterococcus faecalis is a common cause of biofilm-associated opportunistic infections, which are often difficult to treat. The formation of E. faecalis biofilms on the dentinal walls of the root canal is frequently the cause of endodontic treatment failure and secondary apical periodontitis. In a preliminary work, two recognized antifungal peptides, KP and L18R, showed antibacterial activity against planktonic E. faecalis cells at micromolar concentrations. Moreover, L18R proved to reduce the biomass in the early stage of E. faecalis biofilm development on polystyrene plates, while a qualitative biofilm inhibition was demonstrated on hydroxyapatite disks by confocal laser scanning microscopy (CLSM). The aim of this study was to better characterize the effect of both peptides on E. faecalis biofilm. A reduction in metabolic activity after peptide treatment was detected by Alamar Blue assay, while a remarkable impairment in the architecture of E. faecalis biofilms on hydroxyapatite disks, along with a significant reduction in viable bacteria, was caused mostly by L18R, as assessed by CLSM and scanning electron microscopy. The lack of cytotoxicity of the investigated peptides against L929 murine fibroblasts was also determined. Obtained results suggest L18R as a promising candidate for the development of new strategies for endodontic infection control.
FMRP Levels in Human Peripheral Blood Leukocytes Correlates with Intellectual Disability

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. FXS is an X-linked, neurodevelopmental disorder caused by a CGG trinucleotide repeat expansion in the 5′ untranslated region (UTR) of the Fragile X Mental Retardation gene, FMR1. Greater than 200 CGG repeats results in epigenetic silencing of the gene leading to the deficiency or absence of Fragile X mental retardation protein (FMRP). The loss of FMRP is considered the root cause of FXS. The relationship between neurological function and FMRP expression in peripheral blood mononuclear cells (PBMCs) has not been well established. Assays to detect and measure FMR1 and FMRP have been described; however, none are sufficiently sensitive, precise, or quantitative to properly characterize the relationships between cognitive ability and CGG repeat number, FMR1 mRNA expression, or FMRP expression measured in PBMCs. To address these limitations, two novel immunoassays were developed and optimized, an electro-chemiluminescence immunoassay and a multiparameter flow cytometry assay. Both assays were performed on PMBCs isolated from 27 study participants with FMR1 CGG repeats ranging from normal to full mutation. After correcting for methylation, a significant positive correlation between CGG repeat number and FMR1 mRNA expression levels and a significant negative correlation between FMRP levels and CGG repeat expansion was observed. Importantly, a high positive correlation was observed between intellectual quotient (IQ) and FMRP expression measured in PBMCs.
Prospective Evaluation over 15 Years of Six Breast Cancer Risk Models

Simple Summary Australia has one of the world’s highest breast cancer incidences. For most women who are not classified as at high risk, eligibility and frequency of breast cancer screening in Australia is based solely on their age. Breast cancer risk models can help to optimise early detection and management of breast cancer. We evaluated six commonly used models over 15 years follow-up using an Australian community-based cohort of 7608 women aged 50–65 years. The BOADICEA and IBIS models best discriminated women who were at higher risk of developing breast cancer from those at lower risk, but no model apart from BOADICEA accurately predicted absolute risk across the risk spectrum. The BOADICEA model could be of clinical use for women of similar demography. Abstract Prospective validation of risk models is needed to assess their clinical utility, particularly over the longer term. We evaluated the performance of six commonly used breast cancer risk models (IBIS, BOADICEA, BRCAPRO, BRCAPRO-BCRAT, BCRAT, and iCARE-lit). 15-year risk scores were estimated using lifestyle factors and family history measures from 7608 women in the Melbourne Collaborative Cohort Study who were aged 50–65 years and unaffected at commencement of follow-up two (conducted in 2003–2007), of whom 351 subsequently developed breast cancer. Risk discrimination was assessed using the C-statistic and calibration using the expected/observed number of incident cases across the spectrum of risk by age group (50–54, 55–59, 60–65 years) and family history of breast cancer. C-statistics were higher for BOADICEA (0.59, 95% confidence interval (CI) 0.56–0.62) and IBIS (0.57, 95% CI 0.54–0.61) than the other models (p-difference ≤ 0.04). No model except BOADICEA calibrated well across the spectrum of 15-year risk (p-value < 0.03). The performance of BOADICEA and IBIS was similar across age groups and for women with or without a family history. For middle-aged Australian women, BOADICEA and IBIS had the highest discriminatory accuracy of the six risk models, but apart from BOADICEA, no model was well-calibrated across the risk spectrum.
Prevalence and Risk Factors of Psychiatric Symptoms among Swiss Elite Athletes during the First Lockdown of the COVID-19 Pandemic

The COVID-19 pandemic and the associated first lockdown measures may have had a relevant impact on the mental health of competitive athletes. This study aimed to evaluate the prevalence of various mental health issues in a Swiss elite athletes’ cohort during the first lockdown of the pandemic, and to assess their association with different potential risk factors. Elite athletes from different disciplines were interviewed during the first lockdown in spring 2020 by means of an online questionnaire on symptoms of existing anxieties, depression and sleep disorders, as well as on training circumstances and physical performance before and during the lockdown. Additionally, the economic situation, secondary occupations and current physical health problems were surveyed. A total of 203 (92 female, 111 male) athletes met the inclusion criteria and participated in the survey. Training volume and intensity decreased significantly during lockdown from 3.1 to 2.7 h/day. Financial existential fears increased and were associated with higher training volumes and higher trait anxiety scores. Depressive symptoms and insomnia were present but not exceptionally frequent during the lockdown. Depressive symptoms were associated with higher anxiety scores, higher insomnia severity scores, lower training intensity and worse coping with the measures taken by the authorities against the pandemic. Changes in training and daily habits due to the first lockdown may have affected the mental health of elite athletes. Longitudinal studies should, however, further investigate the long-term effects of the pandemic on mental health.
Nonlinear Associations of the Built Environment with Cycling Frequency among Older Adults in Zhongshan, China

The health and welfare of older adults have raised increasing attention due to global aging. Cycling is a physical activity and mode of transportation to enhance the mobility and quality of life among older adults. Nevertheless, the planning strategies to promote cycling among older adults are underutilized. Therefore, this paper describes the nonlinear associations of the built environment with cycling frequency among older adults. The data were collected from the Zhongshan Household Travel Survey (ZHTS) in 2012. The modeling approach was the eXtreme Gradient Boosting (XGBoost) model. The findings demonstrated that nonlinear relationships exist among all the selected built environment attributes. Within specific intervals, the population density, the land-use mixture, the distance from home to the nearest bus stop, and the distance from home to CBD are positively correlated to the cycling among older adults. Additionally, an inverse “U”-shaped relationship appears in the percentage of green space land use among all land uses. Moreover, the intersection density is inversely related to the cycling frequency among older adults. These findings provide nuanced and appropriate guidance for establishing age-friendly neighborhoods.
Epigallocatechin-3-Gallate Suppresses BMP-6-Mediated SMAD1/5/8 Transactivation of Hepcidin Gene by Inducing SMILE in Hepatocytes

Hepcidin, a major regulator of systemic iron homeostasis, is mainly induced in hepatocytes by activating bone morphogenetic protein 6 (BMP-6) signaling in response to changes in the iron status. Small heterodimer partner-interacting leucine zipper protein (SMILE), a polyphenol-inducible transcriptional co-repressor, regulates hepatic gluconeogenesis and lipogenesis. Here, we examine the epigallocatechin-3-gallate (EGCG) effect on BMP-6-mediated SMAD1/5/8 transactivation of the hepcidin gene. EGCG treatment significantly decreased BMP-6-induced hepcidin gene expression and secretion in hepatocytes, which, in turn, abated ferroportin degradation. SMILE overexpression significantly decreased BMP receptor-induced hepcidin promoter activity. SMILE overexpression also significantly suppressed BMP-6-mediated induction of hepcidin mRNA and its secretion in HepG2 and AML12 cells. EGCG treatment inhibited BMP-6-mediated hepcidin gene expression and secretion, which were significantly reversed by SMILE knockdown in hepatocytes. Interestingly, SMILE physically interacted with SMAD1 in the nucleus and significantly blocked DNA binding of the SMAD complex to the BMP-response element on the hepcidin gene promoter. Taken together, these findings suggest that SMILE is a novel transcriptional repressor of BMP-6-mediated hepcidin gene expression, thus contributing to the control of iron homeostasis.
Heart Rate Variability Reflects Similar Cardiac Autonomic Function in Explosive and Aerobically Trained Athletes

Autonomic cardiac function can be indirectly detected non-invasively by measuring the variation in microtiming of heart beats by a method known as heart rate variability (HRV). Aerobic training for sport is associated with reduced risk for some factors associated with cardiovascular diseases (CVD), but effects on autonomic function in different athlete types are less known. To compare cardiac autonomic modulation using a standard protocol and established CVD risk factors in highly trained intercollegiate athletes competing in aerobic, explosive, and cross-trained sports. A total of 176 college athletes were categorized in distinct sports as explosive (EA), aerobic (AA), or cross-trained (mixed) athletes. Eight different HRV measures obtained at rest were compared across training type and five health factors: systolic (SBP), diastolic blood pressure (DBP), body weight (BW), sex, and race. All athletic types shared favorable HRV measures that correlated with low CVD risk factors and indicated normal sympathovagal balance. A significant correlation was reported between DBP and pNN50 (% RR intervals > 50 ms) (β = −0.214, p = 0.011) and between BW and low-frequency (LF) power (β = 0.205, p = 0.006). Caucasian and African American athletes differed significantly (p < 0.05) with respect to four HRV variables: pNN50, HF power, LF power, and LF/HF ratios. Explosive, aerobic and mixed athletes had similar cardiovascular and autonomic HRV results in all eight HRV parameters measured. All athletes reported LF and pNN50 values that were significantly correlated with two CVD risk factors: DBP and BW. Compared with Caucasian teammates, African American athletes demonstrated lower LF/HF and higher pNN50, indicating an even more favorable resting sympathovagal activity and healthy CV function.
The Federal Menu Labeling Law and Twitter Discussions about Calories in the United States: An Interrupted Time-Series Analysis

Public awareness of calories in food sold in retail establishments is a primary objective of the menu labeling law. This study explores the extent to which we can use social media and internet search queries to understand whether the federal calorie labeling law increased awareness of calories. To evaluate the association of the federal menu labeling law with tweeting about calories we retrieved tweets that contained the term “calorie(s)” from the CompEpi Geo Twitter Database from 1 January through 31 December in 2016 and 2018. Within the same time period, we also retrieved time-series data for search queries related to calories via Google Trends (GT). Interrupted time-series analysis was used to test whether the federal menu labeling law was associated with a change in mentions of “calorie(s)” on Twitter and relative search queries to calories on GT. Before the implementation of the federal calorie labeling law on 7 May 2018, there was a significant decrease in the baseline trend of 4.37 × 10−8 (SE = 1.25 × 10−8, p < 0.001) mean daily ratio of calorie(s) tweets. A significant increase in post-implementation slope of 3.19 × 10−8 (SE = 1.34 × 10−8 , p < 0.018) mean daily ratio of calorie(s) tweets was seen compared to the pre-implementation slope. An interrupted time-series (ITS) analysis showed a small, statistically significant upward trend of 0.0043 (SE = 0.036, p < 0.001) weekly search queries for calories pre-implementation, with no significant level change post-implementation. There was a decrease in trend of 1.22 (SE = 0.27, p < 0.001) in search queries for calories post-implementation. The federal calorie labeling law was associated with a 173% relative increase in the trend of mean daily ratio of tweets and a -28381% relative change in trend for search queries for calories. Twitter results demonstrate an increase in awareness of calories because of the addition of menu labels. Google Trends results imply that fewer people are searching for the calorie content of their meal, which may no longer be needed since calorie information is provided at point of purchase. Given our findings, discussions online about calories may provide a signal of an increased awareness in the implementation of calorie labels.
A Multi-Modal Fusion Method Based on Higher-Order Orthogonal Iteration Decomposition

Multi-modal fusion can achieve better predictions through the amalgamation of information from different modalities. To improve the performance of accuracy, a method based on Higher-order Orthogonal Iteration Decomposition and Projection (HOIDP) is proposed, in the fusion process, higher-order orthogonal iteration decomposition algorithm and factor matrix projection are used to remove redundant information duplicated inter-modal and produce fewer parameters with minimal information loss. The performance of the proposed method is verified by three different multi-modal datasets. The numerical results validate the accuracy of the performance of the proposed method having 0.4% to 4% improvement in sentiment analysis, 0.3% to 8% improvement in personality trait recognition, and 0.2% to 25% improvement in emotion recognition at three different multi-modal datasets compared with other 5 methods.
Associating Land Cover Changes with Patterns of Incidences of Climate-Sensitive Infections: An Example on Tick-Borne Diseases in the Nordic Area

Some of the climate-sensitive infections (CSIs) affecting humans are zoonotic vector-borne diseases, such as Lyme borreliosis (BOR) and tick-borne encephalitis (TBE), mostly linked to various species of ticks as vectors. Due to climate change, the geographical distribution of tick species, their hosts, and the prevalence of pathogens are likely to change. A recent increase in human incidences of these CSIs in the Nordic regions might indicate an expansion of the range of ticks and hosts, with vegetation changes acting as potential predictors linked to habitat suitability. In this paper, we study districts in Fennoscandia and Russia where incidences of BOR and TBE have steadily increased over the 1995–2015 period (defined as ’Well Increasing districts’). This selection is taken as a proxy for increasing the prevalence of tick-borne pathogens due to increased habitat suitability for ticks and hosts, thus simplifying the multiple factors that explain incidence variations. This approach allows vegetation types and strengths of correlation specific to the WI districts to be differentiated and compared with associations found over all districts. Land cover types and their changes found to be associated with increasing human disease incidence are described, indicating zones with potential future higher risk of these diseases. Combining vegetation cover and climate variables in regression models shows the interplay of biotic and abiotic factors linked to CSI incidences and identifies some differences between BOR and TBE. Regression model projections up until 2070 under different climate scenarios depict possible CSI progressions within the studied area and are consistent with the observed changes over the past 20 years.