Miracle-dz/UniFAR-FTUs huggingface dataset:
Microvascular Experimentation in the Chick Chorioallantoic Membrane as a Model for Screening Angiogenic Agents including from Gene-Modified Cells

The chick chorioallantoic membrane (CAM) assay model of angiogenesis has been highlighted as a relatively quick, low cost and effective model for the study of pro-angiogenic and anti-angiogenic factors. The chick CAM is a highly vascularised extraembryonic membrane which functions for gas exchange, nutrient exchange and waste removal for the growing chick embryo. It is beneficial as it can function as a treatment screening tool, which bridges the gap between cell based in vitro studies and in vivo animal experimentation. In this review, we explore the benefits and drawbacks of the CAM assay to study microcirculation, by the investigation of each distinct stage of the CAM assay procedure, including cultivation techniques, treatment applications and methods of determining an angiogenic response using this assay. We detail the angiogenic effect of treatments, including drugs, metabolites, genes and cells used in conjunction with the CAM assay, while also highlighting the testing of genetically modified cells. We also present a detailed exploration of the advantages and limitations of different CAM analysis techniques, including visual assessment, histological and molecular analysis along with vascular casting methods and live blood flow observations.
Structural and Dynamic Determinants of Molecular Recognition in Bile Acid-Binding Proteins

Disorders in bile acid transport and metabolism have been related to a number of metabolic disease states, atherosclerosis, type-II diabetes, and cancer. Bile acid-binding proteins (BABPs), a subfamily of intracellular lipid-binding proteins (iLBPs), have a key role in the cellular trafficking and metabolic targeting of bile salts. Within the family of iLBPs, BABPs exhibit unique binding properties including positive binding cooperativity and site-selectivity, which in different tissues and organisms appears to be tailored to the local bile salt pool. Structural and biophysical studies of the past two decades have shed light on the mechanism of bile salt binding at the atomic level, providing us with a mechanistic picture of ligand entry and release, and the communication between the binding sites. In this review, we discuss the emerging view of bile salt recognition in intestinal- and liver-BABPs, with examples from both mammalian and non-mammalian species. The structural and dynamic determinants of the BABP-bile–salt interaction reviewed herein set the basis for the design and development of drug candidates targeting the transcellular traffic of bile salts in enterocytes and hepatocytes.
Impact of Uremic Toxins on Endothelial Dysfunction in Chronic Kidney Disease: A Systematic Review

Patients with chronic kidney disease (CKD) are at a highly increased risk of cardiovascular complications, with increased vascular inflammation, accelerated atherogenesis and enhanced thrombotic risk. Considering the central role of the endothelium in protecting from atherogenesis and thrombosis, as well as its cardioprotective role in regulating vasorelaxation, this study aimed to systematically integrate literature on CKD-associated endothelial dysfunction, including the underlying molecular mechanisms, into a comprehensive overview. Therefore, we conducted a systematic review of literature describing uremic serum or uremic toxin-induced vascular dysfunction with a special focus on the endothelium. This revealed 39 studies analyzing the effects of uremic serum or the uremic toxins indoxyl sulfate, cyanate, modified LDL, the advanced glycation end products N-carboxymethyl-lysine and N-carboxyethyl-lysine, p-cresol and p-cresyl sulfate, phosphate, uric acid and asymmetric dimethylarginine. Most studies described an increase in inflammation, oxidative stress, leukocyte migration and adhesion, cell death and a thrombotic phenotype upon uremic conditions or uremic toxin treatment of endothelial cells. Cellular signaling pathways that were frequently activated included the ROS, MAPK/NF-κB, the Aryl-Hydrocarbon-Receptor and RAGE pathways. Overall, this review provides detailed insights into pathophysiological and molecular mechanisms underlying endothelial dysfunction in CKD. Targeting these pathways may provide new therapeutic strategies reducing increased the cardiovascular risk in CKD.
Differential Analysis of Volumetric Strain Method Characterization in the Context of Phase Change of Water in Carbonate Rocks

Modernized technological processes or increasing demands on building materials force the scientific community to analyze in more detail the suitability of individual raw materials and deposits. New or modernized research methodologies make it possible to better understand not only the geometrical structure of the pore space of materials but also the processes taking place in them and the interaction of many factors at the same time. Despite the extensive literature in the field of research on capillary-porous materials, scientists still face many challenges because not everything is known. Carbonate rocks are the most common (one-tenth of Earth’s crust) sedimentary rocks. Analysis of the test results obtained with the use of the modernized differentia analysis of volumetric strain (DAVS) methodology allows for a better adjustment of rock deposits to the products that can be produced from them. In this manner, it is possible that it will contribute to a more rational use of exhaustible rock deposits and not only carbonate ones. This research subject is of great importance for modern science, which was also noted in many of science publications.
Gestational Diabetes, Colorectal Cancer, Bariatric Surgery, and Weight Loss among Diabetes Mellitus Patients: A Mini Review of the Interplay of Multispecies Probiotics

Diabetes mellitus has been steadily increasing over the past decades and is one of the most significant global public health concerns. Diabetes mellitus patients have an increased risk of both surgical and post-surgical complications. The post-surgical risks are associated with the primary condition that led to surgery and the hyperglycaemia per se. Gut microbiota seems to contribute to glucose homeostasis and insulin resistance. It affects the metabolism through body weight and energy homeostasis, integrating the peripheral and central food intake regulatory signals. Homeostasis of gut microbiota seems to be enhanced by probiotics pre and postoperatively. The term probiotics is used to describe some species of live microorganisms that, when administered in adequate amounts, confer health benefits on the host. The role of probiotics in intestinal or microbial skin balance after abdominal or soft tissue elective surgeries on DM patients seems beneficial, as it promotes anti-inflammatory cytokine production while increasing the wound-healing process. This review article aims to present the interrelation of probiotic supplements with DM patients undergoing elective surgeries.
Androgen Effects on Neural Plasticity

Androgens are synthesized in the brain, gonads, and adrenal glands, in both sexes, exerting physiologically important effects on the structure and function of the central nervous system. These effects may contribute to the incidence and progression of neurological disorders such as autism spectrum disorder, schizophrenia, and Alzheimer's disease, which occur at different rates in males and females. This review briefly summarizes the current state of knowledge with respect to the neuroplastic effects of androgens, with particular emphasis on the hippocampus, which has been the focus of much of the research in this field.
The Interplay between Kinetics and Thermodynamics in Furan Diels–Alder Chemistry for Sustainable Chemicals Production

Abstract Biomass‐derived furanic platform molecules have emerged as promising building blocks for renewable chemicals and functional materials. To this aim, the Diels–Alder (DA) cycloaddition stands out as a versatile strategy to convert these renewable resources in highly atom‐efficient ways. Despite nearly a century worth of examples of furan DA chemistry, clear structure–reactivity–stability relationships are still to be established. Detailed understanding of the intricate interplay between kinetics and thermodynamics in these very particular [4+2] cycloadditions is essential to push further development and truly expand the scope beyond the ubiquitous addend combinations of electron‐rich furans and electron‐deficient olefins. Herein, we provide pertinent examples of DA chemistry, taken from various fields, to highlight trends, establish correlations and answer open questions in the field with the aim to support future efforts in the sustainable chemicals and materials production.
Tongue Leptin Decreases Oro-Sensory Perception of Dietary Fatty Acids

Leptin, an anorectic hormone, regulates food intake, energy expenditure and body weight. We assessed the implication of tongue leptin in the modulation of oro-sensory detection of dietary fatty acids in mice. The RT-PCR analysis showed that mRNA encoding leptin and leptin receptor (Ob-Rb) was expressed in mice taste bud cells (TBC). Confocal microscopic studies showed that the lipid sensor CD36 was co-expressed with leptin in mice TBC. Silencing of leptin or Ob-Rb mRNA in tongue papillae upregulated preference for a long-chain fatty acid (LCFA), i.e., linoleic acid (LA), in a two-bottle paradigm in mice. Furthermore, tongue leptin application decreased the preference for the LCFA. These results suggest that tongue leptin exerts an inhibitory action on fatty acid preference. In isolated mice TBC, leptin decreased LCFA-induced increases in free intracellular calcium concentrations, [Ca2+]i. Leptin and LCFA induced the phosphorylation of ERK1/2 and STAT-3 and there were no additive or opposite effects of the two agents on the degree of phosphorylation. However, leptin, but not the LCFA, induced phosphoinositide-3-kinase (PI-3-K)-dependent Akt phosphorylation in TBC. Furthermore, leptin induced hyperpolarization, whereas LCFA induced depolarization in TBC. Our study demonstrates that tongue leptin exerts an inhibitory action on oro-sensory detection of a dietary fatty acid by interfering with Ca2+ signaling and membrane potential in mice TBC.
Multi-Task Model for Esophageal Lesion Analysis Using Endoscopic Images: Classification with Image Retrieval and Segmentation with Attention

The automatic analysis of endoscopic images to assist endoscopists in accurately identifying the types and locations of esophageal lesions remains a challenge. In this paper, we propose a novel multi-task deep learning model for automatic diagnosis, which does not simply replace the role of endoscopists in decision making, because endoscopists are expected to correct the false results predicted by the diagnosis system if more supporting information is provided. In order to help endoscopists improve the diagnosis accuracy in identifying the types of lesions, an image retrieval module is added in the classification task to provide an additional confidence level of the predicted types of esophageal lesions. In addition, a mutual attention module is added in the segmentation task to improve its performance in determining the locations of esophageal lesions. The proposed model is evaluated and compared with other deep learning models using a dataset of 1003 endoscopic images, including 290 esophageal cancer, 473 esophagitis, and 240 normal. The experimental results show the promising performance of our model with a high accuracy of 96.76% for the classification and a Dice coefficient of 82.47% for the segmentation. Consequently, the proposed multi-task deep learning model can be an effective tool to help endoscopists in judging esophageal lesions.
Measured Hyperelastic Properties of Cervical Tissue with Shear-Wave Elastography

The nonlinear mechanical behaviour of cervical tissue causes unpredictable changes in measured elastograms when pressure is applied. These uncontrolled variables prevent the reliable measurement of tissue elasticity in a clinical setting. Measuring the nonlinear properties of tissue is difficult due to the need for both shear modulus and strain to be taken simultaneously. A simulation-based method is proposed in this paper to resolve this. This study describes the nonlinear behaviour of cervical tissue using the hyperelastic material models of Demiray–Fung and Veronda–Westmann. Elastograms from 33 low-risk patients between 18 and 22 weeks gestation were obtained. The average measured properties of the hyperelastic material models are: Demiray–Fung—A1α = 2.07 (1.65–2.58) kPa, α = 6.74 (4.07–19.55); Veronda–Westmann—C1C2 = 4.12 (3.24–5.04) kPa, C2 = 4.86 (2.86–14.28). The Demiray–Fung and Veronda–Westmann models performed similarly in fitting to the elastograms with an average root mean square deviation of 0.41 and 0.47 ms−1, respectively. The use of hyperelastic material models to calibrate shear-wave speed measurements improved the consistency of measurements. This method could be applied in a large-scale clinical setting but requires updated models and higher data resolution.
Patients’ Perceptions of Integrated Care Among Medicare Beneficiaries by Level of Need for Health Services

Requirements for integrating care across providers, settings, and over time increase with patients’ needs. Health care providers’ ability to offer care that patients experience as integrated may vary among patients with different levels of need. We explore the variation in patients’ perceptions of integrated care among Medicare beneficiaries based on the beneficiary’s level of need using ordinary least square regression for each of four high-need groups: beneficiaries (a) with complex chronic conditions, (b) with frailties, (c) below 65 with disability, and (d) with any (of the first three) high needs. We control for beneficiary demographics and other factors affecting integrated care, and we conduct sensitivity analyses controlling for multiple individual chronic conditions. We find significant positive associations with level of need for provider support for self-directed care and medication and home health management. Controlling for multiple individual chronic conditions reduces effect sizes and number of significant relationships.
Effects of dual chelation therapy with deferasirox and deferoxamine in patients with beta thalassaemia major

Patients with thalassaemia experience complications related to iron overload. In Australia currently, the two main options for iron chelation are deferasirox and deferoxamine. Optimal iron chelation using monotherapy can be limited due to toxicity or tolerability. Dual chelation therapy (DCT) may provide more aggressive iron chelation.
Fault Identification in Electric Servo Actuators of Robot Manipulators Described by Nonstationary Nonlinear Dynamic Models Using Sliding Mode Observers

The problem of fault identification in electric servo actuators of robot manipulators described by nonstationary nonlinear dynamic models under disturbances is considered. To solve the problem, sliding mode observers are used. The suggested approach is based on the reduced order model of the original system having different sensitivity to faults and disturbances. This model is realized in canonical form that enables relaxing the limitation imposed on the original system. Theoretical results are illustrated by practical example.
Splitting the P-Wave: Improved Evaluation of Left Atrial Substrate Modification after Pulmonary Vein Isolation of Paroxysmal Atrial Fibrillation

Atrial substrate modification after pulmonary vein isolation (PVI) of paroxysmal atrial fibrillation (pAF) can be assessed non-invasively by analyzing P-wave duration in the electrocardiogram (ECG). However, whether right (RA) and left atrium (LA) contribute equally to this phenomenon remains unknown. The present study splits fundamental P-wave features to investigate the different RA and LA contributions to P-wave duration. Recordings of 29 pAF patients undergoing first-ever PVI were acquired before and after PVI. P-wave features were calculated: P-wave duration (PWD), duration of the first (PWDon-peak) and second (PWDpeak-off) P-wave halves, estimating RA and LA conduction, respectively. P-wave onset (PWon-R) or offset (PWoff-R) to R-peak interval, measuring combined atrial/atrioventricular and single atrioventricular conduction, respectively. Heart-rate fluctuation was corrected by scaling. Pre- and post-PVI results were compared with Mann–Whitney U-test. PWD was correlated with the remaining features. Only PWD (non-scaling: Δ=−9.84%, p=0.0085, scaling: Δ=−17.96%, p=0.0442) and PWDpeak-off (non-scaling: Δ=−22.03%, p=0.0250, scaling: Δ=−27.77%, p=0.0268) were decreased. Correlation of all features with PWD was significant before/after PVI (p<0.0001), showing the highest value between PWD and PWon-R (ρmax=0.855). PWD correlated more with PWDon-peak (ρ= 0.540–0.805) than PWDpeak-off (ρ= 0.419–0.710). PWD shortening after PVI of pAF stems mainly from the second half of the P-wave. Therefore, noninvasive estimation of LA conduction time is critical for the study of atrial substrate modification after PVI and should be addressed by splitting the P-wave in order to achieve improved estimations.
Role and Involvement of TENM4 and miR-708 in Breast Cancer Development and Therapy

Teneurin 4 (TENM4) is a transmembrane protein that is codified by the ODZ4 gene and is involved in nervous system development, neurite outgrowth, and neuronal differentiation. In line with its involvement in the nervous system, TENM4 has also been implicated in several mental disorders such as bipolar disorder, schizophrenia, and autism. TENM4 mutations and rearrangements have recently been identified in a number of tumors. This, combined with impaired expression in tumors, suggests that it may potentially be involved in tumorigenesis. Most of the TENM4 mutations that are observed in tumors occur in breast cancer, in which TENM4 plays a role in cells’ migration and stemness. However, the functional role that TENM4 plays in breast cancer still needs to be better evaluated, and further studies are required to better understand the involvement of TENM4 in breast cancer progression. Herein, we review the currently available data for TENM4′s role in breast cancer and propose its use as both a novel target with which to ameliorate patient prognosis and as a potential biomarker. Moreover, we also report data on the tumorigenic role of miR-708 deregulation and the possible use of this miRNA as a novel therapeutic molecule, as miR-708 is spliced out from TENM4 mRNA.
S100‐stained perineural invasion is associated with worse prognosis in stage I/II colorectal cancer: Its possible association with immunosuppression in the tumor

Perineural invasion (PNI) is known as a poor prognostic factor in colorectal cancer (CRC). Although histopathological evaluation of PNI is usually conducted on hematoxylin and eosin (HE)‐stained sections (HE‐PNI), it remains controversial whether PNI can be precisely evaluated only by HE‐staining, and its concise mechanisms causing worse prognosis remains elusive. In this study, we examined the impact of PNI evaluated by S‐100‐immunostaining (S100‐PNI) on postoperative mortality in 279 consecutive CRC patients and further investigated its association with the tumor immune microenvironment. S100‐PNI was present in 67.3% of tumors whereas HE‐PNI was present in 18.5%. A 5‐year cumulative incidence of death in the S100‐PNI‐positive group was significantly higher than that in the S100‐PNI‐negative group. Further statistical analyses revealed that S100‐PNI was an independent prognostic factor of all‐cause mortality in stage I/II but not in stage III/IV. Importantly, S100‐PNI was associated with the altered tumor immune microenvironment. Infiltrating immune cell profiling revealed that stromal lymphocytic reaction, which was inversely correlated with postoperative mortality, was significantly reduced in S100‐PNI‐positive tumors compared to S100‐PNI‐negative tumors in stage I/II. These results indicated that S100‐PNI was a poor prognostic factor in stage I/II CRC with possible association with immunosuppression in the tumor.
Reducing misclassification of mild cognitive impairment based on base rate information from the Uniform data set

ABSTRACT The current study aimed to define and validate the criteria for characterizing possible and probable cognitive deficits based on the psychometric approach using the Uniform data set Czech version (UDS-CZ 2.0) to reduce the rate of misdiagnosis. We computed the prevalence of low scores on the 14 subtests of UDS-CZ 2.0 in a normative sample of healthy older adults and validated criteria for possible and probable cognitive impairment on the sample of amnestic Mild Cognitive Impairment (MCI) patients. The misclassification rate of the validation sample using psychometrically derived criteria remained low: for classification as possible impairment, we found 66–76% correct classification in the clinical sample and only 2–8% false positives in the healthy control validation sample, similar results were obtained for probable cognitive impairment. Our findings offer a psychometric approach and a computational tool to minimize the misdiagnosis of mild cognitive impairment compared to traditional criteria for MCI.
High versus low ultrafiltration rates during experimental peritoneal dialysis in rats: Acute effects on plasma volume and systemic haemodynamics

Introduction: Intradialytic hypotension is a common complication of haemodialysis, but uncommon in peritoneal dialysis (PD). This may be due to lower ultrafiltration rates in PD compared to haemodialysis, allowing for sufficient refilling of the blood plasma compartment from the interstitial volume, but the underlying mechanisms are unknown. Here we assessed plasma volume and hemodynamic alterations during experimental PD with high versus low ultrafiltration rates. Methods: Experiments were conducted in two groups of healthy Sprague-Dawley rats: one group with a high ultrafiltration rate (N = 7) induced by 8.5% glucose and a low UF group (N = 6; 1.5% glucose), with an initial assessment of the extracellular fluid volume, followed by 30 min PD with plasma volume measurements at baseline, 5, 10, 15 and 30 min. Mean arterial pressure, central venous pressure and heart rate were continuously monitored during the experiment. Results: No significant changes over time in plasma volume, mean arterial pressure or central venous pressure were detected during the course of the experiments, despite an ultrafiltration (UF) rate of 56 mL/h/kg in the high UF group. In the high UF group, a decrease in extracellular fluid volume of −7 mL (−10.7% (95% confidence interval: −13.8% to −7.6%)) was observed, in line with the average UF volume of 8.0 mL (standard deviation: 0.5 mL). Conclusion: Despite high UF rates, we found that plasma volumes were remarkably preserved in the present experiments, indicating effective refilling of the plasma compartment from interstitial tissues. Further studies should clarify which mechanisms preserve the plasma volume during high UF rates in PD.