Miracle-dz/UniFAR-FTUs huggingface dataset:
Uncertainty Assessment in Reservoir Water Quality Modeling: Implication for Model Improvement

AbstractAs reservoir simulation models become more widely used, there is greater need for uncertainty assessment in water quality modeling. In comparison with the modeling of quantity phenomena, such as hydrological modeling, water quality modeling involves additional uncertainties in the modeling of pollutant loadings and the transport and fate of contaminants in receiving waters. In this work, a general and flexible method based on generalized likelihood uncertainty estimation (GLUE) is used to estimate the uncertainty in reservoir water quality modeling that arises from parameter uncertainty and error in model inputs. A one-dimensional model which was set up to simulate the hydrothermal and water quality of Pepacton Reservoir, part of the New York City water supply system, was used to demonstrate the method. Obtained results show that most model parameters and inputs follow wide non-Gaussian distributions, indicating they are of high uncertainty. The results also show that uncertainty is low for the si.
HIF-1α and Pro-Inflammatory Signaling Improves the Immunomodulatory Activity of MSC-Derived Extracellular Vesicles

Despite the strong evidence for the immunomodulatory activity of mesenchymal stromal cells (MSCs), clinical trials have so far failed to clearly show benefit, likely reflecting methodological shortcomings and lack of standardization. MSC-mediated tissue repair is commonly believed to occur in a paracrine manner, and it has been stated that extracellular vesicles (EVs) secreted by MSCs (EVMSC) are able to recapitulate the immunosuppressive properties of parental cells. As a next step, clinical trials to corroborate preclinical studies should be performed. However, effective dose in large mammals, including humans, is quite high and EVs industrial production is hindered by the proliferative senescence that affects MSCs during massive cell expansion. We generated a genetically modified MSC cell line overexpressing hypoxia-inducible factor 1-alpha and telomerase to increase the therapeutic potency of EVMSC and facilitate their large-scale production. We also developed a cytokine-based preconditioning culture medium to prime the immunomodulatory response of secreted EVs (EVMSC-T-HIFc). We tested the efficacy of this system in vitro and in a delayed-type hypersensitivity mouse model. MSC-T with an HIF-1α-GFP lentiviral vector (MSC-T-HIF) can be effectively expanded to obtain large amounts of EVs without major changes in cell phenotype and EVs composition. EVMSC-T-HIFc suppressed the proliferation of activated T-cells more effectively than did EVs from unmodified MSC in vitro, and significantly blunted the ear-swelling response in vivo by inhibiting cell infiltration and improving tissue integrity. We have developed a long-lived EV source that secretes high quantities of immunosuppressive EVs, facilitating a more standard and cost-effective therapeutic product.
From Laboratory towards Industrial Operation: Biomarkers for Acidophilic Metabolic Activity in Bioleaching Systems

In the actual mining scenario, copper bioleaching, mainly raw mined material known as run-of-mine (ROM) copper bioleaching, is the best alternative for the treatment of marginal resources that are not currently considered part of the profitable reserves because of the cost associated with leading technologies in copper extraction. It is foreseen that bioleaching will play a complementary role in either concentration—as it does in Minera Escondida Ltd. (MEL)—or chloride main leaching plants. In that way, it will be possible to maximize mines with installed solvent-extraction and electrowinning capacities that have not been operative since the depletion of their oxide ores. One of the main obstacles for widening bioleaching technology applications is the lack of knowledge about the key events and the attributes of the technology’s critical events at the industrial level and mainly in ROM copper bioleaching industrial operations. It is relevant to assess the bed environment where the bacteria–mineral interaction occurs to learn about the limiting factors determining the leaching rate. Thus, due to inability to accurately determine in-situ key variables, their indirect assessment was evaluated by quantifying microbial metabolic-associated responses. Several candidate marker genes were selected to represent the predominant components of the microbial community inhabiting the industrial heap and the metabolisms involved in microbial responses to changes in the heap environment that affect the process performance. The microbial community’s predominant components were Acidithiobacillus ferrooxidans, At. thiooxidans, Leptospirillum ferriphilum, and Sulfobacillus sp. Oxygen reduction, CO2 and N2 fixation/uptake, iron and sulfur oxidation, and response to osmotic stress were the metabolisms selected regarding research results previously reported in the system. After that, qPCR primers for each candidate gene were designed and validated. The expression profile of the selected genes vs. environmental key variables in pure cultures, column-leaching tests, and the industrial bioleaching heap was defined. We presented the results obtained from the industrial validation of the marker genes selected for assessing CO2 and N2 availability, osmotic stress response, as well as ferrous iron and sulfur oxidation activity in the bioleaching heap process of MEL. We demonstrated that molecular markers are useful for assessing limiting factors like nutrients and air supply, and the impact of the quality of recycled solutions. We also learned about the attributes of variables like CO2, ammonium, and sulfate levels that affect the industrial ROM-scale operation.
Current Treatment Approaches and Outcomes in the Management of Rectal Cancer Above the Age of 80

Background: The number of cases of rectal cancer in our older cohort is expected to rise with our ageing population. In this study, we analysed patterns in treatment and the long-term outcomes of patients older than 80 years with rectal cancer across a health district. Methods: All cases of rectal cancer managed at the Illawarra Cancer Care Centre, Australia between 2006 and 2018 were analysed from a prospectively maintained database. Patients were stratified into three age groups: ≤65 years, 66–79 years and ≥80 years of age. The clinicopathological characteristics, operative and non-operative treatment approach and survival outcomes of the three groups were compared. Results: Six hundred and ninety-nine patients with rectal cancer were managed, of which 118 (17%) were aged 80 and above. Patients above 80 were less likely to undergo surgery (71% vs. 90%, p < 0.001) or receive adjuvant/neoadjuvant chemoradiotherapy (p < 0.05). Of those that underwent surgical resection, their tumours were on average larger (36.5 vs. 31.5 mm, p = 0.019) and 18 mm closer the anal verge (p = 0.001). On Kaplan–Meier analysis, those above 80 had poorer cancer-specific survival when compared to their younger counterparts (p = 0.032), but this difference was no longer apparent after the first year (p = 0.381). Conclusion: Patients above the age of 80 with rectal cancer exhibit poorer cancer-specific survival, which is accounted for in the first year after diagnosis. Priority should be made to optimise care during this period. There is a need for further research to establish the role of chemoradiotherapy in this population, which appears to be underutilised.
Multiple Micronutrients, Including Zinc, Selenium and Iron, Are Positively Associated with Anemia in New Zealand Aged Care Residents

Anemia is a significant comorbidity for older adults not fully attributable to iron deficiency. Low-grade inflammation and other micronutrient deficiencies also contribute. This cross-sectional study examined the relationships between nutrient and non-nutrient factors with hemoglobin and anemia in 285 residents (>65 years) of 16 New Zealand aged-care facilities. Blood samples were analyzed for hemoglobin, ferritin, sTfR, hepcidin, zinc, selenium, and interleukin-6 (IL-6), (with ferritin, sTfR, zinc and selenium adjusted for inflammation). Linear regression models examined the relationships between micronutrient biomarkers (iron, zinc, selenium, vitamin B-12 and D), age, sex, and health factors with hemoglobin. Thirty-two percent of participants exhibited anemia, although <2% had either depleted iron stores or iron deficiency. Plasma zinc and selenium deficiencies were present in 72% and 38% of participants, respectively. Plasma zinc and total body iron (TBI) were positively associated (p < 0.05) with hemoglobin, while gastric acid suppressing medications, hepcidin, and interleukin-6 were inversely associated. These relationships were maintained after the application of anemia cut-offs. These findings emphasize the importance of considering multiple micronutrient deficiencies as risk factors for anemia.
Assessment of the Neuroprotective and Stemness Properties of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells under Variable (5% vs. 21%) Aerobic Conditions

To optimise the culture conditions for human Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) intended for clinical use, we investigated ten different properties of these cells cultured under 21% (atmospheric) and 5% (physiological normoxia) oxygen concentrations. The obtained results indicate that 5% O2 has beneficial effects on the proliferation rate, clonogenicity, and slowdown of senescence of hWJ-MSCs; however, the oxygen level did not have an influence on the cell morphology, immunophenotype, or neuroprotective effect of the hWJ-MSCs. Nonetheless, the potential to differentiate into adipocytes, osteocytes, and chondrocytes was comparable under both oxygen conditions. However, spontaneous differentiation of hWJ-MSCs into neuronal lineages was observed and enhanced under atmospheric oxygen conditions. The cells relied more on mitochondrial respiration than glycolysis, regardless of the oxygen conditions. Based on these results, we can conclude that hWJ-MSCs could be effectively cultured and prepared under both oxygen conditions for cell-based therapy. However, the 5% oxygen level seemed to create a more balanced and appropriate environment for hWJ-MSCs.
ADAM and ADAMTS Proteins, New Players in the Regulation of Hepatocellular Carcinoma Microenvironment

Simple Summary Members of the adamalysin family are multi-domain proteins involved in many cancer-related functions. In this review, we will examine the literature on the involvement of adamalysins in hepatocellular carcinoma progression and their importance in the tumor microenvironment where they regulate the inflammatory response and the epithelial–mesenchymal transition. We complete this review with an analysis of adamalysin expression in a large cohort of patients with hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) database. These original results give a new insight into the involvement of all adamalysins in the primary liver cancer. Abstract The tumor microenvironment plays a major role in tumor growth, invasion and resistance to chemotherapy, however understanding how all actors from microenvironment interact together remains a complex issue. The tumor microenvironment is classically represented as three closely connected components including the stromal cells such as immune cells, fibroblasts, adipocytes and endothelial cells, the extracellular matrix (ECM) and the cytokine/growth factors. Within this space, proteins of the adamalysin family (ADAM for a disintegrin and metalloproteinase; ADAMTS for ADAM with thrombospondin motifs; ADAMTSL for ADAMTS-like) play critical roles by modulating cell–cell and cell–ECM communication. During last decade, the implication of adamalysins in the development of hepatocellular carcinoma (HCC) has been supported by numerous studies however the functional characterization of most of them remain unsettled. In the present review we propose both an overview of the literature and a meta-analysis of adamalysins expression in HCC using data generated by The Cancer Genome Atlas (TCGA) Research Network.
The Influence of Short-Term Kinesiology Taping on Foot Anthropometry and Pain in Patients Suffering from Hallux Valgus

Background and Objectives: Hallux valgus, one of the most common foot disorders, contributes to the formation of pain, changes foot proportions and hinders everyday functioning. In this study we wanted to verify if kinesiology taping improves hallux valgus and affects the position as well as reducing pain. Materials and Methods: Forty feet with hallux valgus were examined and the parameters were measured at three stages: before the kinesiology taping was applied, just after its application and after a month of use. Measurements were taken with a 3D scanner and a baropodometric platform. Results: When taping was applied, the hallux valgus angle decreased statistically significantly compared with pre-taping (p < 0.01). The use of taping for a month significantly reduced this angle compared with pre-taping (p < 0.05). Parameters such as foot length, the surface of the hindfoot and forefoot and hindfoot pressure on the ground changed. A change in the hallux position due to the taping produced significant changes in the perception of pain (p < 0.001). Conclusion: Kinesiology taping acts on the hallux valgus and foot position mechanically. This makes kinesiology taping an effective method of conservative treatment for patients who are not qualified for surgery.
Detection of Tioman Virus in Pteropus vampyrus Near Flores, Indonesia

Diverse paramyxoviruses have coevolved with their bat hosts, including fruit bats such as flying foxes (Chiroptera: Pteropodidae). Several of these viruses are zoonotic, but the diversity and distribution of Paramyxoviridae are poorly understood. We screened pooled feces samples from three Pteropus vampyrus colonies and assayed tissues, rectal swabs, and oral swabs from 95 individuals of 23 pteropodid species sampled at 17 sites across the Indonesian archipelago with a conventional paramyxovirus PCR; all tested negative. Samples from 43 individuals were screened with next generation sequencing (NGS), and a single Pteropus vampyrus collected near Flores had Tioman virus sequencing reads. Tioman virus is a bat-borne virus in the genus Pararubulavirus with prior evidence of spillover to humans. This work expands the known range of Tioman virus, and it is likely that this isolated colony likely has sustained intergenerational transmission over a long period.
MoS2/h-BN/Graphene Heterostructure and Plasmonic Effect for Self-Powering Photodetector: A Review

A photodetector converts optical signals to detectable electrical signals. Lately, self-powered photodetectors have been widely studied because of their advantages in device miniaturization and low power consumption, which make them preferable in various applications, especially those related to green technology and flexible electronics. Since self-powered photodetectors do not have an external power supply at zero bias, it is important to ensure that the built-in potential in the device produces a sufficiently thick depletion region that efficiently sweeps the carriers across the junction, resulting in detectable electrical signals even at very low-optical power signals. Therefore, two-dimensional (2D) materials are explored as an alternative to silicon-based active regions in the photodetector. In addition, plasmonic effects coupled with self-powered photodetectors will further enhance light absorption and scattering, which contribute to the improvement of the device’s photocurrent generation. Hence, this review focuses on the employment of 2D materials such as graphene and molybdenum disulfide (MoS2) with the insertion of hexagonal boron nitride (h-BN) and plasmonic nanoparticles. All these approaches have shown performance improvement of photodetectors for self-powering applications. A comprehensive analysis encompassing 2D material characterization, theoretical and numerical modelling, device physics, fabrication and characterization of photodetectors with graphene/MoS2 and graphene/h-BN/MoS2 heterostructures with plasmonic effect is presented with potential leads to new research opportunities.
A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease

Simple Summary Castleman disease is a rare hematopoietic disorder with a broad spectrum of clinical presentations. Different subtypes have been described based on how many lymph nodes are involved, histologic appearance, and associated viral infections. Recently, significant molecular and genetic abnormalities associated with Castleman disease have been described. However, we continue to lack a framework of the biological mechanisms driving this disease process. Thus, our aim was to review all published cases of Castleman disease to date that described molecular abnormalities and correlate cytogenetic, molecular, and genetic alterations with disease subtypes. Our comprehensive review identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies for Castleman disease. Abstract Castleman disease (CD) is a rare lymphoproliferative disorder known to represent at least four distinct clinicopathologic subtypes. Large advancements in our clinical and histopathologic description of these diverse diseases have been made, resulting in subtyping based on number of enlarged lymph nodes (unicentric versus multicentric), according to viral infection by human herpes virus 8 (HHV-8) and human immunodeficiency virus (HIV), and with relation to clonal plasma cells (POEMS). In recent years, significant molecular and genetic abnormalities associated with CD have been described. However, we continue to lack a foundational understanding of the biological mechanisms driving this disease process. Here, we review all cases of CD with molecular abnormalities described in the literature to date, and correlate cytogenetic, molecular, and genetic abnormalities with disease subtypes and phenotypes. Our review notes complex karyotypes in subsets of cases, specific mutations in PDGFRB N666S in 10% of unicentric CD (UCD) and NCOA4 L261F in 23% of idiopathic multicentric CD (iMCD) cases. Genes affecting chromatin organization and abnormalities in methylation are seen more commonly in iMCD while abnormalities within the mitogen-activated protein kinase (MAPK) and interleukin signaling pathways are more frequent in UCD. Interestingly, there is a paucity of genetic studies evaluating HHV-8 positive multicentric CD (HHV-8+ MCD) and POEMS-associated CD. Our comprehensive review of genetic and molecular abnormalities in CD identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies.
The Importance of Real-World Validation of Machine Learning Systems in Wearable Exercise Biofeedback Platforms: A Case Study

Machine learning models are being utilized to provide wearable sensor-based exercise biofeedback to patients undertaking physical therapy. However, most systems are validated at a technical level using lab-based cross validation approaches. These results do not necessarily reflect the performance levels that patients and clinicians can expect in the real-world environment. This study aimed to conduct a thorough evaluation of an example wearable exercise biofeedback system from laboratory testing through to clinical validation in the target setting, illustrating the importance of context when validating such systems. Each of the various components of the system were evaluated independently, and then in combination as the system is designed to be deployed. The results show a reduction in overall system accuracy between lab-based cross validation (>94%), testing on healthy participants (n = 10) in the target setting (>75%), through to test data collected from the clinical cohort (n = 11) (>59%). This study illustrates that the reliance on lab-based validation approaches may be misleading key stakeholders in the inertial sensor-based exercise biofeedback sector, makes recommendations for clinicians, developers and researchers, and discusses factors that may influence system performance at each stage of evaluation.
Detection of Local Tissue Reactions after Anti-GnRF Injection in Male Pigs Assessed Using Magnetic Resonance Imaging

Simple Summary Local tissue reactions after injection are known in animals and humans. This study analysed the local tissue reaction after injection of the so-called immunologic castration in pigs using magnetic resonance imaging to achieve insight into the reaction site. Long-lasting reactions, which can be traced to inflammatory reactions, were detected. Further studies are needed to evaluate the impact of these reactions on animal well-being and carcass quality. Abstract This study aimed at evaluating the local tissue reaction of an anti-GnRF product, which is used for the so called “immunocastration” in male pigs. A total of 34 pigs were injected two times (including a booster injection) with an anti-GnRF product. Injection was performed using the prescribed safety vaccinator. Injection sites were evaluated three times post injection using magnetic resonance imaging. Two examinations were performed after the first injection and one after the booster. The local tissue reaction was evaluated three-dimensionally by semi-automatic analyses, by linear measurements of injection depth and length, and by scoring the kind of tissue affected. Results showed a long-lasting reaction in affected muscle tissue. Therefore, needle length should be discussed, and an evaluation of the injection site after slaughter should be performed include behavioural scorings post injection to evaluate the impact on animal well-being and carcass quality.
Evidence of Neurovascular Un-Coupling in Mild Alzheimer’s Disease through Multimodal EEG-fNIRS and Multivariate Analysis of Resting-State Data

Alzheimer’s disease (AD) is associated with modifications in cerebral blood perfusion and autoregulation. Hence, neurovascular coupling (NC) alteration could become a biomarker of the disease. NC might be assessed in clinical settings through multimodal electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Multimodal EEG-fNIRS was recorded at rest in an ambulatory setting to assess NC and to evaluate the sensitivity and specificity of the methodology to AD. Global NC was evaluated with a general linear model (GLM) framework by regressing whole-head EEG power envelopes in three frequency bands (theta, alpha and beta) with average fNIRS oxy- and deoxy-hemoglobin concentration changes in the frontal and prefrontal cortices. NC was lower in AD compared to healthy controls (HC) with significant differences in the linkage of theta and alpha bands with oxy- and deoxy-hemoglobin, respectively (p = 0.028 and p = 0.020). Importantly, standalone EEG and fNIRS metrics did not highlight differences between AD and HC. Furthermore, a multivariate data-driven analysis of NC between the three frequency bands and the two hemoglobin species delivered a cross-validated classification performance of AD and HC with an Area Under the Curve, AUC = 0.905 (p = 2.17 × 10−5). The findings demonstrate that EEG-fNIRS may indeed represent a powerful ecological tool for clinical evaluation of NC and early identification of AD.