Information-based TMS to mid-lateral prefrontal cortex disrupts action goals during emotional processing.

The ability to respond to emotional events in a context-sensitive and goal-oriented manner is essential for adaptive functioning. In models of behavioral and emotion regulation, the lateral prefrontal cortex (LPFC) is postulated to maintain goal-relevant representations that promote cognitive control, an idea rarely tested with causal inference. Here, we altered mid-LPFC function in healthy individuals using a putatively inhibitory brain stimulation protocol (continuous theta burst; cTBS), followed by fMRI scanning. Participants performed the Affective Go/No-Go task, which requires goal-oriented action during affective processing. We targeted mid-LPFC (vs. a Control site) based on the individualized location of action-goal representations observed during the task. cTBS to mid-LPFC reduced action-goal representations in mid-LPFC and impaired goal-oriented action, particularly during processing of negative emotional cues. During negative-cue processing, cTBS to mid-LPFC reduced functional coupling between mid-LPFC and nodes of the default mode network, including frontopolar cortex-a region thought to modulate LPFC control signals according to internal states. Collectively, these results indicate that mid-LPFC goal-relevant representations play a causal role in governing context-sensitive cognitive control during emotional processing.

Forensic investigation on a combined death by food aspiration and acute escitalopram intoxication occurred to a psychiatric subject in a nursing home.

Food aspiration is one of the major health risks for elderly people in nursing homes which could lead to death. Moreover, misconducts in pharmacotherapy may represent a potential risk of adverse drug reactions. It is reported here the toxicological evaluation of a combined death by food aspiration and acute escitalopram intoxication of a psychiatric subject, occurred in a nursing home. An 89-year-old man, suffering from dysphagia and Alzheimer's, was resident in a nursing home. He was fed with a liquid diet administered directly in mouth using a syringe. The man was also being treated with escitalopram 10 mg tablet. One evening, after receiving the meal in the usual way, the man complained of sudden illness. Carried to the emergency room, the man died about 3 h later with a diagnosis of cardiogenic shock subsequentially to ab ingestis. The histological findings revealed the presence of exogenous material, probably food, up to the finest bronchial branches. The toxicological examination revealed the presence of escitalopram and its main metabolite, desmethylcitalopram: in the blood 1972 ng/ml and 285 ng/ml, in the brain 4657 ng/g and 1025 ng/g, in the gastric content 2317 ng/g and 423 ng/g, in the lung 21,771 ng/g and 468 ng/g, respectively. The bad practice of the nurses to dissolve the escitalopram tablet in the liquefied food and to administer the therapy with a syringe directly into the mouth emerged thanks this investigation. Following food aspiration, escitalopram was absorbed by inhalation route, reaching high concentrations in blood and tissues. The death occurred due to a combined mechanism between food aspiration and the escitalopram toxic action.

OPTIma: simplifying calorimetry for proton computed tomography in high proton flux environments.

Objective.Proton computed tomography (pCT) offers a potential route to reducing range uncertainties for proton therapy treatment planning, however the current trend towards high current spot scanning treatment systems leads to high proton fluxes which are challenging for existing systems. Here we demonstrate a novel approach to energy reconstruction, referred to as 'de-averaging', which allows individual proton energies to be recovered using only a measurement of their integrated energy without the need for spatial information from the calorimeter.Approach.The method is evaluated in the context of the Optimising Proton Therapy through Imaging (OPTIma) system which uses a simple, relatively inexpensive, scintillator-based calorimeter that reports only the integrated energy deposited by all protons within a cyclotron period, alongside a silicon strip based tracking system capable of reconstructing individual protons in a high flux environment. GEANT4 simulations have been performed to examine the performance of such a system at a modern commercial cyclotron facility using aσ≈ 10 mm beam for currents in the range 10-50 pA at the nozzle.Main results.Apart from low-density lung tissue, a discrepancy of less than 1% on the Relative Stopping Power is found for all other considered tissues when embedded within a 150 mm spherical Perspex phantom in the 10-30 pA current range, and for some tissues even up to 50 pA.Significance.By removing the need for the calorimeter system to provide spatial information, it is hoped that the de-averaging approach can facilitate clinically relevant, cost effective and less complex calorimeter systems for performing high current pCTs.

Robustness analysis of surface-guided DIBH left breast radiotherapy: personalized dosimetric effect of real intrafractional motion within the beam gating thresholds.

PURPOSE: The robustness of surface-guided (SG) deep-inspiration breath-hold (DIBH) radiotherapy (RT) for left breast cancer was evaluated by investigating any potential dosimetric effects due to the residual intrafractional motion allowed by the selected beam gating thresholds. The potential reduction of DIBH benefits in terms of organs at risk (OARs) sparing and target coverage was evaluated for conformational (3DCRT) and intensity-modulated radiation therapy (IMRT) techniques. METHODS: A total of 192 fractions of SGRT DIBH left breast 3DCRT treatment for 12 patients were analyzed. For each fraction, the average of the real-time displacement between the isocenter on the daily reference surface and on the live surface ("SGRT shift") during beam-on was evaluated and applied to the original plan isocenter. The dose distribution for the treatment beams with the new isocenter point was then calculated and the total plan dose distribution was obtained by summing the estimated perturbed dose for each fraction. Then, for each patient, the original plan and the perturbed one were compared by means of Wilcoxon test for target coverage and OAR dose-volume histogram (DVH) metrics. A global plan quality score was calculated to assess the overall plan robustness against intrafractional motion of both 3DCRT and IMRT techniques. RESULTS: Target coverage and OAR DVH metrics did not show significant variations between the original and the perturbed plan for the IMRT techniques. 3DCRT plans showed significant variations for the left descending coronary artery (LAD) and the humerus only. However, none of the dose metrics exceeded the mandatory dose constraints for any of the analyzed plans. The global plan quality analysis indicated that both 3DCRT and IMRT techniques were affected by the isocenter shifts in the same way and, generally, the residual isocenter shifts more likely tend to worsen the plan in all cases. CONCLUSION: The DIBH technique proved to be robust against residual intrafractional isocenter shifts allowed by the selected SGRT beam-hold thresholds. Small-volume OARs located near high dose gradients showed significant marginal deteriorations in the perturbed plans with the 3DCRT technique only. Global plan quality was mainly influenced by patient anatomy and treatment beam geometry rather than the technique adopted.

InSPECtor: an end-to-end design framework for compressive pixelated hyperspectral instruments.

Classic designs of hyperspectral instrumentation densely sample the spatial and spectral information of the scene of interest. Data may be compressed after the acquisition. In this paper, we introduce a framework for the design of an optimized, micropatterned snapshot hyperspectral imager that acquires an optimized subset of the spatial and spectral information in the scene. The data is thereby already compressed at the sensor level but can be restored to the full hyperspectral data cube by the jointly optimized reconstructor. This framework is implemented with TensorFlow and makes use of its automatic differentiation for the joint optimization of the layout of the micropatterned filter array as well as the reconstructor. We explore the achievable compression ratio for different numbers of filter passbands, number of scanning frames, and filter layouts using data collected by the Hyperscout instrument. We show resulting instrument designs that take snapshot measurements without losing significant information while reducing the data volume, acquisition time, or detector space by a factor of 40 as compared to classic, dense sampling. The joint optimization of a compressive hyperspectral imager design and the accompanying reconstructor provides an avenue to substantially reduce the data volume from hyperspectral imagers.

Surface-guided DIBH radiotherapy for left breast cancer: impact of different thresholds on intrafractional motion monitoring and DIBH stability.

PURPOSE: To compare two left breast cancer patient cohorts (tangential vs. locoregional deep-inspiration breath-hold - DIBH treatment) with different predefined beam gating thresholds and to evaluate their impact on motion management and DIBH stability. METHODS: An SGRT-based clinical workflow was adopted for the DIBH treatment. Intrafractional monitoring was performed by tracking both the respiratory signal and the real-time displacement between the isocenter on the daily reference surface and on the live surface ("SGRT shift"). Beam gating tolerances were 5 mm/4 mm for the SGRT shifts and 5 mm/3 mm for the gating window amplitude for breast tangential and breast + lymph nodes locoregional treatments, respectively. A total of 24 patients, 12 treated with a tangential technique and 12 with a locoregional technique, were evaluated for a total number of 684 fractions. Statistical distributions of SGRT shift and respiratory signal for each treatment fraction, for each patient treatment, and for the two population samples were generated. RESULTS: Lateral cumulative distributions of SGRT shifts for both locoregional and tangential samples were consistent with a null shift, whereas longitudinal and vertical ones were slightly negative (mean values < 1 mm). The distribution of the percentage of beam on time with SGRT shift > 3 mm, > 4 mm, or > 5 mm was extended toward higher values for the tangential sample than for the locoregional sample. The variability in the DIBH respiration signal was significantly greater for the tangential sample. CONCLUSION: Different beam gating thresholds for surface-guided DIBH treatment of left breast cancer can impact motion management and DIBH stability by reducing the frequency of the maximum SGRT shift and increasing respiration signal stability when tighter thresholds are adopted.

The Combination of Dupilumab with Other Monoclonal Antibodies.

INTRODUCTION: Dupilumab is an interleukin-4 (IL-4) receptor alpha antagonist indicated for the treatment of moderate-to-severe atopic dermatitis (AD), which could be associated with atopic and non-atopic comorbidities for which concomitant administration of targeted pharmacotherapy including monoclonal antibodies could be required. However, the safety of combining dupilumab with other monoclonal antibodies for different therapeutic indication may be debated. METHODS: We conducted an extensive search in MEDLINE via PubMed for original articles published from January 1, 2017 to October 22, 2022, reporting clinical cases in which dupilumab has been associated with other monoclonal antibodies. RESULTS: Four small case series were identified reporting data on a total of 16 patients. To them, we have added other patients (n = 8) derived from our clinical practice, achieving a total of 24 cases followed for a period of 2-22 months. Patients were receiving dupilumab mainly because of AD (except one patient for bullous pemphigoid and one for asthma) and other monoclonal antibodies for psoriasis treated with guselkumab (n = 7) and secukinumab (n = 1), asthma with omalizumab or benralizumab (n = 3), Crohn's disease with adalimumab (n = 3), chronic spontaneous urticaria with omalizumab (n = 3), primary familial hypercholesterolemia with evolocumab (n = 2), hidradenitis suppurativa with adalimumab (n = 1), psoriatic arthritis with secukinumab (n = 1), rheumatoid arthritis with abatacept (n = 1), ankylosing spondylitis with secukinumab (n = 1) and colorectal carcinoma with cetuximab (n = 1). No adverse events related to the combination of the two monoclonal antibodies were reported except for a mild injection site reaction (n = 1) and arthralgia, which resolved spontaneously within a few weeks (n = 1). CONCLUSIONS: Because the evidence is modest, the question remains open as to whether dupilumab can be safely combined with other monoclonal antibodies. Dupilumab does not exert immunosuppressive effects and does not impair the activity of cytochrome P450 isozymes.

End-to-end test for lung SBRT: An Italian multicentric pilot experience.

PURPOSE: Set up a lung SBRT end-to-end (e2e) test and perform a multicentre validation. MATERIAL AND METHODS: A group of medical physicists from four hospitals and the Italian Institute of Ionizing Radiation Metrology designed the present e2e test. One sub-group set up the test, while another tested its feasibility and ease of use. A satisfaction questionnaire was used to collect user feedback. Each participating centre (PC) received the ADAM breathing phantom, a microDiamond detector and radiochromic films. Following the e2e protocol, each PC performed its standard internal procedure for simulating, planning, and irradiating the phantom. Each PC uploaded its planning and treatment delivery data in a shared Google Drive. A single centre analyzed all the data. RESULTS: The e2e test was successfully performed by all PCs. Participants' comments indicated that ADAM was well suited to the purpose and the protocol well described. All PCs performed the test in static and dynamic modes. The ratio between measured and planned point dose obtained by PC1, PC2, PC3, PC4 was: 0.99, 0.96, 1.01 and 1.01 (static track) and 0.99, 1.02, 1.01 and 0.94 (dynamic track). The gamma passing rates (3 % global, 3 mm) between planned and measured dose maps were 98.5 %, 94.0 %, 99.1 % and 94.0 % (static track) and 99.5 %, 96.5 %, 86.0 % and 94.5 % (dynamic track) for PC1, PC2, PC3 and PC4, respectively. CONCLUSIONS: An e2e test for lung SBRT has been proposed and tested in a multicentre framework. The results and user feedback prove the validity of the proposed e2e test.

Risk factors and incidence of long-COVID syndrome in hospitalized patients: does remdesivir have a protective effect?

BACKGROUND: The definition of 'long-COVID syndrome' (LCS) is still debated and describes the persistence of symptoms after viral clearance in hospitalized or non-hospitalized patients affected by coronavirus disease 2019 (COVID-19). AIM: In this study, we examined the prevalence and the risk factors of LCS in a cohort of patients with previous COVID-19 and followed for at least 6 months of follow-up. DESIGN: We conducted a prospective study including all hospitalized patients affected by COVID-19 at our center of Infectious Diseases (Vercelli, Italy) admitted between 10 March 2020 and 15 January 2021 for at least 6 months after discharge. Two follow-up visits were performed: after 1 and 6 months after hospital discharge. Clinical, laboratory and radiological data were recorded at each visit. RESULTS: A total of 449 patients were included in the analysis. The LCS was diagnosed in 322 subjects at Visit 1 (71.7%) and in 206 at Visit 2 (45.9); according to the post-COVID-19 functional status scale we observed 147 patients with values 2-3 and 175 with values >3 at Visit 1; at Visit 2, 133 subjects had the score between 2-3 and 73 > 3. In multivariate analysis, intensive care unit (ICU) admission (OR = 2.551; 95% CI = 1.998-6.819; P = 0.019), time of hospitalization (OR = 2.255; 95% CI = 1.018-6.992; P = 0.016) and treatment with remdesivir (OR = 0.641; 95% CI = 0.413-0.782; P < 0.001) were independent predictors of LCS. CONCLUSIONS: Treatment with remdesivir leads to a 35.9% reduction in LCS rate in follow-up. Severity of illness, need of ICU admission and length of hospital stay were factor associated with the persistence of PCS at 6 months of follow-up.

Mejoramiento de arveja (Pisum sativum L): avances del programa de mejoramiento genético de la Universidad Nacional de Rosario / Pea (Pisum sativum L.) breeding: advances of the breeding program at Universidad Nacional de Rosario

RESUMEN En 2005 se inició un programa de mejoramiento de arveja para aumentar la producción en cantidad y calidad en la Facultad de Ciencias Agrarias (FCA), Universidad Nacional de Rosario (UNR). Los primeros pasos fueron reunir una colección activa de germoplasma de todo el mundo y analizar la variabilidad genética a través de rasgos morfo-agronómicos y moleculares. En 2014, el Instituto Nacional de Tecnología Agropecuaria (INTA) y la FCAUNR unieron esfuerzos para promover el desarrollo local de genotipos de arveja adaptados a la región. Este programa, utilizando metodologías convencionales, ha obtenido hasta el momento una nueva variedad comercial (Primogénita FCA-INTA) de color de cotiledón verde, semi-áfila, con alta adaptación a las condiciones agroecológicas locales y alto potencial de rendimiento. El mejoramiento genético, sin embargo, es un proceso lento. El desarrollo de nuevas variedades requiere una década o más utilizando metodologías tradicionales, por lo que se propusieron diferentes alternativas para la reducción de este período. Los haploides duplicados y el cultivo in vitro han sido algunas de las metodologías desarrolladas, sin embargo, en legumbres no se han podido implementar de manera eficiente en los programas de mejoramiento. En este contexto, Speed Breeding surge como una tecnología que permite incrementar la eficiencia de los programas, reduciendo los costos y el trabajo requerido.

ABSTRACT A pea breeding program to increase production in quantity and quality was started in 2005 in the College of Agrarian Sciences (FCA), National University of Rosario (UNR). The first steps were to gather an active collection of germplasm from around the world and to analyze genetic variability through morpho-agronomic and molecular traits in order to set objectives. In 2014, the National Institute of Agropecuarian Technology (INTA) and the FCAUNR, joined forces to unite inter-institutional efforts for promoting the local development of pea genotypes adapted to the region. This program, using conventional methodologies, has so far obtained a new commercial line (Primogénita FCA-INTA) of green cotyledons, semileafless, with high adaptation to local agro ecological conditions and high yield potential. Breeding, nevertheless, is a slow process. Developing new pea varieties usually takes a decade or more when using traditional methodologies; thus, different alternatives were proposed for the reduction of this period. Doubled haploids and in vitro culture have been some of the methodologies developed; in pulses, however, they have not been efficiently implemented in breeding programs. In this context, Speed Breeding emerges as a technology that allows increasing the efficiency of the programs, while reducing costs and the required labor.

Herramientas complementarias utilizadas en el programa de mejoramiento de arveja (Pisum sativum l.) de la Universidad Nacional de Rosario / Complementary tools utilized in the pea (Pisum sativum l.) breeding program at Universidad Nacional de Rosario

RESUMEN El mejoramiento convencional puede ser complementado mediante diferentes estrategias que incrementen la eficiencia de las metodologías y la tasa actual de aumento de los rendimientos a fin de satisfacer la demanda. El uso de marcadores moleculares con el objetivo de desarrollar mapas de ligamiento de la especie, el uso de Blup (Best Linear Unbiased Prediction) para una selección eficiente de progenitores a hibridar, el uso del cultivo in vitro para incrementar artificialmente el número de plantas F1 o el uso de fenotipificación digital para una eficiente caracterización digital que puede realizarse durante la regeneración periódica y rutinaria de accesiones en colecciones de germoplasma.

ABSTRACT Conventional breeding can be complemented by different strategies that increase the efficiency of the methodologies and the current rate of increase in yields in order to meet demand. The use of molecular markers with the aim of developing linkage maps of the species, the use of Blup (Best Linear Unbiased Prediction) for an efficient selection of progenitors to hybridize, the use of in vitro culture to artificially increase the number of F1 plants or the use of digital phenotyping for efficient digital characterization that can be performed during the periodic and routine regeneration of accessions in germplasm collections.

Aplicación de diferentes metodologías en el mejoramiento de lenteja (Lens culinaris Medik) / Application of different methodologies in lentil (Lens culinaris Medik) breeding

RESUMEN La lenteja (Lens culinaris Medik.) es una especie diploide autógama (2n=2x=14) perteneciente a la familia Fabaceae. Es uno de los cultivos más antiguos que se conocen, con 8.000 a 9.000 años de historia, y se encuentra entre los primeros domesticados en Medio Oriente. Las semillas tienen un alto valor nutricional. Este cultivo es un interesante sustituto del trigo en las rotaciones de cereales, pero su importancia es baja debido a la falta de buenas variedades con adaptación local. Uno de los principales problemas que enfrentan los mejoradores en nuestro país es la estrecha base genética del germoplasma cultivado y su bajo potencial de rendimiento. En 2004 se inició un programa de mejoramiento de lentejas para desarrollar nuevas variedades con adaptación a las condiciones predominantes en las áreas de cultivo de Argentina. El germoplasma se obtuvo del ICARDA (Centro Internacional de Investigación Agrícola en las Zonas Áridas) y de productores locales. Se utilizan métodos convencionales de mejoramiento basados en la hibridación y selección. Se han obtenido dos nuevas variedades, una del tipo macrosperma (Boyerito FCA) y la otra del tipo microsperma (Tacuarita FCA) mediante la aplicación de selección masal en poblaciones F2 provenientes de la hibridación de materiales seleccionados. Este programa complementa los métodos de mejora tradicional con técnicas biotecnológicas como la transgénesis, el uso de marcadores moleculares, el cultivo de embriones in vitro combinado con el método SSD para acortar el ciclo generacional, y el fenotipado digital.

ABSTRACT Lentil (Lens culinaris Medik.) is a self-pollinating diploid (2n=2x=14) species belonging to the Fabaceae family. It is one of the oldest crops known, with 8,000 to 9,000 years of history and it is among the earliest domesticates from the Near East Fertile Crescent. The seeds have high nutritional value. This crop is an interesting substitute to wheat in cereal rotations but its importance is low due to a lack of suitable varieties with local adaptation. Some of the major problems that Argentinian lentil breeders face are the narrow genetic base of the current cultivated germplasm and its low yield potential. A lentil breeding program was initiated in 2004 to develop new varieties with adaptation to prevalent conditions in growing areas of Argentina. Germplasm was obtained from ICARDA (International Center for Agricultural Research in the Dry Areas) and local producers. Conventional breeding methods using hybridization and selection are being carried out to develop improved varieties, broad the genetic base, and isolate superior recombinant inbred lines. Two new varieties have been obtained, one of the macrosperm type (Boyerito FCA) and the other of the microsperm type (Tacuarita FCA) through the application of mass selection in F2 populations from the cross of selected materials. This program complements traditional breeding methods with biotechnological techniques such as transgenesis, use of molecular markers, in vitro embryo culture combined with the SSD method to shorten the breeding time, and digital phenotyping.

Long-term aesthetics, patient-reported outcomes, and auricular sensitivity after microtia reconstruction: A systematic review.

BACKGROUND: Auricular reconstruction for microtia is most frequently performed using autologous costal cartilage (ACC) or porous polyethylene (PPE) implants. Short-term results are generally promising, but long-term results remain unclear. Long-term outcomes were explored in this systematic review, and minimal reporting criteria were suggested for future original data studies. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception through October 14, 2020. Articles on auricular reconstruction in patients with microtia using ACC or PPE were included if postsurgical follow-up was at least 1 year. Outcome reporting was split into separate publications, and results on complications were reported previously. This publication focused on long-term aesthetic, patient-reported, and sensitivity outcomes. RESULTS: Forty-one publications reported on these outcomes. Both materials led to aesthetically pleasing results and high rates of patient satisfaction. ACC frameworks grew similarly to contralateral ears, and the anterior surface of auricles regained sensitivity. Furthermore, postoperative health-related quality of life (HRQoL) outcomes were generally good. Data synthesis was limited due to considerable variability between studies and poor study quality. No conclusions could be drawn on the superiority of either method due to the lack of comparative analyses. CONCLUSION: Future studies should minimally report (1) surgical efficacy measured using the tool provided in the UK Care Standards for the Management of Patients with Microtia and Atresia; (2) complications including framework extrusion or exposure, graft loss, framework resorption, wire exposure and scalp/auricular scar complications and (3) HRQoL before and after treatment using the EAR-Q patient-reported outcome measure (PROM).

Long-term complications of microtia reconstruction: A systematic review.

BACKGROUND: Microtia is a rare disorder characterized by malformation or even complete absence of the auricle. Reconstruction is often performed using autologous costal cartilage (ACC) or porous polyethylene implants (PPE). However, the long-term outcomes of both methods are unclear. OBJECTIVE: This systematic review aimed to analyze long-term complications and suggest minimal reporting criteria for future original data studies. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials from inception through October 14, 2020. Articles on auricular reconstruction in patients with microtia using ACC or PPE were included provided that the follow-up period was at least one year. This publication focused on long-term complications reported in patients with a postoperative follow-up period of at least one year. RESULTS: Twenty-nine publications reported on complications during long-term follow-up. Overall long-term complication rates were not reported. The incidence of individual complications during long-term follow-up was less than 10% after ACC reconstruction and less than 15% in PPE reconstruction. Framework resorption and wire exposure were reported even after an extended follow-up of more than five years after ACC reconstruction, while reports on the extended long-term results of PPE reconstruction are limited. Data synthesis was limited due to heterogeneity and poor study quality. CONCLUSIONS: Future studies should report on long-term complications including framework exposure or extrusion, graft loss, framework resorption, wire exposure and scalp and auricular scar complications. We recommend a surgical follow-up of at least five years.

Engineered mucoperiosteal scaffold for cleft palate regeneration towards the non-immunogenic transplantation.

Cleft lip and palate (CL/P) is the most prevalent craniofacial birth defect in humans. None of the surgical procedures currently used for CL/P repair lead to definitive correction of hard palate bone interruption. Advances in tissue engineering and regenerative medicine aim to develop new strategies to restore palatal bone interruption by using tissue or organ-decellularized bioscaffolds seeded with host cells. Aim of this study was to set up a new natural scaffold deriving from a decellularized porcine mucoperiosteum, engineered by an innovative micro-perforation procedure based on Quantum Molecular Resonance (QMR) and then subjected to in vitro recellularization with human bone marrow-derived mesenchymal stem cells (hBM-MSCs). Our results demonstrated the efficiency of decellularization treatment gaining a natural, non-immunogenic scaffold with preserved collagen microenvironment that displays a favorable support to hMSC engraftment, spreading and differentiation. Ultrastructural analysis showed that the micro-perforation procedure preserved the collagen mesh, increasing the osteoinductive potential for mesenchymal precursor cells. In conclusion, we developed a novel tissue engineering protocol to obtain a non-immunogenic mucoperiosteal scaffold suitable for allogenic transplantation and CL/P repair. The innovative micro-perforation procedure improving hMSC osteogenic differentiation potentially impacts for enhanced palatal bone regeneration leading to future clinical applications in humans.