Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic Reprogramming by Reduced Calorie Intake or Pharmacological Caloric Restriction Mimetics for Improved Cancer Immunotherapy

Simple Summary Reduced food intake significantly enhances healthy lifespan in both model animals and humans, and decreases the incidence of cancer and other age-related diseases. This beneficial effect is mediated by the cellular knock-on effects of reduced food intake. Interestingly, these effects differ between cancer and healthy cells because cancer cells have peculiar metabolic requirements. Some compounds called “caloric restriction mimetics” are able to recapitulate the effects of reduced food intake without impacting the nutritional status. Reduced food intake and these mimicking agents are both able to enhance responses to some chemotherapies, as well as to some regimens combining chemotherapy and immunotherapy. There are encouraging preclinical data supporting the use of reduced food intake or caloric restriction mimetics as an adjuvant to cancer chemo-immunotherapies. Clinical data are sparse, but generally favorable, and additional trials are ongoing. Abstract Caloric restriction and fasting have been known for a long time for their health- and life-span promoting effects, with coherent observations in multiple model organisms as well as epidemiological and clinical studies. This holds particularly true for cancer. The health-promoting effects of caloric restriction and fasting are mediated at least partly through their cellular effects—chiefly autophagy induction—rather than reduced calorie intake per se. Interestingly, caloric restriction has a differential impact on cancer and healthy cells, due to the atypical metabolic profile of malignant tumors. Caloric restriction mimetics are non-toxic compounds able to mimic the biochemical and physiological effects of caloric restriction including autophagy induction. Caloric restriction and its mimetics induce autophagy to improve the efficacy of some cancer treatments that induce immunogenic cell death (ICD), a type of cellular demise that eventually elicits adaptive antitumor immunity. Caloric restriction and its mimetics also enhance the therapeutic efficacy of chemo-immunotherapies combining ICD-inducing agents with immune checkpoint inhibitors targeting PD-1. Collectively, preclinical data encourage the application of caloric restriction and its mimetics as an adjuvant to immunotherapies. This recommendation is subject to confirmation in additional experimental settings and in clinical trials. In this work, we review the preclinical and clinical evidence in favor of such therapeutic interventions before listing ongoing clinical trials that will shed some light on this subject.
CeO2 Nanoparticle-Containing Polymers for Biomedical Applications: A Review

The development of advanced composite biomaterials combining the versatility and biodegradability of polymers and the unique characteristics of metal oxide nanoparticles unveils new horizons in emerging biomedical applications, including tissue regeneration, drug delivery and gene therapy, theranostics and medical imaging. Nanocrystalline cerium(IV) oxide, or nanoceria, stands out from a crowd of other metal oxides as being a truly unique material, showing great potential in biomedicine due to its low systemic toxicity and numerous beneficial effects on living systems. The combination of nanoceria with new generations of biomedical polymers, such as PolyHEMA (poly(2-hydroxyethyl methacrylate)-based hydrogels, electrospun nanofibrous polycaprolactone or natural-based chitosan or cellulose, helps to expand the prospective area of applications by facilitating their bioavailability and averting potential negative effects. This review describes recent advances in biomedical polymeric material practices, highlights up-to-the-minute cerium oxide nanoparticle applications, as well as polymer-nanoceria composites, and aims to address the question: how can nanoceria enhance the biomedical potential of modern polymeric materials?
Metasurface-Enhanced Antennas for Microwave Brain Imaging

Stroke is a very frequent disorder and one of the major leading causes of death and disability worldwide. Timely detection of stroke is essential in order to select and perform the correct treatment strategy. Thus, the use of an efficient imaging method for an early diagnosis of this syndrome could result in an increased survival’s rate. Nowadays, microwave imaging (MWI) for brain stroke detection and classification has attracted growing interest due to its non-invasive and non-ionising properties. In this paper, we present a feasibility study with the goal of enhancing MWI for stroke detection using metasurface (MTS) loaded antennas. In particular, three MTS-enhanced antennas integrated in different brain scanners are presented. For the first two antennas, which operate in a coupling medium, we show experimental measurements on an elliptical brain-mimicking gel phantom including cylindrical targets representing the bleeding in haemorrhagic stroke (h-stroke) and the not oxygenated tissue in ischaemic stroke (i-stroke). The reconstructed images and transmission and reflection parameter plots show that the MTS loadings improve the performance of our imaging prototype. Specifically, the signal transmitted across our head model is indeed increased by several dB‘s over the desired frequency range of 0.5–2.0 GHz, and an improvement in the quality of the reconstructed images is shown when the MTS is incorporated in the system. We also present a detailed simulation study on the performance of a new printed square monopole antenna (PSMA) operating in air, enhanced by a MTS superstrate loading. In particular, our previous developed brain scanner operating in an infinite lossy matching medium is compared to two tomographic systems operating in air: an 8-PSMA system and an 8-MTS-enhanced PSMA system. Our results show that our MTS superstrate enhances the antennas’ return loss by around 5 dB and increases the signal difference due to the presence of a blood-mimicking target up to 25 dB, which leads to more accurate reconstructions. In conclusion, MTS structures may be a significant hardware advancement towards the development of functional and ergonomic MWI scanners for stroke detection.
Heart Rate and Heart Rate Variability of Amateur Show Jumping Horses Competing on Different Levels

Simple Summary The increase in the heart rate and various heart parameters play an important role in assessing the fitness of sport horses. The fitness of a horse, that particular horse’s competition routine, and the resulting lower stress affect various cardiac parameters. The aim of this study was to examine the effect of the phases of competition (warm-up, resting period, show jumping course riding, cool-down) and the difficulty of a course (100, 120, 130 cm) on the heart rate and selected heart rate variability parameters of show jumping horses. The heart rate was monitored with a “Polar Equine heart rate monitor” before, during, and after a show jumping course was completed. Neither analysis of the average heart rate nor that of the maximum heart rate were able to detect a statistically proven difference among competition levels. In contrast, according to heart rate variability measures, such as maximum RR intervals, SD1, RMSSD, pNN50, and %VLF picked up differences in workload level. It has been confirmed that lower-class show jumping (up to 120 cm height) is not a strenuous exercise for horses. Abstract Heart rate is one of the gold standards used to assess the workload level and fitness of horses. However, when slight differences need to be detected, it is not sensitive enough. Therefore, the aim of this study was to test the effect of competition level and phase of exercise on the heart rate and heart rate variability parameters in show jumpers. Fourteen horses were examined competing on three different levels: 100 cm (n = 4), 120 cm (n = 6), and 130 cm (n = 4). The length of work (min); average and maximum heart rate; average, maximum and minimum RR intervals (ms); SD1 and SD2 (ms); RMSSD (ms) and pNN50 (%); VLF, LF, HF (%) were analyzed. The measurement was divided into four phases: warm-up, resting period, show jumping course riding, and cool-down. The level of the course had no significant effect on average and maximum heart rates throughout the entire exercise. The maximum RR interval, RMSSD, pNN50, SD1, and %VLF values were significantly different (p < 0.05) in horses competing at 100 cm height from those competing in the 120 cm group. The SD1 value was sensitive for the level of competition, while the SD2 parameter was sensitive for detecting exercise phases. In conclusion, heart rate variability parameters are more sensitive for detecting smaller differences in workload than heart rate alone in lower-level show jumpers.
Microbial Synthesis of (S)- and (R)-Benzoin in Enantioselective Desymmetrization and Deracemization Catalyzed by Aureobasidium pullulans Included in the Blossom Protect™ Agent

In this study, we examined the Aureobasidium pullulans strains DSM 14940 and DSM 14941 included in the Blossom Protect™ agent to be used in the bioreduction reaction of a symmetrical dicarbonyl compound. Both chiral 2-hydroxy-1,2-diphenylethanone antipodes were obtained with a high enantiomeric purity. Mild conditions (phosphate buffer [pH 7.0, 7.2], 30 °C) were successfully employed in the synthesis of (S)-benzoin using two different methodologies: benzyl desymmetrization and rac-benzoin deracemization. Bioreduction carried out with higher reagent concentrations, lower pH values and prolonged reaction time, and in the presence of additives, enabled enrichment of the reaction mixture with (R)-benzoin. The described procedure is a potentially useful tool in the synthesis of chiral building blocks with a defined configuration in a simple and economical process with a lower environmental impact, enabling one-pot biotransformation.
Techniques to Study Inflammasome Activation and Inhibition by Small Molecules

Inflammasomes are immune cytosolic oligomers involved in the initiation and progression of multiple pathologies and diseases. The tight regulation of these immune sensors is necessary to control an optimal inflammatory response and recover organism homeostasis. Prolonged activation of inflammasomes result in the development of chronic inflammatory diseases, and the use of small drug-like inhibitory molecules are emerging as promising anti-inflammatory therapies. Different aspects have to be taken in consideration when designing inflammasome inhibitors. This review summarizes the different techniques that can be used to study the mechanism of action of potential inflammasome inhibitory molecules.
Is a Four-Week Ketogenic Diet an Effective Nutritional Strategy in CrossFit-Trained Female and Male Athletes?

This single-arm interventional study examined the effect of a 4-week ketogenic diet (KD) on aerobic capacity and discipline-specific performance in female (n = 11) and male (n = 11) CrossFit-trained athletes. The participants performed incremental cycling (ICT) and Fight Gone Bad (FGB) tests after consuming a customary diet and a KD. Pre- and post-ICT exercise blood samples were also analysed. Consuming a KD had a slight impact on aerobic capacity and no relevant effect on CrossFit-specific performance. In females, consuming a KD led to an 10.4% decrease in peak oxygen uptake during the ICT (p = 0.027) and resulted in certain alterations in haematological parameters (haemoglobin (HGB), mean corpuscular HGB, and mean corpuscular HGB concentration). Furthermore, in males, alanine aminotransferase activity increased with a simultaneous improvement in the post-ICT blood acid–base balance after consuming a KD. The pre-exercise bilirubin concentration was also elevated in the entire group after consuming a KD. In conclusion, female CrossFit-trained athletes seem to be prone to aerobic performance decrements and increased risk of developing haematological disturbances when consuming a KD. In males who consumed a KD, there was an undesirable alanine aminotransferase elevation and a small tendency towards improved acid–base status. Moreover, consuming a KD had no effect on discipline-specific performance in CrossFit-trained athletes.
Current Developments and Challenges in Plant Viral Diagnostics: A Systematic Review

Plant viral diseases are the foremost threat to sustainable agriculture, leading to several billion dollars in losses every year. Many viruses infecting several crops have been described in the literature; however, new infectious viruses are emerging frequently through outbreaks. For the effective treatment and prevention of viral diseases, there is great demand for new techniques that can provide accurate identification on the causative agents. With the advancements in biochemical and molecular biology techniques, several diagnostic methods with improved sensitivity and specificity for the detection of prevalent and/or unknown plant viruses are being continuously developed. Currently, serological and nucleic acid methods are the most widely used for plant viral diagnosis. Nucleic acid-based techniques that amplify target DNA/RNA have been evolved with many variants. However, there is growing interest in developing techniques that can be based in real-time and thus facilitate in-field diagnosis. Next-generation sequencing (NGS)-based innovative methods have shown great potential to detect multiple viruses simultaneously; however, such techniques are in the preliminary stages in plant viral disease diagnostics. This review discusses the recent progress in the use of NGS-based techniques for the detection, diagnosis, and identification of plant viral diseases. New portable devices and technologies that could provide real-time analyses in a relatively short period of time are prime important for in-field diagnostics. Current development and application of such tools and techniques along with their potential limitations in plant virology are likewise discussed in detail.
The Effects of a Low Sodium Meal Plan on Blood Pressure in Older Adults: The SOTRUE Randomized Feasibility Trial

Reduced sodium meal plans are recommended by the Centers of Disease Control to lower blood pressure in older adults; however, this strategy has not been tested in a clinical trial. The Satter House Trial of Reduced Sodium Meals (SOTRUE) was an individual-level, double-blind, randomized controlled pilot study of adults living in a congregate living facility subsidized by the Federal Department of Housing and Urban Development (HUD). Adults over age 60 years ate 3 isocaloric meals with two snacks daily for 14 days. The meal plans differed in sodium density (<0.95 vs. >2 mg/kcal), but were equivalent in potassium and macronutrients. Seated systolic BP (SBP) was the primary outcome, while urine sodium-creatinine ratio was used to measure compliance. Twenty participants were randomized (95% women; 95% white; mean age 78 ± 8 years), beginning in 7 October 2019. Retention was 100% with the last participant ending 4 November 2019. Mean baseline SBP changed from 121 to 116 mmHg with the typical sodium diet (−5 mmHg; 95% CI: −18, 8) and from 123 to 112 mmHg with the low sodium diet (−11 mmHg; 95% CI: −15.2, −7.7). Compared to the typical sodium meal plan, the low sodium meal plan lowered SBP by 4.8 mmHg (95% CI: −14.4, 4.9; p = 0.31) and urine sodium-creatinine ratio by 36% (−36.0; 95% CI: −60.3, 3.4; p = 0.07), both non-significant. SOTRUE demonstrates the feasibility of sodium reduction in federally mandated meal plans. A longer and larger study is needed to establish the efficacy and safety of low sodium meals in older adults.
Pathogen Dose in Animal Models of Hemorrhagic Fever Virus Infections and the Potential Impact on Studies of the Immune Response

Viral hemorrhagic fever viruses come from a wide range of virus families and are a significant cause of morbidity and mortality worldwide each year. Animal models of infection with a number of these viruses have contributed to our knowledge of their pathogenesis and have been crucial for the development of therapeutics and vaccines that have been approved for human use. Most of these models use artificially high doses of virus, ensuring lethality in pre-clinical drug development studies. However, this can have a significant effect on the immune response generated. Here I discuss how the dose of antigen or pathogen is a critical determinant of immune responses and suggest that the current study of viruses in animal models should take this into account when developing and studying animal models of disease. This can have implications for determination of immune correlates of protection against disease as well as informing relevant vaccination and therapeutic strategies.
Combined COX-2/PPARγ Expression as Independent Negative Prognosticator for Vulvar Cancer Patients

Vulvar cancer incidence numbers have been rising steadily over the past decades. Especially the number of young patients with vulvar cancer increased recently. Therefore, the need to identify new prognostic factors for vulvar carcinoma is more apparent. Cyclooxygenase-2 (COX-2) has long been an object of scientific interest in the context of carcinogenesis. This enzyme is involved in prostaglandin synthesis and the latter binds to nuclear receptors like PPARγ. Therefore, the aim of this study was to investigate COX-2- and PPARγ- expression in tissues of vulvar carcinomas and to analyze their relevance as prognostic factors. The cytoplasmatic expression of COX-2 as well as PPARγ is associated with a significantly reduced survival, whereas nuclear expression of PPARγ results in a better survival. Especially the combined expression of both COX-2 and PPARγ in the cytoplasm is an independent negative prognosticator for vulvar cancer patients.
Optimal Absorbent Evaluation for the CO2 Separating Process by Absorption Loading, Desorption Efficiency, Cost, and Environmental Tolerance

The CO2 absorption capacities of potassium glycinate, potassium sarcosinate (choline, proline), mono-ethanolamine (MEA), and tri-ethanolamine were evaluated to find the optimal absorbent for separating CO2 from gaseous products by a CO2 purification process. The absorption loading, desorption efficiency, cost, and environmental tolerance were assessed to select the optimal absorbent. MEA was found to be the optimum absorbent for separating the CO2 and H2 mixture in gaseous product. The maximum absorption loading rate was 0.77 mol CO2 per mol MEA at temperature of 20°C and absorbent concentration of 2.5 mol/L, whereas desorption efficiency was 90% by heating for 3 h at 130°C. MEA was found to be an optimal absorbent for the purification process of CO2 during gaseous production.
NAC and Vitamin D Restore CNS Glutathione in Endotoxin-Sensitized Neonatal Hypoxic-Ischemic Rats

Therapeutic hypothermia does not improve outcomes in neonatal hypoxia ischemia (HI) complicated by perinatal infection, due to well-described, pre-existing oxidative stress and neuroinflammation that shorten the therapeutic window. For effective neuroprotection post-injury, we must first define and then target CNS metabolomic changes immediately after endotoxin-sensitized HI (LPS-HI). We hypothesized that LPS-HI would acutely deplete reduced glutathione (GSH), indicating overwhelming oxidative stress in spite of hypothermia treatment in neonatal rats. Post-natal day 7 rats were randomized to sham ligation, or severe LPS-HI (0.5 mg/kg 4 h before right carotid artery ligation, 90 min 8% O2), followed by hypothermia alone or with N-acetylcysteine (25 mg/kg) and vitamin D (1,25(OH)2D3, 0.05 μg/kg) (NVD). We quantified in vivo CNS metabolites by serial 7T MR Spectroscopy before, immediately after LPS-HI, and after treatment, along with terminal plasma drug concentrations. GSH was significantly decreased in all LPS-HI rats compared with baseline and sham controls. Two hours of hypothermia alone did not improve GSH and allowed glutamate + glutamine (GLX) to increase. Within 1 h of administration, NVD increased GSH close to baseline and suppressed GLX. The combination of NVD with hypothermia rapidly improved cellular redox status after LPS-HI, potentially inhibiting important secondary injury cascades and allowing more time for hypothermic neuroprotection.
Cell Therapies in Bladder Cancer Management

Currently, bladder cancer (BC) represents a challenging problem in the field of Oncology. The high incidence, prevalence, and progression of BC have led to the exploration of new avenues in its management, in particular in advanced metastatic stages. The recent inclusion of immune checkpoint blockade inhibitors as a therapeutic option for BC represents an unprecedented advance in BC management. However, although some patients show durable responses, the fraction of patients showing benefit is still limited. Notwithstanding, cell-based therapies, initially developed for the management of hematological cancers by infusing immune or trained immune cells or after the engineering of chimeric antigen receptor (CAR) expressing cells, are promising tools to control, or even cure, solid tumors. In this review, we summarize recent cell-based immunotherapy studies, with a special focus on BC.
Hybrid Taguchi–Gray Relation Analysis Method for Design of Metal Powder Injection-Molded Artificial Knee Joints with Optimal Powder Concentration and Volume Shrinkage

Artificial knee joints play a critical role in improving the quality of life of the elderly and those with knee injuries. Such knee joints are fabricated using a composite material consisting of metal alloy particles and polymer resin and are generally produced using the metal powder injection molding (MIM) process. However, if the local powder concentration of the molded product is too low, the mechanical properties and aesthetic appearance of the joint are severely degraded. Similarly, if the product undergoes excessive shrinkage following removal from the mold, the dimensional accuracy will fail to meet the design specifications. Accordingly, the present study applies a hybrid approach based on the Taguchi robust design methodology and gray relation analysis (GRA) theory to determine the optimal MIM processing conditions that simultaneously maximize the powder concentration uniformity while minimizing the volume shrinkage. The feasibility of the proposed approach is demonstrated by means of CAE (Computer Aided Engineering) mold flow simulations. The results show that while the robust Taguchi design method enables the optimal processing parameters that maximize the powder concentration uniformity and minimize the volume shrinkage to be individually determined, the hybrid Taguchi–GRA method enables both quality measures to be optimized simultaneously.