Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma Synthesis of Advanced Metal Oxide Nanoparticles and Their Applications as Transparent Conducting Oxide Thin Films

This article reviews and summarizes work recently performed in this laboratory on the synthesis of advanced transparent conducting oxide nanopowders by the use of plasma. The nanopowders thus synthesized include indium tin oxide (ITO), zinc oxide (ZnO) and tin-doped zinc oxide (TZO), aluminum-doped zinc oxide (AZO), and indium-doped zinc oxide (IZO). These oxides have excellent transparent conducting properties, among other useful characteristics. ZnO and TZO also has photocatalytic properties. The synthesis of these materials started with the selection of the suitable precursors, which were injected into a non-transferred thermal plasma and vaporized followed by vapor-phase reactions to form nanosized oxide particles. The products were analyzed by the use of various advanced instrumental analysis techniques, and their useful properties were tested by different appropriate methods. The thermal plasma process showed a considerable potential as an efficient technique for synthesizing oxide nanopowders. This process is also suitable for large scale production of nano-sized powders owing to the availability of high temperatures for volatilizing reactants rapidly, followed by vapor phase reactions and rapid quenching to yield nano-sized powder.
Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.
The Role of White Matter Dysfunction and Leukoencephalopathy/Leukodystrophy Genes in the Aetiology of Frontotemporal Dementias: Implications for Novel Approaches to Therapeutics

Frontotemporal dementia (FTD) is a common cause of presenile dementia and is characterized by behavioural and/or language changes and progressive cognitive deficits. Genetics is an important component in the aetiology of FTD, with positive family history of dementia reported for 40% of cases. This review synthesizes current knowledge of the known major FTD genes, including C9orf72 (chromosome 9 open reading frame 72), MAPT (microtubule-associated protein tau) and GRN (granulin), and their impact on neuronal and glial pathology. Further, evidence for white matter dysfunction in the aetiology of FTD and the clinical, neuroimaging and genetic overlap between FTD and leukodystrophy/leukoencephalopathy are discussed. The review highlights the role of common variants and mutations in genes such as CSF1R (colony-stimulating factor 1 receptor), CYP27A1 (cytochrome P450 family 27 subfamily A member 1), TREM2 (triggering receptor expressed on myeloid cells 2) and TMEM106B (transmembrane protein 106B) that play an integral role in microglia and oligodendrocyte function. Finally, pharmacological and non-pharmacological approaches for enhancing remyelination are discussed in terms of future treatments of FTD.
Heat-Inactivation of Human Serum Destroys C1 Inhibitor, Pro-motes Immune Complex Formation, and Improves Human T Cell Function

Heat-inactivation of sera is used to reduce possible disturbing effects of complement factors in cell-culture experiments, but it is controversially discussed whether this procedure is appropriate or could be neglected. Here, we report a strong impact of heat-inactivation of human sera on the activation and effector functions of human CD4+ T cells. While T cells cultured with native sera were characterized by a higher proliferation rate and higher expression of CD28, heat-inactivated sera shaped T cells towards on-blast formation, higher cytokine secretion (interferon γ, tumor necrosis factor, and interleukin-17), stronger CD69 and PD-1 expression, and increased metabolic activity. Heat-inactivated sera contained reduced amounts of complement factors and regulators like C1 inhibitor, but increased concentrations of circulating immune complexes. Substitution of C1 inhibitor reduced the beneficial effect of heat-inactivation in terms of cytokine release, whereas surface-molecule expression was affected by the addition of complex forming anti-C1q antibody. Our data clearly demonstrate a beneficial effect of heat-inactivation of human sera for T cell experiments but indicate that beside complement regulators and immune complexes other components might be relevant. Beyond that, this study further underpins the strong impact of the complement system on T cell function.
Trends of COVID-19 Admissions in an Italian Hub during the Pandemic Peak: Large Retrospective Study Focused on Older Subjects

Older multimorbid frail subjects have been severely involved in the coronavirus disease-19 (COVID-19) pandemic. The aim of this retrospective study is to compare the clinical features and outcomes of patients admitted in different phases of the outbreak in a COVID-19 hospital hub, with a particular focus on age, multimorbidity, and functional dependency. The clinical records of 1264 patients with clinical and radiological features compatible with COVID-19 pneumonia admitted in February–June, 2020, were analyzed, retrieving demographical, clinical, laboratory data, and outcomes. All variables were compared after stratification by the period of admission (first phase: rising slope of pandemic wave; second phase: plateau and falling slope), age, results of the first reverse transcriptase-polymerase chain reaction (RT-PCR) test for detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), multimorbidity (≥2 chronic diseases), and presence of disability. Factors independently associated with hospital mortality were determined by multivariate forward-selection logistic regression. Patients admitted during the second phase were older, more frequently multimorbid, disabled, and of female gender. However, on admission they exhibited milder respiratory impairment (PaO2/FiO2 268, IQR 174–361, vs. 238, IQR 126–327 mmHg, p < 0.001) and lower mortality (22% vs. 27%, p < 0.001). Age, respiratory exchanges, positive RT-PCR test, number of chronic diseases (odds ratio (OR) 1.166, 95% confidence interval (CI) 1.036–1.313, p = 0.011), and disability (OR 1.927, 95% CI 1.027–3.618, p = 0.022) were positively associated with mortality, while admission during the second phase exhibited an inverse association (OR 0.427, 95% CI 0.260–0.700, p = 0.001). In conclusion, older multimorbid patients were mainly hospitalized during the second phase of the pandemic wave. The prognosis was strongly influenced by the COVID-19 phenotype and period of admission, not just by age, multimorbidity, and disability.
Age- and Severity-Related In-Hospital Mortality Trends and Risks of Severe Traumatic Brain Injury in Japan: A Nationwide 10-Year Retrospective Study

Traumatic brain injury (TBI) is the major cause of mortality and morbidity in severely-injured patients worldwide. This retrospective nationwide study aimed to evaluate the age- and severity-related in-hospital mortality trends and mortality risks of patients with severe TBI from 2009 to 2018 to establish effective injury prevention measures. We retrieved information from the Japan Trauma Data Bank dataset between 2009 and 2018. The inclusion criteria for this study were patients with severe TBI defined as those with an Injury Severity Score ≥ 16 and TBI. In total, 31,953 patients with severe TBI (32.6%) were included. There were significant age-related differences in characteristics, mortality trend, and mortality risk in patients with severe TBI. The in-hospital mortality trend of all patients with severe TBI significantly decreased but did not improve for patients aged ≤ 5 years and with a Glasgow Coma Scale (GCS) score between 3 and 8. Severe TBI, age ≥ 65 years, fall from height, GCS score 3–8, and urgent blood transfusion need were associated with a higher mortality risk, and mortality risk did not decrease after 2013. Physicians should consider specific strategies when treating patients with any of these risk factors to reduce severe TBI mortality.
Cardioprotective Effect of Quercetin and Sitagliptin in Doxorubicin-Induced Cardiac Toxicity in Rats

Objective A previous study revealed a pronounced protective effect of combining quercetin (QC) with sitagliptin (STN) in testicular tissue. Accordingly, this study was designed to evaluate the cardioprotective effects of QC and STN each alone or in combination in doxorubicin (DOX)-induced cardiotoxicity in the rats. Methodology Thirty male adult Wistar rats were divided into five groups: the first group (control) treated with sodium chloride, the second group treated with DOX (3 mg/kg I.P. injection), the third group treated with DOX with a combination of QC (80 mg/kg), and STN (10 mg/kg), the fourth group treated with DOX and QC and the fifth group treated with DOX and STN. Blood was collected on day 22 and used for assessment of serum troponin, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total lipid profile, C-reactive protein (CRP), and total antioxidant capacity (TAOC). Atherogenic indices were also calculated. Cardiac tissue was sent for histopathological analysis. Results DOX produced a significant increase in the level of troponin, LDH, CKP, CRP, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), and atherogenic index of plasma; and significantly decreased TAOC. The combination of quercetin and sitagliptin was more effective than each treatment alone in restoring the level of troponin, LDH, CKP, CRP, Cholesterol, LDL, TG, atherogenic index of plasma and significantly increased TAOC compared to DOX treated group. The histopathological finding also supports the biochemical results. Conclusion The study revealed the cardioprotective effects of the combination of QC and STN which could be attributed to the additive effects of this combination through antioxidant, anti-inflammatory, lipid lowering and anti-atherogenic activities; suggesting it as a good therapeutic candidate to be tested in the clinical setting.
Mechanical Properties and Biocompatibility of Urethane Acrylate-Based 3D-Printed Denture Base Resin

In this study, five urethane acrylates (UAs), namely aliphatic urethane hexa-acrylate (87A), aromatic urethane hexa-acrylate (88A), aliphatic UA (588), aliphatic urethane triacrylate diluted in 15% HDD (594), and high-functional aliphatic UA (5812), were selected to formulate five UA-based photopolymer resins for digital light processing (DLP)-based 3D printing. Each UA (40 wt%) was added and blended homogenously with ethoxylated pentaerythritol tetraacrylate (40 wt%), isobornyl acrylate (12 wt%), diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (3 wt%), and a pink acrylic (5 wt%). Each UA-based resin specimen was designed using CAD software and fabricated using a DLP 3D printer to specific dimensions. Characteristics, mechanical properties, and cytotoxicity levels of these designed UA-based resins were investigated and compared with a commercial 3D printing denture base acrylic resin (BB base) control group at different UV exposure times. Shore hardness-measurement data and MTT assays were analyzed using a one-way analysis of variance with Bonferroni’s post hoc test, whereas viscosity, maximum strength, and modulus were analyzed using the Kruskal–Wallis test (α = 0.05). UA-based photopolymer resins with tunable mechanical properties were successfully prepared by replacing the UA materials and the UV exposure times. After 15 min of UV exposure, the 5812 and 594 groups exhibited higher viscosities, whereas the 88A and 87A groups exhibited lower viscosities compared with the BB base group. Maximum flexural strength, flexural modulus, and Shore hardness values also revealed significant differences among materials (p < 0.001). Based on MTT assay results, the UA-based photopolymer resins were nontoxic. In the present study, mechanical properties of the designed photopolymer resins could be adjusted by changing the UA or UV exposure time, suggesting that aliphatic urethane acrylate has good potential for use in the design of printable resins for DLP-type 3D printing in dental applications.
Sonic Hedgehog Signaling Promotes Peri-Lesion Cell Proliferation and Functional Improvement after Cortical Contusion Injury

Traumatic brain injury (TBI) is a leading cause of death and disability globally. No drug treatments are available, so interest has turned to endogenous neural stem cells (NSCs) as alternative strategies for treatment. We hypothesized that regulation of cell proliferation through modulation of the sonic hedgehog pathway, a key NSC regulatory pathway, could lead to functional improvement. We assessed sonic hedgehog (Shh) protein levels in the cerebrospinal fluid (CSF) of patients with TBI. Using the cortical contusion injury (CCI) model in rodents, we used pharmacological modulators of Shh signaling to assess cell proliferation within the injured cortex using the marker 5-Ethynyl-2’-deoxyuridine (EdU); 50mg/mL. The phenotype of proliferating cells was determined and quantified. Motor function was assessed using the rotarod test. In patients with TBI there is a reduction of Shh protein in CSF compared with control patients. In rodents, following a severe CCI, quiescent cells become activated. Pharmacologically modulating the Shh signaling pathway leads to changes in the number of newly proliferating injury-induced cells. Upregulation of Shh signaling with Smoothened agonist (SAG) results in an increase of newly proliferating cells expressing glial fibrillary acidic protein (GFAP), whereas the Shh signaling inhibitor cyclopamine leads to a reduction. Some cells expressed doublecortin (DCX) but did not mature into neurons. The SAG-induced increase in proliferation is associated with improved recovery of motor function. Localized restoration of Shh in the injured rodent brain, via increased Shh signaling, has the potential to sustain endogenous cell proliferation and the mitigation of TBI-induced motor deficits albeit without the neuronal differentiation.
The Cambridge Experience With Tibial Plateau Fractures in Older Adults: A Case Series

Complex tibial plateau fractures (TPFs) represent a significant treatment challenge for any Orthopaedic surgeon. Current literature suggests that significantly displaced TPFs in the elderly require operative fixation, an operation that is associated with serious complications including septic and post-operative arthritis. As a result, these patients are five times more likely to require a total knee replacement (TKR). We present a case series of five elderly patients with complex TPFs who made serendipitous recoveries while awaiting operations. Their fractures were deemed so severe that they were being considered for TKR instead of fixation. We discovered their surprising functional improvements while they were being reviewed pre-operatively and decided to delay operating. We are currently unaware of any cases in the literature that have reported such findings. In total, five patients presented in 2019 with closed, varus/valgus stable fractures. They were managed non-operatively in hinged-knee braces, progressively weight-bearing with a minimum follow-up of 10 months. Oxford Knee Scores (OKS) were recorded at zero and four months after their injury. All patients were female with an average age of 69 years. Average fracture depression - 8.48mm, average fracture split - 8.66mm, average OKS reduction - 19%. All patients were able to mobilise independently at four months follow-up. Our results suggest that non-operative management can be considered as primary management in elderly patients with significantly displaced TPFs. Should this fail, or they develop arthritis, a TKR can be performed. This carries two benefits: the patient avoids the significant complications associated with fixation and should a TKR be required, it can more easily be performed in a patient without metalwork in-situ. We feel that the results from this case series might offer insight into a new treatment strategy and continue to closely follow these patients.
Evaluation of Concurrent Validity between a Smartphone Self-Test Prototype and Clinical Instruments for Balance and Leg Strength

The evolving use of sensors to objectively assess movements is a potentially valuable addition to clinical assessments. We have developed a new self-test application prototype, MyBalance, in the context of fall prevention aimed for use by older adults in order to independently assess balance and functional leg strength. The objective of this study was to investigate the new self-test application for concurrent validity between clinical instruments and variables collected with a smartphone. The prototype has two test procedures: static standing balance test in two positions, and leg strength test performed as a sit-to-stand test. Thirty-one older adults were assessed for balance and functional leg strength, in an outpatient physiotherapy setting, using seven different clinical assessments and three sensor-tests. The results show that clinical instruments and sensor measurements correlate to a higher degree for the smartphone leg strength test. For balance tests, only a few moderate correlations were seen in the Feet Together position and no significant correlations for the Semi Tandem Stance. This study served as a first step to develop a smartphone self-test application for older adults to assess functional balance at home. Further research is needed to test validity, reliability, and user-experience of this new self-test application.
Distinct Signatures of Genomic Copy Number Variants Define Subgroups of Merkel Cell Carcinoma Tumors

Simple Summary Cancer results from genetic changes in cells. These changes are often mutations that alter the DNA sequence of critical genes. However, duplications and deletions in cancer-related genes can also contribute to malignant transformation. In this study we use Nanostring technology to assess DNA copy number changes in samples of Merkel cell carcinoma (MCC), a rare and aggressive neuroendocrine skin tumor. We were able to identify recurrent amplifications and deletions in cancer-related genes. We also found that MCC tumors grouped into three distinct copy number variant profiles. The first group consisted of tumors with multiple deletions. The second group contained tumors with low levels of genomic structural alterations. The last group comprised tumors containing multiple amplifications. Our study suggests that most MCC tumors are associated with deletions in cancer-related genes or are lacking in copy number changes, whereas a small percentage of tumors are associated with genomic amplifications. Abstract Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer. Most MCC tumors contain integrated Merkel cell polyomavirus DNA (virus-positive MCC, VP-MCC) and carry a low somatic mutation burden whereas virus-negative MCC (VN-MCC) possess numerous ultraviolet-signature mutations. In contrast to viral oncogenes and sequence mutations, little is known about genomic structural variants in MCC. To identify copy number variants in commonly altered genes, we analyzed genomic DNA from 31 tumor samples using the Nanostring nCounter copy number cancer panel. Unsupervised clustering revealed three tumor groups with distinct genomic structural variant signatures. The first cluster was characterized by multiple recurrent deletions in genes such as RB1 and WT1. The second cluster contained eight VP-MCC and displayed very few structural variations. The final cluster contained one VP-MCC and four VN-MCC with predominantly genomic amplifications in genes like MDM4, SKP2, and KIT and deletions in TP53. Overall, VN-MCC contained more structure variation than VP-MCC but did not cluster separately from VP-MCC. The observation that most MCC tumors demonstrate a deletion-dominated structural group signature, independent of virus status, suggests a shared pathophysiology among most VP-MCC and VN-MCC tumors.
Relationship between Young’s Modulus and Planar Density of Unit Cell, Super Cells (2 × 2 × 2), Symmetry Cells of Perovskite (CaTiO3) Lattice

Calcium titanate-CaTiO3 (perovskite) has been used in various industrial applications due to its dopant/doping mechanisms. Manipulation of defective grain boundaries in the structure of perovskite is essential to maximize mechanical properties and stability; therefore, the structure of perovskite has attracted attention, because without fully understanding the perovskite structure and diffracted planes, dopant/doping mechanisms cannot be understood. In this study, the areas and locations of atoms and diffracted planes were designed and investigated. In this research, the relationship between Young’s modulus and planar density of unit cell, super cells (2 × 2 × 2) and symmetry cells of nano CaTiO3 is investigated. Elastic constant, elastic compliance and Young’s modulus value were recorded with the ultrasonic pulse-echo technique. The results were C11 = 330.89 GPa, C12 = 93.03 GPa, C44 = 94.91 GPa and E = 153.87 GPa respectively. Young’s modulus values of CaTiO3 extracted by planar density were calculated 162.62 GPa, 151.71 GPa and 152.21 GPa for unit cell, super cells (2 × 2 × 2) and symmetry cells, respectively. Young’s modulus value extracted by planar density of symmetry cells was in good agreement with Young’s modulus value measured via ultrasonic pulse-echo.