Miracle-dz/UniFAR-FTUs huggingface dataset:
Biofabrication in Congenital Cardiac Surgery: A Plea from the Operating Theatre, Promise from Science

Despite significant advances in numerous fields of biofabrication, clinical application of biomaterials combined with bioactive molecules and/or cells largely remains a promise in an individualized patient settings. Three-dimensional (3D) printing and bioprinting evolved as promising techniques used for tissue-engineering, so that several kinds of tissue can now be printed in layers or as defined structures for replacement and/or reconstruction in regenerative medicine and surgery. Besides technological, practical, ethical and legal challenges to solve, there is also a gap between the research labs and the patients’ bedside. Congenital and pediatric cardiac surgery mostly deal with reconstructive patient-scenarios when defects are closed, various segments of the heart are connected, valves are implanted. Currently available biomaterials lack the potential of growth and conduits, valves derange over time surrendering patients to reoperations. Availability of viable, growing biomaterials could cancel reoperations that could entail significant public health benefit and improved quality-of-life. Congenital cardiac surgery is uniquely suited for closing the gap in translational research, rapid application of new techniques, and collaboration between interdisciplinary teams. This article provides a succinct review of the state-of-the art clinical practice and biofabrication strategies used in congenital and pediatric cardiac surgery, and highlights the need and avenues for translational research and collaboration.
Homelessness Is Socially Created: Cluster Analysis of Social Determinants of Homelessness (SODH) in North West England in 2020

Poverty creates social conditions that increase the likelihood of homelessness. These include exposure to traumatic life experiences; social disadvantages such as poor educational experiences; being raised in a broken family, care homes or foster care; physical, emotional, and sexual abuse; and neglect at an early age. These conditions reduce people’s ability to negotiate through life challenges. This cross-sectional study documents the clustering and frequency of adverse social conditions among 152 homeless people from four cities in North West England between January and August 2020. Two-step cluster analysis showed that having parents with a criminal record, care history, and child neglect/abuse history was predictive of homelessness. The cluster of indicator variables among homeless people included sexual abuse (χ2 (N = 152) = 220.684, p < 0.001, Cramer’s V = 0.7), inappropriate sexual behaviour (χ2 (N = 152) = 207.737, p < 0.001, Cramer’s V = 0.7), emotional neglect (χ2 (N = 152) = 181.671, p < 0.001, Cramer’s V = 0.7), physical abuse by step-parent (χ2 (N = 152) = 195.882, p < 0.001, Cramer’s V = 0.8), and physical neglect (χ2 (N = 152) = 205.632, p < 0.001, Cramer’s V = 0.8). Poverty and homelessness are intertwined because of the high prevalence of poverty among the homeless. Poverty sets up a chain of interactions between social conditions that increase the likelihood of unfavourable outcomes: homelessness is at the end of the interaction chain. Interventions supporting families to rise out of poverty may also reduce entry into homelessness.
A Systematic Review of MicroRNAs Involved in Cervical Cancer Progression

To obtain a better understanding on the role of microRNAs in the progression of cervical cancer, a systematic review was performed to analyze cervical cancer microRNA studies. We provide an overview of the studies investigating microRNA expression in relation to cervical cancer (CC) progression, highlighting their common outcomes and target gene interactions according to the regulatory pathways. To achieve this, we systematically searched through PubMed MEDLINE, EMBASE, and Google Scholar for all articles between April 2010 and April 2020, in accordance with the PICO acronym (participants, interventions, comparisons, outcomes). From 27 published reports, totaling 1721 cases and 1361 noncancerous control tissue samples, 26 differentially expressed microRNAs (DEmiRNAs) were identified in different International Federation of Gynecology and Obstetrics (FIGO) stages of cervical cancer development. It was identified that some of the dysregulated microRNAs were associated with specific stages of cervical cancer development. The results indicated that DEmiRNAs in different stages of cervical cancer were functionally involved in several key hallmarks of cancer, such as evading growth suppressors, enabling replicative immortality, activation of invasion and metastasis, resisting cell death, and sustained proliferative signaling. These dysregulated microRNAs could play an important role in cervical cancer’s development. Some of the stage-specific microRNAs can also be used as biomarkers for cancer classification and monitoring the progression of cervical cancer.
Methods Used and Application of the Mouse Grimace Scale in Biomedical Research 10 Years on: A Scoping Review

Simple Summary The Mouse Grimace Scale (MGS) was developed as a tool for the measurement of pain in laboratory mice. There have been a number of studies focused on the technique’s validity in different models, and across pain types. With this new information, it is important that a review following systematic methodology is performed on these studies to summarise the methods used, the validity across model types, and the effects of external variables. In this review, we present all of the available evidence on the MGS, together with an indication of the extent of the evidence available for each parameter considered. This review will provide an increased strength of evidence to guide researchers, ethics committees, and policy makers on the use and application of the MGS in biomedical research. Abstract The Mouse Grimace Scale (MGS) was developed 10 years ago as a method for assessing pain through the characterisation of changes in five facial features or action units. The strength of the technique is that it is proposed to be a measure of spontaneous or non-evoked pain. The time is opportune to map all of the research into the MGS, with a particular focus on the methods used and the technique’s utility across a range of mouse models. A comprehensive scoping review of the academic literature was performed. A total of 48 articles met our inclusion criteria and were included in this review. The MGS has been employed mainly in the evaluation of acute pain, particularly in the pain and neuroscience research fields. There has, however, been use of the technique in a wide range of fields, and based on limited study it does appear to have utility for pain assessment across a spectrum of animal models. Use of the method allows the detection of pain of a longer duration, up to a month post initial insult. There has been less use of the technique using real-time methods and this is an area in need of further research.
CMUT-Based Sensor for Acoustic Emission Application: Experimental and Theoretical Contributions to Sensitivity Optimization

The paper deals with a capacitive micromachined ultrasonic transducer (CMUT)-based sensor dedicated to the detection of acoustic emissions from damaged structures. This work aims to explore different ways to improve the signal-to-noise ratio and the sensitivity of such sensors focusing on the design and packaging of the sensor, electrical connections, signal processing, coupling conditions, design of the elementary cells and operating conditions. In the first part, the CMUT-R100 sensor prototype is presented and electromechanically characterized. It is mainly composed of a CMUT-chip manufactured using the MUMPS process, including 40 circular 100 µm radius cells and covering a frequency band from 310 kHz to 420 kHz, and work on the packaging, electrical connections and signal processing allowed the signal-to-noise ratio to be increased from 17 dB to 37 dB. In the second part, the sensitivity of the sensor is studied by considering two contributions: the acoustic-mechanical one is dependent on the coupling conditions of the layered sensor structure and the mechanical-electrical one is dependent on the conversion of the mechanical vibration to electrical charges. The acoustic-mechanical sensitivity is experimentally and numerically addressed highlighting the care to be taken in implementation of the silicon chip in the brass housing. Insertion losses of about 50% are experimentally observed on an acoustic test between unpackaged and packaged silicon chip configurations. The mechanical-electrical sensitivity is analytically described leading to a closed-form amplitude of the detected signal under dynamic excitation. Thus, the influence of geometrical parameters, material properties and operating conditions on sensitivity enhancement is clearly established: such as smaller electrostatic air gap, and larger thickness, Young’s modulus and DC bias voltage.
Cyanocobalamin Ultraflexible Lipid Vesicles: Characterization and In Vitro Evaluation of Drug-Skin Depth Profiles

Atopic dermatitis (AD) and psoriasis are the most common chronic inflammatory skin disorders, which importantly affect the quality of life of patients who suffer them. Among other causes, nitric oxide has been reported as part of the triggering factors in the pathogenesis of both conditions. Cyanocobalamin (vitamin B12) has shown efficacy as a nitric oxide scavenger and some clinical trials have given positive outcomes in its use for treating skin pathologies. Passive skin diffusion is possible only for drugs with low molecular weights and intermediate lipophilicity. Unfortunately, the molecular weight and hydrophilicity of vitamin B12 do not predict its effective diffusion through the skin. The aim of this work was to design new lipid vesicles to encapsulate the vitamin B12 to enhance its skin penetration. Nine prototypes of vesicles were generated and characterized in terms of size, polydispersity, surface charge, drug encapsulation, flexibility, and stability with positive results. Additionally, their ability to release the drug content in a controlled manner was demonstrated. Finally, we found that these lipid vesicle formulations facilitated the penetration of cyanocobalamin to the deeper layers of the skin. The present work shows a promising system to effectively administer vitamin B12 topically, which could be of interest in the treatment of skin diseases such as AD and psoriasis.
The Impacts of Crystalline Structure and Different Surface Functional Groups on Drug Release and the Osseointegration Process of Nanostructured TiO2

In implantable materials, surface topography and chemistry are the most important in the effective osseointegration and interaction with drug molecules. Therefore, structural and surface modifications of nanostructured titanium dioxide (TiO2) layers are reported in the present work. In particular, the modification of annealed TiO2 samples with —OH groups and silane derivatives, confirmed by X-ray photoelectron spectroscopy, is shown. Moreover, the ibuprofen release process was studied regarding the desorption-desorption-diffusion (DDD) kinetic model. The results proved that the most significant impact on the release profile is annealing, and further surface modifications did not change its kinetics. Additionally, the cell adhesion and proliferation were examined based on the MTS test and immunofluorescent staining. The obtained data showed that the proposed changes in the surface chemistry enhance the samples’ hydrophilicity. Moreover, improvements in the adhesion and proliferation of the MG-63 cells were observed.
CUPRAC-Reactive Advanced Glycation End Products as Prognostic Markers of Human Acute Myocardial Infarction

Cardiovascular disorders, especially acute coronary syndromes, are among the leading causes of mortality worldwide, and advanced glycation end products (AGEs) are associated with cardiovascular disease and serve as biomarkers for diagnosis and prediction. In this study, we investigated the utility of AGEs as prognostic biomarkers for acute myocardial infarction (AMI). We measured AGEs in serum samples of AMI patients (N = 27) using the cupric ion reducing antioxidant capacity (CUPRAC) method on days 0, 2, 14, 30, and 90 after AMI, and the correlation of serum AGE concentration and post-AMI duration was determined using Spearman’s correlation analysis. Compared to total serum protein, the level of CUPRAC reactive AGEs was increased from 0.9 to 2.1 times between 0–90 days after AMI incident. Furthermore, the glycation pattern and Spearman’s correlation analysis revealed four dominant patterns of AGE concentration changes in AMI patients: stable AGE levels (straight line with no peak), continuous increase, single peak pattern, and multimodal pattern (two or more peaks). In conclusion, CUPRAC-reactive AGEs can be developed as a potential prognostic biomarker for AMI through long-term clinical studies.
An Overview of Bio-Inspired Intelligent Imprinted Polymers for Virus Determination

The molecular imprinting polymers (MIPs) have shown their potential in various applications including pharmaceuticals, chemical sensing and biosensing, medical diagnosis, and environmental related issues, owing to their artificial selective biomimetic recognition ability. Despite the challenges posed in the imprinting and recognition of biomacromolecules, the use of MIP for the imprinting of large biomolecular oragnism such as viruses is of huge interest because of the necessity of early diagnosis of virus-induced diseases for clinical and point-of-care (POC) purposes. Thus, many fascinating works have been documented in which such synthetic systems undoubtedly explore a variety of potential implementations, from virus elimination, purification, and diagnosis to virus and bacteria-borne disease therapy. This study is focused comprehensively on the fabrication strategies and their usage in many virus-imprinted works that have appeared in the literature. The drawbacks, challenges, and perspectives are also highlighted.
Enterolignan Production in a Flaxseed Intervention Study in Postmenopausal US Women of African Ancestry and European Ancestry

Lignans are phytochemicals studied extensively as dietary factors in chronic disease etiology. Our goal was to examine associations between the gut microbiota and lignan metabolism and whether these associations differ by ethnicity. We conducted a flaxseed (FS) dietary intervention in 252 healthy, postmenopausal women of African ancestry (AA) and European ancestry (EA). Participants consumed ~10 g/d ground flaxseed for 6 weeks and provided overnight urine collections and fecal samples before and after intervention. The gut microbiota was characterized using 16S rRNA gene sequencing and differences in microbial community composition compared by ethnicity and intervention status. We observed a significant difference in the composition of the microbiota measured as beta diversity (p < 0.05) between AA and EA at baseline that was attenuated with FS consumption. Genera that were significantly associated with ENL production (e.g., Klebsiella, Lactobacillus, Slackia, Senegalimassilia) were unique to each group. Bacteria (e.g., Fusobacteria, Pyramidobacter and Odoribacter) previously associated with colorectal cancer and cardiovascular disease, both diet-related chronic diseases, were unique to either AA or EA and were significantly reduced in the FS intervention. This study suggests that ethnic variation in ENL metabolism may be linked to gut microbiota composition, and its impact on disease risk deserves future investigation.
A First-Principles Approach to Studying the Thermal Stability of Oxide Cathode Materials

We present a new method for predicting the thermodynamics of thermal degradation of charged cathode materials for rechargeable Li batteries and demonstrate it on three cathode materials, LixNiO2, LixCoO2, and LixMn2O4. The decomposition of LixNiO2 is a two-step process: the first step is a kinetically controlled exothermic conversion in which the layered structure transforms to the stable spinel structure. The second step is an endothermic decomposition of the spinel into a rocksalt phase, accompanied by the loss of oxygen. The heat generation for the overall reaction from the layered to the rocksalt structure is exothermic when x 0.5. From the calculated phase diagram, a similar mechanism is expected for LixCoO2, but the high migration barrier for Co may inhibit the layered-to-spinel transformation and lead to decomposition into LiCoO2 and Co3O4. For the stable spinel LiMn2O4, high temperature is needed to provide enough thermodynamic driving force for its endothermic deco.
Characteristics of Elderly Care Work That Influence Care Workers’ Turnover Intentions

Turnover and retention of care workers in long-term care (LTC) settings is an important issue. However, much research about turnover in LTC settings has focused on licensed nurses or nurse assistants. Moreover, many studies have utilized quantitative methods. The purpose of this study was to understand the characteristics of elderly care work that influence the turnover intentions of care workers in LTC. In-depth interviews were conducted with 10 care workers and analyzed using the content analysis method. As a result, seven categories were extracted as the characteristics of the elderly care work associated with turnover, including low social appreciation about care work, precarious employment, unprotected labor rights and safety, an unfair wage system, unclear scope and role of work, absence of training and supervision to enhance professionalism, and emotional labor. For the turnover prevention and retention of care workers, it is necessary to resolve the insecurity of care work. In particular, guidelines for improving the wage level and working conditions of care workers should be instituted, and at the same time, government supervision is required. Education is necessary to strengthen the professionalism of care workers and ensure skilled care work.
Human Body Parts Proximity Measurement Using Distributed Tactile Robotic Skin

Safety in human–machine cooperation is the current challenge in robotics. Safe human–robot interaction requires the development of sensors that detect human presence in the robot’s workspace. Detection of this presence should occur before the physical collision of the robot with the human. Human to robot proximity detection should be very fast, allowing machine elements deceleration to velocities safe for human–machine collision. The paper presents a new, low-cost design of distributed robotic skin, which allows real-time measurements of the human body parts proximity. The main advantages of the proposed solution are low cost of its implementation based on comb electrodes matrix and real-time operation due to fast and simple electronic design. The main contribution is the new idea of measuring the distance to human body parts by measuring the operating frequency of a rectangular signal generator, which depends on the capacity of the open capacitor. This capacitor is formed between the comb electrodes matrix and a reference plate located next to the matrix. The capacitance of the open capacitor changes if a human body part is in vicinity. The application of the developed device can be very wide. For example, in the field of cooperative robots, it can lead to the improvement of human–machine interfaces and increased safety of human–machine cooperation. The proposed construction can help to meet the increasing requirements for cooperative robots.
Cyclosporine Lipid Nanocapsules as Thermoresponsive Gel for Dry Eye Management: Promising Corneal Mucoadhesion, Biodistribution and Preclinical Efficacy in Rabbits

An ophthalmic cyclosporine (CsA) formulation based on Lipid nanocapsules (LNC) was developed for dry eye management, aiming to provide targeting to ocular tissues with long-term drug levels and maximum tolerability. CsA-LNC were of small particle size (41.9 ± 4.0 nm), narrow size distribution (PdI ≤ 0.1), and high entrapment efficiency (above 98%). Chitosan (C) was added to impart positive charge. CsA-LNC were prepared as in-situ gels using poloxamer 407 (P). Ex vivo mucoadhesive strength was evaluated using bovine cornea, while in vivo corneal biodistribution (using fluorescent DiI), efficacy in dry eye using Schirmer tear test (STT), and ocular irritation using Draize test were studied in rabbits compared to marketed ophthalmic CsA nanoemulsion (CsA-NE) and CsA in castor oil. LNC incorporation in in-situ gels resulted in an increase in mucoadhesion, and stronger fluorescence in corneal layers seen by confocal microscopy, compared to the other tested formulations. Rate of recovery (days required to restore corneal baseline hydration level) assessed over 10 days, showed that CsA-LNC formulations produced complete recovery by day 7 comparable to CsA-NE. No Ocular irritation was observed by visual and histopathological examination. Based on data generated, CsA-LNC-CP in-situ gel proved to be a promising effective nonirritant CsA ophthalmic formulation for dry eye management.
Kidney-Targeted Epoxyeicosatrienoic Acid Analog, EET-F01, Reduces Inflammation, Oxidative Stress, and Cisplatin-Induced Nephrotoxicity

Although epoxyeicosatrienoic acid (EET) analogs have performed well in several acute and chronic kidney disease models, targeted delivery of EET analogs to the kidney can be reasonably expected to reduce the level of drug needed to achieve a therapeutic effect and obviate possible side effects. For EET analog kidney-targeted delivery, we conjugated a stable EET analog to folic acid via a PEG-diamine linker. Next, we compared the kidney targeted EET analog, EET-F01, to a well-studied EET analog, EET-A. EET-A or EET-F01 was infused i.v. and plasma and kidney tissue collected. EET-A was detected in the plasma but was undetectable in the kidney. On the other hand, EET-F01 was detected in the plasma and kidney. Experiments were conducted to compare the efficacy of EET-F01 and EET-A for decreasing cisplatin nephrotoxicity. Cisplatin was administered to WKY rats treated with vehicle, EET-A (10 mg/kg i.p.) or EET-F01 (20 mg/kg or 2 mg/kg i.p.). Cisplatin increased kidney injury markers, viz., blood urea nitrogen (BUN), N-acetyl-β-(D)-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1), and thiobarbituric acid reactive substances (TBARS). EET-F01 was as effective as EET-A in decreasing BUN, NAG, KIM-1, TBARS, and renal histological injury caused by cisplatin. Despite its almost 2×-greater molecular weight compared with EET-A, EET-F01 was comparably effective in decreasing renal injury at a 10-fold w/w lower dose. EET-F01 decreased cisplatin nephrotoxicity by reducing oxidative stress and inflammation. These data demonstrate that EET-F01 targets the kidney, allows for a lower effective dose, and combats cisplatin nephrotoxicity. In conclusion, we have developed a kidney targeted EET analog, EET-F01, that demonstrates excellent potential as a therapeutic for kidney diseases.