Deferoxamine mesylate enhances mandibular advancement‐induced condylar osteogenesis by promoting H‐type angiogenesis

alexandrossfakianakis shared this article with you from Inoreader Deferoxamine mesylate enhances mandibular advancement‐induced condylar osteogenesis by promoting H‐type angiogenesis via Journal of Oral Rehabilitation Abstract Background The effect of functional orthopedic treatment for mandibular deficiency relies on mandibular advancement (MA)-induced condylar new bone formation. However, this is not easy to achieve, especially in non-growing patients. Therefore, how to obtain reliable MA-induced condylar osteogenesis is much worthy of studying. Objective To investigate whether deferoxamine mesylate (DFM) enhances MA-induced condylar osteogenesis in middle-aged mice. Methods Forty 30-week-old male C57BL/6J mice were randomly divided into 4 groups: the control (Ctrl), DFM, MA+Ctrl, and MA+DFM groups. After a 4-week experimental period, femurs, tibias, and condyles were collected for morphological, micro-computed tomography, and histological evaluation. Results For long bones, DFM reversed osteoporosis in middle-aged mice by promoting H-type angiogenesis. For mandibular condyles, MA promoted condylar osteogenesis in middle-aged mice, thereby allowing the mandible to achieve a stable protruding position. In addition, DFM enhanced the volume and quality of MA-induced condylar new bone formation. Furthermore, histological analysis revealed that DFM enhanced MA-induced condylar subchondral ossification. Mechanistically, it was confirmed that DFM increased the number of H-type vessels and their coupled Osterix+ osteoprogenitors by up-regulating the hypoxia-inducible factor (HIF)-1α signaling pathway, thereby enhancing MA-induced condylar osteogenesis. Conclusion Applying DFM to enhance MA-induced condylar osteogenesis through H-type angiogenesis is expected to be an effective strategy to achieve favorable functional orthopedic treatment effectiveness in non-growing patients. View on Web

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Small Molecule-mediated Disruption of Ribosome Biogenesis Synergizes With FGFR Inhibitors to Suppress Glioma Cell Growth

alexandrossfakianakis shared this article with you from Inoreader Small Molecule-mediated Disruption of Ribosome Biogenesis Synergizes With FGFR Inhibitors to Suppress Glioma Cell Growth via Neuro-Oncology Advance Access Abstract Background High-grade gliomas are malignant brain tumors characterized by aggressiveness and resistance to chemotherapy. Prognosis remains dismal, highlighting the need to identify novel molecular dependencies and targets. Ribosome biogenesis (RiBi), taking place in the nucleolus, represents a promising target as several cancer types rely on high RiBi rates to sustain proliferation. Publicly available transcriptomics data of glioma patients revealed a positive correlation between RiBi rates and histological grades. We, therefore, hypothesized that glioma cells could be susceptible to RiBi inhibition. Methods Transcriptomics data from glioma patients were analyzed for RiBi-related processes. BMH-21, a small molecule inhibitor of RNA polI transcription, was tested in adult and pediatric high-grade glioma cell lines and a zebrafish transplant model. Cellular phenotypes were evaluated by transcriptomics, cell cycle analysis, and vi ability assays. A chemical synergy screen was performed to identify drugs potentiating BMH-21-mediated effects. Results BMH-21 reduced glioma cell viability, induced apoptosis, and impaired the growth of transplanted glioma cells in zebrafish. Combining BMH-21 with TMZ potentiated cytotoxic effects. Moreover, BMH-21 synergized with FGFR inhibitor Erdafitinib, a top hit in the chemical synergy screen. RiBi inhibition using BMH-21, POLR1A siRNA, or Actinomycin D revealed engagement of the FGFR-FGF2 pathway. BMH-21 downregulated FGFR1 and SOX2 levels, whereas FGF2 was induced and released from the nucleolus. Conclusions This study conceptualizes the implementation of RiBi inhibition as a viable future therapeutic strategy for glioma and reveals an FGFR connection to the cellular response upon RiBi inhibition with potential translational value. View on Web

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Wnt Signaling Regulates MFSD2A-dependent Drug Delivery through Endothelial Transcytosis in Glioma

alexandrossfakianakis shared this article with you from Inoreader Wnt Signaling Regulates MFSD2A-dependent Drug Delivery through Endothelial Transcytosis in Glioma via Neuro-Oncology Advance Access Abstract Background Systemic delivery of anti-tumor therapeutic agents to brain tumors is thwarted by the blood-brain barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). A failure of pharmacological compounds to cross BBB is one culprit for the dismal prognosis of glioblastoma (GBM) patients. Identification of novel vascular targets to overcome the challenges posed by the BBB in tumors for GBM treatment is urgently needed. Methods Temozolomide (TMZ) delivery was investigated in CT2A and PDGFB-driven RCAS/tv-a orthotopic glioma models. Transcriptome analysis was performed on ECs from murine gliomas. Mfsd2a deficient, Cav1 deficient and Mfsd2a EC specific inducible mice were developed to study the underlying molecular mechanisms. Results We demonstrated that inhibiting Wnt signaling by LGK974 could increase TMZ delivery and sensitize glioma to chemotherapy in both murine glioma models. Transcriptome analysis of ECs from murine gliomas revealed that Wnt signaling inhibition enhanced vascular transcytosis as indicated by the upregulation of PLVAP and downregulation of MSFD2A. Mfsd2a deficiency in mice enhances TMZ delivery in tumors, whereas constitutive expression of Mfsd2a in ECs suppresses the enhanced TMZ delivery induced by Wnt pathway inhibition in murine glioma. In addition, Wnt signaling inhibition enhanced caveolin-1 (Cav1)-positive caveolae-mediated transcytosis in tumor ECs. Moreover, Wnt signaling inhibitor or Mfsd2a deficiency fails to enhance TMZ penetration in tumors from Cav1-deficient mice. Conclusions These results demonstrated that Wnt signaling regulates MFSD2A-dependent TMZ deli very through a caveolae-mediated EC transcytosis pathway. Our findings identify Wnt signaling as a promising therapeutic target to improve drug delivery for GBM treatment. View on Web

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Disparities in Survival Outcomes Among Black Patients with HPV‐Associated Oropharyngeal Cancer

alexandrossfakianakis shared this article with you from Inoreader Disparities in Survival Outcomes Among Black Patients with HPV‐Associated Oropharyngeal Cancer via Journal of Medical Virology Abstract Purpose/Objective Patients with Human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) have been shown to have a favorable prognosis and excellent overall survival, and studies have demonstrated these findings in predominantly White cohorts. Racial/ethnic (R/E) minorities, particularly Black patients, with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared to White patients. In this study, we aimed to determine if Black patients with HPV-OPSCC have a similar favorable prognosis to the White population. Methods his was a population based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database from 2010-2016. We identified patients with Stage I-IV HPV-associated OPSCC who were treated with radiation, surgery, chemotherapy, or a combination of modalities. Patient outcomes were stratified by R/E groups including White Versus Black patients. The main outcome in this study was overall survival (OS). Analyses for proportions of categorical variables were performed using a Chi-Square or Fisher's Exact test. Univariate and multivariate time-to-event survival analyses were performed using Kaplan Meier product limit estimates and log-rank test to test the differences between strata. A Cox proportional hazards regression model was used to assess the association between covariates and risk of death (OS). Results We identified 9,256 OPSCC patients who met inclusion criteria and were treated between 2010-2016, of which 7,912 were white (85.5%) and 1,344 were Black (14.5%). 1,727 were HPV-OPSCC, of which 1598 were White (92.5%) and 129 (7.5%) were Black. By race, the 5-year OS for White Vs Black OPSCC patients was 42% versus 23%, respectively (log-rank, p<0.0001). Among HPV-Positive OPSCC patients, the 5-year OS for White vs Black patients was 65% versus 39% (log-rank, p<0.0001). Among HPV negative patients the 5-year OS for White vs Black patients was 36% versus 13% (log-rank, p<0.0001). On multivariate analysis, after accounting for age, sex, insurance status, income, Charlson-Deyo score, receipt of surgery, distance from facility, and total treatment time, Black race trended towards, but was not associated with worse survival. (HR:1.24, 95% CI 0.85-1.81, p=0.255) Conclusions This national cohort study of OPSCC patients demonstrates that Black patients with HPV-OPSCC have a poor prognosis and overall survival similar to HPV-negative White patients. This may be partly due to socioeconomic barriers such as insurance and income. Further work is needed to better understand the specific drivers of inferior survival outcomes in this specific patient population. This article is protected by copyright. All rights reserved. View on Web

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H‐Type Tracheoesophageal Fistula Cannulation for Rapid Intraoperative Localization

alexandrossfakianakis shared this article with you from Inoreader H‐Type Tracheoesophageal Fistula Cannulation for Rapid Intraoperative Localization via The Laryngoscope Various techniques for tracheoesophageal fistula cannulation have been reported. In this case, we created a loop using a plastic catheter. The loop allowed us to create traction for rapid intraoperative localization and to pull a difficult-to-reach fistula, superiorly into the neck, to be reached through a cervical approach. Laryngoscope, 2022 View on Web

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Clinical evaluation and patient related outcomes of one‐ and two‐piece zirconia implants at five years of loading: A case series study

alexandrossfakianakis shared this article with you from Inoreader Clinical evaluation and patient related outcomes of one‐ and two‐piece zirconia implants at five years of loading: A case series study via Journal of Esthetic and Restorative Dentistry Abstract Objective The objective of this study was to investigate the survival and biological and mechanical complications of one-piece and two-piece zirconia implants at five years of loading. Materials and Methods Consecutive patients receiving zirconia implants were studied, collecting data at five years of loading on their clinical history, peri-implant health status, mechanical complications, esthetic results, and patient related outcomes. Results The study included 18 patients with 29 implants. The survival rate was 86% in implant-based analysis and 78% in patient-based analysis. There were no cases of peri-implantitis, but mucositis was present in 53% of implants. A mean of 4.1 ± 0.81 mm was obtained for probing depth and 1.6 ± 0.9 mm for crestal bone loss (radiographic assessment). There were no implant fractures. Major (10%) and minor (10%) prosthesis complications were observed. The esthetic outcome was moderate to almost perfect, with a high level of patient satisfaction. No significant association was found between survival rate and the presence of mucositis around one- or two-piece implants or any other study variable. Conclusions The survival rate is low for one- and two-piece zirconia implants. Both types of implants demonstrated a low mechanical complication rate. The incidence of periimplantitis is low but mucositis is present in 50%. Patient satisfaction related to esthetics and function is moderate to high. They represent a good option for patients requiring an alternative to titanium implants. Clinical Relevance Zirconia implants appear to be an alternative to the titanium option and may be indicated for patients requiring "metal-free" restorations. View on Web

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DSCS, a New Cell Line Developed in vitro From Human Stem Cells of the Apical Papilla

alexandrossfakianakis shared this article with you from Inoreader DSCS, a New Cell Line Developed in vitro From Human Stem Cells of the Apical Papilla via International Endodontic Journal Abstract Aim To establish and fully characterize a new cell line from human stem cells of the apical papilla (SCAPs) through immortalization with an SV40 large T antigen. Methodology Human SCAPs were isolated and transfected with an SV40 large T antigen and treated with puromycin to select the infected population. Expression of human mesenchymal surface markers CD73, CD90 and CD105 was assessed in the new cell line named Dental Stem Cells SV40 (DSCS) by flow cytometry at early and late passages. Cell and proliferation were also analysed. To evaluate trilineage differentiation; quantitative polymerase chain reaction and histological staining were performed. Results DSCS cell flow cytometry confirmed expression of mesenchymal surface markers even in late passages (100% positive for CD73 and CD90 and 98.9% for CD105 at passage (P) 25). Fewer than 0.5% were positive for haematopoietic cell markers (CD45 and CD34). DSCS cells also showed increased proliferation when compared with the primary culture after 48 h, with a doubling time of 23.46 h for DSCS cells and 40.31 h for SCAPs, and retained the capacity to grow for >45 passages (150 population doubling) and their spindle shape morphology. Trilineage differentiation potential was confirmed through histochemical staining and gene expression of the chondrogenic markers SOX9 and COL2A1, adipogenic markers CEBPA and LPL, and osteogenic markers COL1A1 and ALPL. Conclusions The new cell line derived from human SCAPs has multipotency, retains its morphology and expression of mesenchymal surface markers, and shows higher proliferative capacity even at late passages (P45). DSCS cells can be used for in vitro study of root development and to achieve better understanding of the regenerative mechanisms. View on Web

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Three‐point sectional‐cast digital method for transferring the interocclusal relationship for full‐mouth rehabilitation of worn dentition

alexandrossfakianakis shared this article with you from Inoreader Three‐point sectional‐cast digital method for transferring the interocclusal relationship for full‐mouth rehabilitation of worn dentition via Journal of Prosthodontics Abstract For full-mouth rehabilitation of worn dentition, "diagnostic" interim restorations are required to reestablish the interocclusal relationship. It is important but challenging to transfer the interocclusal relationship, and to map the basic form and contour of interim restorations to the final restorations. Alignment of interim restorations and working casts is difficult when using digital workflows because of a lack of consistent hard tissue reference points. The digital workflow presented in this study used a "3-point sectional-cast digital cross-mounting method" to transfer the interocclusal relationship during full-mouth rehabilitation. An intermediate cast was made with 3 interim restorations: 1 on an incisor and 2 on molars. The interocclusal relationship and occlusal morphologies of the diagnostic interim prostheses were transferred and aligned to working casts using the 3-point sectional casts. This article is protected by copyright. All rights reserved View on Web

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Künstliche Intelligenz auf dem Vormarsch – Hohe Vorhersage-Genauigkeit bei der Früherkennung pigmentierter Melanome

alexandrossfakianakis shared this article with you from Inoreader Künstliche Intelligenz auf dem Vormarsch – Hohe Vorhersage-Genauigkeit bei der Früherkennung pigmentierter Melanome via Laryngo-Rhino-Otologie Laryngorhinootologie DOI: 10.1055/a-1949-3639 Weltweit steigt die Inzidenz des malignen Melanoms an. Bei frühzeitiger Erkennung ist das Melanom gut behandelbar, eine Früherkennung ist also lebenswichtig.Die Hautkrebs-Früherkennung hat sich in den letzten Jahrzehnten bspw. durch die Einführung des Screenings im Jahr 2008 und die Dermatoskopie deutlich verbessert. Dennoch bleibt die visuelle Erkennung insbesondere von frühen Melanomen eine Herausforderung, weil diese viele morphologische Überlappungen mit Nävi zeigen. Daher ist der medizinische Bedarf weiterhin hoch, die Methoden zur Hautkrebsfrüherkennung gezielt weiterzuentwickeln, um Melanome bereits in einem sehr frühen Stadium sicher diagnostizieren zu können.Die Routinediagnostik zur Hautkrebs-Früherkennung umfasst die visuelle Ganzkörperinspektion, oft ergänzt durch die Dermatoskopie, durch die sich die diagnostische Treffsicherheit erfahrener Hautärzte deutlich erhöhen lässt. E in Verfahren, was in einigen Praxen und Kliniken zusätzlich angeboten wird, ist die kombinierte Ganzkörperfotografie mit der digitalen Dermatoskopie für die Früherkennung maligner Melanome, insbesondere für das Monitoring von Hochrisiko-Patienten.In den letzten Jahrzenten wurden zahlreiche nicht invasive zusatzdiagnostische Verfahren zur Beurteilung verdächtiger Pigmentmale entwickelt, die das Potenzial haben könnten, eine verbesserte und z. T. automatisierte Bewertung dieser Läsionen zu ermöglichen. In erster Linie ist hier die konfokale Lasermikroskopie zu nennen, ebenso die elektrische Impedanzspektroskopie, die Multiphotonen-Lasertomografie, die Multispektralanalyse, die Raman-Spektroskopie oder die optische Kohärenztomografie. Diese diagnostischen Verfahren fokussieren i. d. R. auf hohe Sensitivität, um zu vermeiden, ein malignes Melanom zu übersehen. Dies bedingt allerdings üblicherweise eine geringere Spezifität, was im Screening zu unnötigen Exzisionen vieler gutartiger Läsionen führen kann. Auch sind einige der Verfahren zeitaufwendig und kostenintensiv,was die Anwendbarkeit im Screening ebenfalls einschränkt.In naher Zukunft wird insbesondere die Nutzung von künstlicher Intelligenz die Diagnosefindung in vielfältiger Weise verändern. Vielversprechend ist v. a. die Analyse der makroskopischen und dermatoskopischen Routine-Bilder durch künstliche Intelligenz. Für die Klassifizierung von pigmentierten Hautläsionen anhand makroskopischer und dermatoskopischer Bilder erzielte die künstliche Intelligenz v. a. in Form neuronaler Netze unter experimentellen Bedingungen in zahlreichen Studien bereits eine vergleichbare diagnostische Genauigkeit wie Dermatologen. Insbesondere bei der binären Klassifikationsaufgabe Melanom/Nävus erreichte sie hohe Genauigkeiten, doch auch in der Multiklassen-Differenzierung von verschiedenen Hauterkrankungen zeigt sie sich vergleichbar gut wie Dermatologen. Der Nachweis der grundsätzlichen Anwendbark eit und des Nutzens solcher Systeme in der klinischen Praxis steht jedoch noch aus. Noch zu schaffende Grundvoraussetzungen für die Translation solcher Diagnosesysteme in die dermatologischen Routine sind Möglichkeiten für die Nutzer, die Entscheidungen des Systems nachzuvollziehen, sowie eine gleichbleibend gute Leistung der Algorithmen auf Bilddaten aus fremden Kliniken und Praxen.Derzeit zeichnet sich ab, dass computergestützte Diagnosesysteme als Assistenzsysteme den größten Nutzen bringen könnten, denn Studien deuten darauf hin, dass eine Kombination von Mensch und Maschine die besten Ergebnisse erzielt. Diagnosesysteme basierend auf künstlicher Intelligenz sind in der Lage, Merkmale schnell, quantitativ, objektiv und reproduzierbar zu erfassen, und könnten somit die Medizin auf eine mathematische Grundlage stellen – zusätzlich zur ärztlichen Erfahrung. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on Web

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Dysphagie bei tracheotomierten Patienten nach Langzeitbeatmung

alexandrossfakianakis shared this article with you from Inoreader Dysphagie bei tracheotomierten Patienten nach Langzeitbeatmung via Laryngo-Rhino-Otologie Laryngorhinootologie 2023; 102: 27-31 DOI: 10.1055/a-1076-9686 Unabhängig von der Art der kritischen Erkrankung haben tracheotomierte Patienten ein hohes Risiko für die Entwicklung einer Schluckstörung. Diese ist potenziell lebensbedrohlich, da sie zu Aspiration und Pneumonie führen kann. Vor einer oralen Nahrungsgabe sollte daher unbedingt eine Schluckdiagnostik mittels Bolusfärbetest und/oder FEES durchgeführt werden. Da ein physiologischer Luftstrom durch den Larynx und ein adäquater subglottischer Druck Schlüsselkomponenten eines effektiven Schluckaktes sind, sollte eine Oralisierung bei geblockter Trachealkanüle möglichst vermieden werden. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on Web

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