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This literature review rigorously examines the growing scientific interest in computational methods for Tissue Engineering and Regenerative Medicine biofabrication, a leading-edge area in biomedical innovation, emphasizing the need for accurate, multi-stage, and multi-component biofabrication process models. The paper presents a comprehensive bibliometric and contextual analysis, followed by a literature review, to shed light on the vast potential of computational methods in this domain. It reveals that most existing methods focus on single biofabrication process stages and components, and there is a significant gap in approaches that utilize accurate models encompassing both biological and technological aspects. This analysis underscores the indispensable role of these methods in understanding and effectively manipulating complex biological systems and the necessity for developing computational methods that span multiple stages and components. The review concludes that such comprehensive computational methods are essential for developing innovative and efficient Tissue Engineering and Regenerative Medicine biofabrication solutions, driving forward advancements in this dynamic and evolving field.

Abstract Background The BCR::ABL1 is a hallmark of chronic myeloid leukemia (CML) and is also found in acute lymphoblastic leukemia (ALL). Most genomic breaks on the BCR side occur in two regions - Major and minor - leading to p210 and p190 fusion proteins, respectively. Methods By multiplex long-distance PCR or next-generation sequencing technology we characterized the BCR::ABL1 genomic fusion in 971 patients (adults and children, with CML and ALL: pediatric ALL: n = 353; pediatric CML: n = 197; adult ALL: n = 166; adult CML: n = 255 patients) and designed “Break-App” web tool to allow visualization and various analyses of the breakpoints. Pearson’s Chi-Squared test, Kolmogorov-Smirnov test and logistic regression were used for statistical analyses. Results Detailed analysis showed a non-random distribution of breaks in both BCR regions, whereas ABL1 breaks were distributed more evenly. However, we found a significant difference in the distribution of breaks between CML and ALL. We found no association of breakpoints with any type of interspersed repeats or DNA motifs. With a few exceptions, the primary structure of the fusions suggests non-homologous end joining being responsible for the BCR and ABL1 gene fusions. Analysis of reciprocal ABL1::BCR fusions in 453 patients showed mostly balanced translocations without major deletions or duplications. Conclusions Taken together, our data suggest that physical colocalization and chromatin accessibility, which change with the developmental stage of the cell (hence the difference between ALL and CML), are more critical factors influencing breakpoint localization than presence of specific DNA motifs.

Abstract Background The Biology System Description Language (BiSDL) is an accessible, easy-to-use computational language for multicellular synthetic biology. It allows synthetic biologists to represent spatiality and multi-level cellular dynamics inherent to multicellular designs, filling a gap in the state of the art. Developed for designing and simulating spatial, multicellular synthetic biological systems, BiSDL integrates high-level conceptual design with detailed low-level modeling, fostering collaboration in the Design-Build-Test-Learn cycle. BiSDL descriptions directly compile into Nets-Within-Nets (NWNs) models, offering a unique approach to spatial and hierarchical modeling in biological systems. Results BiSDL’s effectiveness is showcased through three case studies on complex multicellular systems: a bacterial consortium, a synthetic morphogen system and a conjugative plasmid transfer process. These studies highlight the BiSDL proficiency in representing spatial interactions and multi-level cellular dynamics. The language facilitates the compilation of conceptual designs into detailed, simulatable models, leveraging the NWNs formalism. This enables intuitive modeling of complex biological systems, making advanced computational tools more accessible to a broader range of researchers. Conclusions BiSDL represents a significant step forward in computational languages for synthetic biology, providing a sophisticated yet user-friendly tool for designing and simulating complex biological systems with an emphasis on spatiality and cellular dynamics. Its introduction has the potential to transform research and development in synthetic biology, allowing for deeper insights and novel applications in understanding and manipulating multicellular systems.

Pouchitis is an idiopathic inflammatory disease that may occur in ileal pouches, and it can lead to ileal pouch failure. This was a single-center, randomized, double-blinded, placebo-controlled trial that assessed the effect of Lactobacillus casei (L. casei) DG®, a probiotic strain, on the ileal pouch mucosa to determine the crosstalk between microbiota and mucosal immune system. Fifty-two patients undergoing restorative proctocolectomy were recruited and randomly assigned to receive a daily oral supplementation of L. casei DG® (n = 26) or placebo (n = 26) for 8 weeks from the ileostomy closure (T0) to a pouch endoscopy after 8 weeks (T1) and 1 year (T2). Ileal pouch mucosa samples were collected at T0, T1, and T2. At T1, the L. casei DG®-supplemented group showed a significant reduction of inflammatory cytokines levels compared to T0 baseline levels in the pouch mucosa, whereas in the placebo group cytokines levels resulted stable. In conclusion, probiotic manipulation of mucosal microbiota by L. casei DG®-supplementation after stoma closure in patients who underwent restorative proctocolectomy has a beneficial impact on the ileal pouch microenvironment. Registration number: NCT03136419 (http://www.clinicaltrials.gov).

The use of allergen immunotherapy (AIT) in Brazil has specific regional conditions owing to the pattern of allergen sensitization, as well as to genetic, socioeconomic, and cultural characteristics. This review article aims to discuss the clinical practice of AIT by the subcutaneous or sublingual route in Brazil, addressing the possibilities of transition between these forms of administration. A systematic review using the PubMed and Cochrane databases was performed, and the websites of major allergy and immunology organizations were consulted. Knowledge of the mechanism of action of subcutaneous immunotherapy and sublingual immunotherapy, together with Brazilian real-life experience, allowed us to establish recommendations regarding switching routes of AIT administration in selected cases. Careful analysis of each clinical situation is necessary to perform the transition between subcutaneous and sublingual allergen immunotherapy.

Combining multiple drugs broadens the window of therapeutic opportunities and is crucial for diseases that are currently lacking fully curative treatments. A powerful emerging tool for selecting effective drugs and combinations is the high-throughput drug screening (HTP). The histone deacetylase inhibitor (HDACi) givinostat (ITF2357) has been shown to act effectively against CRLF2-rearranged pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), a subtype characterized by poor outcome and enriched in children with Down Syndrome, very fragile patients with a high susceptibility to treatment-related toxicity. The aim of this study is to investigate possible synergies with givinostat for these difficult-to-treat patients by performing HTP screening with a library of 174 drugs, either approved or in preclinical studies. By applying this approach to the CRLF2-r MHH-CALL-4 cell line, we identified 19 compounds with higher sensitivity in combination with givinostat compared to the single treatments. Next, the synergy between givinostat and the promising candidates was further validated in CRLF2r cell lines with a broad matrix of concentrations. The combinations with trametinib (MEKi) or venetoclax (BCL2i) were found to be the most effective and with the greatest synergy across three metrics (ZIP, HAS, Bliss). Their efficacy was confirmed in primary blasts treated ex vivo at concentration ranges with a safe profile on healthy cells. Finally, we described givinostat-induced modifications in gene expression of MAPK and BCL-2 family members, supporting the observed synergistic interactions. Overall, our study represents a model of drug repurposing strategy using HTP screening for identifying synergistic, efficient, and safe drug combinations.

Introduction Neuropsychiatric disorders are the leading cause of disability worldwide, as seen in cases such as depression, anxiety, bipolar mood disorder and schizophrenia, which can be developed or exacerbated by the use of psychoactive substances. Most mental disorders have an early onset, often leading to early and/or permanent disability, increasing the need and cost of healthcare. Therefore, it is necessary to improve the identification of the epidemiological profile of these cases in the South of Brazil in order to enhance the diagnosis and reduce the costs associated with managing these disorders. Objectives The present study aimed to analyze statistical data regarding hospitalizations related to mental disorders caused by the use of psychoactive substances and alcohol in the southern region of Brazil, highlighting the pathological scenario and identifying the most prevalent profiles of these disorders in this region. Methods A cross-sectional, descriptive, retrospective, and quantitative study was conducted on hospitalizations of individuals diagnosed with mental and behavioral disorders due to the use of psychoactive substances and alcohol in the states of the Southern region of Brazil (Paraná, Santa Catarina, and Rio Grande do Sul) between February 2020 and December 2022. Data of January 2020 were not available. The data used were collected through the Department of Health Informatics of the Brazilian Unified Health System (DATASUS) in the “Hospital Information System of SUS” section, gathering information regarding the nature of the care, age range, gender, and ethnicity of the patients. Results The study covers the years 2020 to 2022, indicating a total of 81,608 hospitalizations, with the year 2022 having the highest number of cases (≈ 37.13%), followed by 2021 (≈ 33.30%) and 2020 (≈ 29.55%). The states with the highest number of hospitalizations were Rio Grande do Sul (≈ 54.90%), Paraná (≈ 29.29%), and Santa Catarina (≈ 15.79%). Urgent hospitalizations accounted for ≈ 87.29% of the total. The most affected age group was 30 to 39 years old (≈ 25.61%). Men were more affected than women (≈ 81.70% and ≈ 18.28%, respectively). Caucasians accounted for ≈ 64.29% of the hospitalizations. The average length of stay was 20.8 days, and the mortality rate was 0.32%. Conclusions There is a clear increase in the number of hospitalizations related to mental disorders caused by the use of psychoactive substances in the period from 2020 to 2022 in the southern region of Brazil, with the highest number of cases in the state of Rio Grande do Sul. The most affected population consisted of Caucasian men aged 30 to 39 years old. Furthermore, these results may be related to the increasing trend of psychoactive substance use among the Brazilian population and also the COVID-19 pandemic, which led to a period of underreporting due to social isolation. Disclosure of Interest None Declared

Introduction Epilepsy is one of the most common serious brain illness, with symptoms influenced by multiple risk factors and a strong genetic predisposition, rather than having a single expression and cause¹. Neuropsychiatric symptoms in epilepsy can encompass manifestations such as mood alterations, anxiety, sleep disturbances, psychosis, and behavioral disorders. While the motor and sensory manifestations of epileptic seizures are widely recognized, neuropsychiatric symptoms accompanying epilepsy are often underestimated. Therefore, it is essential to understand the most prevalent epidemiological profile of these patients to improve the diagnosis and management of these symptoms. Objectives Our goal was to evaluate the neuropsychiatric behavior of epilepsy patients in Brazilian over the past 3 years through hospitalization data in order to outline an epidemiological and behavioral profile. Methods A cross-sectional, descriptive, retrospective, and quantitative study was conducted on hospitalizations of individuals simultaneously diagnosed with epilepsy, schizotypal and delusional disorders, and mood disorders in all five regions of Brazil (South, Southeast, Midwest, North, and Northeast) between February 2020 and December 2022. Data from January 2020 were not available. The data used were collected through the Department of Health Informatics of the Brazilian Unified Health System (DATASUS) in the “Hospital Information System of SUS” section, gathering information regarding the nature of care, age range, gender, and ethnicity of the patients. Results The analysis covers the years 2020 to 2022, totaling 503,045 hospitalizations. In 2022, the highest number of cases occurred (≈ 37.55%), followed by 2021 (≈ 33.62%) and 2020 (≈ 28.81%). Urgent hospitalizations represented ≈ 90.85% of the total. The most affected age group was 30 to 39 years old (≈ 18.30%). Men were more affected than women (≈ 52.03% and ≈ 47.96%, respectively), and Caucasians accounted for ≈ 36.07% of the hospitalizations. The average length of stay was 19.1 days, and the mortality rate was 1.4%. Conclusions Thus, there is a gradual and annual increase in the number of hospitalizations during the observed period. While there is a minimal disparity between the affected genders, it is evident that the profile of male, caucasian, and adult patients is the most prevalent. Moreover, the predominantly urgent nature of hospitalizations points to an alarming scenario regarding this issue. From the analysis of the data obtained in the study, there is a clear need for interventions capable of reducing the prevalence of hospitalizations for neuropsychiatric symptoms in epilepsy patients in Brazil. Disclosure of Interest None Declared

Introduction In recent years, mental health has gained prominence in public health, prompting thorough investigations into psychiatric condition trends. This study conducts a comprehensive epidemiological analysis of hospitalizations for Schizophrenia, Schizotypal, and Delirium Disorders in Rio Grande do Sul (RS) over the past five years. By revealing these patterns, it enhances our understanding of regional mental health dynamics and offers insights for intervention strategies, resource planning, and improved mental healthcare. The ultimate goal is to advance more effective and accessible mental healthcare in RS and beyond. Objectives This study aims to analyze the prevalence and epidemiological profile of hospitalizations due to psychiatric disorders to assist in the diagnosis and outcome of affected patients. Methods A cross-sectional, descriptive, retrospective, and quantitative study was conducted regarding hospitalizations for Schizophrenia, Schizotypal Disorders, and Delirium in the state of RS between January 2018 and November 2022. Data were collected from the Department of Informatics of the Brazilian Unified Health System (DATASUS) in the “Hospital Information System of SUS” section, focusing on the nature of care, age group, gender, and ethnicity of the patients. The information was aggregated over the five-year period based on the four mentioned descriptors and subsequently analyzed to establish a profile of hospitalizations during that period. Results The analysis spans from 2018 to 2022, encompassing a total of 28,345 hospitalizations. In 2019, there was the highest number of cases (22.21%), followed by 2018 (21.08%). Urgent care admissions constituted 85.34% of the total. The age group most affected was 35 to 39 years (11.8%). Men were more affected than women (60.18%), and the majority of hospitalizations were among the Caucasian ethnicity (75.12%). The average length of stay was 23.7 days, and the mortality rate stood at 0.26%. Conclusions The increasing trend in hospitalizations, peaking in 2019, highlights the need for preventive measures. Urgent admissions (85.34%) underscore the demand for accessible mental health resources. Men in the 35 to 39 age group are disproportionately affected, suggesting specific risk factors. The predominance of Caucasian ethnicity emphasizes the need for culturally sensitive care. A longer average length of stay (23.7 days) underscores treatment complexity, while a low mortality rate (0.26%) signals effective medical care. In essence, these findings inform tailored mental health policies to enhance service quality and prioritize patient-centered approaches. Disclosure of Interest None Declared

Abstract Objectives Statins are a category of medications widely used to reduce plasma LDL-cholesterol levels, that also possess antibacterial, anti-inflammatory, and immunomodulatory action. The aim of this systematic review was to explore the effects of systemic statins therapy on the development and treatment of apical periodontitis (AP) on humans and animals. Material and methods Three electronic databases (PubMed, Web of Science, and Scopus) and grey literature were searched from their inception until February, 20 2023 (PROSPERO CRD42021246231). For the quality assessment and risk of bias, different guidelines were used according to the typology of the studies considered (Animal Research Reporting of In Vivo Experiments, Newcastle–Ottawa Quality Assessment Form for Cohort Studies, Systematic Review Centre for Laboratory animal Experimentation Risk of Bias tool and Tool to assess risk of bias in cohort studies of CLARITY Group). Results Seven hundred eleven records were screened, and six articles were included for this qualitative review. The eligible studies showed a moderate overall quality and risk of bias. Human patients in treatment with statins exhibited a higher healing rate of AP following root canal treatment. In experimental animal models, statins had a beneficial effect on the development of AP. Conclusions Despite the limited number of studies and considering that most of them are on animals, our findings suggest that systemically administered statins make a positive contribution to prevent the development and help healing of AP. Clinical relevance There is an increased evidence that a pharmacologic adjunct to endodontic treatment may be considered to enhance healing of AP. Among other medications, statins seem to have a positive impact on the disease.

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumor microenvironment (TME). The aim of this study is to determine the potential significant TME immune markers of long-term survival. Methods: We retrospectively included patients with a diagnosis of resectable PDAC having undergone upfront surgery. Immunohistochemical (IHC) staining using tissue microarray for PD-L1, CD3, CD4, CD8, FOXP3, CD20, iNOS and CD163 was performed in order to characterize the TME. The primary endpoint was long-term survival, defined as the Overall Survival > 24 months from surgery. Results: A total of 38 consecutive patients were included, and 14 (36%) of them were long-term survivors. Long-term survivors showed a higher density of CD8+ lymphocytes intra- and peri-acinar (p = 0.08), and a higher CD8/FOXP3 intra- and peri-tumoral ratio (p = 0.05). A low density of intra- and peri-tumoral FOXP3 infiltration is a good predictor of long-term survival (p = 0.04). A significant association of the low density of intra- and peri-tumoral tumor-associated macrophages (TAMs) iNOS+ with long-term survival was detected (p = 0.04). Conclusions: Despite the retrospective nature and small sample size, our study showed that the high infiltration of CD8+ lymphocytes and low infiltration of FOXP3+ and TAMs iNOS+ are predictors of good prognosis. A preoperative assessment of these potential immune markers could be useful and determinant in the staging process and in PDAC management.

Abstract Chiral molecules are known to behave as spin filters due to the chiral induced spin selectivity (CISS) effect. Chirality can be implemented in molecular semiconductors in order to study the role of the CISS effect in charge transport and to find new materials for spintronic applications. In this study, the design and synthesis of a new class of enantiopure chiral organic semiconductors based on the well‐known dinaphtho[2,3‐b:2,3‐f]thieno[3,2‐b]thiophene (DNTT) core functionalized with chiral alkyl side chains is presented. When introduced in an organic field‐effect transistor (OFET) with magnetic contacts, the two enantiomers, (R)‐DNTT and (S)‐DNTT, show an opposite behavior with respect to the relative direction of the magnetization of the contacts, oriented by an external magnetic field. Each enantiomer displays an unexpectedly high magnetoresistance over one preferred orientation of the spin current injected from the magnetic contacts. The result is the first reported OFET in which the current can be switched on and off upon inversion of the direction of the applied external magnetic field. This work contributes to the general understanding of the CISS effect and opens new avenues for the introduction of organic materials in spintronic devices.

Abstract Brain organoids are becoming increasingly relevant to dissect the molecular mechanisms underlying psychiatric and neurological conditions. The in vitro recapitulation of key features of human brain development affords the unique opportunity of investigating the developmental antecedents of neuropsychiatric conditions in the context of the actual patients’ genetic backgrounds. Specifically, multiple strategies of brain organoid (BO) differentiation have enabled the investigation of human cerebral corticogenesis in vitro with increasing accuracy. However, the field lacks a systematic investigation of how closely the gene co-expression patterns seen in cultured BO from different protocols match those observed in fetal cortex, a paramount information for ensuring the sensitivity and accuracy of modeling disease trajectories. Here we benchmark BO against fetal corticogenesis by integrating transcriptomes from in-house differentiated cortical BO (CBO), other BO systems, human fetal brain samples processed in-house, and prenatal cortices from the BrainSpan Atlas. We identified co-expression patterns and prioritized hubs of human corticogenesis and CBO differentiation, highlighting both well-preserved and discordant trends across BO protocols. We evaluated the relevance of identified gene modules for neurodevelopmental disorders and psychiatric conditions finding significant enrichment of disease risk genes especially in modules related to neuronal maturation and synapsis development. The longitudinal transcriptomic analysis of CBO revealed a two-step differentiation composed of a fast-evolving phase, corresponding to the appearance of the main cell populations of the cortex, followed by a slow-evolving one characterized by milder transcriptional changes. Finally, we observed heterochronicity of differentiation across BO models compared to fetal cortex. Our approach provides a framework to directly compare the extent of in vivo/in vitro alignment of neurodevelopmentally relevant processes and their attending temporalities, structured as a resource to query for modeling human corticogenesis and the neuropsychiatric outcomes of its alterations.

Children with Down syndrome have an augmented risk for B-cell acute lymphoblastic leukemia (DS-ALL), which is associated with lower survival than in non-DS-ALL. It is known that cytogenetic abnormalities common in childhood ALL are less frequent in DS-ALL, while other genetic aberrancies (ie, CRLF2 overexpression and IKZF1 deletions) are increased. A possible cause for the lower survival of DS-ALL that we herewith evaluated for the first time was the incidence and prognostic value of the Philadelphia-like (Ph-like) profile and the IKZF1plus pattern. These features have been associated with poor outcome in non-DS ALL and therefore introduced in current therapeutic protocols. Forty-six out of 70 DS-ALL patients treated in Italy from 2000 to 2014 displayed Ph-like signature, mostly characterized by CRLF2 (n = 33) and IKZF1 (n = 16) alterations; only 2 cases were positive for ABL-class or PAX5-fusion genes. Moreover, in an Italian and German joint cohort of 134 DS-ALL patients, we observed 18% patients positive for IKZF1plus feature. Ph-like signature and IKZF1 deletion were associated with poor outcome (cumulative incidence of relapse: 27.7 ± 6.8% versus 13 ± 7%; P = 0.04 and 35.2 ± 8.6% versus 17 ± 3.9%; P = 0.007, respectively), which further worsens when IKZF1 deletion was co-occurring with P2RY8::CRLF2, qualifying for the IKZF1plus definition (13/15 patients had an event of relapse or treatment-related death). Notably, ex vivo drug screening revealed sensitivity of IKZF1plus blasts for drugs active against Ph-like ALL such as Birinapant and histone deacetylase inhibitors. We provided data in a large setting of a rare condition (DS-ALL) supporting that these patients, not associated with other high-risk features, need tailored therapeutic strategies.

The aim of this scoping review is to analyse the biological effects of the orthodontic tooth movement (OTM) in areas with bone defects that are undergoing regeneration using different types of regenerative materials and techniques. The electronic research was performed on four databases as follows: PubMed, Scopus, EMBASE, and Web of Science. Data were extracted according to publication information, study design, sample characteristics, parameters of OTM, biological repercussions on the periodontium complex, methods of analysis, and conclusions. A total of thirty studies were included in the final review. In twenty-two studies, the most widely adopted grafting materials were alloplastics. In most studies, the orthodontic force used was 10 or 100 g, and the timing of application ranged from immediate to 6 months after grafting surgery. Twenty-four studies showed an increase in osteogenesis; in five studies, the clinical attachment level (CAL) increased; in five others, the probing pocket depth (PPD) decreased; in sixteen studies, there was root resorption of a different magnitude. Though the effects of OTM on the periodontium in the grafted areas were positive, the outcomes should be interpreted with caution as future preclinical and clinical studies are needed to extrapolate more valid conclusions.

Declining support for US higher education and the corporatization of this institution shape students' experiences. This ethnography describes a campus culture stratified by an ideology called "majorism." Majorism, a term particular to this study's site, is the preferential treatment of science and technology over the Liberal Arts. By understanding majorism through the lived experiences of undergraduates, we can better understand what the US academy values, its purpose, and whom it does and does not serve.

Background and Aims Epidemiological studies have shown that subnormal levels of vitamin D (25[OH]D) are associated with a more aggravated clinical course of ulcerative colitis [UC]. Despite an increased focus on the therapeutic importance of vitamin D and vitamin D receptor [VDR] signalling, the mechanisms underlying the effects of the vitamin D–VDR axis on UC remain elusive. Therefore, we aimed to investigate whether exposure to active vitamin D (1,25[OH]2D3/VDR) signalling in human organoids could influence the maintenance of the colonic epithelium. Methods Intestinal VDR expression was studied by immunohistochemistry, RNA expression arrays, and single-cell RNA sequencing of colonic biopsy specimens obtained from patients with UC and healthy individuals. To characterise the functional and transcriptional effects of 1,25[OH]2D3, we used patient-derived colonic organoids. The dependency of VDR was assessed by knocking out the receptor with CRISPR/Cas9. Results Our results suggest that 1,25[OH]2D3/VDR stimulation supports differentiation of the colonic epithelium and that impaired 1,25[OH]2D3/VDR signalling thereby may compromise the structure of the intestinal epithelial barrier, leading to flares of UC. Furthermore, a transcriptional response to VDR activity was observed primarily in fully differentiated cells at the top of the colonic crypt, and this response was reduced during flares of UC. Conclusions We identified an important role of vitamin D signalling in supporting differentiated cell states in the human colonic epithelium, and thereby maintenance of the intestinal barrier integrity. This makes the vitamin D–VDR signalling axis an interesting target for therapeutic efforts to achieve and maintain remission in patients with UC. [ABSTRACT FROM AUTHOR]

The small intestine forms via crosstalk between epithelial and mesenchymal cell compartments. Here, the authors show that a gradient of Wnt signalling along the anterior-posterior axis regulates Sonic Hedgehog which is required for correct formation and regionalization of the small intestine.

Background: Allergen Immunotherapy (AIT) represents one of the pillars in the treatment of allergic diseases. AIT is the only therapeutic strategy with curative potential, promoting the reduction of drug use and long-term symptom control even after the end of the treatment. The European Academy of Allergy, Asthma and Immunology (EAACI) guidelines, position papers of World Allergy Organization (WAO), and the US Practice Parameters are the leading official documents that set scientific standard for the use of AIT in the world. The use of AIT in Brazil has specific regional conditions due to the pattern of allergen sensitization, as well as genetic, socioeconomic, and cultural characteristics, climate conditions, and the availability of allergenic extracts. The most prevalent house dust mites are Dermatophagoides pteronyssinus, Dermatophagoides farinae and their allergens have the highest clinical relevance. Blomia tropicalis is also very frequent. This position paper has been prepared by the Brazilian Association of Allergy and Clinical Immunology (ASBAI) Taskforce on AIT for respiratory allergy and Hymenoptera venom allergy. Objective: According to the current scientific literature adapted to the Brazilian reality, this position paper aims to establish the main recommendations for the good clinical practice parameters for AIT in Brazil. Methods: A systematic review using the Pub Med and Cochrane databases was performed, and the websites of major allergy and immunology organizations were consulted. The research was limited to English language literature and was conducted between March 30, 2002, and March 30, 2022. The terms used for the research were: Allergen Immunotherapy, sublingual immunotherapy (SLIT), subcutaneous immunotherapy (SCIT), venom-specific immunotherapy (VIT), and allergen extract. Results: The several recommendations that establish the clinical practices for AIT recommended by the main Allergy, Asthma and Immunology world organizations were analyzed and adapted to the Brazilian situation. Conclusion: This position paper establishes the main recommendations for the effective clinical practice of AIT in Brazil, using current knowledge of evidence-based medicine and precision medicine.

Este artigo apresenta o relato de experiência do projeto de ensino “Integrar, Aprender, Crescer: oficinas de planejamento de estudos e desenvolvimento profissional no Instituto Federal de Santa Catarina - câmpus Tubarão”, composto por um conjunto de oficinas que visam à elevação da permanência e êxito dos discentes, bem como o combate à evasão e retenção, por meio do aumento da efetividade do tempo de estudo e a orientação profissional. O projeto foi planejado e executado de julho a dezembro de 2018. Nesse sentido, duas dimensões foram trabalhadas pelas oficinas: a primeira diz respeito aos métodos, técnicas e ferramentas utilizadas pelos discentes em seus tempos de estudo. A segunda, refere-se a preparação profissional, demonstrando a relação entre desempenho acadêmico e profissional. A integração das temáticas faz-se necessária no sentido da complexidade do enfrentamento à evasão e retenção, por meio do envolvimento da comunidade interna e externa do Instituto Federal de Santa Catarina – câmpus Tubarão. Ao final do projeto conclui-se que os objetivos foram alcançados e foram atendidos nas atividades executadas aproximadamente 120 alunos.

Summary: Background: Despite intensive risk-based treatment protocols, 15% of paediatric patients with B-Cell Precursor Acute Lymphoblastic Leukaemia (BCP-ALL) experience relapse. There is urgent need of novel strategies to target poor prognosis subgroups, like PAX5 translocated. Methods: We considered 289 childhood BCP-ALL cases consecutively enrolled in Italy in the AIEOP-BFM ALL2000/R2006 protocols and we performed extensive molecular profiling, integrating gene expression, copy number analyses and fusion genes discovery by target-capture NGS. We developed preclinical strategies to target PAX5 fusion genes. Findings: We identified 135 cases without recurrent genetic rearrangements. Among them, 59 patients (43·7%) had a Ph-like signature; the remaining cases were identified as ERG-related (26%), High-Hyperdiploid-like (17%), ETV6::RUNX1-like (8·9%), MEF2D-rearranged (2·2%) or KMT2A-like (1·5%). A poor prognosis was associated with the Ph-like signature, independently from other high-risk features.Interestingly, PAX5 was altered in 54·4% of Ph-like compared to 16·2% of non-Ph-like cases, with 7 patients carrying PAX5 fusions (PAX5t), involving either novel (ALDH18A1, IKZF1, CDH13) or known (FBRSL1, AUTS2, DACH2) partner genes. PAX5t cases have a specific driver activity signature, extending to multiple pathways including LCK hyperactivation. Among FDA-approved drugs and inhibitors, we selected Dasatinib, Bosutinib and Foretinib, in addition to Nintedanib, known to be LCK ligands. We demonstrated the efficacy of the LCK-inhibitor BIBF1120/Nintedanib, as single agent or in combination with conventional chemotherapy, both ex vivo and in patient-derived xenograft model, showing a synergistic effect with dexamethasone. Interpretation: This study provides new insights in high-risk Ph-like leukaemia and identifies a potential therapy for targeting PAX5-fusion poor risk group. Funding: Ricerca Finalizzata-Giovani Ricercatori (Italian Ministry of Health), AIRC, Transcall, Fondazione Cariparo.

© 2016 The Author(s). Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field.

In Brazil, the process of surface water potabilization for public supply generates sludge, but information on this waste is scarce, and its disposal in landfills and waterways, without prior treatment, generates pollution. This experimental study evaluated the incorporation of aluminum and ferric sludge, commonly generated in Brazil, into different soils for road pavement infrastructure. Sludge generated in two water treatment plants in the state of São Paulo was characterized regarding risks to human health and the environment and individually incorporated into clayey sand soil and sandy soil in proportions of 25 and 50%. Evaluation of the mechanical tests of the soil sludge mixtures and their suitability for road construction found that i) all percentages of aluminum and ferric sludge incorporated into clayey sand soils and sandy soil met the mechanical standards for use in embankment; ii) aluminum sludge incorporated into sandy soils proved to be suitable for use in pavement subbase; iii) the percentual incorporation is higher than previous research; iv) the use of sludge as a partial replacement for virgin soil makes road construction cleaner. Analyses of variance on the mechanical properties of the soil-sludge mixtures showed that soil type is the only factor influencing this variable. Only the interaction of water treatment sludge (WTS) type with the other factors is significant for the CBR and Swell data.

BackgroundIn 10%–20% of cases it is impossible to make a differential diagnosis between ulcerative colitis and Crohn's colitis. A 50% failure rate of J pouch ilea-anal anastomosis is observed in Crohn's colitis. In 2009, we created the Padua Prognostic Score for Colitis (PPSC) to predict the long-term clinical and functional outcome and quality of life of patients undergoing restorative proctocolectomy with J pouch. The aim of the present study is to establish and validate the accuracy of a prognostic score for chronic inflammatory bowel diseases (IBD).Patient population and methodsThe PPSC was created in 2009 by integrating clinical and histological information of patients undergoing RPC. It included preoperative perianal abscess or fistula, rectal sparing, terminal ileum involvement, skip lesions and histological diagnosis of indeterminate colitis or Crohn's colitis on the operative specimen. The validity of this score was tested in predicting postoperative abscess or fistula, anal canal disease, pouchitis, pouch failure and new diagnosis of Crohn's disease. Correlation analysis, ROC curve analysis and survival analysis were used to validate the PPSC in a different cohort from the previous one.ResultsWe retrospectively enrolled in this study 138 consecutive patients undergoing CPR for ulcerative colitis (n = 127) or indeterminate colitis (n = 11) in our institution since 2005 to 2020. In this period, we observed 11 patients with postoperative abscess or fistula, 3 with anal canal disease, 40 with pouchitis, 6 with pouch failure and 6 with new diagnosis of Crohn's disease. In the new validation cohort, the PPSC confirmed to have a good accuracy in predicting the onset of postoperative CD (AUC = 74.5%, p = 0.018). Kaplan Meier curves demonstrate how a PPSC over 1 can reliably predicts the long-term onset of, pouchitis (p = 0.002) and anal abscess or fistulae (p = 0.04).ConclusionsIn this validation study we confirmed the accuracy of the PPSC in predicting postoperative fistulas or abscesses and pouchitis. Therefore, we believe that in clinical practice patients with a PPSC score greater than 1 should be warned of this risk of possible Crohn’s disease diagnosis and pouch failure.

Abstract The charge transport of crystalline organic semiconductors is limited by dynamic disorder that tends to localize charges. It is the main hurdle to overcome in order to significantly increase charge carrier mobility. An innovative design that combines a chemical structure based on sulfur‐rich thienoacene with a solid‐state herringbone (HB) packing is proposed and the synthesis, physicochemical characterization, and charge transport properties of two new thienoacenes bearing a central tetrathienyl core fused with two external naphthyl rings: naphtho[2,3‐b]thieno‐[2′′′,3′′′:4′′,5′′]thieno[2″,3″:4′,5′]thieno[3′,2′‐b]naphtho[2,3‐b]thiophene (DN4T) and naphtho[1,2‐b]thieno‐[2′′′,3′′′:4′′,5′′]thieno[2′′,3′′:4′,5′]thieno[3′,2′‐b]naphtho[1,2‐b]thiophene are presented. Both compounds crystallize with a HB pattern structure and present transfer integrals ranging from 33 to 99 meV (for the former) within the HB plane of charge transport. Molecular dynamics simulations point toward an efficient resilience of the transfer integrals to the intermolecular sliding motion commonly responsible for strong variations of the electronic coupling in the crystal. Best device performances are reached with DN4T with hole mobility up to μ = 2.1 cm2 V−1s−1 in polycrystalline organic field effect transistors, showing the effectiveness of the electronic coupling enabled by the new aromatic core. These promising results pave the way to the design of high‐performing materials based on this new thienoacene, notably through the introduction of alkyl side‐chains.