Virtual Surgical Planning for Temporomandibular Joint Reconstruction with Stock TMJ Prostheses: Pilot Study.

The temporomandibular joint (TMJ) is one of the most complex joints in the human anatomy. In advanced degenerative stages, conservative or minimally invasive surgical therapies have failed to restore joint function, and joint replacement with prostheses has been required. Stock prostheses, compared to custom-made prostheses, are much less expensive and require less pre-operative preparation time. Four patients followed for years for temporomandibular dysfunction and previously operated on by arthroscopy or open joint surgery that have been reconstructed with stock TMJ prostheses (STMJP) through virtual surgical planning (VSP) and an STL model with surgical and positioning guides were included. The median follow-up was 15 months; the median number of previous TMJ surgeries was 2. The mean preoperative MIO was 24.6 mm and at longest follow-up was 36.4 mm. The median preoperative TMJ pain score was 8, and the median postoperative TMJ pain was 3. All patients have improved their mandibular function with a clear improvement of their initial situation. In conclusion, we believe that stock TMJ prostheses with virtual surgical planning and surgical guides are a good alternative for TMJ reconstruction at the present time. Nonetheless, prospective and randomized trials are required with long-term follow up to assess their performance and safety.

ß-Variational autoencoders and transformers for reduced-order modelling of fluid flows.

Variational autoencoder architectures have the potential to develop reduced-order models for chaotic fluid flows. We propose a method for learning compact and near-orthogonal reduced-order models using a combination of a ß-variational autoencoder and a transformer, tested on numerical data from a two-dimensional viscous flow in both periodic and chaotic regimes. The ß-variational autoencoder is trained to learn a compact latent representation of the flow velocity, and the transformer is trained to predict the temporal dynamics in latent-space. Using the ß-variational autoencoder to learn disentangled representations in latent-space, we obtain a more interpretable flow model with features that resemble those observed in the proper orthogonal decomposition, but with a more efficient representation. Using Poincaré maps, the results show that our method can capture the underlying dynamics of the flow outperforming other prediction models. The proposed method has potential applications in other fields such as weather forecasting, structural dynamics or biomedical engineering.

Net-clipping as a top-down approach for the prediction of topologies of MOFs built from reduced-symmetry linkers.

Reticular materials constructed from regular molecular building blocks (MBBs) have been widely explored in the past three decades. Recently, there has been increasing interest in the assembly of novel, intricate materials using less-symmetric ligands; however, current methods for predicting structure are not amenable to this increased complexity. To address this gap, we propose herein a generalised version of the net-clipping approach for anticipating the topology of metal-organic frameworks (MOFs) assembled from organic linkers and different polygonal and polyhedral MBBs. It relies on the generation of less-symmetric nets with less-connected linkers, via the rational deconstruction of more-symmetric and more-connected linkers in edge-transitive nets. We applied our top-down strategy to edge-transitive nets containing 4-c tetrahedral, 6-c hexagonal, 8-c cubic or 12-c hexagonal prism linkers, envisaging the formation of 102 derived and 46 clipped nets. Among these, we report 33 new derived nets (icn7-icn39) and 6 new clipped nets (icn1-icn6). Importantly, the feasibility of using net-clipping to anticipate clipped nets is supported by literature examples and new experimental additions. Finally, we suggest and illustrate that net-clipping can be extended to less-regular, non-edge transitive nets as well as to covalent-organic frameworks (COFs), thus opening new avenues for the rational design of new reticular materials exhibiting unprecedented topologies.

Depth of Invasion: Influence of the Latest TNM Classification on the Prognosis of Clinical Early Stages of Oral Tongue Squamous Cell Carcinoma and Its Association with Other Histological Risk Factors.

BACKGROUND: The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors. METHODS: A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan-Meier method. Statistical significance was established for p values below 0.05. RESULTS: Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival (p = 0.043), but not with respect to overall survival (p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes (p = 0.012), perineural invasion (p = 0.004) and tumour differentiation grade (p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion. CONCLUSIONS: Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade.

Synthesis of α,α-Diaryl-α-amino Acid Precursors by Reaction of Isocyanoacetate Esters with o-Quinone Diimides.

A novel procedure for the synthesis of α,α-diaryl-α-amino acid derivatives has been developed. Silver oxide catalyzes the conjugate addition of α-aryl isocyanoacetates to o-quinone diimide, affording the corresponding α,α-diarylisocyano esters in excellent yields and regioselectivities in short reaction times. Acid hydrolysis of the isocyano group provides the corresponding amino acids bearing a diarylated tetrasubstituted carbon atom. The reaction is also amenable to the synthesis of α-alkyl-α-arylisocyano esters, while the reaction with 3-hydroxy o-quinone diimides provides 4H-benzo[e][1,3]oxazines via a conjugate addition/cyclization process.

Organophotoredox 1,6-Addition of 3,4-Dihydroquinoxalin-2-ones to para-Quinone Methides Using Visible Light.

An organophotoredox 1,6-radical addition of 3,4-dihidroquinoxalin-2-ones to para-quinone methides catalyzed by Fukuzumi's photocatalyst is described under the irradiation of a HP Single LED (455 nm). The corresponding 1,1-diaryl compounds bearing a dihydroquinoxalin-2-one moiety (20 examples) are obtained with good to excellent yields under mild reaction conditions. Several experiments have been carried out in order to propose a reaction mechanism.

A Cu-BOX catalysed enantioselective Mukaiyama-aldol reaction with difluorinated silyl enol ethers and acylpyridine N-oxides.

A Cu(II)/BOX complex catalyses the enantioselective addition of difluorinated silyl enol ethers to acylpyridine N-oxides. The reaction provides difluorinated chiral tertiary alcohols of great interest in medicinal chemistry. These compounds are obtained in moderate to excellent yields and with high enantioselectivities. The stereochemical outcome of the reaction has been explained by DFT calculations.

Organocatalytic enantioselective Mannich reaction of isoxazol-5(4H)-ones to isatin-derived ketimines.

An efficient organocatalytic asymmetric Mannich reaction between isoxazol-5(4H)-ones and isatin-derived ketimines has been developed. A bifunctional squaramide/Brønsted base organocatalyst catalyzed the enantioselective Mannich addition to afford chiral 3-aminooxindoles bearing a tetrasubstituted stereocenter at C3 decorated with an isoxazole moiety in good yields and with excellent enantioselectivities. Additionally, several synthetic transformations were described showing the versatility of the prepared compounds.

Radical Addition of Dihydroquinoxalin-2-ones to Trifluoromethyl Ketones under Visible-Light Photoredox Catalysis.

A visible-light photocatalytic radical addition reaction of dihydroquinoxalin-2-ones to trifluoromethyl ketones has been established using Ru(bpy)3Cl2 as photocatalyst, acetonitrile as solvent, and HP Single Blue LED as the source of light. The reaction provides a straightforward approach to the synthesis of dihydroquinoxalin-2-ones bearing a trifluoromethyl-substituted tertiary alcohol moiety in moderate to good yields under mild conditions.

Metal-Free Diastereo- and Enantioselective Dearomative Formal [3 + 2] Cycloaddition of 2-Nitrobenzofurans and Isocyanoacetate Esters.

The diastereo- and enantioselective dearomative formal [3 + 2] cycloaddition of 2-nitrobenzofurans and α-aryl-α-isocyanoacetate esters provides tricyclic compounds bearing the 3a,8b-dihydro-1H-benzofuro[2,3-c]pyrrole framework with three consecutive stereogenic centers. The reaction was enabled by a cupreine-ether organocatalyst. The reaction products were obtained with almost full diastereoselectivity and with excellent enantiomeric excesses for a number of substituted 2-nitrobenzofurans and isocyanoacetates.

Catalytic Diastereo- and Enantioselective Synthesis of Tertiary Trifluoromethyl Carbinols through a Vinylogous Aldol Reaction of Alkylidenepyrazolones with Trifluoromethyl Ketones.

A diastereo- and enantioselective organocatalytic aldol reaction between alkylidenepyrazolones and trifluoromethyl ketones leading to chiral tertiary alcohols bearing a trifluoromethyl group is presented. The methodology is based on the use of a bifunctional organocatalyst in order to activate the γ-hydrogen atoms of the alkylidenepyrazolone nucleophile and the carbonyl group of the trifluoromethylarylketone providing highly functionalized trifluoromethyl alcohols with moderate yields, excellent diastereoselectivity, and moderate to good enantioselectivity. Experiments monitoring the conversion by 1H NMR and the enantiomeric excess by HPLC with the reaction time showed that full conversion of the starting materials is not achieved and that the enantiomeric excess decreases upon extended times, probably due to the reversibility of the reaction.

Collaborative manufacturing of ergonomic personal protective equipment (PPE) accessories to prevent infectious disease.

Throughout history there have been epidemics and pandemics of all kinds, however the most recent ones have been respiratory diseases that have had a significant effect on the society and that have caused high mortality rates. The preventive measures to minimize the risk of contagion by contact with infected surfaces include ergonomic accessories including personal protective equipment (PPE) to prevent hands to be in contact with surfaces that could be infected by viruses, bacteria, fungi, etc., thus avoiding infection by the usual entry routes (mouth, nose, and eyes) to the human body of highly contagious diseases such as COVID-19. The collaborative manufacture of these safety accessories at the site of consumption is a current option that minimizes infectious diseases and reduces costs. Accessories such as the so-called "ear saver" and "anti-contact keys" can be produced by 3D printing with a general CAD/CAM and allow users in hospitals, and schools, such as medical and teaching staff and society in general to extend the life of N95 respirator fasteners (protective masks) and avoid contagion. These devices can be used to open doors and windows and control elevators, etc. The accessories can be optimized ergonomically for individual use by providing a custom design. The collaborative manufacture of these elements allows the product design stages to be carried out autonomously. In the manufacturing stage, 3D printers can be used to produce the devices at the point of use, thus saving on transport and distribution costs. This paper describes a comparative analysis of their design, manufacture and use in hospitals, schools, universities, and commercial areas with the aim of improving the current design.

Intraosseous Venous Malformation of the Zygomatic Bone: Comparison between Virtual Surgical Planning and Standard Surgery with Review of the Literature.

Intraosseous venous malformations affecting the zygomatic bone are infrequent. Primary reconstruction is usually accomplished with calvarial grafts, although the use of virtual surgical planning, cutting guides and patient-specific implants (PSI) have had a major development in recent years. A retrospective study was designed and implemented in patients diagnosed with intraosseous venous malformation during 2006-2021, and a review of the scientific literature was also performed to clarify diagnostic terms. Eight patients were treated, differentiating two groups according to the technique: four patients were treated through standard surgery with resection and primary reconstruction of the defect with calvarial graft, and four patients underwent resection and primary reconstruction through virtual surgical planning (VSP), cutting guides, STL models developed with CAD-CAM technology and PSI (titanium or Polyether-ether-ketone). In the group treated with standard surgery, 75% of the patients developed sequelae or morbidity associated with this technique. The operation time ranged from 175 min to 210 min (average 188.7 min), the length of hospital ranged from 4 days to 6 days (average 4.75 days) and the postoperative CT scan showed a defect surface coverage of 79.75%. The aesthetic results were "excellent" in 25% of the patients, "good" in 50% and "poor" in 25%. In the VSP group, 25% presented sequelae associated with surgical treatment. The operation time ranged from 99 min to 143 min (average 121 min), the length of hospital stay ranged from 1 to 2 days (average of 1.75 days) and 75% of the patients reported "excellent" results. Postoperative CT scan showed 100% coverage of the defect surface in the VSP group. The multi-stage implementation of virtual surgical planning with cutting guides, STL models and patient-specific implants increases the reconstructive accuracy in the treatment of patients diagnosed with intraosseous venous malformation of the zygomatic bone, reducing sequelae, operation time and average hospital stay, providing a better cover of the defect, and improving the precision of the reconstruction and the aesthetic results compared to standard technique.

Clinical and Surgical Outcomes in Extensive Scalp Reconstruction after Oncologic Resection: A Comparison of Anterolateral Thigh, Latissimus Dorsi and Omental Free Flaps.

Microsurgical scalp reconstruction is indicated in patients with large scalp defects. The aim of this study was to compare the outcomes of scalp reconstruction in oncologic patients reconstructed with latissimus dorsi (LD), anterolateral thigh (ALT), and omental (OM) free flaps. Thirty oncologic patients underwent scalp reconstruction with LD (10), ALT (11), and OM (9) flaps. The length of the vascular pedicle, the operation time, the possibility of a two-team approach, the length of hospital stays, the complications, and the aesthetic results were evaluated. The OM flap was the flap with the shortest vascular pedicle length with a mean of 6.26 ± 0.16 cm, compared to the LD flap, which was 12.34 ± 0.55 cm and the ALT flap with 13.20 ± 0.26 cm (p < 0.05). The average time of surgery was 6.6 ± 0.14 h in patients reconstructed with OM, compared to the LD flap, which was 8.91 ± 0.32 h and the ALT flap with 7.53 ± 0.22 h (p < 0.05). A two-team approach was performed in all patients for OM flaps and ALT flaps, but only in two patients reconstructed with the LD flap (p < 0.001). In patients reconstructed with the OM flap, a very satisfactory or satisfactory result was reported in seven patients (77.8%). Eight patients reported a very unsatisfactory or unsatisfactory result with LD flap (80%) and 10 patients with ALT flap (90.9%) (p = 0.002). The mean hospital stay after surgery was not statistically significant (p > 0.05). As for complications, two patients reconstructed with OM flap, five LT flaps, and two ALT flaps developed complications, not statistically significant (p = 0.235). Omental flap, latissimus dorsi flap, and anterolateral thigh flap fulfill most of the characteristics for complex scalp reconstruction. The decision on which flap to use should be based on clinical aspects of the patients taking into account that the three flaps show similar rates of complications and length of hospital stay. Regarding the aesthetic outcome, OM flap or LD flap should be considered for reconstruction of extensive scalp defects.

Catalytic Diastereo- and Enantioselective Vinylogous Mannich Reaction of Alkylidenepyrazolones to Isatin-Derived Ketimines.

A valuable organocatalytic vinylogous Mannich reaction between alkylidenepyrazolones and isatin-derived ketimines has been successfully established. Squaramide organocatalyst, prepared from quinine, catalyzed the diastereo- and enantioselective vinylogous Mannich addition, affording a range of aminooxindole-pyrazolone adducts (24 examples) with excellent outcomes: up to 98% yield with complete diastereoselectivity and excellent enantioselectivity (up to 99% ee). Additionally, different synthetic transformations were performed with the chiral pyrazolone-oxindole adducts.

Enantioselective Friedel-Crafts reaction of hydroxyarenes with nitroenynes to access chiral heterocycles via sequential catalysis.

Naphthols, hydroxyindoles and an activated phenol are reacted with differently substituted (E)-nitrobut-1-en-3-ynes using the commercially available Rawal's chiral squaramide. The corresponding ß-nitroalkynes were obtained with good yields and excellent enantioselectivities. Moreover, dihydronaphthofurans can be accessed via silver catalysed cyclization in a tandem one-pot procedure, with high preservation of the optical purity.

Preoperative Doppler Ultrasonography Allen Test for Radial Forearm Free Flap in Oral Cancer Reconstruction: Implications in Clinical Practice.

The Radial Forearm Free Flap (RFFF) is one of the most widely used microsurgical flaps for intraoral reconstruction. Although the Clinical Allen Test (CAT) is the most widely used preoperative diagnostic method with which to study the distal patency of the hand prior to the use of RFFF, several authors have reported potentially preventable serious vascular complications. This study included 87 consecutive patients with cancer of the oral cavity and RFFF as the flap of choice who were treated between 2010 and 2020, and compares the results of the Clinical Allen Test (CAT), the Doppler Allen Test (DAT) and the Surgical Allen Test (SAT). The preoperative vascular study found vascular abnormalities severe enough for the surgical team to change the preoperative flap of choice in 39% of patients. The Kappa index showed a weak concordance between the CAT and DAT. The study reflected a total concordance in the preoperative results of the Doppler study and the intraoperative results of the SAT. Due to its excellent agreement with SAT, the DAT would be the preoperative test of choice in patients who are candidates for RFFF. This study of vascular mapping tests with Doppler is intended to inform therapeutic decisions and present methods to gain information that cannot be obtained by physical examination alone.

Functional Outcomes with Facial Artery Musculo-Mucosal (FAMM) Flap and Dental Implants for Reconstruction of Floor of the Mouth and Tongue Defects in Oncologic Patients.

Optimal functional outcomes in oncologic patients with squamous cell carcinoma (SCCA) of the tongue and floor of the mouth require good lingual mobility, adequate facial competence, the cheek suction effect and dental rehabilitation with osseointegrated implants. In this study, twenty-two oncologic patients who had been diagnosed with intraoral SCCA affecting the tongue and the floor of the mouth and who had undergone wide resection of the tumor and immediate reconstruction with an inferiorly pedicled FAMM flap and immediate osseointegrated implants were assessed. Lingual mobility, speech articulation, deglutition, implant success rate, mouth opening, and aesthetic results were evaluated. All patients were staged as T2 and the defect size ranged from 3.7 × 2.1 cm to 6.3 × 4.2 cm. A selective neck dissection was performed in all patients as part of their oncologic treatment, either electively or for node positive disease. Thirteen patients (59%) were diagnosed with node positive disease and underwent adjuvant radiotherapy. A total of 101 osseointegrated implants were placed for prosthetic rehabilitation and 8 implants were lost (7.9%), of which 7 received radiotherapy (87.5%). The implant success rate was 92.1%. Mouth opening was reported as normal in 19 patients (86.3%). Tongue tip elevation was reported as excellent in 19 patients (86.3%) and good in 3 patients (13.6%). Lingual protrusion was referred to as excellent in 15 patients (68.2%) and good in 6 patients (27.2%). Lateral excursion was reported as excellent in 14 patients (63.6%) and good in 7 patients (31.8%). In terms of speech articulation, 20 patients reported normal speech (90.9%). Regarding deglutition, 19 patients (86.3%) reported a regular diet while a soft diet was reported by 3 patients (13.7%). Aesthetic results were referred to as excellent in 17 patients (77.3%). FAMM flaps, immediate implants and fixed prostheses enable the functional rehabilitation of oncologic patients, optimizing aesthetics and functional outcomes even in patients undergoing irradiation, thus returning oncologic patients to an excellent quality of life.

Visible-light-accelerated amination of quinoxalin-2-ones and benzo[1,4]oxazin-2-ones with dialkyl azodicarboxylates under metal and photocatalyst-free conditions.

A direct sp3 C-H amination of cyclic amines (dihydroquinoxalinones and dihydrobenzoxazinones) with dialkyl azo dicarboxylates accelerated by visible-light irradiation under metal and photocatalyst-free conditions is described. This protocol features very mild reaction conditions for the synthesis of aminal quinoxaline and benzoxazine derivatives with good to high yields (up to 99%). These aminal derivatives respresent versatile building blocks for the divergent synthesis of quinoxalin-2-one derivatives.

Virtual Surgical Planning, Stereolitographic Models and CAD/CAM Titanium Mesh for Three-Dimensional Reconstruction of Fibula Flap with Iliac Crest Graft and Dental Implants.

Mandibular reconstruction with fibula flap shows a 3D discrepancy between the fibula and the remnant mandible. Eight patients underwent three-dimensional reconstruction of the fibula flap with iliac crest graft and dental implants through virtual surgical planning (VSP), stereolitographic models (STL) and CAD/CAM titanium mesh. Vertical ridge augmentation and horizontal dimensions of the fibula, peri-implant bone resorption of the iliac crest graft, implant success rate and functional and aesthetic results were evaluated. Vertical reconstruction ranged from 13.4 mm to 10.1 mm, with an average of 12.22 mm. Iliac crest graft and titanium mesh were able to preserve the width of the fibula, which ranged from 8.9 mm to 11.7 mm, with an average of 10.1 mm. A total of 38 implants were placed in the new mandible, with an average of 4.75 ± 0.4 implants per patient and an osseointegration success rate of 94.7%. Two implants were lost during the osseointegration period (5.3%). Bone resorption was measured as peri-implant bone resorption at the mesial and distal level of each implant, with a variation between 0.5 mm and 2.4 mm, and with a mean of 1.43 mm. All patients were rehabilitated with a fixed implant prosthesis with good aesthetic and functional results.