Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic regulation of newborn telomere length is mediated and modified by DNA methylation

Telomere length at birth determines later life telomere length and potentially predicts ageing-related diseases. However, the genetic and epigenetic settings of telomere length in newborns have not been analyzed. In addition, no study yet has reported how the interplay between genetic variants and genome-wide cytosine methylation explains the variation in early-life telomere length. In this study based on 281 mother-newborn pairs from the ENVIRONAGE birth cohort, telomere length and whole-genome DNA methylation were assessed in cord blood and 26 candidate single nucleotide polymorphism related to ageing or telomere length were genotyped. We identified three genetic variants associated with cord blood telomere length and 57 cis methylation quantitative trait loci (cis-mQTLs) of which 22 mQTLs confirmed previous findings and 35 were newly identified. Five SNPs were found to have significant indirect effects on cord blood telomere length via the mediating CpGs. The association between rs911874 (SOD2) and newborn telomere length was modified by nearby DNA methylation indicated by a significant statistical interaction. Our results suggest that DNA methylation in cis might have a mediation or modification effect on the genetic difference in newborn telomere length. This novel approach warrants future follow-up studies that are needed to further confirm and extend these findings.
Estimating distribution shifts for predicting cross-subject generalization in electroencephalography-based mental workload assessment

Assessment of mental workload in real-world conditions is key to ensuring the performance of workers executing tasks that demand sustained attention. Previous literature has employed electroencephalography (EEG) to this end despite having observed that EEG correlates of mental workload vary across subjects and physical strain, thus making it difficult to devise models capable of simultaneously presenting reliable performance across users. Domain adaptation consists of a set of strategies that aim at allowing for improving machine learning systems performance on unseen data at training time. Such methods, however, might rely on assumptions over the considered data distributions, which typically do not hold for applications of EEG data. Motivated by this observation, in this work we propose a strategy to estimate two types of discrepancies between multiple data distributions, namely marginal and conditional shifts, observed on data collected from different subjects. Besides shedding light on the assumptions that hold for a particular dataset, the estimates of statistical shifts obtained with the proposed approach can be used for investigating other aspects of a machine learning pipeline, such as quantitatively assessing the effectiveness of domain adaptation strategies. In particular, we consider EEG data collected from individuals performing mental tasks while running on a treadmill and pedaling on a stationary bike and explore the effects of different normalization strategies commonly used to mitigate cross-subject variability. We show the effects that different normalization schemes have on statistical shifts and their relationship with the accuracy of mental workload prediction as assessed on unseen participants at training time.
Progressive resistance training for children with cerebral palsy: A randomized controlled trial evaluating the effects on muscle strength and morphology

Children with spastic cerebral palsy often present with muscle weakness, resulting from neural impairments and muscular alterations. While progressive resistance training (PRT) improves muscle weakness, the effects on muscle morphology remain inconclusive. This investigation evaluated the effects of a PRT program on lower limb muscle strength, morphology and gross motor function. Forty-nine children with spastic cerebral palsy were randomized by minimization. The intervention group (nparticipants = 26, age: 8.3 ± 2.0 years, Gross Motor Function Classification System [GMFCS] level I/II/III: 17/5/4, nlegs = 41) received a 12-week PRT program, consisting of 3-4 sessions per week, with exercises performed in 3 sets of 10 repetitions, aiming at 60%–80% of the 1-repetition maximum. Training sessions were performed under supervision with the physiotherapist and at home. The control group (nparticipants = 22, age: 8.5 ± 2.1 year, GMFCS level I/II/III: 14/5/3, nlegs = 36) continued usual care including regular physiotherapy and use of orthotics. We assessed pre- and post-training knee extension, knee flexion and plantar flexion isometric strength, rectus femoris, semitendinosus and medial gastrocnemius muscle morphology, as well as functional strength, gross motor function and walking capacity. Data processing was performed blinded. Linear mixed models were applied to evaluate the difference in evolution over time between the control and intervention group (interaction-effect) and within each group (time-effect). The α-level was set at p = 0.01. Knee flexion strength and unilateral heel raises showed a significant interaction-effect (p ≤ 0.008), with improvements in the intervention group (p ≤ 0.001). Moreover, significant time-effects were seen for knee extension and plantar flexion isometric strength, rectus femoris and medial gastrocnemius MV, sit-to-stand and lateral step-up in the intervention group (p ≤ 0.004). Echo-intensity, muscle lengths and gross motor function showed limited to no changes. PRT improved strength and MV in the intervention group, whereby strength parameters significantly or close to significantly differed from the control group. Although, relative improvements in strength were larger than improvements in MV, important effects were seen on the maintenance of muscle size relative to skeletal growth. In conclusion, this study proved the effectiveness of a home-based, physiotherapy supervised, PRT program to improve isometric and functional muscle strength in children with SCP without negative effects on muscle properties or any serious adverse events. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03863197.
Host community composition, community assembly pattern, and disease transmission mode jointly determine the direction and strength of the diversity-disease relationship

Rapid global biodiversity loss and increasing emerging infectious diseases underscore the significance of identifying the diversity-disease relationship. Although experimental evidence supports the existence of dilution effects in several natural ecosystems, we still know very little about the conditions under which a dilution effect will occur. Using a multi-host Susceptible-Infected-Recovered model, we found when disease transmission was density-dependent, the diversity-disease relationship could exhibit an increasing, decreasing, or non-monotonic trend, which mainly depended on the patterns of community assembly. However, the combined effects of the host competence-abundance relationship and species extinction order may reverse or weaken this trend. In contrast, when disease transmission was frequency-dependent, the diversity-disease relationship only showed a decreasing trend, the host competence-abundance relationship and species extinction order did not alter this decreasing trend, but it could reduce the detectability of the dilution effect and affect disease prevalence. Overall, a combination of disease transmission mode, community assembly pattern, and host community composition determines the direction or strength of the diversity-disease relationship. Our work helps explain why previous studies came to different conclusions about the diversity-disease relationship and provides a deeper understanding of the pathogen transmission dynamics in actual communities.
In vitro selection and optimization of high-affinity aptamer for milk allergen α-lactalbumin and its application in dual-mode detection

Milk is one of the most common sources of protein in people’s daily lives, and it is also recognized by the World Health Organization (WHO) as one of the eight categories of food allergies to human beings. α-lactalbumin (α-La) is the main cause of milk allergy. In this study, a single-stranded DNA aptamer with high binding affinity to α-La were selected using systematic evolution of ligands by exponential enrichment (SELEX) method. Compared with the full-length sequence, the binding affinity of the truncated aptamer LA-1t for α-La was increased six times using fluorescence analysis. Circular dichroism (CD) indicated that the secondary structure of LA-1t contained a typical hairpin structure. Through the docking simulation of LA-1t and α-La, these experimental results were further explained theoretically, and the recognition mechanism was explained. Finally, the colorimetric and fluorescence signal of boron nitride quantum dots anchored to porous CeO2 nanorods (BNQDs/CeO2) were modulated by FAM-labeled LA-1t to achieve highly selective and sensitive determination of α-La. This dual-mode sensing strategy displayed sensitive recognition for α-La in a linear range of 5–4,000 ng/ml with the LOD was 3.32 ng/ml (colorimetry) and 0.71 ng/ml (fluorescence), respectively. Simultaneously, the colorimetry/fluorescence dual-mode sensing strategy was applied for detecting α-La in spiked real samples and demonstrated good stability and reliability.
Elevated expression of cholesterol transporter LRP-1 is crucially implicated in the pathobiology of glioblastoma

Glioblastoma (GBM) is the most common primary malignant brain tumor with a grave prognosis. The present study evaluated the expression of Cholesterol transporter [importer -Lipoprotein Receptor-related Protein-1 (LRP-1) and exporter -ATP-binding cassette transporters-1 (ABCA-1)] in GBM and their implications in tumor-biology, clinical outcome and therapeutic potentials. The mRNA and protein expression was assessed by qRT-PCR and immunohistochemistry, respectively, in 85 GBMs. For comparison, 25 lower-grade astrocytomas (IDH-mutant, grade-2/3) [LGA] 16 cases of high-grade astrocytomas (IDH-mutant, grade-4) [HGA] were also evaluated. In-vitro analysis was performed on U87MG and LN229 glioma cell line. The expression of LRP-1 (mRNA and protein) was significantly higher in GBM than LGA, HGA and normal brain (NB) [p-values 0.007, 0.003 and <0.001 for mRNA; 0.024, <0.001 and <0.001 for immunohistochemistry]. Majority of the GBMs (82.4%) showed strong immunoreactivity for LRP-1, and all tumor cases were positive while the normal brain was negative. LRP-1 immunoreactivity positively correlated with the MIB-1 labeling index (p-value-0.013). LRP-1 knockdown in-vitro was associated with decreased cell survival, proliferation, migration, invasion, and increased apoptosis. Similar effect was also demonstrated by Receptor Associated Protein (RAP), a LRP-1 inhibitory drug. The silencing of LRP-1 was also associated with decreased cholesterol level. The ABCA-1 expression was higher in GBM than LGA and NB (p-value 0.011 and <0.001), however there was no significant association with other parameters. LRP-1 showed a positive correlation with ABCA-1 and associated with decreased expression with LRP-1 knock-down in-vitro. The expression of LRP-1 and ABCA-1 didn't correlate with overall survival in GBMs. Hence, LRP-1 is crucial for the tumor cells' survival and aggressive biological behavior which is maintain through the regulation of high intracellular cholesterol import. Its expression is significantly higher in GBMs and also implicated in the regulation of ABCA-1 expression. Considering its immune-positivity only in the neoplastic cell and strong positivity in GBM it may be a useful adjunct to the diagnosis. For the first time, the present study emphasized its role as a potential therapeutic target in the form of RAP which is presently being used in other neurological diseases under clinical trials.
Cardioprotective potential of the antioxidant-rich bioactive fraction of Garcinia pedunculata Roxb. ex Buch.-Ham. against isoproterenol-induced myocardial infarction in Wistar rats

This Study aimed to characterise the phenolic compounds in Garcinia pedunculata extract and assess their potential antioxidant activity as well as its cardioprotective potential in isoproterenol-induced cardiac hypertrophy in an experimental animal model. In vitro antioxidant properties were determined using DPPH, ABTS, FRAP, PMD assays. In vitro lipid peroxidation experiment was also performed with heart tissues. Cardioprotective and cardiotoxicity effects were determined using the cell line studies. The cardioprotective effect of GP was assessed in a rat model of isoproterenol-(ISO-) induced cardiac hypertrophy by subcutaneous administration. Heart weight/tail length ratio and cardiac hypertrophy indicators were reduced after oral administration of GP. Additionally, GP reduced oxidative stress and heart inflammation brought on by ISO. In H9c2 cells, the antihypertrophic and anti-inflammatory effects of the extract of GP were seen in the presence of ISO, which were further supported by the in vivo observations. This study makes a compelling case for the possibility that supplementing with dried GP fruit can prevent heart hypertrophy by reducing oxidative stress and inflammation.
Acute ethanol-induced liver injury is prevented by betaine administration

Binge drinking is the most common form of excessive alcohol use. Repeated episodes of binge drinking cause multiple organ injuries, including liver damage. We previously demonstrated that chronic ethanol administration causes a decline in the intrahepatic ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). This decline causes impairments in essential methylation reactions that result in alcohol-induced fatty liver (steatosis) and other features of alcohol-associated liver disease (ALD). Co-treatment with betaine during chronic ethanol feeding, normalizes hepatocellular SAM:SAH ratio and alleviates many features of liver damage including steatosis. Here, we sought to examine whether betaine treatment similarly protects against liver injury in an alcohol binge-drinking model. We hypothesized that ethanol binge with prior or simultaneous betaine administration would prevent or attenuate acute alcohol-induced liver damage. Male C57Bl/6 mice were gavaged twice, 12 h apart, with either 6 g ethanol/kg BW or with an equal volume/kg BW of 0.9% NaCl. Two separate groups of mice (n = 5/group) were gavaged with 4 g betaine/kg BW, either 2 h before or simultaneously with the ethanol or saline gavages. All mice were sacrificed 8 h after the last gavage and serum and liver parameters were quantified. Ethanol binges caused a 50% decrease in hepatic SAM:SAH ratio and a >3-fold rise in liver triglycerides (p ≤ 0.05). These latter changes were accompanied by elevated serum AST and ALT activities and blood alcohol concentrations (BAC) that were ∼three-times higher than the legal limit of intoxication in humans. Mice that were treated with betaine 2 h before or simultaneously with the ethanol binges exhibited similar BAC as in mice given ethanol-alone. Both betaine treatments significantly elevated hepatic SAM levels thereby normalizing the SAM:SAH ratio and attenuating hepatic steatosis and other injury parameters, compared with mice given ethanol alone. Simultaneous betaine co-administration with ethanol was more effective in preventing or attenuating liver injury than betaine given before ethanol gavage. Our findings confirm the potential therapeutic value of betaine administration in preventing liver injury after binge drinking in an animal model.
Development and feasibility evaluation of an AR-assisted radiotherapy positioning system

Purpose The aim of this study is to develop an augmented reality (AR)–assisted radiotherapy positioning system based on HoloLens 2 and to evaluate the feasibility and accuracy of this method in the clinical environment. Methods The obtained simulated computed tomography (CT) images of an “ISO cube”, a cube phantom, and an anthropomorphic phantom were reconstructed into three-dimensional models and imported into the HoloLens 2. On the basis of the Vuforia marker attached to the “ISO cube” placed at the isocentric position of the linear accelerator, the correlation between the virtual and real space was established. First, the optimal conditions to minimize the deviation between virtual and real objects were explored under different conditions with a cube phantom. Then, the anthropomorphic phantom–based positioning was tested under the optimal conditions, and the positioning errors were evaluated with cone-beam CT. Results Under the normal light intensity, the registration and tracking angles are 0°, the distance is 40 cm, and the deviation reached a minimum of 1.4 ± 0.3 mm. The program would not run without light. The hologram drift caused by the light change, camera occlusion, and head movement were 0.9 ± 0.7 mm, 1.0 ± 0.6 mm, and 1.5 ± 0.9 mm, respectively. The anthropomorphic phantom–based positioning errors were 3.1 ± 1.9 mm, 2.4 ± 2.5 mm, and 4.6 ± 2.8 mm in the X (lateral), Y (vertical), and Z (longitudinal) axes, respectively, and the angle deviation of Rtn was 0.26 ± 0.14°. Conclusion The AR-assisted radiotherapy positioning based on HoloLens 2 is a feasible method with certain advantages, such as intuitive visual guidance, radiation-free position verification, and intelligent interaction. Hardware and software upgrades are expected to further improve accuracy and meet clinicalbrendaannmae requirements.
Physics-based manifold learning in scaffolds for tissue engineering: Application to inverse problems

In the field of bone regeneration, insertion of scaffolds favours bone formation by triggering the differentiation of mesenchymal cells into osteoblasts. The presence of Calcium ions (Ca 2+) in the interstitial fluid across scaffolds is thought to play a relevant role in the process. In particular, the Ca 2+ patterns can be used as an indicator of where to expect bone formation. In this work, we analyse the inverse problem for these distribution patterns, using an advection-diffusion nonlinear model for the concentration of Ca 2+. That is, given a set of observables which are related to the amount of expected bone formation, we aim at determining the values of the parameters that best fit the data. The problem is solved in a realistic 3D-printed structured scaffold for two uncertain parameters: the amplitude of the velocity of the interstitial fluid and the ionic release rate from the scaffold. The minimization in the inverse problem requires multiple evaluations of the nonlinear model. The computational cost is alleviated by the combination of standard Proper Orthogonal Decomposition (POD), to reduce the number of degrees of freedom, with an adhoc hyper-reduction strategy, which avoids the assembly of a full-order system at every iteration of the Newton’s method. The proposed hyper-reduction method is formulated using the Principal Component Analysis (PCA) decomposition of suitable training sets, devised from the weak form of the problem. In the numerical tests, the hyper-reduced formulation leads to accurate results with a significant reduction of the computational demands with respect to standard POD.
Proteomic and metabolomic studies on chilling injury in peach and nectarine

Peaches and nectarines are temperate climate stone fruits, which should be stored at 0°C to prevent the ripening of these climacteric fruits. However, if stored for too long or if stored at a higher temperature (4 or 5°C), they develop chilling injury. Chilling injury damage includes (1) dry, mealy, wooly (lack of juice) fruits, (2) hard-textured fruits with no juice (leatheriness), (3) flesh browning, and (4) flesh bleeding or internal reddening. There are genetic components to these disorders in that early season fruits are generally more resistant than late season fruits, and white-fleshed fruits are more susceptible to internal browning than yellow-fleshed fruits. A recent review covered the recent research in genomic and transcriptomic studies, and this review examines findings from proteomic and metabolomics studies. Proteomic studies found that the ethylene synthesis proteins are decreased in cold compromised fruits, and this affects the processes initiated by ethylene including cell wall and volatile changes. Enzymes in metabolic pathways were both higher and lower in abundance in CI fruits, an indication of an imbalance in energy production. Stress proteins increased in both fruits with or without CI, but were higher in damaged fruits. Metabolomics showed the role of levels of sugars, sucrose, raffinose, galactinol, and glucose-6-phosphate in protection against chilling injury, along with other membrane stabilizers such as polyamines. Amino acid changes were inconsistent among the studies. Lipid species changes during storage could be correlated with sensitivity or resistance to CI, but more studies are needed.
Maximizing Screening for Cervical Cancer Annals of Gynecologic Cancer

Ann 2021; 4(1): 1005. Abstract Since the introduction of cytology or Pap test (Pap) in 1943, the cervicovaginal Pap has been used as the standard screening test for cervical cancer and its dissemination con tributed to the reduction of incidence and mortality for cer vical cancer worldwide, the incidence of cervical cancer has steadily declined, cases of deaths related to cervical cancer, are reported every year due to false negative results. There -fore, new detection methods have been proposed. Liquid-Based Cytology (LBC) was introduced in 1996 to overcome the limitations of conventional Pap tests. Since then, other methods of LBC have been developed and used, includ ing the High-risk Human Papillomavirus (HPV-hr) test, as a method with greater sensitivity that requires less screening. Cervical cancer can be prevented by early detection and treatment of precancerous lesions that are mainly caused by infection with high-risk strains of the HPV-hr. Screening with Pap and with the use of HPV-hr tests, as an option for women aged 30 to 65, allows prolonged screening intervals. Evidence that evaluates screening programs that involve the HPV-hr Co-testing and HPV-hr test) inform new detection strategies. The evidence supporting the is well established, the HPV-ar test, to the alone, in the detection of provide better protection and allow for greater re evaluation intervals. rates are low in are significant in the the HPV-hr of that risk of is a of to evaluate subsequent management, including rou tine close frequent screening
Pauli equation on noncommutative plane and the Seiberg-Witten map

We study the Pauli equation in noncommutative two dimensional plane which exhibits the supersymmetry algebra when the gyro-magnetic ratio is $2$. The significance of the Seiberg-Witten map in this context is discussed and its effect in the problem is incorporated to all orders in $\theta$. We map the noncommutative problem to an equivalent commutative problem by using a set of generalised Bopp-shift transformations containing a scaling parameter. The energy spectrum of the noncommutative Pauli Hamiltonian is obtained and found to be $\theta$ corrected which is valid to all orders in $\theta$.