HPV16 E6 Oncogene Contributes to Cancer Immune Evasion by Regulating PD-L1 Expression through a miR-143/HIF-1a Pathway.

Human Papillomaviruses have been associated with the occurrence of cervical cancer, the fourth most common cancer that affects women globally, while 70% of cases are caused by infection with the high-risk types HPV16 and HPV18. The integration of these viruses' oncogenes E6 and E7 into the host's genome affects a multitude of cellular functions and alters the expression of molecules. The aim of this study was to investigate how these oncogenes contribute to the expression of immune system control molecules, using cell lines with integrated HPV16 genome, before and after knocking out E6 viral gene using the CRISPR/Cas9 system, delivered with a lentiviral vector. The molecules studied are the T-cell inactivating protein PD-L1, its transcription factor HIF-1a and the latter's negative regulator, miR-143. According to our results, in the E6 knock out (E6KO) cell lines an increased expression of miR-143 was recorded, while a decrease in the expression of HIF-1a and PD-L1 was exhibited. These findings indicate that E6 protein probably plays a significant role in enabling cervical cancer cells to evade the immune system, while we propose a molecular pathway in cervical cancer, where PD-L1's expression is regulated by E6 protein through a miR-143/HIF-1a axis.

Exploration of Methodologies for Developing Antimicrobial Fused Filament Fabrication Parts.

Composite 3D printing filaments integrating antimicrobial nanoparticles offer inherent microbial resistance, mitigating contamination and infections. Developing antimicrobial 3D-printed plastics is crucial for tailoring medical solutions, such as implants, and cutting costs when compared with metal options. Furthermore, hospital sustainability can be enhanced via on-demand 3D printing of medical tools. A PLA-based filament incorporating 5% TiO2 nanoparticles and 2% Joncryl as a chain extender was formulated to offer antimicrobial properties. Comparative analysis encompassed PLA 2% Joncryl filament and a TiO2 coating for 3D-printed specimens, evaluating mechanical and thermal properties, as well as wettability and antimicrobial characteristics. The antibacterial capability of the filaments was explored after 3D printing against Gram-positive Staphylococcus aureus (S. aureus, ATCC 25923), as well as Gram-negative Escherichia coli (E. coli, ATCC 25922), and the filaments with 5 wt.% embedded TiO2 were found to reduce the viability of both bacteria. This research aims to provide the optimal approach for antimicrobial and medical 3D printing outcomes.

Human Papillomavirus 16 DNA Methylation Patterns and Investigation of Integration Status in Head and Neck Cancer Cases.

Persistent high-risk human papillomavirus (HPV) infection is a pivotal factor in the progression of cervical cancer. In recent years, an increasing interest has emerged in comprehending the influence of HPV on head and neck squamous cell carcinoma (HNSCC). Notably, it is well established that HPV-associated HNSCC show cases with distinct molecular and clinical attributes compared to HPV-negative cases. The present study delves into the epigenetic landscape of HPV16, specifically its L1 gene and untranslated region (UTR), through pyrosequencing, while the HPV16 DNA physical status was evaluated using E2/E6 ratio analysis in HPV16-positive HNSCC FFPE biopsies. Our findings reveal substantial methylation across six sites within the HPV16 L1 gene and seven sites in the UTR. Specifically, methylation percentages of two L1 CpG sites (7136, 7145) exhibit significant associations with tumor histological grade (p < 0.01), while proving concurrent methylation across multiple sites. The HPV16 DNA physical status was not correlated with the methylation of viral genome or tumor characteristics. This is the first study that examines epigenetic modifications and the HPV16 DNA physical status in Greek HNSCC patients. Our findings suggest an orchestrated epigenetic modulation among specific sites, impacting viral gene expression and intricate virus-host interactions.

Factors Influencing Functional Outcomes in Supracondylar Humerus Fractures: A Retrospective Study of Paediatric Patients in a Level One Trauma Centre.

Background The outcomes after fixation of the supracondylar humerus fracture (SCHF) are not documented in the current literature. In our study, we endeavour to determine the factors that influence the functional outcome and gauge their respective impact. Methodology We retrospectively reviewed the outcomes of patients who presented to our tertiary care centre (Royal London Hospital) with SCHFs between September 2017 and February 2018. We analysed patient records to assess several clinical parameters, including age, Gartland's classification, comorbidities, time to treatment, and fixation configuration. We conducted a multiple linear regression analysis to determine each of the clinical parameter's impact on the functional and cosmetic outcome, as reflected in Flynn's criteria. Results We included 112 patients in our study. Pediatric SCHFs had good functional outcomes based on Flynn's criteria. There was no significant statistical difference in functional outcomes with respect to sex (p= 0.713), age (p= 0.96), fracture type (p= 0.14), K-wire configuration (p=0.83), and time elapsed since surgery (p= 0.240). Conclusions Our results demonstrate that good functional outcomes can be expected with paediatric SCHFs based on Flynn's criteria, regardless of age at injury, sex, or pin configuration, provided satisfactory reduction is achieved and maintained. The only variable with statistical significance was Gartland's grade; Grades III and IV were correlated with poorer outcomes.

Digital Innovation Enabled Nanomaterial Manufacturing; Machine Learning Strategies and Green Perspectives.

Machine learning has been an emerging scientific field serving the modern multidisciplinary needs in the Materials Science and Manufacturing sector. The taxonomy and mapping of nanomaterial properties based on data analytics is going to ensure safe and green manufacturing with consciousness raised on effective resource management. The utilization of predictive modelling tools empowered with artificial intelligence (AI) has proposed novel paths in materials discovery and optimization, while it can further stimulate the cutting-edge and data-driven design of a tailored behavioral profile of nanomaterials to serve the special needs of application environments. The previous knowledge of the physics and mathematical representation of material behaviors, as well as the utilization of already generated testing data, received specific attention by scientists. However, the exploration of available information is not always manageable, and machine intelligence can efficiently (computational resources, time) meet this challenge via high-throughput multidimensional search exploration capabilities. Moreover, the modelling of bio-chemical interactions with the environment and living organisms has been demonstrated to connect chemical structure with acute or tolerable effects upon exposure. Thus, in this review, a summary of recent computational developments is provided with the aim to cover excelling research and present challenges towards unbiased, decentralized, and data-driven decision-making, in relation to increased impact in the field of advanced nanomaterials manufacturing and nanoinformatics, and to indicate the steps required to realize rapid, safe, and circular-by-design nanomaterials.

Remote Follow-up of Shoulder Arthroplasty Patients During COVID-19 Pandemic - Is This the way Forward?

BACKGROUND: The COVID-19 Pandemic has affected the way health care systems function across the globe. Apart from eliminating the risk of being in a vulnerable environment during the pandemic such as a hospital setting, virtual arthroplasty follow-up reduces the demand on funding and resources on the National Health Services (NHS). METHODS: We retrospectively reviewed our shoulder arthroplasty patients (55) operated between October 2018 to November 2020 at both our hospital sites. For remote follow-up, patients were contacted on a scheduled appointment date via telephone by an orthopaedic surgeon to enquire about their wound, pain and function. Patients were questioned as per questionnaire from the Oxford Shoulder Score (OSS) and American Shoulder and Elbow Surgeons (ASES) Standardised Assessment form. RESULTS: 50 patients were included in the final data set after excluding those who had died (5 patients). All patients had had final x-rays with full Covid-19 precautions at the time of final follow-up. No patient had wound problems except one who had concerns of wound appearance. There were no cases of notching, impingement, deep infection, dislocation or nerve injury. Of the 50 patients, 40 (80%) patients were satisfied to have a remote follow-up. 36 (72%) patients said they wouldn't mind a remote follow-up appointment. CONCLUSION: Remote follow-up via audio consultation may be an effective alternative to in person visits after shoulder arthroplasty. Patients in this series demonstrated a high level of satisfaction with virtual visits and post-operative complications were effectively identified.

The Management of Posterior Malleolus Fractures in Unstable Ankle Injuries: Where Do We Stand Now?

The evaluation and treatment of the posterior malleolus fracture in unstable ankle injuries remain a topic of controversy. The main objective of this systematic review was to examine the available literature and identify the variables that affect the management of posterior malleolar fractures and how these are related to the outcomes. To that end, a systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of MEDLINE, Embase, and Cochrane Library was conducted. The search terms used were as follows: "posterior malleolar", "ankle fractures", "trimalleolar fractures", "ORIF", "surgery", "operative", and "conservative". The available studies were screened against the inclusion and exclusion criteria. Based on the review of the available literature, we have concluded that the size of the posterior malleolar fragment is not an accurate indicator, and clinicians should consider other factors such as fracture configuration and articular surface congruity. Also, the risk for the development of post-traumatic arthritis increases when the joint surface is not restored regardless of the surgical intervention and fragment size. The complications of posterior malleolus fractures necessitate evidence-based management. The assessment and the final treatment of these injuries in unstable ankle fractures should not be based on the traditional fragment-size parameters. Clinicians should assess the fracture configuration through imaging modalities and try to preserve the articular surface congruity so as to achieve optimal outcomes. Finally, more studies with high-level evidence are required in order to determine the most appropriate management pathway for these patients.

Mechanical Properties, Surface Assessment, and Structural Analysis of Functionalized CFRPs after Accelerated Weathering.

The present study focuses on the effect of two novel carbon fibre surface treatments, electropolymerisation of methacrylic acid and air pressure plasma, on the mechanical properties and structural integrity of carbon-fibre-reinforced composites under operational conditions. Extensive mechanical testing was applied, both in nano- and macro-scale, to assess the performance of the composites and the interphase properties after ultraviolet/humidity weathering. The results of the mechanical assessment are supported by structure, surface, and chemistry examination in order to reveal the failure mechanism of the composites. Composites with the electropolymerisation treatment exhibited an increase of 11.8% in interlaminar shear strength, while APP treatment improved the property of 23.9%, rendering both surface treatments effective in increasing the fibre-matrix adhesion. Finally, it was proven that the developed composites can withstand operational conditions in the long term, rendering them suitable for a wide variety of structural and engineering applications.

Carbon Fiber Reinforced Composites: Study of Modification Effect on Weathering-Induced Ageing via Nanoindentation and Deep Learning.

The exposure of carbon-fiber-reinforced polymers (CFRPs) to open-field conditions was investigated. Establishment of structure-property relations with nanoindentation enabled the observation of modification effects on carbon-fiber interfaces, and impact resistance. Mapping of nanomechanical properties was performed using expectation-maximization optimization of Gaussian fitting for each CFRPs microstructure (matrix, interface, carbon fiber), while Weibull analysis connected the weathering effect to the statistically representative behavior of the produced composites. Plasma modification demonstrated reduced defect density and improved nanomechanical properties after weathering. Artificial intelligence for anomaly detection provided insights on condition monitoring of CFRPs. Deep-learning neural networks with three hidden layers were used to model the resistance to plastic deformation based on nanoindentation parameters. This study provides new assessment insights in composite engineering and quality assurance, especially during exposure under service conditions.

Mid- to long-term survivorship of the cemented, semiconstrained Discovery total elbow arthroplasty.

BACKGROUND: The incidence of total elbow arthroplasty (TEA) is increasing, and an improved understanding of elbow kinematics and biomaterials has driven advances in implant design. In modern practice, cemented, semiconstrained devices are most frequently used. The Discovery TEA has demonstrated promising early results, although there are a paucity of follow-up studies and no dedicated mid- to long-term series. We therefore present the longest, most complete such study to date. METHODS: A prospectively maintained local joint registry was interrogated to yield a consecutive series of Discovery TEAs performed at a single non-design center. The minimum follow-up period was set at 5 years. Revision procedures and TEAs performed for acute trauma were excluded. The primary outcome was survivorship of the implant. The secondary outcomes included clinical, radiographic, and patient-reported outcomes. RESULTS: We identified 67 TEAs in 58 patients for inclusion at a mean of 98.5 ± 20.4 months from surgery. Four cases (6%) were lost to follow-up, and implant survival was censored accordingly. The implant was revised in 14 cases (20.9%). The Kaplan-Meier method showed an implant survivorship rate of 76.8% at 119 months. A significant difference in survival was found between dominant and nondominant elbows (P = .012, Breslow test), with elbow dominance conferring a 4.5-fold increased risk of revision (relative risk, 4.5; 95% confidence interval, 1.1-18.5). Pooled clinical outcomes (70.9% follow-up at minimum of 60 months and median of 77.8 months) were also determined. CONCLUSIONS: We present the longest-term and most complete single-center follow-up study of the Discovery TEA to date. Further long-term survival studies are required to elucidate the performance of this implant compared with more established designs. We have also demonstrated differences in implant survivorship owing to hand dominance for the first time.

Testing Novel Portland Cement Formulations with Carbon Nanotubes and Intrinsic Properties Revelation: Nanoindentation Analysis with Machine Learning on Microstructure Identification.

Nanoindentation was utilized as a non-destructive technique to identify Portland Cement hydration phases. Artificial Intelligence (AI) and semi-supervised Machine Learning (ML) were used for knowledge gain on the effect of carbon nanotubes to nanomechanics in novel cement formulations. Data labelling is performed with unsupervised ML with k-means clustering. Supervised ML classification is used in order to predict the hydration products composition and 97.6% accuracy was achieved. Analysis included multiple nanoindentation raw data variables, and required less time to execute than conventional single component probability density analysis (PDA). Also, PDA was less informative than ML regarding information exchange and re-usability of input in design predictions. In principle, ML is the appropriate science for predictive modeling, such as cement phase identification and facilitates the acquisition of precise results. This study introduces unbiased structure-property relations with ML to monitor cement durability based on cement phases nanomechanics compared to PDA, which offers a solution based on local optima of a multidimensional space solution. Evaluation of nanomaterials inclusion in composite reinforcement using semi-supervised ML was proved feasible. This methodology is expected to contribute to design informatics due to the high prediction metrics, which holds promise for the transfer learning potential of these models for studying other novel cement formulations.

Use of stem cells and growth factors in rotator cuff tendon repair.

The management of rotator cuff tears continues to prove challenging for orthopaedic surgeons. Such tears affect most age groups and can lead to significant morbidity in patients. The aetiology of these tears is likely to be multifactorial; however, an understanding of the mechanisms involved is still under review. Despite advancements in surgical operative techniques and the materials used, post-operative recurrence rates after surgical repair remain high. A growing area of research surrounds biological adjuncts used to improve the healing potential of the repaired tissues. This review of recent publications focuses on the strengths and limitations of using stem cells and growth factors in rotator cuff repair.

Sevoflurane versus propofol anesthesia in patients undergoing lumbar spondylodesis: a randomized trial.

BACKGROUND: Spondylodesis is a procedure aiming at providing stability in one or more spinal segments. The aim of our study was to compare sevoflurane and propofol as induction and maintenance agents, focusing on hemodynamic stability, recovery characteristics, postoperative nausea and vomiting, and pain intensity. MATERIALS AND METHODS: Seventy patients, with a physical status according to American Society of Anesthesiologists (ASA) I-II, 50-72 y old, undergoing selective lumbar spondylodesis were enrolled. RESULTS: There was no statistically significant difference between groups in overall mean hemodynamic parameters. No differences in fluid administration and vasoactive substances used were noted. Postoperatively, there was a significant difference in overall mean visual analog score at rest and at cough, with the sevoflurane group showing lower values. No differences in the incidence of nausea, vomiting, shivering, postoperative sedation scores, and orientation to place were revealed. Orientation to time exhibited a statistically significant difference at the time just after transfer to the post-anesthesia care unit, where more patients of the sevoflurane group seemed to be well oriented. CONCLUSIONS: Sevoflurane and propofol anesthesia for lumbar spondylodesis surgery provide safe and comparable results.