Miracle-dz/UniFAR-FTUs huggingface dataset:
Incubation with sodium nitrite attenuates fatigue development in intact single mouse fibres at physiological PO2

Dietary nitrate supplementation increases plasma nitrite concentration, which provides an oxygen‐independent source of nitric oxide and can delay skeletal muscle fatigue. Nitrate supplementation has been shown to increase myofibre calcium release and force production in mouse skeletal muscle during contractions at a supra‐physiological oxygen tension, but it is unclear whether nitrite exposure can delay fatigue development and improve myofibre calcium handling at a near‐physiological oxygen tension. Single mouse muscle fibres acutely treated with nitrite had a lower force and cytosolic calcium concentration during single non‐fatiguing contractions at a near‐physiological oxygen tension. Nitrite treatment delayed fatigue development during repeated fatiguing isometric contractions at near‐physiological, but not at supra‐physiological, oxygen tension in combination with better maintenance of myofilament calcium sensitivity and sarcoplasmic reticulum calcium pumping. These findings improve understanding of the mechanisms by which increased skeletal muscle nitrite exposure might be ergogenic and imply that this is related to improved calcium handling.
Regulatory Macrophages Inhibit Alternative Macrophage Activation and Attenuate Pathology Associated with Fibrosis

Key Points RMϕs inhibit alternative Mϕ activation. Inhibition of alternate activation by RMϕs was not entirely dependent on IL-10. RMϕ attenuated alternative activated Mϕ-mediated pathological conditions in peritoneal fibrosis. Diversity and plasticity are the hallmarks of macrophages. The two most well-defined macrophage subsets are the classically activated macrophages (CAMϕs) and the IL-4–derived alternatively activated macrophages (AAMϕs). Through a series of studies, we previously identified and characterized a distinct population of macrophages with immunoregulatory functions, collectively termed regulatory macrophages (RMϕs). Although considerable advances have been made in understanding these various macrophage subsets, it is not known whether macrophages of one activation state can influence the other. In this study, we examined whether RMϕs capable of inhibiting inflammatory responses of CAMϕs could also inhibit AAMϕs and their profibrotic responses. Our results demonstrated that RMϕs significantly dampened the alternate activation phenotype of AAMϕs generated in vitro and intrinsically occurring AAMϕs from TACI−/− macrophages. Further, RMϕs inhibited AAMϕ-promoted arginase activity and fibroblast proliferation in vitro. This inhibition occurred regardless of the strength, duration, and mode of alternative activation and was only partially dependent on IL-10. In the chlorhexidine gluconate–induced peritoneal fibrosis model, AAMϕs worsened the fibrosis, but RMϕs rescued mice from AAMϕ-mediated pathological conditions. Taken together, our study demonstrates that RMϕs are a specialized subset of macrophages with a nonredundant role in limiting overt proregenerative functions of AAMϕs, a role distinct from their well-defined role of suppression of inflammatory responses by CAMϕs.
Morphological, microbiological and ultrastructural aspects of sepsis by Aeromonas hydrophila in Piaractus mesopotamicus

Aeromonas bacteria can cause an infection characterized by septicemia and is one of the most common pathogens in tropical fish. This disease is responsible for high morbidity and mortality rates, causing considerable losses in aquaculture. Thus, the understanding of its pathophysiology is crucial to develop control strategies of this bacterial infection in farmed fish. This study aimed to characterize early pathological aspects of acute sepsis in pacu (Piaractus mesopotamicus) experimentally infected with Aeromonas hydrophila. A total of 160 juvenile pacus were inoculated intraperitoneally with A. hydrophila (1.78 x 109 CFU/mL) and at 0 (control), 1, 3, 6, and 9 hours post-inoculation (hpi), animals were anesthetized and samples were collected for microbiological, light microscopy and transmission electron microscopy (TEM) analyzes. The results showed the occurrence of hemodynamic alterations, such as hemorrhage and congestion, which were observed mainly after 6 and 9 hpi. It was possible to re-isolate Aeromonas at all sampling times except in control group. However, just after 9 hpi it was possible to find the bacteria in all fish and tissues. Light microscopy analyses revealed a degenerative process, necrosis and vascular damage mainly at 6 and 9 hpi. According to the ultrastructural examination, areas of cellular death were identified in all examined tissues, especially at 6 and 9 hpi. However, the most severe, related to necrosis, were observed after 6 and 9 hpi. The findings suggested that this bacterium spreads in the first hpi through the fish organs, mainly affecting spleen, liver and kidney, causing irreversible lesions at the molecular level.
Heat Shock Proteins and Ovarian Cancer: Important Roles and Therapeutic Opportunities

Ovarian cancer is a serious cause of death in gynecological oncology. Delayed diagnosis and poor survival rates associated with late stages of the disease are major obstacles against treatment efforts. Heat shock proteins (HSPs) are stress responsive molecules known to be crucial in many cancer types including ovarian cancer. Clusterin (CLU), a unique chaperone protein with analogous oncogenic criteria to HSPs, has also been proven to confer resistance to anti-cancer drugs. Indeed, these chaperone molecules have been implicated in diagnosis, prognosis, metastasis and aggressiveness of various cancers. However, relative to other cancers, there is limited body of knowledge about the molecular roles of these chaperones in ovarian cancer. In the current review, we shed light on the diverse roles of HSPs as well as related chaperone proteins like CLU in the pathogenesis of ovarian cancer and elucidate their potential as effective drug targets.
Real-time use of artificial intelligence in the evaluation of cancer in Barrett’s oesophagus

Based on previous work by our group with manual annotation of visible Barrett oesophagus (BE) cancer images, a real-time deep learning artificial intelligence (AI) system was developed. While an expert endoscopist conducts the endoscopic assessment of BE, our AI system captures random images from the real-time camera livestream and provides a global prediction (classification), as well as a dense prediction (segmentation) differentiating accurately between normal BE and early oesophageal adenocarcinoma (EAC). The AI system showed an accuracy of 89.9% on 14 cases with neoplastic BE. This paper follows up on our prior publication on the application of AI and deep learning in the evaluation of BE.1 2 In our initial publications, we developed a computer-aided diagnosis (CAD) model and demonstrated promising performance scores in the classification and segmentation domains during BE assessment.1 2 However, these results were achieved on optimal endoscopic images, which may not mirror the real-life situation sufficiently. To enable the seamless integration of AI-based image classification into the clinical workflow, our previous system was developed further to increase the speed of image analysis for classification and the resolution of the dense prediction, which shows the color-coded spatial distribution of cancer probabilities.1 2 Still based on deep convolutional neural nets (CNNs) and a residual net (ResNet) architecture with DeepLab V.3+, a state-of-the-art encoder–decoder network was adapted.3 To transfer the endoscopic livestream to our AI system, a capture card (Avermedia, Taiwan) was plugged to the endoscopic monitor. Online supplementary video 1 shows the setting of AI-based BE evaluation in the endoscopy room of the University Hospital Augsburg (figure 1). The AI prediction can be started at any time using either a button on the keyboard or a foot switch. The video clip shows examples of …
Meeting the review family: exploring review types and associated information retrieval requirements.

BACKGROUND AND OBJECTIVES The last decade has witnessed increased recognition of the value of literature reviews for advancing understanding and decision making. This has been accompanied by an expansion in the range of methodological approaches and types of review. However, there remains uncertainty over definitions and search requirements beyond those for the 'traditional' systematic review. This study aims to characterise health related reviews by type and to provide recommendations on appropriate methods of information retrieval based on the available guidance. METHODS A list of review types was generated from published typologies and categorised into 'families' based on their common features. Guidance on information retrieval for each review type was identified by searching pubmed, medline and Google Scholar, supplemented by scrutinising websites of review producing organisations. RESULTS Forty-eight review types were identified and categorised into seven families. Published guidance reveals increasing specification of methods for information retrieval; however, much of it remains generic with many review types lacking explicit requirements for the identification of evidence. CONCLUSIONS Defining review types and utilising appropriate search methods remain challenging. By familiarising themselves with a range of review methodologies and associated search methods, information specialists will be better equipped to select suitable approaches for future projects.
Correlation of Bite Force Interpretation in Maximal Intercuspal Position among Patient, Clinician, and T-Scan III System

Abstract Objective The main purpose of this article was to determine the correlation of bite force in maximal intercuspal position (MIP) among patient’s perceptions, clinician subjective interpretation, and T-Scan III system. Materials and Methods Forty-three dental students at Naresuan University (Phitsanulok, Thailand) participated in the study. Subjects were positioned by Frankfurt horizontal plane paralleled to the horizontal plane and asked to bilaterally clenched in MIP. Patient’s perception was evaluated by asking which side of the jaw had heavier bite force (right, left, or equally on both sides). Then, the clinician subjective interpretation was assessed using traditional occlusal indicators. Furthermore, patient’s bite force was analyzed using T-Scan III. Statistical Analysis Cohen’s weighted kappa test was used to evaluate the correlation of bite force. Results The best correlation between patient’s perception and T-Scan III was at the ± 7.5% cutoff range with 15 subject agreements. While the best correlation between clinician subjective interpretation and T-Scan III was at ± 5.0% cutoff range with 23 subject agreements. Cohen’s weighted kappa indicated slight agreement between T-Scan III and patient’s perception and fair agreement between T-Scan III and clinician. Conclusions Clinician subjective interpretation is more clinically reliable than patient’s perception when T-Scan III is used as a gold standard.
Catechol-Loading Nanofibrous Membranes for Eco-Friendly Iron Nutrition of Plants

Modern agriculture requires more efficient and low-impact products and formulations than traditional agrochemicals to improve crop yields. Iron is a micronutrient essential for plant growth and photosynthesis, but it is mostly present in insoluble forms in ecosystems so that it is often limiting for plants. This study was aimed at combining natural strategies and biodegradable nanostructured materials to create environmentally friendly and low-toxic bioactive products capable of both supplying iron to Fe-deficient plants and reducing the impact of agricultural products on the environment. Consequently, free-standing electrospun nanofibrous polycaprolactone/polyhydroxybutyrate thin membranes loaded with catechol (CL-NMs) as an iron-chelating natural agent (at two concentrations) were fabricated on purpose to mobilize Fe from insoluble forms and transfer it to duckweed (Lemna minor L.) plants. The effectiveness of CL-NMs in providing iron to Fe-deficient plants, upon catechol release, tested in duckweeds grown for 4 days under controlled hydroponic conditions, displayed temporal variations in both photosynthetic efficiency and biometric parameters measured by chlorophyll fluorescence and growth imaging. Duckweeds supplied with CL-NMs hosting higher catechol concentrations recovered most of the physiological and growth performances previously impaired by Fe limitation. The absence of short-term toxicity of these materials on duckweeds also proved the low impact on ecosystems of these products.
Conceptual Development of Immunotherapeutic Approaches to Gastrointestinal Cancer

Gastrointestinal (GI) cancer is one of the common causes of cancer-related death worldwide. Chemotherapy and/or immunotherapy are the current treatments, but some patients do not derive clinical benefits. Recently, studies from cancer molecular subtyping have revealed that tumor molecular biomarkers may predict the immunotherapeutic response of GI cancer patients. However, the therapeutic response of patients selected by the predictive biomarkers is suboptimal. The tumor immune-microenvironment apparently plays a key role in modulating these molecular-determinant predictive biomarkers. Therefore, an understanding of the development and recent advances in immunotherapeutic pharmacological intervention targeting tumor immune-microenvironments and their potential predictive biomarkers will be helpful to strengthen patient immunotherapeutic efficacy. The current review focuses on an understanding of how the host-microenvironment interactions and the predictive biomarkers can determine the efficacy of immune checkpoint inhibitors. The contribution of environmental pathogens and host immunity to GI cancer is summarized. A discussion regarding the clinical evidence of predictive biomarkers for clinical trial therapy design, current immunotherapeutic strategies, and the outcomes to GI cancer patients are highlighted. An understanding of the underlying mechanism can predict the immunotherapeutic efficacy and facilitate the future development of personalized therapeutic strategies targeting GI cancers.
Effects of Partial Replacement of Conventional with Alternative Feeds on Nutrient Intake, Digestibility, Milk Yield and Composition of Awassi Ewes and Lambs

Simple Summary Alternative feeds have been used to feed animals for decades by replacing traditional feeds to increase the profit of raising livestock. In this study, alternative feeds (dried distillers grains with solubles, carob pods, olive cake, and bread by-product) were fed to Awassi ewes and ewe lambs at 0, 200, and 400 g/kg. Chemical composition was similar among diets. Feed intake, body weight change, and milk yield did not differ among diets. Cost of milk production decreased in alternative feeds containing diets, with no negative effect on health, welfare, and productivity. Abstract Two experiments were done to assess the effects of alternative feeds (AF; dried distillers grains with solubles, carob pods, olive cake, and bread by-product) on lactating performance of ewes and digestibility and nitrogen (N) retention of lambs. Diets were: no AF (CON); 200 g/kg AF (AF200); and 400 g/kg AF (AF400). In Experiment 1, 27 Awassi ewes were randomly distributed into three groups, and each was fed one of the diets described before (9 ewes/diet). Evaluation of milk composition and yield was performed at the beginning of the experiment and on days 18, 36, and 54. In Experiment 2, 18 Awassi lambs were allocated to the same diets (6 ewe lambs/diet) during a 21-day trial (14 days housed individually in shaded pens and 7 days in metabolic cages). In Experiment 1, no differences in body weight (BW) of the ewes and their lambs were detected. With the exception of neutral detergent fiber intake, which was lower in the AF-containing diets compared with CON, dry matter, crude protein, and acid detergent fiber intake were not affected by dietary treatment. Milk yield and composition was comparable among diets, and the cost of milk production was lower in AF compared to CON diet. In Experiment 2, nutrient digestibility and N retention were not affected by the diet. Results showed the possibility of including different AF in ewe and lamb diets to mitigate production cost without negatively affecting intake, milk yield, and composition, digestibility, and animal welfare and health.
The Associations of Vitamin D Status with Athletic Performance and Blood-borne Markers in Adolescent Athletes: A Cross-Sectional Study

The purpose of this study was to examine the associations of vitamin D status with athletic performance and blood-borne markers in adolescent athletes. This cross-sectional study included forty-seven Taekwondo athletes, aged 15–18 years old. Athletic performance was assessed using maximal oxygen consumption (VO2max), Wingate anaerobic power test, vertical jump, agility T-test, lower limb muscle strength, and fatigue resistance. Blood samples were collected to assess serum 25-hydroxyvitamin D [25(OH)D], free-testosterone, cortisol, creatine kinase, and urea. One-way ANOVAs were applied using Bonferroni adjusted alpha levels, which was 0.02 (i.e., 0.05/3). Multiple linear regressions analyses as well as Pearson and partial correlation analyses were used to examine the relationship among 25(OH)D concentration, athletic performance, and blood-borne markers. The participants 25(OH)D concentration were ranged from 16 to 73.25 nmol/L, indicating that 74.5% of the adolescent athletes have vitamin D insufficiency or deficiency. The vitamin D status did not show any significant effects on the performance factors or blood-borne markers. Serum 25(OH)D concentration was positively correlated with mean power output (r = 0.359, p < 0.05) and relative mean power output (r = 0.325, p < 0.05) after adjusting for bone age, height, weight, training experience, lean body mass, and fat mass. However, 25(OH)D concentration was not associated with other performance-related factors and blood-borne markers. In addition, multiple linear regressions analyses revealed that serum 25(OH)D concentration were not significant predictors of athletic performance in adolescent athletes. In conclusion, vitamin D status is weakly correlated with anaerobic capacity; moreover, the underlying mechanisms of how vitamin D influence anaerobic performance is unclear in the present study. Nevertheless, the importance of vitamin D on health benefits should not be underestimated, especially during growth periods.
Microstructure, Microhardness and Corrosion Resistance of WE43 Alloy Based Composites after High-Pressure Torsion

The structure and properties of a composite consisting of Mg-Y-Nd-Zr alloy (WE43) and various oxides are studied. The particles of the WE43 powder were coated by the nanocrystalline oxide layer by means of a wet chemical deposition process. After that the powder is compressed into solid samples and deformed using high-pressure torsion at room temperature. A second phase is present, both, in pure WE43 alloy and in the one with deposited oxides. We observed that the modification of the alloy by the oxide layer deposition and deformation by high-pressure torsion changes the phase composition and properties of the samples. The samples modified by TiO2 showed the best microhardness and corrosion resistance.
The Anti-Apoptotic Effect of ASC-Exosomes in an In Vitro ALS Model and Their Proteomic Analysis

Stem cell therapy represents a promising approach in the treatment of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). The beneficial effect of stem cells is exerted by paracrine mediators, as exosomes, suggesting a possible potential use of these extracellular vesicles as non-cell based therapy. We demonstrated that exosomes isolated from adipose stem cells (ASC) display a neuroprotective role in an in vitro model of ALS. Moreover, the internalization of ASC-exosomes by the cells was shown and the molecules and the mechanisms by which exosomes could exert their beneficial effect were addressed. We performed for the first time a comprehensive proteomic analysis of exosomes derived from murine ASC. We identified a total of 189 proteins and the shotgun proteomics analysis revealed that the exosomal proteins are mainly involved in cell adhesion and negative regulation of the apoptotic process. We correlated the protein content to the anti-apoptotic effect of exosomes observing a downregulation of pro-apoptotic proteins Bax and cleaved caspase-3 and upregulation of anti-apoptotic protein Bcl-2 α, in an in vitro model of ALS after cell treatment with exosomes. Overall, this study shows the neuroprotective effect of ASC-exosomes after their internalization and their global protein profile, that could be useful to understand how exosomes act, demonstrating that they can be employed as therapy in neurodegenerative diseases.
The Controversial History of Hormone Replacement Therapy

The history of hormone replacement therapy (HRT) started in the 1960s, with very high popularity in the 1990s. The first clinical trials on HRT and chronic postmenopausal conditions were started in the USA in the late 1990s. After the announcement of the first results of the Women’s Health Initiative (WHI) in 2002, which showed that HRT had more detrimental than beneficial effects, HRT use dropped. The negative results of the study received wide publicity, creating panic among some users and new guidance for doctors on prescribing HRT. The clear message from the media was that HRT had more risks than benefits for all women. In the following years, a reanalysis of the WHI trial was performed, and new studies showed that the use of HRT in younger women or in early postmenopausal women had a beneficial effect on the cardiovascular system, reducing coronary disease and all-cause mortality. Notwithstanding this, the public opinion on HRT has not changed yet, leading to important negative consequences for women’s health and quality of life.
Urinary Taurine Excretion and Risk of Late Graft Failure in Renal Transplant Recipients

Taurine is a sulfur containing nutrient that has been shown to protect against oxidative stress, which has been implicated in the pathophysiology leading to late graft failure after renal transplantation. We prospectively investigated whether high urinary taurine excretion, reflecting high taurine intake, is associated with low risk for development of late graft failure in renal transplant recipients (RTR). Urinary taurine excretion was measured in a longitudinal cohort of 678 stable RTR. Prospective associations were assessed using Cox regression analyses. Graft failure was defined as the start of dialysis or re-transplantation. In RTR (58% male, 53 ± 13 years old, estimated glomerular filtration rate (eGFR) 45 ± 19 mL/min/1.73 m2), urinary taurine excretion (533 (210–946) µmol/24 h) was significantly associated with serum free sulfhydryl groups (β = 0.126; P = 0.001). During median follow-up for 5.3 (4.5–6.0) years, 83 (12%) patients developed graft failure. In Cox regression analyses, urinary taurine excretion was inversely associated with graft failure (hazard ratio: 0.74 (0.67–0.82); P < 0.001). This association remained significant independent of potential confounders. High urinary taurine excretion is associated with low risk of late graft failure in RTR. Therefore, increasing taurine intake may potentially support graft survival in RTR. Further studies are warranted to determine the underlying mechanisms and the potential of taurine supplementation.