Miracle-dz/UniFAR-FTUs huggingface dataset:
Biochemical and Immunological implications of Lutein and Zeaxanthin

Throughout history, nature has been acknowledged for being a primordial source of various bioactive molecules in which human macular carotenoids are gaining significant attention. Among 750 natural carotenoids, lutein, zeaxanthin and their oxidative metabolites are selectively accumulated in the macular region of living beings. Due to their vast applications in food, feed, pharmaceutical and nutraceuticals industries, the global market of lutein and zeaxanthin is continuously expanding but chemical synthesis, extraction and purification of these compounds from their natural repertoire e.g., plants, is somewhat costly and technically challenging. In this regard microbial as well as microalgal carotenoids are considered as an attractive alternative to aforementioned challenges. Through the techniques of genetic engineering and gene-editing tools like CRISPR/Cas9, the overproduction of lutein and zeaxanthin in microorganisms can be achieved but the commercial scale applications of such procedures needs to be done. Moreover, these carotenoids are highly unstable and susceptible to thermal and oxidative degradation. Therefore, esterification of these xanthophylls and microencapsulation with appropriate wall materials can increase their shelf-life and enhance their application in food industry. With their potent antioxidant activities, these carotenoids are emerging as molecules of vital importance in chronic degenerative, malignancies and antiviral diseases. Therefore, more research needs to be done to further expand the applications of lutein and zeaxanthin.
Micro- and Macroscale Assessment of Posterior Cruciate Ligament Functionality Based on Advanced MRI Techniques

T2 mapping assesses tissue ultrastructure and composition, yet the association of imaging features and tissue functionality is oftentimes unclear. This study aimed to elucidate this association for the posterior cruciate ligament (PCL) across the micro- and macroscale and as a function of loading. Ten human cadaveric knee joints were imaged using a clinical 3.0T scanner and high-resolution morphologic and T2 mapping sequences. Emulating the posterior drawer test, the joints were imaged in the unloaded (δ0) and loaded (δ1) configurations. For the entire PCL, its subregions, and its osseous insertion sites, loading-induced changes were parameterized as summary statistics and texture variables, i.e., entropy, homogeneity, contrast, and variance. Histology confirmed structural integrity. Statistical analysis was based on parametric and non-parametric tests. Mean PCL length (37.8 ± 1.8 mm [δ0]; 44.0 ± 1.6 mm [δ1] [p < 0.01]), mean T2 (35.5 ± 2.0 ms [δ0]; 37.9 ± 1.3 ms [δ1] [p = 0.01]), and mean contrast values (4.0 ± 0.6 [δ0]; 4.9 ± 0.9 [δ1] [p = 0.01]) increased significantly under loading. Other texture features or ligamentous, osseous, and meniscal structures remained unaltered. Beyond providing normative T2 values across various scales and configurations, this study suggests that ligaments can be imaged morphologically and functionally based on joint loading and advanced MRI acquisition and post-processing techniques to assess ligament integrity and functionality in variable diagnostic contexts.
Pancreatic Neuroendocrine Tumors: Molecular Mechanisms and Therapeutic Targets

Simple Summary Pancreatic neuroendocrine tumors (pNETs) are rare, indolent cancers whose causation is only partly understood. An increasing number of studies have uncovered molecular changes associated with pNETs, helping to identify common disease mechanisms. This knowledge has guided current pNET therapies that can effectively slow progression of the disease. However, tumors often become resistant to available therapies, necessitating a deeper understanding of mechanisms driving disease progression in order to develop new treatments. Here, we provide a comprehensive review of pNET-associated molecular alterations and existing pNET models to illustrate potential areas for advancement in research and therapy. Abstract Pancreatic neuroendocrine tumors (pNETs) are unique, slow-growing malignancies whose molecular pathogenesis is incompletely understood. With rising incidence of pNETs over the last four decades, larger and more comprehensive ‘omic’ analyses of patient tumors have led to a clearer picture of the pNET genomic landscape and transcriptional profiles for both primary and metastatic lesions. In pNET patients with advanced disease, those insights have guided the use of targeted therapies that inhibit activated mTOR and receptor tyrosine kinase (RTK) pathways or stimulate somatostatin receptor signaling. Such treatments have significantly benefited patients, but intrinsic or acquired drug resistance in the tumors remains a major problem that leaves few to no effective treatment options for advanced cases. This demands a better understanding of essential molecular and biological events underlying pNET growth, metastasis, and drug resistance. This review examines the known molecular alterations associated with pNET pathogenesis, identifying which changes may be drivers of the disease and, as such, relevant therapeutic targets. We also highlight areas that warrant further investigation at the biological level and discuss available model systems for pNET research. The paucity of pNET models has hampered research efforts over the years, although recently developed cell line, animal, patient-derived xenograft, and patient-derived organoid models have significantly expanded the available platforms for pNET investigations. Advancements in pNET research and understanding are expected to guide improved patient treatments.
Use of Alternative Gelling Agents Reveals the Role of Rhamnolipids in Pseudomonas aeruginosa Surface Motility

Pseudomonas aeruginosa is a motile bacterium able to exhibit a social surface behaviour known as swarming motility. Swarming requires the polar flagellum of P. aeruginosa as well as the secretion of wetting agents to ease the spread across the surface. However, our knowledge on swarming is limited to observed phenotypes on agar-solidified media. To study the surface behaviour and the impact of wetting agents of P. aeruginosa on other surfaces, we assessed surface motility capabilities of the prototypical strain PA14 on semi-solid media solidified with alternative gelling agents, gellan gum and carrageenan. We found that, on these alternative surfaces, the characteristic dendritic spreading pattern of P. aeruginosa is drastically altered. One striking feature is the loss of dependence on rhamnolipids to spread effectively on plates solidified with these alternative gelling agents. Indeed, a rhlA-null mutant unable to produce its wetting agents still spreads effectively, albeit in a circular shape on both the gellan gum- and carrageenan-based media. Our data indicate that rhamnolipids do not have such a crucial role in achieving surface colonization of non-agar plates, suggesting a strong dependence on the physical properties of the tested surface. The use of alternative gelling agent provides new means to reveal unknown features of bacterial surface behaviour.
The Role of Human Satellite III (1q12) Copy Number Variation in the Adaptive Response during Aging, Stress, and Pathology: A Pendulum Model

The pericentric satellite III (SatIII or Sat3) and II tandem repeats recently appeared to be transcribed under stress conditions, and the transcripts were shown to play an essential role in the universal stress response. In this paper, we review the role of human-specific SatIII copy number variation (CNV) in normal stress response, aging and pathology, with a focus on 1q12 loci. We postulate a close link between transcription of SatII/III repeats and their CNV. The accrued body of data suggests a hypothetical universal mechanism, which provides for SatIII copy gain during the stress response, alongside with another, more hypothetical reverse mechanism that might reduce the mean SatIII copy number, likely via the selection of cells with excessively large 1q12 loci. Both mechanisms, working alternatively like swings of the pendulum, may ensure the balance of SatIII copy numbers and optimum stress resistance. This model is verified on the most recent data on SatIII CNV in pathology and therapy, aging, senescence and response to genotoxic stress in vitro.
SIRT3 and Metabolic Reprogramming Mediate the Antiproliferative Effects of Whey in Human Colon Cancer Cells

Simple Summary Colorectal cancer (CRC) is the second leading cause of cancer-related deaths and the most frequently diagnosed cancer type. CRC risk can be preventable by modifiable risk factors, including diet. This study provides evidence on the antiproliferative and pro-apoptotic effects of whey from Mediterranean water buffalo (Bubalus bubalis) milk in HT-29, HCT 116, LoVo, and SW480 cells. Results showed that whey induced metabolic dysfunctions and modulated the bioenergetic signature of CRC cells by targeting SIRT3 expression. These findings unveil the anti-neoplastic effects of whey and pave the way for the use of this by-product, rich in bioactive nutrients, in the setting of novel prevention strategies to reduce the risk of CRC. Abstract Emerging strategies to improve healthy aging include dietary interventions as a tool to promote health benefits and reduce the incidence of aging-related comorbidities. The health benefits of milk are also linked to its richness in betaines and short-chain acylcarnitines, which act synergistically in conferring anticancer, anti-inflammatory, and antioxidant properties. Whey, despite being a dairy by-product, still has a considerable content of bioactive betaines and acylcarnitines. Here, we investigated the anticancer properties of whey from Mediterranean water buffalo (Bubalus bubalis) milk by testing its antiproliferative effects in colorectal cancer (CRC) cells HT-29, HCT 116, LoVo and SW480. Results indicated that treatment with whey for 72 h inhibited cell proliferation (p < 0.001), induced cell cycle arrest, and apoptosis via caspase-3 activation, and modulated cell metabolism by limiting glucose uptake and interfering with mitochondrial energy metabolism with the highest effects observed in HT-29 and HCT 116 cells. At molecular level, these effects were accompanied by upregulation of sirtuin 3 (SIRT3) (p < 0.01) and peroxisome proliferator-activated receptor (PPAR)-γ expression (p < 0.001), and downregulation of lactate dehydrogenase A (LDHA) (p < 0.01), sterol regulatory-element binding protein 1 (SREBP1) (p < 0.05), and PPAR-α (p < 0.01). Transient SIRT3 gene silencing blocked the effects of whey on the LDHA, PPAR-γ, and PPAR-α protein expressions (p < 0.01) suggesting that the whey capacity of perturbating the metabolic homeostasis in CRC cell lines is mediated by SIRT3.
Changes of Neural Pathways after Vojta Approach in a Child with Developmental Delay

The development of motor function is related to the development of neural pathways in the white matter. Children with developmental delay (DD) and hypotonia have reduced motor function, and their neural pathways are observed differently from those of typically developed children. We investigated changes in neural pathways through diffusion tensor imaging (DTI) after utilizing the Vojta approach. The participant was a child with DD and hypotonia, and had delayed motor function. Although he had no brain damage on magnetic resonance imaging findings, damage to the neural pathway was confirmed through DTI due to cytomegalovirus infection in the mother’s womb. From 11 months of age, the Vojta approach was performed for a total of 8 months. In this study, we found that in CST, the left FA and right TV increased in follow-up DTI more than in the initial DTI. In CRP, Wallerian degeneration was observed in the left FA, MD, and TV in follow-up DTI. GMFM-88 improved after intervention. The structural change of neural pathways through the Vojta approach influenced the improvement of gross motor function. Therefore, it is thought that the Vojta approach can be suggested as a meaningful intervention for children with DD and hypotonia.
A Novel Factor Graph and Cubature Kalman Filter Integrated Algorithm for Single-Transponder-Aided Cooperative Localization

Cooperative localization (CL) of underwater multi-AUVs is vital for numerous underwater operations. Single-transponder-aided cooperative localization (STCL) is regarded as a promising scheme for multi-AUVs CL, benefiting from the fact that an accurate reference is adopted. To improve the positioning accuracy and robustness of STCL, a novel Factor Graph and Cubature Kalman Filter (FGCKF)-integrated algorithm is proposed in this paper. In the proposed FGCKF, historical information can be efficiently used in measurement updating to overcome uncertain observation environments, which greatly helps to improve the performance of filtering progress. Furthermore, Adaptive CKF, sum product, and Maximum Correntropy Criterion (MCC) methods are designed to deal with outliers of acoustic transmission delay, sound velocity, and motion velocity, respectively. Simulations and experiments are conducted, and it is verified that the proposed FGCKF algorithm can improve positioning accuracy and robustness greatly than traditional filtering methods.
Systematic Review of RCTs Assessing the Effectiveness of mHealth Interventions to Improve Statin Medication Adherence: Using the Behaviour-Change Technique Taxonomy to Identify the Techniques That Improve Adherence

Statin non-adherence is a common problem in the management of cardiovascular disease (CVD), increasing patient morbidity and mortality. Mobile health (mHealth) interventions may be a scalable way to improve medication adherence. The objectives of this review were to assess the literature testing mHealth interventions for statin adherence and to identify the Behaviour-Change Techniques (BCTs) employed by effective and ineffective interventions. A systematic search was conducted of randomised controlled trials (RCTs) measuring the effectiveness of mHealth interventions to improve statin adherence against standard of care in those who had been prescribed statins for the primary or secondary prevention of CVD, published in English (1 January 2000–17 July 2020). For included studies, relevant data were extracted, the BCTs used in the trial arms were coded, and a quality assessment made using the Risk of Bias 2 (RoB2) questionnaire. The search identified 17 relevant studies. Twelve studies demonstrated a significant improvement in adherence in the mHealth intervention trial arm, and five reported no impact on adherence. Automated phone messages were the mHealth delivery method most frequently used in effective interventions. Studies including more BCTs were more effective. The BCTs most frequently associated with effective interventions were “Goal setting (behaviour)”, “Instruction on how to perform a behaviour”, and “Credible source”. Other effective techniques were “Information about health consequences”, “Feedback on behaviour”, and “Social support (unspecified)”. This review found moderate, positive evidence of the effect of mHealth interventions on statin adherence. There are four primary recommendations for practitioners using mHealth interventions to improve statin adherence: use multifaceted interventions using multiple BCTs, consider automated messages as a digital delivery method from a credible source, provide instructions on taking statins, and set adherence goals with patients. Further research should assess the optimal frequency of intervention delivery and investigate the generalisability of these interventions across settings and demographics.
A Scoping Review on Minimum Foot Clearance Measurement: Sensing Modalities

Background: Falls are a major public health issue and tripping is the most common self-reported cause of outdoor falls. Minimum foot clearance (MFC) is a key parameter for identifying the probability of tripping. Optical motion capture systems are commonly used to measure MFC values; however, there is a need to identify alternative modalities that are better suited to collecting data in real-world settings. Objective: This is the first of a two-part scoping review. The objective of this paper is to identify and evaluate alternative measurement modalities to optical motion capture systems for measuring level-ground MFC. A companion paper identifies conditions that impact MFC and the range of MFC values individuals that these conditions exhibit. Methods: We searched four electronic databases, where peer-reviewed journals and conference papers reporting level-ground MFC characteristics were identified. The papers were screened by two independent reviewers for inclusion. The reporting was done in keeping with the PRISMA-ScR reporting guidelines. Results: From an initial search of 1571 papers, 17 papers were included in this paper. The identified technologies were inertial measurement units (IMUs) (n = 10), ultrasonic sensors (n = 2), infrared sensors (IR) (n = 2), optical proximity sensors (OPS) (n = 1), laser ranging sensors (n = 1), and ultra-wideband sensors (n = 1). From the papers, we extracted the sensor type, the analysis methods, the properties of the proposed system, and its accuracy and validation methods. Conclusions: The two most commonly used alternative modalities were IMUs and OPS. There was a lack of standardization among studies utilizing the same measurement modalities, as well as discrepancies in the methods used to assess performance. We provide a list of recommendations for future work to allow for more meaningful comparison between modalities as well as future research directions.
7-Epitaxol Induces Apoptosis and Autophagy in Head and Neck Squamous Cell Carcinoma through Inhibition of the ERK Pathway

As the main derivative of paclitaxel, 7-Epitaxol is known to a have higher stability and cytotoxicity. However, the anticancer effect of 7-Epitaxol is still unclear. The purpose of this study was to explore the anticancer effects of 7-Epitaxol in squamous cell carcinoma of the head and neck (HNSCC). Our study findings revealed that 7-Epitaxol potently suppressed cell viability in SCC-9 and SCC-47 cells by inducing cell cycle arrest. Flow cytometry and DAPI staining demonstrated that 7-Epitaxol treatment induced cell death, mitochondrial membrane potential and chromatin condensation in OSCC cell lines. The compound regulated the proteins of extrinsic and intrinsic pathways at the highest concentration, and also increased the activation of caspases 3, 8, 9, and PARP in OSCC cell lines. Interestingly, a 7-Epitaxol-mediated induction of LC3-I/II expression and suppression of p62 expression were observed in OSCC cells lines. Furthermore, the MAPK inhibitors indicated that 7-Epitaxol induces apoptosis and autophagy marker proteins (cleaved-PARP and LC3-I/II) by reducing the phosphorylation of ERK1/2. In conclusion, these findings indicate the involvement of 7-Epitaxol in inducing apoptosis and autophagy through ERK1/2 signaling pathway, which identify 7-Epitaxol as a potent cytotoxic agent in HNSCC.
Recent Advances in Portable and Handheld NIR Spectrometers and Applications in Milk, Cheese and Dairy Powders

Quality and safety monitoring in the dairy industry is required to ensure products meet a high-standard based on legislation and customer requirements. The need for non-destructive, low-cost and user-friendly process analytical technologies, targeted at operators (as the end-users) for routine product inspections is increasing. In recent years, the development and advances in sensing technologies have led to miniaturisation of near infrared (NIR) spectrometers to a new era. The new generation of miniaturised NIR analysers are designed as compact, small and lightweight devices with a low cost, providing a strong capability for on-site or on-farm product measurements. Applying portable and handheld NIR spectrometers in the dairy sector is increasing; however, little information is currently available on these applications and instrument performance. As a result, this review focuses on recent developments of handheld and portable NIR devices and its latest applications in the field of dairy, including chemical composition, on-site quality detection, and safety assurance (i.e., adulteration) in milk, cheese and dairy powders. Comparison of model performance between handheld and bench-top NIR spectrometers is also given. Lastly, challenges of current handheld/portable devices and future trends on implementing these devices in the dairy sector is discussed.
Potential Implications of Mammalian Transient Receptor Potential Melastatin 7 in the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review

The transient receptor potential (TRP) superfamily of ion channels is involved in the molecular mechanisms that mediate neuroimmune interactions and activities. Recent advancements in neuroimmunology have identified a role for TRP cation channels in several neuroimmune disorders including amyotropic lateral sclerosis, multiple sclerosis, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating disorder with an obscure aetiology, hence considerable examination of its pathobiology is warranted. Dysregulation of TRP melastatin (TRPM) subfamily members and calcium signalling processes are implicated in the neurological, immunological, cardiovascular, and metabolic impairments inherent in ME/CFS. In this review, we present TRPM7 as a potential candidate in the pathomechanism of ME/CFS, as TRPM7 is increasingly recognized as a key mediator of physiological and pathophysiological mechanisms affecting neurological, immunological, cardiovascular, and metabolic processes. A focused examination of the biochemistry of TRPM7, the role of this protein in the aforementioned systems, and the potential of TRPM7 as a molecular mechanism in the pathophysiology of ME/CFS will be discussed in this review. TRPM7 is a compelling candidate to examine in the pathobiology of ME/CFS as TRPM7 fulfils several key roles in multiple organ systems, and there is a paucity of literature reporting on its role in ME/CFS.