Self-Trapped Excitons in Metal-Halide Perovskites Investigated by Time-Dependent Density Functional Theory.

We present a theoretical study of the formation of self-trapped excitons (STEs) and the associated broadband emission in metal-halide perovskites Cs4SnBr6 and Cs2AgInCl6, using time-dependent density functional theory (TDDFT) with the dielectric-dependent hybrid (DDH) functional. Our approach allows for an accurate description of the excitonic effect and geometry relaxation in the electronic excited states and yields optical gap, STE emission energy, and emission spectra in reasonable agreement with experiments. We point out the significance of considering geometry relaxations in the electronic excited state by showing that the exciton-phonon coupling computed in the ground-state atomic geometry is insufficient to describe the physical properties of STEs. Overall, we find that TDDFT with the DDH hybrid functional is a suitable approach for the study of the formation of STEs in perovskite and provides insights for designing metal-halide perovskites with tailored emission properties.

Excited State Properties of Point Defects in Semiconductors and Insulators Investigated with Time-Dependent Density Functional Theory.

We present a formulation of spin-conserving and spin-flip hybrid time-dependent density functional theory (TDDFT), including the calculation of analytical forces, which allows for efficient calculations of excited state properties of solid-state systems with hundreds to thousands of atoms. We discuss an implementation on both GPU- and CPU-based architectures along with several acceleration techniques. We then apply our formulation to the study of several point defects in semiconductors and insulators, specifically the negatively charged nitrogen-vacancy and neutral silicon-vacancy centers in diamond, the neutral divacancy center in 4H silicon carbide, and the neutral oxygen-vacancy center in magnesium oxide. Our results highlight the importance of taking into account structural relaxations in excited states in order to interpret and predict optical absorption and emission mechanisms in spin defects.

Extracorporeal membrane oxygenation and effects on tendon tissue: A vibrational spectroscopy study.

Extracorporeal membrane oxygenation (ECMO) is an invasive medical technique used to provide life support in persons with insufficient cardiac and respiratory functionalities, or to preserve, postmortem, and organ function addressing organ/tissue transplant. Although a lot of information is available about organs in their entirety, the safety and effectiveness of allogeneic tissues collected from ECMO donors have not been fully elucidated. In this preliminary study, samples of tibial and peroneal human tendons were analyzed along their length with Raman microspectroscopy and attenuated total reflection-Fourier transform infrared micro-imaging. Both techniques evidenced a different chemical composition in the terminal with respect to the central part of the tendon. Thus, a differentiated analysis was performed depending on the specific position with respect to the bone or the muscle junctions. Spectroscopic analyses showed significant differences in the characteristics of the extracellular matrix between tendons from ECMO and non-ECMO donors, suggesting changes in the amino acid (proline and hydroxyproline) content and protein structure.

Nonempirical Range-Separated Hybrid Functional with Spatially Dependent Screened Exchange.

Electronic structure calculations based on density functional theory (DFT) have successfully predicted numerous ground-state properties of a variety of molecules and materials. However, exchange and correlation functionals currently used in the literature, including semilocal and hybrid functionals, are often inaccurate to describe the electronic properties of heterogeneous solids, especially systems composed of building blocks with large dielectric mismatch. Here, we present a dielectric-dependent range-separated hybrid functional, screened-exchange range-separated hybrid (SE-RSH), for the investigation of heterogeneous materials. We define a spatially dependent fraction of exact exchange inspired by the static Coulomb-hole and screened-exchange (COHSEX) approximation used in many-body perturbation theory, and we show that the proposed functional accurately predicts the electronic structure of several nonmetallic interfaces, three- and two-dimensional, pristine, and defective solids and nanoparticles.

The Intraoperative Use of Defensive Antibacterial Coating (DAC®) in the Form of a Gel to Prevent Peri-Implant Infections in Orthopaedic Surgery: A Clinical Narrative Review.

Periprosthetic joint infections (PJIs) in arthroplasty and osteosynthesis-associated infections (OAIs) in reconstructive surgery still represent a challenging complication in orthopaedics and traumatology causing a burden worsening the patient's quality of life, for caregiver and treating physicians, and for healthcare systems. PJIs and OAIs are the result of bacterial adhesion over an implant surface with subsequent biofilm formation. Therefore, the clinical pathological outcome is a difficult-to-eradicate persistent infection. Strategies to treat PJIs and OAIs involve debridement, the replacement of internal fixators or articular prostheses, and intravenous antibiotics. However, long treatments and surgical revision cause discomfort for patients; hence, the prevention of PJIs and OAIs represents a higher priority than treatment. Local antibiotic treatments through coating-release systems are becoming a smart approach to prevent this complication. Hydrophilic coatings, loaded with antibiotics, simultaneously provide a barrier effect against bacterial adhesion and allow for the local delivery of an antibiotic. The intraoperative use of a hyaluronan (HY)-derivative coating in the form of a gel, loaded with antibiotics to prevent PJI, has recently raised interest in orthopaedics. Current evidence supports the use of this coating in the prophylaxis of PJI and IRIs in terms of clinical outcomes and infection reduction. Thus, the purpose of this narrative review is to assess the use of a commercially available HY derivative in the form of a gel, highlighting the characteristics of this biomaterial, which makes it attractive for the management of PJIs and IRIs in orthopaedics and traumatology.

Sense of smell in chronic rhinosinusitis: A multicentric study on 811 patients.

Introduction: The impairment of the sense of smell is often related to chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP, CRSsNP). CRSwNP is a frequent condition that drastically worsens the quality of life of those affected; it has a higher prevalence than CRSsNP. CRSwNP patients experience severe loss of smell with earlier presentation and are more likely to experience recurrence of their symptoms, often requiring revision surgery. Methods: The present study performed a multicentric data collection, enrolling 811 patients with CRS divided according to the inflammatory endotype (Type 2 and non-Type 2). All patients were referred for nasal endoscopy for the assessment of nasal polyposis using nasal polyp score (NPS); Sniffin' Sticks olfactory test were performed to measure olfactory function, and SNOT-22 (22-item sinonasal outcome test) questionnaire was used to assess patients' quality of life; allergic status was evaluated with skin prick test and nasal cytology completed the evaluation when available. Results: Data showed that Type 2 inflammation is more common than non-type 2 (656 patients versus 155) and patients suffer from worse quality of life and nasal polyp score. Moreover, 86.1% of patients with Type 2 CRSwNP were affected by a dysfunction of the sense of smell while it involved a lesser percentage of non-Type 2 patients. Indeed, these data give us new information about type-2 inflammation patients' characteristics. Discussion: The present study confirms that olfactory function weights on patients' QoL and it represents an important therapeutic goal that can also improve patients' compliance when achieved. In a future - and present - perspective of rhinological precision medicine, an impairment of the sense of smell could help the clinician to characterize patients better and to choose the best treatment available.

Hip Labral Morphological Changes in Patients with Femoroacetabular Impingement Speed Up the Onset of Early Osteoarthritis.

Over the last decade, evidence has mounted for a prominent etiologic role of femoroacetabular impingement (FAI) in the development of early hip osteoarthritis (OA). The aim of this study was to compare the ultrastructure and tissue composition of the hip labrum in healthy and pathological conditions, as FAI and OA, to provide understanding of structural changes which might be helpful in the future to design targeted therapies and improve treatment indications. We analyzed labral tissue samples from five healthy multi-organ donors (MCDs) (median age, 38 years), five FAI patients (median age, 37 years) and five late-stage OA patients undergoing total hip replacement (median age, 56 years). We evaluated morpho-functional by histology and transmission electron microscopy. Extracellular matrix (ECM) structure changes were similar in specimens from FAI compared to those from patients with OA (more severe in the latter) showing disorganization of collagen fibers and increased proteoglycan content. In FAI and in OA nuclei the chromatin was condensed, organelle degenerated and cytoplasm vacuolized. Areas of calcification were mainly observed in FAI and OA labrum, as well as apoptotic-like features. We showed that labral tissue of patients with FAI had similar pathological alterations of tissue obtained from OA patients, suggesting that FAI patients might have high susceptibility to develop OA.

Quantum Simulations of Fermionic Hamiltonians with Efficient Encoding and Ansatz Schemes.

We propose a computational protocol for quantum simulations of fermionic Hamiltonians on a quantum computer, enabling calculations on spin defect systems which were previously not feasible using conventional encodings and a unitary coupled-cluster ansatz of variational quantum eigensolvers. We combine a qubit-efficient encoding scheme mapping Slater determinants onto qubits with a modified qubit-coupled cluster ansatz and noise-mitigation techniques. Our strategy leads to a substantial improvement in the scaling of circuit gate counts and in the number of required qubits, and to a decrease in the number of required variational parameters, thus increasing the resilience to noise. We present results for spin defects of interest for quantum technologies, going beyond minimum models for the negatively charged nitrogen vacancy center in diamonds and the double vacancy in 4H silicon carbide (4H-SiC) and tackling a defect as complex as negatively charged silicon vacancy in 4H-SiC for the first time.

Brillouin-Raman micro-spectroscopy and machine learning techniques to classify osteoarthritic lesions in the human articular cartilage.

In this study, Brillouin and Raman micro-Spectroscopy (BRamS) and Machine Learning were used to set-up a new diagnostic tool for Osteoarthritis (OA), potentially extendible to other musculoskeletal diseases. OA is a degenerative pathology, causing the onset of chronic pain due to cartilage disruption. Despite this, it is often diagnosed late and the radiological assessment during the routine examination may fail to recognize the threshold beyond which pharmacological treatment is no longer sufficient and prosthetic replacement is required. Here, femoral head resections of OA-affected patients were analyzed by BRamS, looking for distinctive mechanical and chemical markers of the progressive degeneration degree, and the result was compared to standard assignment via histological staining. The procedure was optimized for diagnostic prediction by using a machine learning algorithm and reducing the time required for measurements, paving the way for possible future in vivo characterization of the articular surface through endoscopic probes during arthroscopy.

Allogenic bone grafts and postoperative surgical site infection: are positive intraoperative swab cultures predictive for a higher infectious risk?

In spine surgery, allogenic bone grafts are often required to ensure bone fusion, however, the main concern regarding their use is the infection risk: therefore, an intraoperative swab for culture test is performed. The cost-effectiveness of these swabs and their influence on the patients' postoperative course have often been questioned. This study aims at determining whether positive spine allograft culture results are predictive of an increased risk of surgical site infection and whether they influence the surgeon's choices in postoperative management. The records of 340 patients who received allogenic bone graft during spinal fusion surgery in our institution were reviewed, for a total of 677 allografts. Each graft was swabbed intraoperatively. All patients were followed clinically for postoperative complications. Infection was diagnosed based on clinical data, blood tests and radiographic images, all assessed by an infectious disease specialist. Only 4 of the 677 allografts used (0.6%) resulted positive at the intraoperative swab culture. Three cultures were positive for Staphylococcus epidermidis and one culture for S. warneri. No clinical infection occurred in any of these patients. Twenty-eight of the 340 patients (8.2%) developed an infection, but none of them had a positive intraoperative swab culture. The most common microbiologic pathogen isolated from this cohort was S. aureus. According to our series, intraoperative swab culture results were not predictive for higher risk of infection and did not affect the clinical behavior of the surgeons in postoperative management.

An Observational Prospective Clinical Study for the Evaluation of a Collagen-Hydroxyapatite Composite Scaffold in Hip Revision Surgery.

One of the greatest challenges of hip revision surgery is the need to restore extensive bone loss by creating a stable reconstruction with long-term durability. The present observational, investigator-initiated prospective study was carried out to evaluate the clinical and radiological results of the use of a commercial biomimetic collagen-hydroxyapatite composite biomaterial (RegenOss) applied in hip revision surgery. Thirty-three patients who underwent hip revision were included in this study, and 29 received up to 2 years of follow-up. The acetabulum was reconstructed using an uncemented hemispherical shell both with or without an iliac fixation stem. Functional recovery was assessed according to the Harris Hip Score (HHS) at the pre-hospitalisation check-up, and at 6-, 12-, and 24-month follow-ups. Radiological evaluation consisting of X-ray analyses (6, 12, and 24 month follow-ups) and CT scan exams (within 10 weeks post-surgery and at 12-month follow-up) were performed to evaluate the reduction in bone defect and new bone regeneration. All the patients reported a complete recovery and a considerable improvement in functional outcome assessed by the HHS, which was significantly higher at all the follow-ups than at pre-hospitalisation. Moreover, radiological assessments revealed good scaffold integration. Overall, collected data suggest that RegenOss is a valid and safe alternative to restoring acetabular bone loss in revision hip arthroplasty.

Computational Protocol to Evaluate Electron-Phonon Interactions Within Density Matrix Perturbation Theory.

We present a computational protocol, based on density matrix perturbation theory, to obtain non-adiabatic, frequency-dependent electron-phonon self-energies for molecules and solids. Our approach enables the evaluation of electron-phonon interaction using hybrid functionals, for spin-polarized systems, and the computational overhead to include dynamical and non-adiabatic terms in the evaluation of electron-phonon self-energies is negligible. We discuss results for molecules, as well as pristine and defective solids.

GPU Acceleration of Large-Scale Full-Frequency GW Calculations.

Many-body perturbation theory is a powerful method to simulate electronic excitations in molecules and materials starting from the output of density functional theory calculations. By implementing the theory efficiently so as to run at scale on the latest leadership high-performance computing systems it is possible to extend the scope of GW calculations. We present a GPU acceleration study of the full-frequency GW method as implemented in the WEST code. Excellent performance is achieved through the use of (i) optimized GPU libraries, e.g., cuFFT and cuBLAS, (ii) a hierarchical parallelization strategy that minimizes CPU-CPU, CPU-GPU, and GPU-GPU data transfer operations, (iii) nonblocking MPI communications that overlap with GPU computations, and (iv) mixed precision in selected portions of the code. A series of performance benchmarks has been carried out on leadership high-performance computing systems, showing a substantial speedup of the GPU-accelerated version of WEST with respect to its CPU version. Good strong and weak scaling is demonstrated using up to 25 920 GPUs. Finally, we showcase the capability of the GPU version of WEST for large-scale, full-frequency GW calculations of realistic systems, e.g., a nanostructure, an interface, and a defect, comprising up to 10 368 valence electrons.

Green's Function Formulation of Quantum Defect Embedding Theory.

We present a Green's function formulation of the quantum defect embedding theory (QDET) where a double counting scheme is rigorously derived within the G0W0 approximation. We then show the robustness of our methodology by applying the theory with the newly derived scheme to several defects in diamond. Additionally, we discuss a strategy to obtain converged results as a function of the size and composition of the active space. Our results show that QDET is a promising approach to investigate strongly correlated states of defects in solids.

Custom Massive Allograft in a Case of Pelvic Bone Tumour: Simulation of Processing with Computerised Numerical Control vs. Robotic Machining.

The use of massive bone allografts after the resection of bone tumours is still a challenging process. However, to overcome some issues related to the processing procedures and guarantee the best three-dimensional matching between donor and recipient, some tissue banks have developed a virtual tissue database based on the scanning of the available allografts for using their 3D shape during virtual surgical planning (VSP) procedures. To promote the use of future VSP bone-shaping protocols useful for machining applications within a cleanroom environment, in our work, we simulate a massive bone allograft machining with two different machines: a four-axes (computer numerical control, CNC) vs. a five-axes (robot) milling machine. The allograft design was based on a real case of allograft reconstruction after pelvic tumour resection and obtained with 3D Slicer and Rhinoceros software. Machining simulations were performed with RhinoCAM and graphically and mathematically analysed with CloudCompare and R, respectively. In this case, the geometrical differences of the allograft design are not clinically relevant; however, the mathematical analysis showed that the robot performed better than the four-axes machine. The proof-of-concept presented here paves the way towards massive bone allograft cleanroom machining. Nevertheless, further studies, such as the simulation of different types of allografts and real machining on massive bone allografts, are needed.

Quality Control Platform for the Standardization of a Regenerative Medicine Product.

Adipose tissue is an attractive source of stem cells due to its wide availability. They contribute to the stromal vascular fraction (SVF), which is composed of pre-adipocytes, tissue-progenitors, and pericytes, among others. Because its direct use in medical applications is increasing worldwide, new quality control systems are required. We investigated the ability of the Non-Equilibrium Earth Gravity Assisted Dynamic Fractionation (NEEGA-DF) method to analyze and separate cells based solely on their physical characteristics, resulting in a fingerprint of the biological sample. Adipose tissue was enzymatically digested, and the SVF was analyzed by NEEGA-DF. Based on the fractogram (the UV signal of eluting cells versus time of analysis) the collection time was set to sort alive cells. The collected cells (F-SVF) were analyzed for their phenotype, immunomodulation ability, and differentiation potential. The SVF profile showed reproducibility, and the alive cells were collected. The F-SVF showed intact adhesion phenotype, proliferation, and differentiation potential. The methodology allowed enrichment of the mesenchymal component with a higher expression of mesenchymal markers and depletion of debris, RBCs, and an extracellular matrix still present in the digestive product. Moreover, cells eluting in the last minutes showed higher circularity and lower area, proving the principles of enrichment of a more homogenous cell population with better characteristics. We proved the NEEGA-DF method is a "gentle" cell sorter that purifies primary cells obtained by enzymatic digestion and does not alter any stem cell function.

Fiber Thickness and Porosity Control in a Biopolymer Scaffold 3D Printed through a Converted Commercial FDM Device.

3D printing has opened exciting new opportunities for the in vitro fabrication of biocompatible hybrid pseudo-tissues. Technologies based on additive manufacturing herald a near future when patients will receive therapies delivering functional tissue substitutes for the repair of their musculoskeletal tissue defects. In particular, bone tissue engineering (BTE) might extensively benefit from such an approach. However, designing an optimal 3D scaffold with adequate stiffness and biodegradability properties also guaranteeing the correct cell adhesion, proliferation, and differentiation, is still a challenge. The aim of this work was the rewiring of a commercial fuse deposition modeling (FDM) 3D printer into a 3D bioplotter, aiming at obtaining scaffold fiber thickness and porosity control during its manufacturing. Although it is well-established that FDM is a fast and low-price technology, the high temperatures required for printing lead to limitations in the biomaterials that can be used. In our hands, modifying the printing head of the FDM device with a custom-made holder has allowed to print hydrogels commonly used for embedding living cells. The results highlight a good resolution, reproducibility and repeatability of alginate/gelatin scaffolds obtained via our custom 3D bioplotter prototype, showing a viable strategy to equip a small-medium laboratory with an instrument for manufacturing good-quality 3D scaffolds for cell culture and tissue engineering applications.

Do Pomegranate Hydrolyzable Tannins and Their Derived Metabolites Provide Relief in Osteoarthritis? Findings from a Scoping Review.

Osteoarthritis (OA) is the most common form of arthritis affecting both the elderly and the middle-aged population. Although various therapeutics have been developed to arrest the structural deterioration of cartilage, the current treatments are limited to delay the progress of OA clinically. Therefore, it is pivotal to study new therapeutic agents for chondroprotection and the prevention of cartilage degeneration. Hydrolyzable tannin (HT)-containing foods aroused considerable interest in recent years for their relevant anti-inflammatory effects. The focus of this scoping review is to provide an overview of the evidence of the therapeutic potential of HTs and their metabolites in preventing or alleviating the course of OA. A broad search of PubMed and Scopus databases on this topic resulted in 156 articles. After the exclusion of reviews and not relevant records, 31 articles were retrieved. Although only some papers did not consider the biotransformation of HTs, most recent studies also have investigated the effect of HT metabolites. Further larger clinical trials, with an in-deep analysis of HT metabolization, are still needed to unravel the potential benefits of these compounds in OA, paving the way towards the development of a dietary strategy for the improvement of pro-inflammatory cytokine-induced chondrocyte dysfunctions and injuries.

Quantum embedding theories to simulate condensed systems on quantum computers.

Quantum computers hold promise to improve the efficiency of quantum simulations of materials and to enable the investigation of systems and properties that are more complex than tractable at present on classical architectures. Here, we discuss computational frameworks to carry out electronic structure calculations of solids on noisy intermediate-scale quantum computers using embedding theories, and we give examples for a specific class of materials, that is, solid materials hosting spin defects. These are promising systems to build future quantum technologies, such as quantum computers, quantum sensors and quantum communication devices. Although quantum simulations on quantum architectures are in their infancy, promising results for realistic systems appear to be within reach.

Management of cochlear fistula and the role of hearing: a five-case report.

OBJECTIVE: Cochlear fistula (CF) is a rare finding, usually associated with extensive middle ear cholesteatoma. There is agreement on the fact that removing the cholesteatoma matrix on a CF exposes the ear to a high risk of sensorineural hearing loss or dead ear. The aim of the study is to describe the presentation, possible treatment strategies and related outcomes for patients with CF in chronic otitis media (COM). METHODS: The study considers a retrospective case series of patients with CF diagnosis supported by CT-scan and intraoperative/otoscopic evidence. RESULTS: Five cases of CF were identified, 4 associated with cholesteatoma and 1 associated with non-cholesteatomatous COM. Two patients presenting with anacusis underwent a subtotal petrosectomy. Two patients with useful hearing underwent a radical mastoidectomy in order to preserve the cholesteatoma matrix on the promontorium. One patient with good hearing and COM was treated conservatively. CONCLUSIONS: Conservative management should be considered for rare cases of CF in COM with residual hearing. Matrix preservation through radical/modified radical mastoidectomy is strongly advised in the presence of useful preoperative bone conduction. Subtotal petrosectomy should be considered the preferred option in presence of cholesteatoma with preoperative profound hearing loss.