Miracle-dz/UniFAR-FTUs huggingface dataset:
Descriptive Histopathological and Ultrastructural Study of Hepatocellular Alterations Induced by Aflatoxin B1 in Rats

Simple Summary Aflatoxins can affect hepatocytes, which results in a series of histological and ultrastructural changes to the cells. We investigated the hepatocellular alterations induced by aflatoxin B1 in rats. Interestingly, we observed several histopathological and ultrastructural alterations in hepatocytes, including necrotic changes and massive vacuolar degeneration. Ultrastructural examinations of treated groups revealed damage to the sinusoidal endothelium, as well as aggregations of hyperactive Kupffer cells in the space of Disse and damaged telocytes. Our findings provide novel insights into the induction of a series of irreversible adverse effects on hepatocytes by aflatoxin B1. Based on our results, we suggest future investigations for the exploration of mechanistic pathways related to these induced hepatocellular alterations. Abstract Liver sinusoids are lined by fenestrated endothelial cells surrounded by perisinusoidal cells, Kupffer cells, and pit cells, as well as large granular lymphocytes. The functional ability of the liver cells can be substantially modified by exposure to toxins. In the current work, we assessed the histopathological and ultrastructural effects of a time-course exposure to aflatoxin B1 (AFB1) on the hepatic structures of rats. A total of 30 adult female Wistar rats were randomly divided into three groups: a control group, a group orally administered 250 µg/kg body weight/day of AFB1 for 5 days/week over 4 weeks, and a group that received the same AFB1 treatment but over 8 weeks. Histopathological and ultrastructural examinations of hepatocytes revealed massive vacuolar degeneration and signs of necrosis. Furthermore, the rat liver of the treated group exhibited damage to the sinusoidal endothelium, invasion of the space of Disse with hyperactive Kupffer cells, and some immune cells, as well as Ito cells overloaded with lipids. In addition, damaged telocytes were observed. Taken together, our results indicate that AFB1 induces irreversible adverse effects on the livers of rats.
Effect of Compaction Pressure and Moisture Content on Post-Agglomeration Elastic Springback of Pellets

Renewable energy sources (RES) represent an increasing share of global energy production. Biomass has the highest potential of all RES. Biomass is used to produce solid biofuels, liquid biofuels, and gaseous biofuels. One of the main directions of research on solid biofuels is to optimize the agglomeration process. The main factors determining the characteristics of the final product in the production of pellets are process and material parameters. Process parameters include compaction pressure, temperature, and geometry of the matrix channel. The parameters of the material are the type of biomass, moisture content, degree of fragmentation, and method of preparation of the material (e.g., drying). The process of pressure compaction is always associated with the negative phenomenon of elastic springback. The aim of this work was to check the influence of compaction pressure and material moisture content on the springback value. The research was conducted on three materials (giant miscanthus, cup plant and Virginia mallow), using four different pressures (131, 196, 262, and 327 MPa) and three different moisture levels (8, 11, and 14%). For all material springback values, the range was 9–16%. Statistical analysis showed that for all plants tested, the effects of compaction pressure and moisture content significantly affected the elastic springback value. Areas of high value springback in the pattern of process parameters were determined.
Association of Thigh Muscle Strength with Texture Features Based on Proton Density Fat Fraction Maps Derived from Chemical Shift Encoding-Based Water–Fat MRI

Purpose: Based on conventional and quantitative magnetic resonance imaging (MRI), texture analysis (TA) has shown encouraging results as a biomarker for tissue structure. Chemical shift encoding-based water–fat MRI (CSE-MRI)-derived proton density fat fraction (PDFF) of thigh muscles has been associated with musculoskeletal, metabolic, and neuromuscular disorders and was demonstrated to predict muscle strength. The purpose of this study was to investigate PDFF-based TA of thigh muscles as a predictor of thigh muscle strength in comparison to mean PDFF. Methods: 30 healthy subjects (age = 30 ± 6 years; 15 females) underwent CSE-MRI of the lumbar spine at 3T, using a six-echo 3D spoiled gradient echo sequence. Quadriceps (EXT) and ischiocrural (FLEX) muscles were segmented to extract mean PDFF and texture features. Muscle flexion and extension strength were measured with an isokinetic dynamometer. Results: Of the eleven extracted texture features, Variance(global) showed the highest significant correlation with extension strength (p < 0.001, R2adj = 0.712), and Correlation showed the highest significant correlation with flexion strength (p = 0.016, R2adj = 0.658). Multivariate linear regression models identified Variance(global) and sex, but not PDFF, as significant predictors of extension strength (R2adj = 0.709; p < 0.001), while mean PDFF, sex, and BMI, but none of the texture features, were identified as significant predictors of flexion strength (R2adj = 0.674; p < 0.001). Conclusions: Prediction of quadriceps muscle strength can be improved beyond mean PDFF by means of TA, indicating the capability to quantify muscular fat infiltration patterns.
Underutilized Mexican Plants: Screening of Antioxidant and Antiproliferative Properties of Mexican Cactus Fruit Juices

Cacti fruits are known to possess antioxidant and antiproliferative activities among other health benefits. The following paper evaluated the antioxidant capacity and bioactivity of five clarified juices from different cacti fruits (Stenocereus spp., Opuntia spp. and M. geomettizans) on four cancer cell lines as well as one normal cell line. Their antioxidant compositions were measured by three different protocols. Their phenolic compositions were quantified through high performance liquid chromatography and the percentages of cell proliferation of fibroblasts as well as breast, prostate, colorectal, and liver cancer cell lines were evaluated though in vitro assays. The results were further processed by principal component analysis. The clarified juice from M. geomettizans fruit showed the highest concentration of total phenolic compounds and induced cell death in liver and colorectal cancer cells lines as well as fibroblasts. The clarified juice extracted from yellow Opuntia ficus-indica fruit displayed antioxidant activity as well as a selective cytotoxic effect on a liver cancer cell line with no toxic effect on fibroblasts. In conclusion, the work supplies evidence on the antioxidant and antiproliferative activities that cacti juices possess, presenting potential as cancer cell proliferation preventing agents.
Footwear Affects Conventional and Sumo Deadlift Performance

Barefoot weightlifting has become a popular training modality in recent years due to anecdotal suggestions of improved performance. However, research to support these anecdotal claims is limited. Therefore, the purpose of this study was to assess the differences between the conventional deadlift (CD) and the sumo deadlift (SD) in barefoot and shod conditions. On day one, one-repetition maximums (1 RM) were assessed for thirty subjects in both the CD and SD styles. At least 72 h later, subjects returned to perform five repetitions in four different conditions (barefoot and shod for both CD and SD) at 70% 1 RM. A 2 × 2 (footwear × lifting style) MANOVA was used to assess differences between peak vertical ground reaction force (VGRF), total mechanical work (WORK), barbell vertical displacement (DISP), peak vertical velocity (PV) and lift time (TIME) during the concentric phase. The CD displayed significant increases in VGRF, DISP, WORK, and TIME over the SD. The shod condition displayed increased WORK, DISP, and TIME compared to the barefoot condition. This study suggests that lifting barefoot does not improve performance as no differences in VGRF or PV were evident. The presence of a shoe does appear to increase the DISP and WORK required to complete the lift, suggesting an increased work load is present while wearing shoes.
An Oncolytic Adenovirus Encoding SA-4-1BBL Adjuvant Fused to HPV-16 E7 Antigen Produces a Specific Antitumor Effect in a Cancer Mouse Model

Human papillomaviruses (HPVs) are responsible for about 25% of cancer cases worldwide. HPV-16 E7 antigen is a tumor-associated antigen (TAA) commonly expressed in HPV-induced tumors; however, it has low immunogenicity. The interaction of 4-1BBL with its receptor induces pleiotropic effects on innate, adaptive, and regulatory immunity and, if fused to TAAs in DNA vaccines, can improve the antitumor response; however, there is low transfection and antitumor efficiency. Oncolytic virotherapy is promising for antitumor gene therapy as it can be selectively replicated in tumor cells, inducing cell lysis, and furthermore, tumor cell debris can be taken in by immune cells to potentiate antitumor responses. In this study, we expressed the immunomodulatory molecule SA-4-1BBL fused to E7 on an oncolytic adenovirus (OAd) system. In vitro infection of TC-1 tumor cells and NIH-3T3 non-tumor cells with SA/E7/4-1BBL OAd demonstrated that only tumor cells are selectively destroyed. Moreover, protein expression is targeted to the endoplasmic reticulum in both cell lines when a signal peptide (SP) is added. Finally, in an HPV-induced cancer murine model, the therapeutic oncolytic activity of OAd can be detected, and this can be improved when fused to E7 and SP.
Multimodal Signal Analysis for Pain Recognition in Physiotherapy Using Wavelet Scattering Transform

Fascial therapy is an effective, yet painful, procedure. Information about pain level is essential for the physiotherapist to adjust the therapy course and avoid potential tissue damage. We have developed a method for automatic pain-related reaction assessment in physiotherapy due to the subjectivity of a self-report. Based on a multimodal data set, we determine the feature vector, including wavelet scattering transforms coefficients. The AdaBoost classification model distinguishes three levels of reaction (no-pain, moderate pain, and severe pain). Because patients vary in pain reactions and pain resistance, our survey assumes a subject-dependent protocol. The results reflect an individual perception of pain in patients. They also show that multiclass evaluation outperforms the binary recognition.
Sarcopenic Obesity in Liver Cirrhosis: Possible Mechanism and Clinical Impact

The picture of chronic liver diseases (CLDs) has changed considerably in recent years. One of them is the increase of non-alcoholic fatty liver disease. More and more CLD patients, even those with liver cirrhosis (LC), tend to be presenting with obesity these days. The annual rate of muscle loss increases with worsening liver reserve, and thus LC patients are more likely to complicate with sarcopenia. LC is also characterized by protein-energy malnutrition (PEM). Since the PEM in LC can be invariable, the patients probably present with sarcopenic obesity (Sa-O), which involves both sarcopenia and obesity. Currently, there is no mention of Sa-O in the guidelines; however, the rapidly increasing prevalence and poorer clinical consequences of Sa-O are recognized as an important public health problem, and the diagnostic value of Sa-O is expected to increase in the future. Sa-O involves a complex interplay of physiological mechanisms, including increased inflammatory cytokines, oxidative stress, insulin resistance, hormonal disorders, and decline of physical activity. The pathogenesis of Sa-O in LC is diverse, with a lot of perturbations in the muscle–liver–adipose tissue axis. Here, we overview the current knowledge of Sa-O, especially focusing on LC.
Long-Term Shaping of Corticostriatal Synaptic Activity by Acute Fasting

Food restriction is a robust nongenic, nonsurgical and nonpharmacologic intervention known to improve health and extend lifespan in various species. Food is considered the most essential and frequently consumed natural reward, and current observations have demonstrated homeostatic responses and neuroadaptations to sustained intermittent or chronic deprivation. Results obtained to date indicate that food deprivation affects glutamatergic synapses, favoring the insertion of GluA2-lacking α-Ammino-3-idrossi-5-Metil-4-idrossazol-Propionic Acid receptors (AMPARs) in postsynaptic membranes. Despite an increasing number of studies pointing towards specific changes in response to dietary restrictions in brain regions, such as the nucleus accumbens and hippocampus, none have investigated the long-term effects of such practice in the dorsal striatum. This basal ganglia nucleus is involved in habit formation and in eating behavior, especially that based on dopaminergic control of motivation for food in both humans and animals. Here, we explored whether we could retrieve long-term signs of changes in AMPARs subunit composition in dorsal striatal neurons of mice acutely deprived for 12 hours/day for two consecutive days by analyzing glutamatergic neurotransmission and the principal forms of dopamine and glutamate-dependent synaptic plasticity. Overall, our data show that a moderate food deprivation in experimental animals is a salient event mirrored by a series of neuroadaptations and suggest that dietary restriction may be determinant in shaping striatal synaptic plasticity in the physiological state.
Dielectrophoretic Characterization of Tenogenically Differentiating Mesenchymal Stem Cells

Tendons are collagenous musculoskeletal tissues that connect muscles to bones and transfer the forces necessary for movement. Tendons are susceptible to injury and heal poorly, with long-term loss of function. Mesenchymal stem cell (MSC)-based therapies are a promising approach for treating tendon injuries but are challenged by the difficulties of controlling stem cell fate and of generating homogenous populations of stem cells optimized for tenogenesis (differentiation toward tendon). To address this issue, we aim to explore methods that can be used to identify and ultimately separate tenogenically differentiated MSCs from non-tenogenically differentiated MSCs. In this study, baseline and tenogenically differentiating murine MSCs were characterized for dielectric properties (conductivity and permittivity) of their outer membrane and cytoplasm using a dielectrophoretic (DEP) crossover technique. Experimental results showed that unique dielectric properties distinguished tenogenically differentiating MSCs from controls after three days of tenogenic induction. A single shell model was used to quantify the dielectric properties and determine membrane and cytoplasm conductivity and permittivity. Together, cell responses at the crossover frequency, cell morphology, and shell models showed that changes potentially indicative of early tenogenesis could be detected in the dielectric properties of MSCs as early as three days into differentiation. Differences in dielectric properties with tenogenesis indicate that the DEP-based label-free separation of tenogenically differentiating cells is possible and avoids the complications of current label-dependent flow cytometry-based separation techniques. Overall, this work illustrates the potential of DEP to generate homogeneous populations of differentiated stem cells for applications in tissue engineering and regenerative medicine.
Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models

Chordomas are rare, slow-growing tumors of the axial skeleton. These tumors are locally aggressive and refractory to conventional therapies. Radical surgery and radiation remain the first-line treatments. Despite these aggressive treatments, chordomas often recur and second-line treatment options are limited. The mechanisms underlying chordoma radioresistance remain unknown, although several radioresistant cancer cells have been shown to respond favorably to aldehyde dehydrogenase (ALDH) inhibition. The study of chordoma has been delayed by small patient cohorts and few available models due to the scarcity of these tumors. We thus created cellular 3D models of chordoma by using low-adherence culture systems. Then, we evaluated their radiosensitivity using colony-forming and spheroid size assays. Finally, we determined whether pharmacologically inhibiting ALDH increased their radiosensitivity. We found that 3D cellular models of chordoma (derived from primary, relapse, and metastatic tumors) reproduce the histological and gene expression features of the disease. The metastatic, relapse, and primary spheroids displayed high, medium, and low radioresistance, respectively. Moreover, inhibiting ALDH decreased the radioresistance in all three models.
Feline Leukemia Virus p27 Antigen Concentration and Proviral DNA Load Are Associated with Survival in Naturally Infected Cats

Longitudinal studies of cats naturally infected with feline leukemia virus (FeLV) are important for understanding disease outcomes. Levels of p27 antigen and copy numbers of proviral DNA have been associated with FeLV-infection courses. The purpose of this prospective study was to establish cutoff values for p27 antigen concentration and proviral DNA load that distinguished high positive from low positive groups of cats and to evaluate an association with survival. At enrollment, 254 cats were tested by point-of-care and microtiter plate enzyme-linked immunosorbent assays (ELISAs) for p27 antigen and real-time polymerase chain reaction (PCR) for proviral DNA. The 127 positive cats were retested monthly for six months and monitored for survival over the four-year study. A receiver operating characteristic-based analysis of samples with concordant or discordant qualitative results for p27 antigen and proviral DNA was used to establish cutoff values, and when applied to test results at enrollment for classifying cats as high positive or low positive, a significant difference in survival was observed. High positive cats had a median survival of 1.37 years (95% CI 0.83–2.02) from time of enrollment, while most low positive cats were still alive (93.1% survival). Quantitative results for p27 antigen concentration and proviral DNA load were highly correlated with survival times in FeLV-infected cats.
Defects in Graphene/h-BN Planar Heterostructures: Insights into the Interfacial Thermal Transport Properties

In this work, the defects (local stress generated) induce the formation of graphene/h-BN planar heterostructure (Gr-hBN-PH) to form "unsteady structure". Then, the coupling effects of external field (heat flow direction, strain and temperature field) and internal field (defect number, geometry shape and interfacial configuration) on the interface thermal conductivity (ITC) of Gr-hBN-PH were studied. The results show phonon transmission is less affected by compression deformation under the action of force-heat-defect coupling, while phonon transmission of heterostructure is more affected by tensile deformation. The non-harmonic interaction of the atoms in the composite system is strengthened, causing the softening of high-frequency phonons. The greater reduction of thermal transport at the interface of heterostructures will be. The interface bonding morphology plays a significant role on the ITC of the Gr-hBN-PH. The relationship between structure and properties in the low dimension is analyzed from the perspective of defect energy. It is helpful for us to understand the physical mechanism of low-dimensional structure, realize multiple structural forms, and even explore new uses.
Implementing Precision Medicine in Human Frailty through Epigenetic Biomarkers

The main epigenetic features in aging are: reduced bulk levels of core histones, altered pattern of histone post-translational modifications, changes in the pattern of DNA methylation, replacement of canonical histones with histone variants, and altered expression of non-coding RNA. The identification of epigenetic mechanisms may contribute to the early detection of age-associated subclinical changes or deficits at the molecular and/or cellular level, to predict the development of frailty, or even more interestingly, to improve health trajectories in older adults. Frailty reflects a state of increased vulnerability to stressors as a result of decreased physiologic reserves, and even dysregulation of multiple physiologic systems leading to adverse health outcomes for individuals of the same chronological age. A key approach to overcome the challenges of frailty is the development of biomarkers to improve early diagnostic accuracy and to predict trajectories in older individuals. The identification of epigenetic biomarkers of frailty could provide important support for the clinical diagnosis of frailty, or more specifically, to the evaluation of its associated risks. Interventional studies aimed at delaying the onset of frailty and the functional alterations associated with it, would also undoubtedly benefit from the identification of frailty biomarkers. Specific to the article yet reasonably common within the subject discipline.
Differential Effects of Trp53 Alterations in Murine Colorectal Cancer

Simple Summary Although colorectal cancer is among the most frequent malignant tumors, there are currently no mouse models available that reliably mimic both tumor biology as well as treatment response. In this article, we describe a novel mouse model in which mutations relevant to colorectal cancer are induced in mice, leading to tumor formation in the distal colon. The tumors are monitored via colonoscopy, and the survival and the histology of the tumors are examined. We demonstrate that this model can closely model the human disease clinically, histologically and genetically. In addition, the response of this model to classical colorectal cancer treatments is more realistic than that of other mouse models. The effects of different mutations in the Trp53 gene on tumor cells show striking differences, similar to the effects in other tumor diseases. In summary, the new model allows more accurate and predictive experiments in colorectal cancer. Abstract Background: Colorectal cancer (CRC) development is a multi-step process resulting in the accumulation of genetic alterations. Despite its high incidence, there are currently no mouse models that accurately recapitulate this process and mimic sporadic CRC. We aimed to develop and characterize a genetically engineered mouse model (GEMM) of Apc/Kras/Trp53 mutant CRC, the most frequent genetic subtype of CRC. Methods: Tumors were induced in mice with conditional mutations or knockouts in Apc, Kras, and Trp53 by a segmental adeno-cre viral infection, monitored via colonoscopy and characterized on multiple levels via immunohistochemistry and next-generation sequencing. Results: The model accurately recapitulates human colorectal carcinogenesis clinically, histologically and genetically. The Trp53 R172H hotspot mutation leads to significantly increased metastatic capacity. The effects of Trp53 alterations, as well as the response to treatment of this model, are similar to human CRC. Exome sequencing revealed spontaneous protein-modifying alterations in multiple CRC-related genes and oncogenic pathways, resulting in a genetic landscape resembling human CRC. Conclusions: This model realistically mimics human CRC in many aspects, allows new insights into the role of TP53 in CRC, enables highly predictive preclinical studies and demonstrates the value of GEMMs in current translational cancer research and drug development.