Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of C5aR1 and C5L2 Receptors in Ischemia-Reperfusion Injury

The role of C5a receptors (C5aR1 and C5L2) in renal ischemia-reperfusion injury (IRI) is uncertain. We generated an in vitro model of hypoxia/reoxygenation with human proximal tubule epithelial cells to mimic some IRI events. C5aR1, membrane attack complex (MAC) and factor H (FH) deposits were evaluated with immunofluorescence. Quantitative polymerase chain reaction evaluated the expression of C5aR1, C5L2 genes as well as genes related to tubular injury, inflammation, and profibrotic pathways. Additionally, C5aR1 and C5L2 deposits were evaluated in kidney graft biopsies (KB) from transplant patients with delayed graft function (DGF, n = 12) and compared with a control group (n = 8). We observed higher immunofluorescence expression of C5aR1, MAC and FH as higher expression of genes related to tubular injury, inflammatory and profibrotic pathways and of C5aR1 in the hypoxic cells; whereas, C5L2 gene expression was unaffected by the hypoxic stimulus. Regarding KB, C5aR1 was detected in the apical and basal membrane of tubular epithelial cells, whereas C5L2 deposits were observed in endothelial cells of peritubular capillaries (PTC). DGF-KB showed more frequently diffuse C5aR1 staining and C5L2 compared to controls. In conclusion, C5aR1 expression is increased by hypoxia and IRI, both in vitro and in human biopsies with an acute injury. C5L2 expression in PTC could be related to endothelial cell damage during IRI.
Generalized Joint Hypermobility and Injuries: A Prospective Cohort Study of 185 Pre-Professional Contemporary Dancers

Generalized joint hypermobility (GJH) has been mentioned as one of the factors associated with dance injuries, but the findings are inconclusive. This study aims to investigate whether GJH, based on different Beighton score cut-off points, is a potential risk factor for injuries in pre-professional dancers. Four cohorts of first-year pre-professional dancers (N = 185), mean age 19.1 ± 1.3 years, were screened on musculoskeletal functioning at the start of their academic year. The Beighton score was used to measure GJH. During the academic year, the dancers completed monthly questionnaires about their physical and mental health. Based on the Oslo Sports Trauma Research Centre Questionnaire on Health Problems (OSTRC), three injury definitions were used (i.e., all complaints, substantial injury, and time-loss injury). To examine potential risk factors for injuries, univariate and multivariate regression models were applied. The response rate of monthly completed questionnaires was 90%. The overall mean (SD) Beighton score was 2.8. The 1-year injury incidence proportion was 67.6% (n = 125), 43.2% (n = 80), and 54.6% (n = 101) for all complaint injuries, substantial injuries, and time-loss injuries, respectively. The multivariate analyses showed a significant association between a previous long lasting injury in the past year and the three injury definitions (p < 0.05). Pre-professional contemporary dancers are at high risk for injuries and hypermobility. However, these two variables are not associated with each other. Health professionals should take injury history into account when assessing dance students, because this variable is associated with increased injury risk.
BST204 Protects Dexamethasone-Induced Myotube Atrophy through the Upregulation of Myotube Formation and Mitochondrial Function

BST204 is a purified ginseng dry extract that has an inhibitory effect on lipopolysaccharide-induced inflammatory responses, but its effect on muscle atrophy is yet to be investigated. In this study, C2C12 myoblasts were induced to differentiate for three days followed by the treatment of dexamethasone (DEX), a corticosteroid drug, with vehicle or BST204 for one day and subjected to immunoblotting, immunocytochemistry, qRT-PCR and biochemical analysis for mitochondrial function. BST204 alleviates the myotube atrophic effect mediated by DEX via the activation of protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling. Through this pathway, BST204 suppresses the expression of muscle-specific E3 ubiquitin ligases contributing to the enhanced myotube formation and enlarged myotube diameter in DEX-treated myotubes. In addition, BST204 treatment significantly decreases the mitochondrial reactive oxygen species production in DEX-treated myotubes. Furthermore, BST204 improves mitochondrial function by upregulating the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in DEX-induced myotube atrophy. This study provides a mechanistic insight into the effect of BST204 on DEX-induced myotube atrophy, suggesting that BST204 has protective effects against the toxicity of a corticosteroid drug in muscle and promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy.
Traditional and Novel Adiposity Indicators and Pancreatic Cancer Risk: Findings from the UK Women’s Cohort Study

Simple Summary Pancreatic cancer has a poor survival rate and its modifiable risks are poorly understood. We investigated the association between both traditional (BMI, waist and hip circumference and waist–hip ratio) and novel (standard UK clothing sizes) adiposity indicators as predictors of pancreatic cancer risk among women enrolled in the UK women’s cohort study (UKWCS). When adjusted for known confounders like age, education, smoking and physical activity, hip circumference and skirt size were both significant predictors of pancreatic cancer risk in the median follow-up of approximately 19 years. BMI became a significant predictor of pancreatic cancer risk when potential latent cases of pancreatic cancer were excluded from the analysis. Thus, adiposity indicators, specifically hip circumference and standard skirt size, are useful to predict pancreatic cancer among women and should therefore be routinely documented in both national surveys and epidemiological studies. Abstract (1) Background: We studied the association of both conventional (BMI, waist and hip circumference and waist–hip ratio) and novel (UK clothing sizes) obesity indices with pancreatic cancer risk in the UK women’s cohort study (UKWCS). (2) Methods: The UKWCS recruited 35,792 women from England, Wales and Scotland from 1995 to 1998. Cancer diagnosis and death information were obtained from the National Health Service (NHS) Central Register. Cox’s proportional hazards regression was used to evaluate the association between baseline obesity indicators and pancreatic cancer risk. (3) Results: This analysis included 35,364 participants with a median follow-up of 19.3 years. During the 654,566 person-years follow up, there were 136 incident pancreatic cancer cases. After adjustments for age, smoking, education and physical activity, each centimetre increase in hip circumference (HR: 1.03, 95% CI: 1.01–1.05, p = 0.009) and each size increase in skirt size (HR: 1.12, 95% CI: 1.02–1.23, p = 0.041) at baseline increased pancreatic cancer risk. Baseline BMI became a significant predictor of pancreatic cancer risk (HR: 1.04, 95% CI: 1.00–1.08, p = 0.050) when latent pancreatic cancer cases were removed. Only baseline hip circumference was associated with pancreatic cancer risk (HR: 1.03, 95% CI: 1.00–1.05, p = 0.017) when participants with diabetes at baseline were excluded to control for reverse causality. (4) Conclusion: Hip circumference and skirt size were significant predictors of pancreatic cancer risk in the primary analysis. Thus, hip circumference is useful to assess body shape relationships. Additionally, standard skirt sizes offer an economical and objective alternative to conventional obesity indices for evaluating pancreatic cancer risk in women.
A Review: Point Cloud-Based 3D Human Joints Estimation

Joint estimation of the human body is suitable for many fields such as human–computer interaction, autonomous driving, video analysis and virtual reality. Although many depth-based researches have been classified and generalized in previous review or survey papers, the point cloud-based pose estimation of human body is still difficult due to the disorder and rotation invariance of the point cloud. In this review, we summarize the recent development on the point cloud-based pose estimation of the human body. The existing works are divided into three categories based on their working principles, including template-based method, feature-based method and machine learning-based method. Especially, the significant works are highlighted with a detailed introduction to analyze their characteristics and limitations. The widely used datasets in the field are summarized, and quantitative comparisons are provided for the representative methods. Moreover, this review helps further understand the pertinent applications in many frontier research directions. Finally, we conclude the challenges involved and problems to be solved in future researches.
The "CUPID" method for calculating the continuous probability distribution of rotamers from NMR data

We present a new method, ContinUous ProbabIlity Distribution of rotamers (CUPID), for determining the distribution of rotamer probability p(X) about a dihedral angle χ. This method utilizes measured vicinal homonuclear and heteronuclear spin-spin coupling constants (J) and nuclear Overhauser enhancements (NOEs) from NMR spectra and demands no prior assumption about the conformations or the degree of flexibility across the bond
Genetic Predisposition to Myelodysplastic Syndromes: A Challenge for Adult Hematologists

Myelodysplastic syndromes (MDS) arising in the context of inherited bone marrow failure syndromes (IBMFS) differ in terms of prognosis and treatment strategy compared to MDS occurring in the adult population without an inherited genetic predisposition. The main molecular pathways affected in IBMFS involve telomere maintenance, DNA repair, biogenesis of ribosomes, control of proliferation and others. The increased knowledge on the genes involved in MDS pathogenesis and the wider availability of molecular diagnostic assessment have led to an improvement in the detection of IBMFS genetic predisposition in MDS patients. A punctual recognition of these disorders implies a strict surveillance of the patient in order to detect early signs of progression and promptly offer allogeneic hematopoietic stem cell transplantation, which is the only curative treatment. Moreover, identifying an inherited mutation allows the screening and counseling of family members and directs the choice of donors in case of need for transplantation. Here we provide an overview of the most recent data on MDS with genetic predisposition highlighting the main steps of the diagnostic and therapeutic management. In order to highlight the pitfalls of detecting IBMFS in adults, we report the case of a 27-year-old man affected by MDS with an underlying telomeropathy.
Data Stream Processing for Packet-Level Analytics †

One of the most challenging tasks for network operators is implementing accurate per-packet monitoring, looking for signs of performance degradation, security threats, and so on. Upon critical event detection, corrective actions must be taken to keep the network running smoothly. Implementing this mechanism requires the analysis of packet streams in a real-time (or close to) fashion. In a softwarized network context, Stream Processing Systems (SPSs) can be adopted for this purpose. Recent solutions based on traditional SPSs, such as Storm and Flink, can support the definition of general complex queries, but they show poor performance at scale. To handle input data rates in the order of gigabits per seconds, programmable switch platforms are typically used, although they offer limited expressiveness. With the proposed approach, we intend to offer high performance and expressive power in a unified framework by solely relying on SPSs for multicores. Captured packets are translated into a proper tuple format, and network monitoring queries are applied to tuple streams. Packet analysis tasks are expressed as streaming pipelines, running on general-purpose programmable network devices, and a second stage of elaboration can process aggregated statistics from different devices. Experiments carried out with an example monitoring application show that the system is able to handle realistic traffic at a 10 Gb/s speed. The same application scales almost up to 20 Gb/s speed thanks to the simple optimizations of the underlying framework. Hence, the approach proves to be viable and calls for the investigation of more extensive optimizations to support more complex elaborations and higher data rates.
ANT1 Activation and Inhibition Patterns Support the Fatty Acid Cycling Mechanism for Proton Transport

Adenine nucleotide translocase (ANT) is a well-known mitochondrial exchanger of ATP against ADP. In contrast, few studies have shown that ANT also mediates proton transport across the inner mitochondrial membrane. The results of these studies are controversial and lead to different hypotheses about molecular transport mechanisms. We hypothesized that the H+-transport mediated by ANT and uncoupling proteins (UCP) has a similar regulation pattern and can be explained by the fatty acid cycling concept. The reconstitution of purified recombinant ANT1 in the planar lipid bilayers allowed us to measure the membrane current after the direct application of transmembrane potential ΔΨ, which would correspond to the mitochondrial states III and IV. Experimental results reveal that ANT1 does not contribute to a basal proton leak. Instead, it mediates H+ transport only in the presence of long-chain fatty acids (FA), as already known for UCPs. It depends on FA chain length and saturation, implying that FA’s transport is confined to the lipid-protein interface. Purine nucleotides with the preference for ATP and ADP inhibited H+ transport. Specific inhibitors of ATP/ADP transport, carboxyatractyloside or bongkrekic acid, also decreased proton transport. The H+ turnover number was calculated based on ANT1 concentration determined by fluorescence correlation spectroscopy and is equal to 14.6 ± 2.5 s−1. Molecular dynamic simulations revealed a large positively charged area at the protein/lipid interface that might facilitate FA anion’s transport across the membrane. ANT’s dual function—ADP/ATP and H+ transport in the presence of FA—may be important for the regulation of mitochondrial membrane potential and thus for potential-dependent processes in mitochondria. Moreover, the expansion of proton-transport modulating drug targets to ANT1 may improve the therapy of obesity, cancer, steatosis, cardiovascular and neurodegenerative diseases.
Calcium-Alkali Syndrome: Historical Review, Pathophysiology and Post-Modern Update

Milk-alkali syndrome or calcium-alkali syndrome (CAS) is the triad of hypercalcemia, metabolic alkalosis and renal impairment. It is often related to ingestion of high amounts of calcium carbonate, which was used historically for the treatment of peptic ulcer disease. The incidence of the syndrome decreased dramatically after the introduction of newer peptic ulcer medications such as proton pump inhibitors and histamine blocking agents. However, a resurgence was seen in the late 1980s with the wide use of over-the-counter calcium supplements, mainly by females for osteoporosis prophylaxis. The modern version of the syndrome continues to evolve along with medical management. This review focuses on the historical context of CAS, pathogenesis, resurgence of the condition with variable presentations, and contemporary management.
Sodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in Lipopolysaccharide-Induced Neonatal Mice

Background Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms. Methods WT, Nrf2-/- mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested. Results The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2-/- neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs. Conclusion SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.
Development of Novel Inhibitors Targeting the D-Box of the DNA Binding Domain of Androgen Receptor

The inhibition of the androgen receptor (AR) is an established strategy in prostate cancer (PCa) treatment until drug resistance develops either through mutations in the ligand-binding domain (LBD) portion of the receptor or its deletion. We previously identified a druggable pocket on the DNA binding domain (DBD) dimerization surface of the AR and reported several potent inhibitors that effectively disrupted DBD-DBD interactions and consequently demonstrated certain antineoplastic activity. Here we describe further development of small molecule inhibitors of AR DBD dimerization and provide their broad biological characterization. The developed compounds demonstrate improved activity in the mammalian two-hybrid assay, enhanced inhibition of AR-V7 transcriptional activity, and improved microsomal stability. These findings position us for the development of AR inhibitors with entirely novel mechanisms of action that would bypass most forms of PCa treatment resistance, including the truncation of the LBD of the AR.
Granulocyte Colony Stimulating Factor Expression in Breast Cancer and Its Association with Carbonic Anhydrase IX and Immune Checkpoints

Simple Summary Preclinical studies suggest that interactions between granulocyte colony-stimulating factor (G-CSF) and hypoxia-induced carbonic anhydrase IX regulate the trafficking and function of immune cells in the tumour microenvironment. We investigated the clinical significance of this crosstalk by analyzing the protein expression of G-CSF and macrophage markers by immunohistochemistry on a well-characterized tissue microarray series of invasive breast cancers. We report that high expression of G-CSF on breast carcinoma cells is linked with significantly improved survival in an important group of breast cancers that do not respond to hormonal therapy. These tumours were infiltrated by immune cells expressing biomarkers that can be targeted with immune checkpoint inhibitor drugs. In contrast, carbonic anhydrase IX expression was associated with unfavourable outcomes. Abstract Purpose: Granulocyte colony-stimulating factor (G-CSF) and hypoxia modulate the tumour immune microenvironment. In model systems, hypoxia-induced carbonic anhydrase IX (CAIX) has been associated with G-CSF and immune responses, including M2 polarization of macrophages. We investigated whether these associations exist in human breast cancer specimens, their relation to breast cancer subtypes, and clinical outcome. Methods: Using validated protocols and prespecified scoring methodology, G-CSF expression on carcinoma cells and CD163 expression on tumour-associated macrophages were assayed by immunohistochemistry and applied to a tissue microarray series of 2960 primary excision specimens linked to clinicopathologic, biomarker, and outcome data. Results: G-CSFhigh expression showed a significant positive association with ER negativity, HER2 positivity, presence of CD163+ M2 macrophages, and CAIX expression. In univariate analysis, G-CSFhigh phenotype was associated with improved survival in non-luminal cases, although the CAIX+ subset had a significantly adverse prognosis. A significant positive association was observed between immune checkpoint biomarkers on tumour-infiltrating lymphocytes and both G-CSF- and CAIX-expressing carcinoma cells. Immune checkpoint biomarkers correlated significantly with favourable prognosis in G-CSFhigh/non-luminal cases independent of standard clinicopathological features. Conclusions: The prognostic associations linking G-CSF to immune biomarkers and CAIX strongly support their immunomodulatory roles in the tumour microenvironment.
Optically Induced Dielectrophoresis Based Automatic Assembly of Micro/Nano-Devices

Optically induced dielectrophoresis (ODEP) provides a powerful method for parallel manipulation of micro/nano-scale particles with dynamic optical patterns. Until now, few ODEP-related researches has been done for automatic assembly of micro/nano-devices which have a profound effect on the application of nanomaterials. In this paper, an innovative ODEP platform is investigated for automatic and repeatable micro/nano-scale material assembly by integrating image acquisition module, image analysis module, light pattern generation module with micro step motion module. Image analysis module was successfully designed to automatically analyze the images obtained from the image acquisition module and recognize the shape and position of the manipulated objects in the images. The programed light pattern generation module allows for arbitrary and reconfigurable optical patterns based on the recognition results. A high resolution 3D motorized stage upon which the ODEP chip is fixed offers rapid and precise movement of the chip in micro scale. The automatic patterning of polystyrene beads and assembling of multi-walled carbon nanotubes (MWCNTs) into array had been accomplished by the ODEP platform. Experiment results proved that our platform is very effective and shows a promising potential for automatic assembly of micro/nano-devices in wafer-scale requiring massively parallel manipulation.
The Nerves to Conduct a Multiple Sclerosis Crime Investigation

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative autoimmune disease characterized by the aberrant infiltration of immune cells into the central nervous system (CNS) and by the loss of myelin. Sclerotic lesions and various inhibitory factors hamper the remyelination processes within the CNS. MS patients typically experience gradual cognitive and physical disabilities as the disease progresses. The etiology of MS is still unclear and emerging evidence suggests that microbiome composition could play a much more significant role in disease pathogenesis than was initially thought. Initially believed to be isolated to the gut microenvironment, we now know that the microbiome plays a much broader role in various tissues and is essential in the development of the immune system. Here, we present some of the unexpected roles that the microbiome plays in MS and discuss approaches for the development of next-generation treatment strategies.