Miracle-dz/UniFAR-FTUs huggingface dataset:
The Glymphatic System (En)during Inflammation

The glymphatic system is a fluid-transport system that accesses all regions of the brain. It facilitates the exchange of cerebrospinal fluid and interstitial fluid and clears waste from the metabolically active brain. Astrocytic endfeet and their dense expression of the aquaporin-4 water channels promote fluid exchange between the perivascular spaces and the neuropil. Cerebrospinal and interstitial fluids are together transported back to the vascular compartment by meningeal and cervical lymphatic vessels. Multiple lines of work show that neurological diseases in general impair glymphatic fluid transport. Insofar as the glymphatic system plays a pseudo-lymphatic role in the central nervous system, it is poised to play a role in neuroinflammation. In this review, we discuss how the association of the glymphatic system with the meningeal lymphatic vessel calls for a renewal of established concepts on the CNS as an immune-privileged site. We also discuss potential approaches to target the glymphatic system to combat neuroinflammation.
Butyrate Feeding Reverses CypD-Related Mitoflash Phenotypes in Mouse Myofibers

Mitoflashes are spontaneous transients of the biosensor mt-cpYFP. In cardiomyocytes, mitoflashes are associated with the cyclophilin D (CypD) mediated opening of mitochondrial permeability transition pore (mPTP), while in skeletal muscle they are considered hallmarks of mitochondrial respiration burst under physiological conditions. Here, we evaluated the potential association between mitoflashes and the mPTP opening at different CypD levels and phosphorylation status by generating three CypD derived fusion constructs with a red shifted, pH stable Ca2+ sensor jRCaMP1b. We observed perinuclear mitochondrial Ca2+ efflux accompanying mitoflashes in CypD and CypDS42A (a phosphor-resistant mutation at Serine 42) overexpressed myofibers but not the control myofibers expressing the mitochondria-targeting sequence of CypD (CypDN30). Assisted by a newly developed analysis program, we identified shorter, more frequent mitoflash activities occurring over larger areas in CypD and CypDS42A overexpressed myofibers than the control CypDN30 myofibers. These observations provide an association between the elevated CypD expression and increased mitoflash activities in hindlimb muscles in an amyotrophic lateral sclerosis (ALS) mouse model previously observed. More importantly, feeding the mice with sodium butyrate reversed the CypD-associated mitoflash phenotypes and protected against ectopic upregulation of CypD, unveiling a novel molecular mechanism underlying butyrate mediated alleviation of ALS progression in the mouse model.
The Role of PI3K/AKT and MAPK Signaling Pathways in Erythropoietin Signalization

Erythropoietin (EPO) is a glycoprotein cytokine known for its pleiotropic effects on various types of cells and tissues. EPO and its receptor EPOR trigger signaling cascades JAK2/STAT5, MAPK, and PI3K/AKT that are interconnected and irreplaceable for cell survival. In this article, we describe the role of the MAPK and PI3K/AKT signaling pathways during red blood cell formation as well as in non-hematopoietic tissues and tumor cells. Although the central framework of these pathways is similar for most of cell types, there are some stage-specific, tissue, and cell-lineage differences. We summarize the current state of research in this field, highlight the novel members of EPO-induced PI3K and MAPK signaling, and in this respect also the differences between erythroid and non-erythroid cells.
Deciphering the mechanism by which the yeast Phaffia rhodozyma responds adaptively to environmental, nutritional, and genetic cues

Abstract Phaffia rhodozyma is a basidiomycetous yeast that synthesizes astaxanthin (ASX), which is a powerful and highly valuable antioxidant carotenoid pigment. P. rhodozyma cells accrue ASX and gain an intense red-pink coloration when faced with stressful conditions such as nutrient limitations (e.g., nitrogen or copper), the presence of toxic substances (e.g., antimycin A), or are affected by mutations in the genes that are involved in nitrogen metabolism or respiration. Since cellular accrual of ASX occurs under a wide variety of conditions, this yeast represents a valuable model for studying the growth conditions that entail oxidative stress for yeast cells. Recently, we proposed that ASX synthesis can be largely induced by conditions that lead to reduction–oxidation (redox) imbalances, particularly the state of the NADH/NAD+ couple together with an oxidative environment. In this work, we review the multiple known conditions that elicit ASX synthesis expanding on the data that we formerly examined. When considered alongside the Mitchell's chemiosmotic hypothesis, the study served to rationalize the induction of ASX synthesis and other adaptive cellular processes under a much broader set of conditions. Our aim was to propose an underlying mechanism that explains how a broad range of divergent conditions converge to induce ASX synthesis in P. rhodozyma. The mechanism that links the induction of ASX synthesis with the occurrence of NADH/NAD+ imbalances may help in understanding how other organisms detect any of a broad array of stimuli or gene mutations, and then adaptively respond to activate numerous compensatory cellular processes.
Medicolegal Causation Investigation of Bacterial Endocarditis Associated with an Oral Surgery Practice Using the INFERENCE Approach

Investigating causation is a primary goal in forensic/legal medicine, aiming to establish the connection between an unlawful/negligent act and an adverse outcome. In malpractice litigation involving a healthcare-associated infection due to a failure of infection prevention and control practices, the medicolegal causal analysis needs to quantify the individual causal probabilities to meet the evidentiary requirements of the court. In this paper, we present the investigation of the most probable cause of bacterial endocarditis in a patient who underwent an invasive procedure at a dental/oral surgical practice where an outbreak of bacterial endocarditis had already been identified by the state Department of Health. We assessed the probability that the patient’s endocarditis was part of the outbreak versus that it was an unrelated sporadic infection using the INFERENCE (Integration of Forensic Epidemiology and the Rigorous Evaluation of Causation Elements) approach to medicolegal causation analysis. This paper describes the step-by-step application of the INFERENCE approach to demonstrate its utility in quantifying the probability of causation. The use of INFERENCE provides the court with an evidence-based, transparent, and reliable guide to determine liability, causation, and damages.
An Approximation for Metal-Oxide Sensor Calibration for Air Quality Monitoring Using Multivariable Statistical Analysis

Good air quality is essential for both human beings and the environment in general. The three most harmful air pollutants are nitrogen dioxide (NO2), ozone (O3) and particulate matter. Due to the high cost of monitoring stations, few examples of this type of infrastructure exist, and the use of low-cost sensors could help in air quality monitoring. The cost of metal-oxide sensors (MOS) is usually below EUR 10 and they maintain small dimensions, but their use in air quality monitoring is only valid through an exhaustive calibration process and subsequent precision analysis. We present an on-field calibration technique, based on the least squares method, to fit regression models for low-cost MOS sensors, one that has two main advantages: it can be easily applied by non-expert operators, and it can be used even with only a small amount of calibration data. In addition, the proposed method is adaptive, and the calibration can be refined as more data becomes available. We apply and evaluate the technique with a real dataset from a particular area in the south of Spain (Granada city). The evaluation results show that, despite the simplicity of the technique and the low quantity of data, the accuracy obtained with the low-cost MOS sensors is high enough to be used for air quality monitoring.
Microstructure Evolution during Hot Deformation of UNS S32750 Super-Duplex Stainless Steel Alloy

The present paper analyzes UNS S32750 Super-Duplex Stainless Steel hot deformation behavior during processing by upsetting. The objective of this paper is to determine the optimum range of deformation temperatures, considering that both austenite and ferrite have different deformation behaviors due to their different morphology, physical, and mechanical properties. Because the capability of plastic deformation accommodation of ferrite is reduced when compared to austenite, side cracks and fissures can form during the hot deformation process. Consequently, it is important to find the optimum conditions of deformation of this type of stainless steel to establish the best processing parameters without deteriorating the material. The experimental program involved the application of hot deformation by the upsetting method on a series of samples between 1000 °C and 1275 °C, with a total degree of deformation of 30%. The resultant samples were examined by SEM-EBSD to establish and analyze the evolution of the phases present in the structure from several points of view: nature, distribution, morphology (size and shape), and their structural homogeneity. The GROD (Grain Reference Orientation Deviation) distribution map was also determined while taking into account the possible precipitation of the secondary austenite phase (γ2-phase) and the analysis of the dynamic recrystallization process according to the applied deformation temperature. The main conclusion was that UNS S32750 SDSS steel can be safely deformed by upsetting between 1050–1275 °C, with an experimented total degree of deformation of 30%.
Efficient and Consumer-Centered Item Detection and Classification with a Multicamera Network at High Ranges

In the EU project SHAREWORK, methods are developed that allow humans and robots to collaborate in an industrial environment. One of the major contributions is a framework for task planning coupled with automated item detection and localization. In this work, we present the methods used for detecting and classifying items on the shop floor. Important in the context of SHAREWORK is the user-friendliness of the methodology. Thus, we renounce heavy-learning-based methods in favor of unsupervised segmentation coupled with lenient machine learning methods for classification. Our algorithm is a combination of established methods adjusted for fast and reliable item detection at high ranges of up to eight meters. In this work, we present the full pipeline from calibration, over segmentation to item classification in the industrial context. The pipeline is validated on a shop floor of 40 sqm and with up to nine different items and assemblies, reaching a mean accuracy of 84% at 0.85 Hz.
Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies

Retinoic acid (RA) agents possess anti-tumor activity through their ability to induce cellular differentiation. However, retinoids have not yet been translated into effective systemic treatments for most solid tumors. RA signaling is mediated by the following two nuclear retinoic receptor subtypes: the retinoic acid receptor (RAR) and the retinoic X receptor (RXR), and their isoforms. The identification of mutations in retinoid receptors and other RA signaling pathway genes in human cancers offers opportunities for target discovery, drug design, and personalized medicine for distinct molecular retinoid subtypes. For example, chromosomal translocation involving RARA occurs in acute promyelocytic leukemia (APL), and all-trans retinoic acid (ATRA) is a highly effective and even curative therapeutic for APL patients. Thus, retinoid-based target discovery presents an important line of attack toward designing new, more effective strategies for treating other cancer types. Here, we review retinoid signaling, provide an update on retinoid agents and the current clinical research on retinoids in cancer, and discuss how the retinoid pathway genotype affects the ability of retinoid agents to inhibit the growth of colorectal cancer (CRC) cells. We also deliberate on why retinoid agents have not shown clinical efficacy against solid tumors and discuss alternative strategies that could overcome the lack of efficacy.
Adoptive cellular therapy in solid tumor malignancies: review of the literature and challenges ahead

While immune checkpoint inhibitors (ICIs) have ushered in major changes in standards of care for many solid tumor malignancies, primary and acquired resistance is common. Insufficient antitumor T cells, inadequate function of these cells, and impaired formation of memory T cells all contribute to resistance mechanisms to ICI. Adoptive cellular therapy (ACT) is a form of immunotherapy that is rapidly growing in clinical investigation and has the potential to overcome these limitations by its ability to augment the number, specificity, and reactivity of T cells against tumor tissue. ACT has revolutionized the treatment of hematologic malignancies, though the use of ACT in solid tumor malignancies is still in its early stages. There are currently three major modalities of ACT: tumor-infiltrating lymphocytes (TILs), genetically engineered T-cell receptors (TCRs), and chimeric antigen receptor (CAR) T cells. TIL therapy involves expansion of a heterogeneous population of endogenous T cells found in a harvested tumor, while TCRs and CAR T cells involve expansion of a genetically engineered T-cell directed toward specific antigen targets. In this review, we explore the potential of ACT as a treatment modality against solid tumors, discuss their advantages and limitations against solid tumor malignancies, discuss the promising therapies under active investigation, and examine future directions for this rapidly growing field.
Characterization, Spatial Variation and Management Strategy of Sewer Sediments Collected from Combined Sewer System: A Case Study in Longgang District, Shenzhen

In the urban drainage system, the formation of sewer sediments is inevitable, and the removal of sewer sediments is necessary for system maintenance. Disposal of arisings from sewer sediment removal is becoming a serious environmental issue. The current knowledge of sewer sediments is limited, which is restrained to sewer sediments management. To better understand this municipal waste, the sewer sediments of a combined sewer system in Longgang District, Shenzhen were collected and characterized, and the spatial distribution characteristics of contaminants were analyzed. Based on the bivariate correlation analysis, it is found that many contaminants in sewer sediments have a strong relationship with spatial variables. Compared to the sewer sediments in industrial areas, those in residential areas contain higher concentrations of Hg and phosphorus. The sediments in the sewage conduit also contain more organic matter (OM), phosphorus, Cu, and Ni, and the sediments in the rainwater conduit contain a higher concentration of Cd. Moreover, the sediments produced in different catchments also show huge differences in the content of contaminants. These spatial distribution characteristics may provide help for the further classification of sewer sediments, thereby making the disposal of sediments more targeted. According to the local standards of sludge disposal, land application and incineration are not suitable for managing sewer sediments due to the low OM content and poor lower heating value (LHV). Although sanitary landfill is feasible for sewer sediments disposal, the complicated composition of sewer sediments still poses the risk of polluting the surrounding environment. The management of sewer sediments via the production of building materials is a promising technical route that can avoid the migration of hazardous contaminants and produce valuable products. This study may improve our understanding of sewer sediments and provide a reliable recommendation for sewer sediment management.
Patterns of Tobacco Smoking and Nicotine Vaping among University Students in the United Arab Emirates: A Cross-Sectional Study

Various forms of tobacco smoking and nicotine vaping tools are available on the market. This study quantified the prevalence of and identified factors associated with patterns of smoking and nicotine vaping among university students in the United Arab Emirates (UAE). A cross-sectional sample of students enrolled in three public universities was surveyed. Self-reported current smoking and nicotine vaping were recorded. Of 1123 students, 81.7% completed the online survey (mean age, 20.7 ± 3.4 (SD) years; 70.7% females). The prevalence of current smoking was 15.1% while the prevalence of current nicotine vaping was nearly 4.0%. Among current smokers, 54.7% reported conventional smoking only, 15.1% reported nicotine vaping only, and 28.8% were poly-users. Conventional midwakh (47.5%), followed by conventional shisha/waterpipe (36.7%), conventional cigarettes (36.7%), electronic shisha/waterpipe (25.2%), and electronic cigarettes (24.5%), were most commonly reported by students. Students aged 20–25 years (adjusted odds ratios (aOR): 2.08, 95% confidence interval (CI): 1.18–3.67) or >25 years (aOR: 4.24, 95% CI: 1.41–12.80) had higher odds of being current smokers compared to those aged 17–19 years. The male gender was also independently associated with higher odds of being a current smoker (aOR: 5.45, 95% CI: 3.31–8.97) as well as higher odds of smoking cigarettes, shisha, and midwakh, or nicotine vaping compared to being female. Of nicotine vaping users, 36.1% reported using nicotine vaping because they enjoyed the flavor and vaporizing experience and 34.4% used it to help them to quit smoking. A relatively high prevalence of self-reported smoking was reported among university students in the UAE. The findings also suggest that nicotine vaping use is relatively widespread, but still less common than traditional smoking. Vigilant and tailored university-based smoking control and preventive measures are warranted.
The Bidirectional Relationship between Body Weight and Depression across Gender: A Simultaneous Equation Approach

Purpose: This study investigates the bidirectional relationship between body weight and depression for both males and females in the U.S. Methods: Data are drawn from the 2019 Behavioral Risk Factor Surveillance System (BRFSS), and a simultaneous ordered probability system is estimated with maximum likelihood estimation (MLE) to accommodate the two-way causality between depression and body weight categories. The variable of depression is measured by individuals’ past depressive records and current mental health status. Results: Depression and body weight are found to affect each other positively for both males and females on average. In a randomized population, the results of average treatment effects suggest significant body weight differences between depressed and non-depressed individuals. Age and other sociodemographic factors affect body weight differently between genders and between the people with depression and those without. Conclusion: The positive bidirectional relationship between body weight and depression is found. The effect of depression on body weight is significant among both males and females in a randomized population, and females who experience depression are most likely to be obese and less likely to have normal weight compared to females without depression. The risks of overweight and obesity are high among people who are less educated or unable, who have poor health statuses, and who had high blood pressure.
Opportunities and Challenges of Liquid Biopsy in Thyroid Cancer

Thyroid cancer is the most common malignancy of the endocrine system, encompassing different entities with distinct histological features and clinical behavior. The diagnostic definition, therapeutic approach, and follow-up of thyroid cancers display some controversial aspects that represent unmet medical needs. Liquid biopsy is a non-invasive approach that detects and analyzes biological samples released from the tumor into the bloodstream. With the use of different technologies, tumor cells, free nucleic acids, and extracellular vesicles can be retrieved in the serum of cancer patients and valuable molecular information can be obtained. Recently, a growing body of evidence is accumulating concerning the use of liquid biopsy in thyroid cancer, as it can be exploited to define a patient’s diagnosis, estimate their prognosis, and monitor tumor recurrence or treatment response. Indeed, liquid biopsy can be a valuable tool to overcome the limits of conventional management of thyroid malignancies. In this review, we summarize currently available data about liquid biopsy in differentiated, poorly differentiated/anaplastic, and medullary thyroid cancer, focusing on circulating tumor cells, circulating free nucleic acids, and extracellular vesicles.
A Low Cost Inkjet-Printed Mass Sensor Using a Frequency Readout Strategy

The development of low-cost mass sensors is of unique interest for the scientific community due to the wide range of fields requiring these kind of devices. In this paper, a full inkjet-printed mass sensor is proposed. The device is based on a PolyEthylene Terephthalate (PET) cantilever beam (operating in its first natural frequency) where a strain-sensor and a planar coil have been realized by a low-cost InkJet Printing technology to implement the sensing and actuation strategies, respectively. The frequency readout strategy of the sensor presents several advantages, such as the intrinsic robustness against instabilities of the strain sensor, the residual stress of the cantilever beam, the target mass material, and the distance between the permanent magnet and the actuation coil (which changes as a function of the target mass values). However, the frictionless actuation mode represents another shortcoming of the sensor. The paper describes the sensor design, realization, and characterization while investigating its expected behavior by exploiting dedicate models. The working span of the device is 0–0.36 g while its resolution is in the order of 0.001 g, thus addressing a wide range of potential applications requiring very accurate mass measurements within a narrow operating range.