Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Hypoxia and the Adenosine System in Immune Evasion and Prognosis of Patients with Brain Metastases of Melanoma: A Multiplex Whole Slide Immunofluorescence Study

Simple Summary The introduction of immune-checkpoint inhibitors improved the therapeutic landscape for patients with advanced malignant melanoma. However, many patients, including patients with melanoma brain metastases, do not derive benefit from immune-checkpoint blockade. Hence, biomarkers are needed to identify potential mechanisms of resistance and optimize patient selection. This study aimed to explore the role of hypoxia-mediated immunosuppression within the tumor microenvironment of patients with metastatic melanoma using multiplex immunofluorescence. We analyzed the prognostic relevance of the hypoxia surrogate marker GLUT-1, the adenosine-synthesizing ectoenzymes CD73/CD39, and the infiltration by CD8 positive lymphocytes, and evaluated their spatial interaction within the tumor microenvironment (TME). Finally, we outlined the role of the melanoma immune phenotype for the patient’s prognosis and discussed the importance of tumor hypoxia and the adenosine system in shaping the tumor immune phenotype. Abstract Following the introduction of immune checkpoint inhibitors, a substantial prolongation of the overall survival has been achieved for many patients with multiple brain metastases from melanoma. However, heterogeneity between individual tumor responses is incompletely understood. In order to determine the impact of the individual tumor phenotype on the prognosis of melanoma patients, we examined surgical sections from 33 patients who were treated with radiotherapy (whole-brain radiotherapy, WBRT, stereotactic radiotherapy, STX, or both) and Ipilimumab. We analyzed multiplex staining of the hypoxia marker GLUT-1, the adenosine (ADO)-associated enzymes CD73 and CD39, and CD8, a marker of cytotoxic T lymphocytes (CTL) on a single-cell basis using QuPath. Additionally, the MOSAIC interaction analysis algorithm was used to explore the hypothesis that CTL systematically avoid GLUT-1high tumor areas. Our results revealed, that a strong GLUT-1 expression, low numbers of CTL, or exclusion of CTL from the tumor were correlated with significant prognostic detriment. Hypoxic tumors overall have smaller amounts of CTL, and spatial analysis revealed a repellent effect of hypoxia on CTL. In contrast to in vitro studies, specific upregulation of ADO-related enzymes CD73 and CD39 in GLUT-1high tumor regions was never observed. In this study, we could show direct in vivo evidence for hypoxia-mediated immunosuppression in melanoma. Moreover, this study suggests a significant prognostic relevance of the tumor immune phenotype, the strength of CD8 infiltration in the tumor, and the expression of hypoxia marker GLUT-1 on melanoma cells. Last, our results suggest a temporal stability of the microenvironment-mediated immunosuppressive phenotype in melanoma.
Antioxidant Properties of Second-Generation Antipsychotics: Focus on Microglia

Recent studies suggest a primary role of oxidative stress in an early phase of the pathogenesis of schizophrenia and a strong neurobiological link has been found between dopaminergic system dysfunction, microglia overactivation, and oxidative stress. Different risk factors for schizophrenia increase oxidative stress phenomena raising the risk of developing psychosis. Oxidative stress induced by first-generation antipsychotics such as haloperidol significantly contributes to the development of extrapyramidal side effects. Haloperidol also exerts neurotoxic effects by decreasing antioxidant enzyme levels then worsening pro-oxidant events. Opposite to haloperidol, second-generation antipsychotics (or atypical antipsychotics) such as risperidone, clozapine, and olanzapine exert a strong antioxidant activity in experimental models of schizophrenia by rescuing the antioxidant system, with an increase in superoxide dismutase and glutathione (GSH) serum levels. Second-generation antipsychotics also improve the antioxidant status and reduce lipid peroxidation in schizophrenic patients. Interestingly, second-generation antipsychotics, such as risperidone, paliperidone, and in particular clozapine, reduce oxidative stress induced by microglia overactivation, decreasing the production of microglia-derived free radicals, finally protecting neurons against microglia-induced oxidative stress. Further, long-term clinical studies are needed to better understand the link between oxidative stress and the clinical response to antipsychotic drugs and the therapeutic potential of antioxidants to increase the response to antipsychotics.
Hydrogen-Rich Gas Production from Palm Kernel Shell by Applying Air Gasification in Fluidized Bed Reactor

An experimental study of gasification of palm kernel shell residues from the palm oil industry, as a potential hydrogen feedstock, is investigated. The gasification is conducted in a bench-scale fluidized bed gasifier with 55 mm diameter and 850 mm height. The operating conditions were studied in the following ranges: reaction temperature in gasification zone (750–1100 °C), feeding rate (0.20–1.21 kg/h), feedstock particle size (0.1–5 mm), and equivalence ratio (ER) (0.23–0.27). The increasing temperature and equivalence ratio was found to significantly influence the gas yield (up to 90 wt % conversion on the raw biomass) at 1000 °C and hence hydrogen composition (40 vol %). The feedstock particle size and feeding rate only showed minor influence. In conclusion, palm kernel shell is a potential candidate for hydrogen production.
Increased Stromal Infiltrating Lymphocytes Are Associated with the Risk of Disease Progression in Mesenchymal Circulating Tumor Cell-Positive Primary Breast Cancer Patients

Circulating tumor cells (CTCs) and the immune infiltration of tumors are closely related to clinical outcomes. This study aimed to verify the influence of stromal lymphocyte infiltration and the immune context of tumor microenvironment on the hematogenous spread and prognosis of 282 chemotherapy naïve primary BC patients. To detect the presence of mesenchymal CTCs, RNA extracted from CD45-depleted peripheral blood was interrogated for the expression of mesenchymal gene transcripts. Tumor-infiltrating lymphocytes (TILs) were detected in the stromal areas by immunohistochemistry, using CD3, CD8, and CD45RO antibodies. The concentrations of 51 plasma cytokines were measured by multiplex bead arrays. TILs infiltration in mesenchymal CTC-positive patients significantly decreased their progression-free survival (HR = 4.88, 95% CI 2.30–10.37, p < 0.001 for CD3high; HR = 6.17, 95% CI 2.75–13.80, p < 0.001 for CD8high; HR = 6.93, 95% CI 2.86–16.81, p < 0.001 for CD45ROhigh). Moreover, the combination of elevated plasma concentrations of transforming growth factor beta-3 (cut-off 662 pg/mL), decreased monocyte chemotactic protein-3 (cut-off 52.5 pg/mL) and interleukin-15 (cut-off 17.1 pg/mL) significantly increased the risk of disease recurrence (HR = 4.838, 95% CI 2.048–11.427, p < 0.001). Our results suggest a strong impact of the immune tumor microenvironment on BC progression, especially through influencing the dissemination and survival of more aggressive, mesenchymal CTC subtypes.
4Pi‐confocal images with axial superresolution

We present two‐photon excitation 4Pi‐confocal images of clustered fluorescence beads demonstrating three‐dimensional far‐field light microscopy with unprecedented resolution. For an excitation wavelength of 760 nm, the lateral and axial resolution amounts to 200 and 145 nm, respectively. The four‐fold improved axial resolution is achieved by engineering the point‐spread function through a suitable combination of aperture enlargement, two‐photon excitation, confocalization and three‐point deconvolution. In contrast to their confocal counterparts, 4Pi‐confocal images do not exhibit the typical axial elongation. The axial resolution in the 4Pi‐confocal images corresponds to about one‐fifth of the wavelength and surpasses the lateral resolution by 25%.
Unconventional Secretion of Nigerolysins A from Aspergillus Species

Aegerolysins are small lipid-binding proteins particularly abundant in fungi. Aegerolysins from oyster mushrooms interact with an insect-specific membrane lipid and, together with MACPF proteins produced by the same organism, form pesticidal pore-forming complexes. The specific interaction with the same membrane lipid was recently demonstrated for nigerolysin A2 (NigA2), an aegerolysin from Aspergillus niger. In Aspergillus species, the aegerolysins were frequently found as secreted proteins, indicating their function in fungal defense. Using immunocytochemistry and live-cell imaging we investigated the subcellular localization of the nigerolysins A in A. niger, while their secretion was addressed by secretion prediction and Western blotting. We show that both nigerolysins A are leaderless proteins that reach the cell exterior by an unconventional protein secretion. NigA proteins are evenly distributed in the cytoplasm of fungal hyphae. A detailed bioinformatics analysis of Aspergillus aegerolysins suggests that the same function occurs only in a limited number of aegerolysins. From alignment, analysis of chromosomal loci, orthology, synteny, and phylogeny it follows that the same or a similar function described for pairs of pesticidal proteins of Pleurotus sp. can be expected in species of the subgenus Circumdati, section Nigri, series Nigri, and some other species with adjacent pairs of putative pesticidal proteins.
Magnetic Resonance Methods as a Prognostic Tool for the Biorelevant Behavior of Xanthan Tablets

Hydrophilic matrix tablets with controlled drug release have been used extensively as one of the most successful oral drug delivery systems for optimizing therapeutic efficacy. In this work, magnetic resonance imaging (MRI) is used to study the influence of various pHs and mechanical stresses caused by medium flow (at rest, 80, or 150 mL/min) on swelling and on pentoxifylline release from xanthan (Xan) tablets. Moreover, a bimodal MRI system with simultaneous release testing enables measurements of hydrogel thickness and drug release, both under the same experimental conditions and at the same time. The results show that in water, the hydrogel structure is weaker and less resistant to erosion than the Xan structure in the acid medium. Different hydrogel structures affect drug release with erosion controlled release in water and diffusion controlled release in the acid medium. Mechanical stress simulating gastrointestinal contraction has no effect on the hard hydrogel in the acid medium where the release is independent of the tested stress, while it affects the release from the weak hydrogel in water with faster release under high stress. Our findings suggest that simultaneous MR imaging and drug release from matrix tablets together provide a valuable prognostic tool for prolonged drug delivery design.
Quality of Infrared Dried Apple Slices

Abstract The aim of this work was to compare quality of apple slices dried by near infrared heating and convection in such parameters in which final material temperature in both methods was similar. The infrared drying was done at the distance between the emitters (with total power of 7.875 kW/m2) and heated surface equal to 10, 20, and 30 cm. Flow of ambient air was set at 0.5, 1.0, and 1.5 m/s. Convective drying was done in the same dryer using hot air at 65 and 75°C flowing with velocity 1.5 m/s. Quality attributes measured in this work included: color, kinetics of water adsorption, mechanical properties, and microstructure. It was stated that the changes in chromaticity coefficients are not dependent on the mode of heat supply, but are related to the final temperature of the dried material. Luminance of dried apple slices was affected by temperature as well. Final material temperature, not the way heat is supplied, could be responsible for the differences in the ability of dry apple slices to adsorb water. The similar correlation was stated for mechanical properties: slope of initial part of the deformation curve (crispness), breaking force (hardness or crispness), and work of breaking were all related to the final material temperature. Microstructure of convective and infrared dried apple were different but it seems that the drying rate can be responsible for observed differences.
Organophosphate pesticide exposure among farm women and children: Status of micronutrients, acetylcholinesterase activity, and oxidative stress

Abstract Nutritional status plays a major role in determining the possible adverse health outcomes due to pesticide toxicity. The objective of the present study was to assess the organophosphorus pesticide residue levels among farm women (FW) (24-45years) and farm children (FC) (9-12 and 13-15years) belonging to the Rangareddy district (Telangana, India) along with their micronutrient status, inhibition of acetylcholinesterase activity, and oxidative stress levels. Residues of Chlorpyrifos, Diazinon, Malathion, Monocrotophos and Phosalone were found in the serum samples of FW and FC along with significantly low levels of vitamins and minerals. Inhibition of AChE activity was observed in FW and FC and altered oxidative stress parameters among FW. Correlation studies have found significant associations between the pesticide residues, micronutrients and antioxidant enzymes. The study suggests an association between pesticide exposure coupled with micronutrient deficiency, induced AChE inhibition, and oxidative stress.
Breath Analysis: Comparison among Methodological Approaches for Breath Sampling

Despite promising results obtained in the early diagnosis of several pathologies, breath analysis still remains an unused technique in clinical practice due to the lack of breath sampling standardized procedures able to guarantee a good repeatability and comparability of results. The most diffuse on an international scale breath sampling method uses polymeric bags, but, recently, devices named Mistral and ReCIVA, able to directly concentrate volatile organic compounds (VOCs) onto sorbent tubes, have been developed and launched on the market. In order to explore performances of these new automatic devices with respect to sampling in the polymeric bag and to study the differences in VOCs profile when whole or alveolar breath is collected and when pulmonary wash out with clean air is done, a tailored experimental design was developed. Three different breath sampling approaches were compared: (a) whole breath sampling by means of Tedlar bags, (b) the end-tidal breath collection using the Mistral sampler, and (c) the simultaneous collection of the whole and alveolar breath by using the ReCIVA. The obtained results showed that alveolar fraction of breath was relatively less affected by ambient air (AA) contaminants (p-values equal to 0.04 for Mistral and 0.002 for ReCIVA Low) with respect to whole breath (p-values equal to 0.97 for ReCIVA Whole). Compared to Tedlar bags, coherent results were obtained by using Mistral while lower VOCs levels were detected for samples (both breath and AA) collected by ReCIVA, likely due to uncorrected and fluctuating flow rates applied by this device. Finally, the analysis of all data also including data obtained by explorative analysis of the unique lung cancer (LC) breath sample showed that a clean air supply might determine a further confounding factor in breath analysis considering that lung wash-out is species-dependent.
Co-Solvent Selection for Supercritical Fluid Extraction (SFE) of Phenolic Compounds from Labisia pumila

A preliminary study was conducted to study the effects of different types and concentrations of co-solvents based on yield, composition and antioxidants capacity of extract prior to optimization studies of supercritical fluid extraction (SFE) of Labisia pumila (locally referred to as ‘kacip fatimah’). The following co-solvents were studied prior to the optimization of supercritical carbon dioxide (SC–CO2) technique: ethanol, water, methanol, as well as aqueous solutions of ethanol–water and methanol–water (50% and 70% v/v). By using the selected co-solvents, identification of phenolic acids (gallic acid, methyl gallate and caffeic acid) was determined by using High-Performance Liquid Chromatography (HPLC). Then, the antioxidant capacity was evaluated by using three different assays: total phenolic content (TPC), ferric reducing/antioxidant power (FRAP) and free radical-scavenging capacity of 2,2-diphenyl-1-picrylhydrazyl (DPPH). SC–CO2 with 70% ethanol–water co-solvent was superior in terms of a higher combination of phenolic compounds extracted and antioxidants capacity. Overall, SC–CO2 with co-solvent 70% ethanol–water technique was efficient in extracting phenolic compounds from L. pumila, and thus the usage of this solvent system should be considered for further optimization studies.
Analysis of the Athletic Career and Retirement Depending on the Type of Sport: A Comparison between Individual and Team Sports

The type of sport practiced may shape the athletic career, considered as the period in which an athlete is dedicated to obtaining their maximum performance in one or more sports. The aim of this study was to compare athletic careers and retirement in individual and team sports. Four hundred and ten former elite athletes (38.5 ± 7.6 years) answered an ad hoc questionnaire; 61.5% were men and 38.5% women; 45.1% were from individual sports, while 54.9% were from team sports. It emerged that the age of maximum sports performance and the retirement age occurred significantly later in team sports than in individual sports (U = 15,042 and U = 12,624.5, respectively p < 0.001). Team sports athletes combined their athletic career with work to a greater extent than those from individual sports (χ2 (3, N = 408) = 14.2; p = 0.003; Cv = 0.187). Individual sports athletes trained more hours per week (30.0 ± 11.7 h) than those involved in team sports (19.2 ± 10.7 h; U = 9682; p < 0.001). These athletes (team sports) were in a better economic and working situation at retirement transition (χ2 (3, N = 406) = 23.9; p < 0.001; Cv = 0.242). Individual sports athletes perform physical activity more frequently than team sports athletes (U = 16,267.5; p = 0.045), while team sports athletes participate more actively in veteran competitions (χ2 (1, N = 390) = 3.9; p = 0.047; Cv = 0.104) and more frequently attend events as spectators (χ2 (1, N = 390) = 8.4; p = 0.004; Cv = 0.151). dual career support providers should be aware that team sports athletes enjoy a longer athletic career, and they are in a better position to face the retirement transition than individual sports athletes.
Socio-economic-demographic determinants of depression in Indonesia: A hospital-based study

The association of socio-economic-demographic (SED; e.g., income-related) factors with depression is widely confirmed in the literature. We conducted a hospital-based case–control study of 160 patients with psychiatrist-diagnosed clinical depression. The control group comprised 160 participants recruited from local communities. We used a questionnaire to collect SED data from all participants. We replaced missing values using multiple imputation analyses and further analyzed the pooled data of five imputations. We also recorded the results from the original analysis and each imputation. Univariate analyses showed income was associated with depression. Multiple logistic regression analyses revealed that, among all SED variables, high income (odds ratio = 2.088 [95% confidence interval = 1.178–3.700]; p = 0.012), middle-level (completed junior or senior high school) education (1.688 [1.042–2.734]; p = 0.033) and cohabitating with four or more family members (1.632 [1.025–2.597]; p = 0.039) were significant predictors for the case group. We conclude that cash income is a determinant of depression in hospital outpatients in Indonesia. This study suggests health policy implications toward better hospital access and service for people with depression in middle- or low-income households, and recommends considering high income as correlated with a high risk of depression, owing to socio-cultural changes.
Gbx2 Is Required for the Migration and Survival of a Subpopulation of Trigeminal Cranial Neural Crest Cells

The development of key structures within the mature vertebrate hindbrain requires the migration of neural crest (NC) cells and motor neurons to their appropriate target sites. Functional analyses in multiple species have revealed a requirement for the transcription factor gastrulation-brain-homeobox 2 (Gbx2) in NC cell migration and positioning of motor neurons in the developing hindbrain. In addition, loss of Gbx2 function studies in mutant mouse embryos, Gbx2neo, demonstrate a requirement for Gbx2 for the development of NC-derived sensory neurons and axons constituting the mandibular branch of the trigeminal nerve (CNV). Our recent GBX2 target gene identification study identified multiple genes required for the migration and survival of NC cells (e.g., Robo1, Slit3, Nrp1). In this report, we performed loss-of-function analyses using Gbx2neo mutant embryos, to improve our understanding of the molecular and genetic mechanisms regulated by Gbx2 during anterior hindbrain and CNV development. Analysis of Tbx20 expression in the hindbrain of Gbx2neo homozygotes revealed a severely truncated rhombomere (r)2. Our data also provide evidence demonstrating a requirement for Gbx2 in the temporal regulation of Krox20 expression in r3. Lastly, we show that Gbx2 is required for the expression of Nrp1 in a subpopulation of trigeminal NC cells, and correct migration and survival of cranial NC cells that populate the trigeminal ganglion. Taken together, these findings provide additional insight into molecular and genetic mechanisms regulated by Gbx2 that underlie NC migration, trigeminal ganglion assembly, and, more broadly, anterior hindbrain development.
Understanding the Self-Perceived Barriers and Enablers toward Adopting a Mediterranean Diet in Australia: An Application of the Theory of Planned Behaviour Framework

The transferability of a Mediterranean diet (MedDiet) in non-Mediterranean populations is appealing. However, little is known about the perceived enablers or barriers toward adherence, particularly in Australia. This study aimed to investigate the perceived beliefs, barriers, and enablers toward adherence to a MedDiet in Australian adults. Barriers and enablers were assessed using a self-administered online questionnaire, which included questions aligned with the Theory of Planned Behaviour (TPB). The survey was completed by n = 606 participants. Barriers and enablers toward adherence to MedDiet were grouped under the three core constructs of the TPB: attitudes (suitability, taste, restrictive, food waste); social norms (food culture); and perceived behavioural control (PBC) (motivation, affordability, time/effort, food access, knowledge, food outlets, natural conditions, cooking skills). PBC emerged as the most prominent construct influencing intention to follow a MedDiet. Perceived health benefits (n = 445; 76.5%) and improved diet quality (n = 224; 38.5%) were identified as major advantages. In contrast, dietary adherence (n = 147; 39.7%) was perceived as an important disadvantage. Future MedDiet interventions, in both research and clinical settings, should consider adopting strategies aimed at improving self-efficacy to reduce self-perceived barriers and facilitate dietary adherence.