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Background and Aim: Smear layer acts as a physical barrier that hinders full effectiveness of Ca(OH) 2 via interacting with the transfusion of hydroxyle and calcium ions through dentinal tubules. The purpose of this study was to measure the pH changes of the external root surface of human teeth due to hydroxyle ion diffusion using different chelating agents. Materials and Methods: In this in vitro study, 96 anterior maxillary teeth were prepared to a master apical size of #40 4%. Samples were randomly divided into 4 experimental groups of 12, group1: EDTA17% + NaOCl 1.3%; group2: Citric acid 20% + NaOCl 1.3%; group3: Noni + EDTA17%; group4: NaOCl 1.3% + MTAD; and 4 control groups. After removing the smear layer, Ca(OH)2 was placed in experimental samples. Root canal surface pH was measured for 30 days. Data were analyzed using t-test, one way ANOVA and Tuckey multiple comparisons. Result: Noni+ EDTA showed the highest average of PH among experimental (pH=8.02) and control (pH=7.61) groups (p≤0.036), followed by MTAD+ NaOCl, EDTA+ NaOCl & Citric acid+ NaOCl, respectively. (pH=7.73, 7.64, 7.65) Conclusion:It was concluded that Noni +EDTA17% promoted greater hydoxyle ion transfusion and subsequent alkalization in the outer surface of the root due to better omission of smear layer. [ABSTRACT FROM AUTHOR]

Background and Aim: Human dental pulp stem cells have substantial proliferative and differentiation potential. The isolated stem cells or progenitor cells of the pulp can differentiate into odontoblasts or /and osteoblast-like cells and aid in repair as well as reconstruction of tooth structure. Several ways have been introduced for isolation and tracing of these cells. The aim of this study was to isolate mesenchymal stem cells from deciduous dental pulps as well as labeling them with Technetium (Tc99m) to investigate the effect of Tc labeling on the survival rate of stem cells. Materials and Methods: In this experimental study, exfoliated deciduous teeth of 6-11 year old children without any history of systemic disease were collected. Enzymatic and non-enzymatic methods were used to expedite cell isolation and isolated cells (10000) from dental pulp were mixed with 25 millicurie of Tc for tracing purposes. Individual cell activity as well as culture medium activation was evaluated separately afterwards. Data was analyzed using ANOVA statistical test. Results: Isolated dental pulp cells formed single cell derived colonies which showed fibroblast-like growth with solo cloning morphology. Specific staining of the cells indicated them to be stem cells and confirmed their differentiation into bone and fat. Moreover, Technetium significantly decreased the activity of cells. The survival rates of the cells in the period of 1,3,6,24,48 hours were reported to be 95.5%, 85.5%, 77.4%, 68.4%, and 57.3% respectively. Conclusion: The dental pulp stem cells have a significant capacity to differentiate into bone and fat. Tracing the cells with Tc M99 will reduce their survival rate over time. [ABSTRACT FROM AUTHOR]

In preclinical studies, p53 loss of function impacts chemotherapy response, but this has not been consistently validated clinically. We trained a TP53-loss phenocopy gene expression signature from pan-cancer clinical samples in the TCGA. In vitro, the TP53-loss phenocopy signature predicted chemotherapy response across cancer types. In a clinical dataset of 3003 breast cancer samples treated with neoadjuvant chemotherapy, the TP53-loss phenocopy samples were 56% more likely to have a pathologic complete response (pCR), with a significant association between TP53-loss phenocopy and pCR in both ER positive and ER negative tumors. In an independent clinical validation in the I-SPY2 trial (N = 987), we confirmed the association with neoadjuvant chemotherapy pCR and found higher rates of chemoimmunotherapy response in TP53-loss phenocopy tumors compared to non-TP53-loss phenocopy tumors (64% vs. 28%). The TP53-loss phenocopy signature predicts chemotherapy response across cancer types in vitro, and in a proof-of-concept clinical validation is associated with neoadjuvant chemotherapy response across multiple clinical breast cancer cohorts., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: This study aimed to synthesize dentin powder surface modified with alginate, a potential substance for dental pulp regeneration, and evaluate its effects on the viability and proliferation of human dental pulp stem cells in vitro and its biocompatibility in vivo., Methods: In the in vitro phase, dentin powder was synthesized in 3 size groups (150-250 μm, 250-500 μm, and 500-1000 μm) after demineralization and atelopeptidization which is used to remove dentin collagen telopeptides and eliminate host immune response. Surface modification with alginate was performed and followed by field-emission scanning electron microscopy, energy dispersive X-ray spectroscopy, and cell viability and proliferation testing for 14 days with human dental pulp stem cells studied. In the in vivo phase, dentin powders were implanted in rat calvarial defects for 8 weeks, and histologic analysis was conducted. All nonparametric data were analyzed with the Kruskal-Wallis test, and all the quantitative data were analyzed by 1-way analysis of variance using SPSS, and P < .05 was considered statistically significant., Results: Demineralization and atelopeptidization were successful in all groups. Cell viability was optimal and equal (P > .05) in all groups. The 500- to 1000-μm group exhibited significantly higher cell proliferation (P < .05). Histologic assessment shows acceptable biocompatibility in all groups; the angiogenesis score was significantly greater in both 250-500 and 500-1000, and minimal inflammatory response was noted in the 500- to 1000-μm group, and the amount of newly formed bone in this group was higher than other groups., Conclusions: Surface modification of demineralized and atelopeptidized dentin powder with alginate enhanced surface physical properties and cell proliferation while showing great biocompatibility within tissue and reducing the host immune response. These findings hold promise for dentin-pulp complex regeneration., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Histopathologic diagnosis and classification of cancer plays a critical role in guiding treatment. Advances in next-generation sequencing have ushered in new complementary molecular frameworks. However, existing approaches do not independently assess both site-of-origin (e.g. prostate) and lineage (e.g. adenocarcinoma) and have minimal validation in metastatic disease, where classification is more difficult. Utilizing gradient-boosted machine learning, we developed ATLAS, a pair of separate AI Tumor Lineage and Site-of-origin models from RNA expression data on 8249 tumor samples. We assessed performance independently in 10,376 total tumor samples, including 1490 metastatic samples, achieving an accuracy of 91.4% for cancer site-of-origin and 97.1% for cancer lineage. High confidence predictions (encompassing the majority of cases) were accurate 98-99% of the time in both localized and remarkably even in metastatic samples. We also identified emergent properties of our lineage scores for tumor types on which the model was never trained (zero-shot learning). Adenocarcinoma/sarcoma lineage scores differentiated epithelioid from biphasic/sarcomatoid mesothelioma. Also, predicted lineage de-differentiation identified neuroendocrine/small cell tumors and was associated with poor outcomes across tumor types. Our platform-independent single-sample approach can be easily translated to existing RNA-seq platforms. ATLAS can complement and guide traditional histopathologic assessment in challenging situations and tumors of unknown primary., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Injectable biomaterials that can completely fill the root canals and provide an appropriate environment will have potential application for pulp regeneration in endodontics. This study aimed to fabricate and characterize a novel injectable human amniotic membrane (HAM) hydrogel scaffold crosslinked with genipin, enabling the proliferation of Dental Pulp Stem Cells (DPSCs) and optimizing pulp regeneration., Methods: HAM extracellular matrix (ECM) hydrogels (15, 22.5, and 30 mg/ml) crosslinked with different genipin concentrations (0, 0.1, 0.5, 1, 5, and 10 mM) were evaluated for mechanical properties, tooth discoloration, cell viability, and proliferation of DPSCs. The hydrogels were subcutaneously injected in rats to assess their immunogenicity. The hydrogels were applied in a root canal model and subcutaneously implanted in rats to determine their regenerative potential for eight weeks, and histological and immunostaining analyses were performed., Results: Hydrogels crosslinked with low genipin concentration demonstrated low tooth discoloration, but 0.1 mM genipin crosslinked hydrogels were excluded due to their unfavourable mechanical properties. The degradation ratio was lower in hydrogels crosslinked with 0.5 mM genipin. The 30 mg/ml-0.5 mM crosslinked hydrogel exhibited a microporous structure, and the modulus of elasticity was 1200 PA. In vitro, cell culture showed maximum viability and proliferation in 30 mg/ml-0.5 mM crosslinked hydrogel. All groups elicited minimum immunological responses, and highly vascularized pulp-like tissue was formed in human tooth roots in both groups with/without DPSCs., Significance: Genipin crosslinking improved the biodegradability of injectable HAM hydrogels and conferred higher biocompatibility. Hydrogels encapsulated with DPSCs can support stem cell viability and proliferation. In addition, highly vascularized pulp-like tissue formation by this biomaterial displayed potential for pulp regeneration., (Copyright © 2023 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Background: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA)., Methods: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus., Results: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated., Conclusion: This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy., (© 2022 ARS-AAOA, LLC.)

Developing radiation tumor biomarkers that can guide personalized radiotherapy clinical decision making is a critical goal in the effort towards precision cancer medicine. High-throughput molecular assays paired with modern computational techniques have the potential to identify individual tumor-specific signatures and create tools that can help understand heterogenous patient outcomes in response to radiotherapy, allowing clinicians to fully benefit from the technological advances in molecular profiling and computational biology including machine learning. However, the increasingly complex nature of the data generated from high-throughput and "omics" assays require careful selection of analytical strategies. Furthermore, the power of modern machine learning techniques to detect subtle data patterns comes with special considerations to ensure that the results are generalizable. Herein, we review the computational framework of tumor biomarker development and describe commonly used machine learning approaches and how they are applied for radiation biomarker development using molecular data, as well as challenges and emerging research trends., (Published by Elsevier Inc.)

BackgroundNeuroendocrine prostate cancer (NEPC) is an aggressive subtype, the presence of which changes the prognosis and management of metastatic prostate cancer.MethodsWe performed analytical validation of a Circulating Tumor Cell (CTC) multiplex RNA qPCR assay to identify the limit of quantification (LOQ) in cell lines, synthetic cDNA, and patient samples. We next profiled 116 longitudinal samples from a prospectively collected institutional cohort of 17 patients with metastatic prostate cancer (7 NEPC, 10 adenocarcinoma) as well as 265 samples from 139 patients enrolled in 3 adenocarcinoma phase II trials of androgen receptor signaling inhibitors (ARSIs). We assessed a NEPC liquid biomarker via the presence of neuroendocrine markers and the absence of androgen receptor (AR) target genes.ResultsUsing the analytical validation LOQ, liquid biomarker NEPC detection in the longitudinal cohort had a per-sample sensitivity of 51.35% and a specificity of 91.14%. However, when we incorporated the serial information from multiple liquid biopsies per patient, a unique aspect of this study, the per-patient predictions were 100% accurate, with a receiver-operating-curve (ROC) AUC of 1. In the adenocarcinoma ARSI trials, the presence of neuroendocrine markers, even while AR target gene expression was retained, was a strong negative prognostic factor.ConclusionOur analytically validated CTC biomarker can detect NEPC with high diagnostic accuracy when leveraging serial samples that are only feasible using liquid biopsies. Patients with expression of NE genes while retaining AR-target gene expression may indicate the transition to neuroendocrine differentiation, with clinical characteristics consistent with this phenotype.FundingNIH (DP2 OD030734, 1UH2CA260389, R01CA247479, and P30 CA014520), Department of Defense (PC190039 and PC200334), and Prostate Cancer Foundation (Movember Foundation - PCF Challenge Award).

Purpose: Liquid biopsies in metastatic renal cell carcinoma (mRCC) provide a unique approach to understand the molecular basis of treatment response and resistance. This is particularly important in the context of immunotherapies, which target key immune-tumor interactions. Unlike metastatic tissue biopsies, serial real-time profiling of mRCC is feasible with our noninvasive circulating tumor cell (CTC) approach., Methods: We collected 457 longitudinal liquid biopsies from 104 patients with mRCC enrolled in one of two studies, either a prospective cohort or a phase II multicenter adaptive immunotherapy trial. Using a novel CTC capture and automated microscopy platform, we profiled CTC enumeration and expression of HLA I and programmed cell death-ligand 1 (PD-L1). Given their diametric immunological roles, we focused on the HLA I to PD-L1 ratio (HP ratio)., Results: Patients with radiographic responses showed significantly lower CTC abundances throughout treatment. Furthermore, patients whose CTC enumeration trajectory was in the highest quartile (> 0.12 CTCs/mL annually) had shorter overall survival (median 17.0 months v 21.1 months, P < .001). Throughout treatment, the HP ratio decreased in patients receiving immunotherapy but not in patients receiving tyrosine kinase inhibitors. Patients with an HP ratio trajectory in the highest quartile (≥ 0.0012 annually) displayed significantly shorter overall survival (median 18.4 months v 21.2 months, P = .003)., Conclusion: In the first large longitudinal CTC study in mRCC to date to our knowledge, we identified the prognostic importance of CTC enumeration and the change over time of both CTC enumeration and the HP ratio. These insights into changes in both tumor burden and the molecular profile of tumor cells in response to different treatments provide potential biomarkers to predict and monitor response to immunotherapy in mRCC.

DNA mutations in specific genes can confer preferential benefit from drugs targeting those genes. However, other molecular perturbations can "phenocopy" pathogenic mutations, but would not be identified using standard clinical sequencing, leading to missed opportunities for other patients to benefit from targeted treatments. We hypothesized that RNA phenocopy signatures of key cancer driver gene mutations could improve our ability to predict response to targeted therapies, despite not being directly trained on drug response. To test this, we built gene expression signatures in tissue samples for specific mutations and found that phenocopy signatures broadly increased accuracy of drug response predictions in-vitro compared to DNA mutation alone, and identified additional cancer cell lines that respond well with a positive/negative predictive value on par or better than DNA mutations. We further validated our results across four clinical cohorts. Our results suggest that routine RNA sequencing of tumors to identify phenocopies in addition to standard targeted DNA sequencing would improve our ability to accurately select patients for targeted therapies in the clinic., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Aim: In order to obtain a 3-dimentional scaffold with predictable clinical results for pulp regeneration, this study aims to fabricate and characterize a porous decellularized human amniotic membrane (HAM) extracellular matrix (ECM) scaffold, and evaluate its potential to promote pulp regeneration in vitro and in vivo., Methodology: The HAM was decellularized, and its histology and DNA content were analysed to confirm decellularization. The scaffolds were synthesized with 15, 22.5 and 30 mg/ml concentrations. The porosity, pore size, phosphate-buffered saline (PBS) absorption and degradation rate of the scaffolds were assessed. In vitro experiments were performed on human dental pulp stem cells (hDPSCs) to assess their viability, proliferation, adhesion and migration on the scaffolds. The optimal group was selected for in vivo immunogenicity assessment and was also used as the cell-free or cell-loaded scaffold in root segment models to evaluate pulp regeneration. All nonparametric data were analysed with the Kruskal-Wallis test followed by Dunn's post hoc test, whilst quantitative data were analysed with one-way anova., Results: Decellularization of HAM was confirmed (p < .05). The porosity of all scaffolds was more than 95%, and the pore size decreased with an increase in ECM concentration (p < .01). PBS absorption was not significantly different amongst the groups, whilst 30 mg/ml ECM scaffold had the highest degradation rate (p < .01). The hDPSCs adhered to the scaffold, whilst their proliferation rate increased over time in all groups (p < .001). Cell migration was higher in 30 mg/ml ECM scaffold (p < .05). In vivo investigation with 30 mg/ml ECM scaffold revealed mild to moderate inflammatory response. In root segments, both cell-free and cell-loaded 30 mg/ml scaffolds were replaced with newly formed, pulp-like tissue with no significant difference between groups. Immunohistochemical assessments revealed high revascularization and collagen content with no significant difference amongst the groups., Conclusion: The 30 mg/ml HAM ECM scaffold had optimal physical properties and better supported hDPSC migration. The HAM ECM scaffold did not interfere with formation of pulp-like tissue and revascularization within the root canal when employed as both cell-free and cell-loaded scaffold. These results highlight the potential of HAM ECM membrane for further investigations in regenerative endodontics., (© 2021 British Endodontic Society. Published by John Wiley & Sons Ltd.)

Background: Stem cells from human exfoliated deciduous teeth (SHEDs) can transform into odontoblasts in vitro and in vivo . The role of 1α, 25-dihydroxyvitamin D3 (1α,25 vitD3) has been reported in the mineralization of hard tissues and teeth, as well as osteoblastic differentiation. This study aimed to assess the effect of different concentrations of 1α,25 vitD3 on odontogenic differentiation of SHEDs., Materials and Methods: In this experimental study, second-passage SHEDs were exposed to odontogenic medium along with 0, 10, 50, 100, and 150 nmol concentrations of in 1α, 25 vitD3 to determine its optimal concentration for odontogenic differentiation. The methyl thiazolyl tetrazolium (MTT) assay was performed. Odontogenic differentiation was evaluated by QRT- polymerase chain reaction for dentin matrix protein (DMP1) and dentin sialophosphoprotein (DSPP) genes. Morphology of differentiated cells was studied by Scanning Electron Microscopy. Data were analyzed using the Kruskal-Wallis, Mann-Whitney, Friedman, and Chi-square test. P < 0.05 is considered statistically significant., Results: MTT test result showed the two groups of odontogenic medium + 10 nm 1α,25 vitD3 and odontogenic medium + 150 nm 1α,25 vitD3 provided the most suitable conditions for cell viability at 72 h. Expression of both genes significantly increased in the presence of 1α,25 vitD3 ( P < 0.001). Expression of both genes was significantly higher at 14 days compared with 7 days ( P < 0.01). At both time points, expression of both genes was significantly higher in the presence of 150 nm 1α,25 vitD3 compared with 10 nm ( P < 0.01). The accumulation of cells with odontoblastic morphology, cell interactions, and calcifications were evident., Conclusion: 1α,25 vitD3 upregulates DMP1 and DSPP and results in odontogenic differentiation of SHEDs in odontogenic medium. This upregulation increases with time and by an increase in concentration of 1α,25 vitD3., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or non-financial in this article., (Copyright: © 2022 Dental Research Journal.)

Introduction: Inconsistencies in the definitions of endodontic outcome terminology jeopardize evaluations of proposed interventions and patient care quality. This scoping review aimed to provide groundwork to develop a set of basic outcomes in endodontics., Methods: We performed a comprehensive literature search for randomized controlled trials, cohort studies, case-control studies, and case series (≥10 patients) published after 1980 with patients ≥10 years of age with any preoperative pulpal and periapical diagnosis in permanent teeth requiring nonsurgical root canal treatment, retreatment, or apexification. Abstracted data on outcome assessment methods, assessors, and domains were reported after univariate and bivariate analyses., Results: Treatment outcomes were evaluated radiographically (88%) or clinically (73%). Although 2-dimensional radiography exceeded 3-dimensional radiography, the use of the latter has increased since 2010, mostly for nonsurgical retreatments. Of 19 identified outcomes, 5 were most frequent: success (168 studies, 40%), radiographic healing (128 studies, 30%), survival (of an asymptomatic tooth [48 studies, 12%] or of a procedure code in administrative databases [31 studies, 7%]), pain assessment (14 studies, 3%), and quality of life (11 studies, 3%). Clinician-centered outcomes have been most frequently studied since the 1980s (71%), in academic settings (76%), and using a prospective design (45%). Patient-centered outcomes were reported in 19% of studies before 2010 and 30% since 2010. They were more common among retrospective studies (49%)., Conclusions: Patient-centered outcome measures are lacking in endodontic studies. The state of available research can provide a baseline for the development of a core outcome set in endodontics, which should represent the important patient-centered outcomes in conjunction with well-validated clinician-centered outcomes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite initiatives to standardize reports, variances in study design, outcomes assessed, and tools used are persistent in the literature. This review scoped the existing literature on endodontic outcome studies for future development of core outcome sets., Methods: A comprehensive literature search of randomized controlled trials, cohort studies, case-control studies, and case series (≥10 patients) published after 1980 including patients ≥10 years of age with any preoperative pulpal and periapical diagnosis in permanent teeth requiring nonsurgical root canal treatment (NS-RCT), retreatment (NS-ReTx), or apexification was performed. Abstracted data were reported through descriptive statistics., Results: Of the 9957 studies screened, 354 were included. An increase in the quantity of endodontic outcome publications and levels of evidence in their study design was noted over the past 4 decades. Although 41% of the studies included participants 26-50 years of age, literature including participants >50 years old has increased since 2000. Apexification and NS-ReTx were mostly provided by specialists and postgraduate students. The most common follow-up period was 2-5 years (35%), and most randomized controlled trials (58%) reported follow-up times <1 year. Multiple-visit treatment was most common in apexification studies (85%). Deficiency, inconsistency, and ambiguity were observed across many reports., Conclusions: NS-ReTx and NS-RCT/NS-ReTx studies have increased over the past 2 decades, particularly those focusing on molars and patients >50 years old. Despite the progress in endodontic research, heterogeneity in reporting styles yields considerable limitations, particularly data standardization challenges and inconsistencies in methods and results reporting. This scoping review highlighted the state of available research and supported the development of standardized guidelines for future investigations., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Luminal and basal subtypes of primary prostate cancer have been shown to be molecularly distinct and clinically important in predicting response to therapy. These subtypes have not been described in metastatic prostate cancer., Objectives: To identify clinical and molecular correlates of luminal and basal subtypes in metastatic castration-resistant prostate cancer (mCRPC) and investigate differences in survival, particularly after treatment with androgen-signaling inhibitors (ASIs)., Design, Setting, and Participants: In this cohort study, a retrospective analysis was conducted of 4 cohorts with mCRPC (N = 634) across multiple academic centers. Treatment was at the physicians' discretion. Details of the study cohorts have been published elsewhere between 2016 and 2019. Data were analyzed from March 2018 to February 2021., Main Outcomes and Measures: The primary clinical end point was overall survival from the date of tissue biopsy/molecular profiling. Luminal and basal subtypes were also stratified by postbiopsy ASI treatment. The primary molecular analyses included associations with small cell/neuroendocrine prostate cancer (SCNC), molecular pathways, and DNA alterations., Results: In the 634 patients, 288 (45%) had tumors classified as luminal, and 346 (55%) had tumors classified as basal. However, 53 of 59 (90%) SCNC tumors were basal (P < .001). Similar to primary prostate cancer, luminal tumors exhibited overexpression of AR pathway genes. In basal tumors, a significantly higher rate of RB1 loss (23% basal vs 4% luminal; P < .001), FOXA1 alterations (36% basal vs 27% luminal; P = .03) and MYC alterations (73% basal vs 56% luminal; P < .001) were identified. Patients with basal tumors had worse overall survival compared with those with luminal tumors only in patients treated with an ASI postbiopsy (East Coast Dream Team: hazard ratio [HR], 0.39; 95% CI, 0.20-0.74; P = .004; West Coast Dream Team: HR, 0.57; 95% CI, 0.33-0.97; P = .04). Among patients with luminal tumors, those treated with an ASI had significantly better survival (HR, 0.27; 95% CI, 0.14-0.53; P < .001), whereas patients with basal tumors did not (HR, 0.62; 95% CI, 0.36-1.04, P = .07). The interaction term between subtype and ASI treatment was statistically significant (HR, 0.42; 95% CI, 0.20-0.89; P = .02)., Conclusions and Relevance: These findings represent the largest integrated clinical, transcriptomic, and genomic analysis of mCRPC samples to date, and suggest that mCRPC can be classified as luminal and basal tumors. Analogous to primary prostate cancer, these data suggest that the benefit of ASI treatment is more pronounced in luminal tumors and support the use of ASIs in this population. In the basal tumors, a chemotherapeutic approach could be considered in some patients given the similarity to SCNC and the diminished benefit of ASI therapy. Further validation in prospective clinical trials is warranted.

The Ultraviolet-visible (UV-Vis) spectra indicate that anthracenyl chalcones (ACs) have high maximum wavelengths and good transparency windows for optical applications and are suitable for optoelectronic applications owing to their HOMO-LUMO energy gaps (2.93 and 2.76 eV). Different donor substituents on the AC affect their dipole moments and nonlinear optical (NLO) responses. The positive, negative, and neutral electrostatic potential regions of the molecules were identified using molecular electrostatic potential (MEP). The stability of the molecule on account of hyperconjugative interactions and accompanying charge delocalization was analyzed using natural bond orbital (NBO) analysis. Open and closed aperture Z-scans were performed using a continuous-wave frequency-doubled diode-pumped solid-state (DPSS) laser to measure the nonlinear absorption and nonlinear refractive index coefficients, respectively. The valley-to-peak profile of AC indicated a negative nonlinear refractive index coefficient. The obtained single crystals possess reverse saturation absorption due to excited-state absorption. The structural and nonlinear optical properties of the molecules have been discussed, along with the role of anthracene substitution for enhancing the nonlinear optical properties. The calculated third-order susceptibility value was 1.10 x10-4 esu at an intensity of 4.1 kW/cm2, higher than the reported values for related chalcone derivatives. The NLO response for both ACs offers excellent potential in optical switching and limiting applications., Competing Interests: The authors have declared that no competing interests exist.

We are now in an era of molecular medicine, where specific DNA alterations can be used to identify patients who will respond to specific drugs. However, there are only a handful of clinically used predictive biomarkers in oncology. Herein, we describe an approach utilizing in vitro DNA and RNA sequencing and drug response data to create TreAtment Response Generalized Elastic-neT Signatures (TARGETS). We trained TARGETS drug response models using Elastic-Net regression in the publicly available Genomics of Drug Sensitivity in Cancer (GDSC) database. Models were then validated on additional in-vitro data from the Cancer Cell Line Encyclopedia (CCLE), and on clinical samples from The Cancer Genome Atlas (TCGA) and Stand Up to Cancer/Prostate Cancer Foundation West Coast Prostate Cancer Dream Team (WCDT). First, we demonstrated that all TARGETS models successfully predicted treatment response in the separate in-vitro CCLE treatment response dataset. Next, we evaluated all FDA-approved biomarker-based cancer drug indications in TCGA and demonstrated that TARGETS predictions were concordant with established clinical indications. Finally, we performed independent clinical validation in the WCDT and found that the TARGETS AR signaling inhibitors (ARSI) signature successfully predicted clinical treatment response in metastatic castration-resistant prostate cancer with a statistically significant interaction between the TARGETS score and PSA response (p = 0.0252). TARGETS represents a pan-cancer, platform-independent approach to predict response to oncologic therapies and could be used as a tool to better select patients for existing therapies as well as identify new indications for testing in prospective clinical trials., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Introduction: This study aimed to characterize the decellularization effects of different treatment protocols on the bovine dental pulp extracellular matrix (ECM) for tissue regeneration., Methods: Seven different decellularization protocols consisting of trypsin/EDTA (for 1 hour, 24 hours, or 48 hours), sodium dodecyl sulfate (SDS, for 24 hours or 48 hours), Triton X-100 (for 1 hour), and deoxyribonuclease treatments were tested on bovine dental pulp tissue. The posttreatment samples were evaluated for remaining DNA and cellular contents, structural durability, immunofluorescence analysis, and in vivo immune responses., Results: A complete decellularization process in all of the experimental groups was observed. The protocol that included 1 hour of Triton X-100 treatment and 12 hours of trypsin/EDTA treatment with no SDS treatment (P7 [12E-0S-1T]) showed the highest retention of glycosaminoglycan and the absence of nuclei in 4,6-diamidino-2-phenylindole. All groups showed significantly lower DNA content compared with native pulp tissue (P < .05), whereas compared with other protocols, protocols 1 (1 hour of EDTA/trypsin, 24 hours of SDS, and 1 hour of Triton X-100) and 4 (1 hour of EDTA/Trypsin, 48 hours of SDS, and no Triton X-100) resulted in the highest DNA contents (P < .05). Based on these results, P7 was further evaluated by immunofluorescence and in vivo immunogenicity. P7 specimens preserved collagen type I, whereas mononuclear cell infiltration along with neovascularization was observed in vivo., Conclusions: All tested treatments displayed the potential ability to decellularize pulp tissue and are viable options for a xenogeneic dental pulp ECM scaffold. The P7 (12E-0S-1T) protocol resulted in decellularized ECM with minimal organic matrix/ultrastructural detriments and an acceptable host immune response., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Two organometallic compounds known as (E)-1-ferrocenyl-(3-fluorophenyl)prop-2-en-1-one (Fc1) and (E)-1-ferrocenyl-(3-fluoro-4-methoxyphenyl)prop-2-en-1-one (Fc2) are designed and synthesized for application in dye-sensitized solar cell (DSSC) based on a donor-π-acceptor (D-π-A) architecture. By strategically introducing a methoxy group into the acceptor side of the compound, Fc2 which has adopted a D-π-A-AD structure are compared with the basic D-π-A structure of Fc1. Both compounds were characterized by utilizing the IR, NMR and UV-Vis methods. Target compounds were further investigated by X-ray analysis and studied computationally using Density Functional Theory (DFT) and Time-Dependent DFT (TD-DFT) approaches to explore their potential performances in DSSCs. An additional methoxy group has been proven in enhancing intramolecular charge transfer (ICT) by improving the planarity of Fc2 backbone. This good electronic communication leads to higher HOMO energy level, larger dipole moment and better short-circuit current density (Jsc) values. Eventually, the presence of methoxy group in Fc2 has improved the conversion efficiency as in comparison to Fc1 under the same conditions., Competing Interests: The authors have declared that no competing interests exist.

Biomedical values of organic natural cinnamon that are buried in their bulk counterpart can be exposed and customised via nanosizing. Based on this factor, a new type of spherical cinnamon nanoclusters (Cin-NCs) were synthesised using eco-friendly nanosecond pulse laser ablation in liquid (PLAL) approach. As-grown nontoxic Cin-NCs suspended in the citric acid of pH 4.5 (acted as organic solvent) were characterised thoroughly to evaluate their structural, optical and bactericidal properties. The effects of various laser fluences (LF) at the fixed wavelength (532 nm) on the physiochemical properties of these Cin-NCs were determined. The FTIR spectra of the Cin-NCs displayed the symmetric-asymmetric stretching of the functional groups attached to the heterocyclic/cinnamaldehyde compounds. The HR-TEM image of the optimum sample revealed the nucleation of the crystalline spherical Cin-NCs with a mean diameter of approximately 10 ± 0.3 nm and lattice fringe spacing around 0.14 nm. In addition, the inhibition zone diameter (IZD) and optical density (OD 600 ) of the proposed Cin-NCs were measured to assess their antibacterial potency against the Staphylococcus aureus (IZD ≈ 24 mm) and Escherichia coli (IZD ≈ 25 mm) bacterial strains. The strong UV absorption (in the range of 269 and 310 nm) shown by these NCs was established to be useful for the antibacterial drug development and food treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier Ltd. All rights reserved.)

Introduction: This study aims to develop and characterize the regenerative potential of an atelopeptidized treated dentin matrix xenograft using in vitro and in vivo models., Methods: Freshly extracted bovine dentin was pulverized into 250- to 500-μm particles and demineralized with 17% EDTA for 1, 7, and 13 days. The samples were atelopeptidized with pepsin. The degree of demineralization and the effect of atelopeptidization were assessed using field emission scanning electron microscopy combined with energy-dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy, respectively. The expression of dentin matrix acidic phosphoprotein 1, dentin sialophosphoprotein, and osteopontin was evaluated in dental pulp stem cells using quantitative real-time polymerase chain reaction. The samples were then implanted intramuscularly in rats for 30 days, and the inflammatory cells were quantified histologically., Results: Field emission scanning electron microscopy combined with energy-dispersive X-ray spectroscopy revealed an exposed tubular structure of dentin after 1 and 7 days of demineralization. Fourier transform infrared spectroscopy confirmed the absence of amide peaks at 1260 to 1640/cm after atelopeptidization. The dental pulp stem cell expression of dentin matrix acidic phosphoprotein 1 and dentin sialophosphoprotein increased in all compared with the untreated control group (P < .05). The maximum expression rates were observed for the 1-day demineralized and atelopeptidized group. The 1-day demineralized group elicited the highest inflammatory response compared with the 7- or 13-day demineralized groups (P < .001). Atelopeptidization significantly decreased the inflammatory response only in the 1-day demineralized dentin group (P < .05)., Conclusions: Atelopeptidization of 1-day demineralized dentin xenograft preserved the collagen structure, minimized the immune reaction, and provided sufficient regenerative potential., (Copyright © 2019 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Objective: Recent studies suggest xenogeneic extracellular matrices as potential regenerative tools in dental pulp regeneration. This study aimed to fabricate and characterize a novel three-dimensional macroporous pulp-derived scaffold that enables the attachment, penetration, proliferation and differentiation of mesenchymal stem cells., Method: Bovine pulp was decellularized and characterized with histological and DNA content methods. This scaffold was prepared using finely milled lyophilized decellularized pulp extracellular matrix (ECM) digested with pepsin. Three different concentrations of ECM (1.50, 2.25 and 3.00mg/ml) were freeze-dried and were tested with/without chemical crosslinking. The specimens were subjected to physicochemical characterization, cell viability and quantitative real time polymerase chain reaction assessments with human bone marrow mesenchymal stem cells (hBMMSCs). All scaffolds were subcutaneously implanted in rats for two weeks and histological and immunostaining analyses were performed., Results: Histological and DNA analysis confirmed complete decellularization. All samples demonstrated more than 97% porosity and 1.50mg/ml scaffold demonstrated highest water absorption. The highest cell viability and proliferation of hBMMSCs was observed on the 3.00mg/ml crosslinked scaffolds. The gene expression analysis showed a significant increase of dmp-1 and collagen-I on 3.00mg/ml crosslinked scaffolds compared to the other scaffolds. Histological examination of subcutaneous implanted scaffolds revealed low immunological response, and enhanced angiogenesis in cross-linked samples compared to non-crosslinked samples., Significance: The three-dimensional macroporous pulp-derived injectable scaffold developed and characterized in this study displayed potential for regenerative therapy. While the scaffold biodegradability was decreased by crosslinking, the biocompatibility of post-crosslinked scaffold was significantly improved., (Copyright © 2019 The Academy of Dental Materials. All rights reserved.)

Background: A successful endodontic treatment depends on efficient cleaning and shaping and effective irrigation of root canals. The irrigating solution may not be effective in some areas in the canal. The manufacturer of XP-Endo finisher claims that it can effectively clean the root canals with complex morphology. This study aimed to assess the effect of XP-Endo finisher on the amount of residual debris and smear layer on the root canal walls of mandibular second premolars., Materials and Methods: In this In vitro study Fifty extracted mandibular second premolars with a root curvature <20° were collected. Root canals were prepared using BioRaCe rotary system. The root canals were in contact with the file and different irrigating solutions for 1 min. The teeth were then randomly divided into four experimental ( n = 10) and one positive control group as follows: (1) XPF + saline, (2) XPF + ethylenediaminetetraacetic acid (EDTA), (3) XPF + sodium hypochlorite (NaOCl), (4) XPF + EDTA + NaOCl and (control) EDTA + NaOCl. The teeth were longitudinally sectioned into two halves and the amount of debris and smear layer remaining in the coronal, middle, and apical thirds of the roots was quantified and scored under an electron microscope. The Kruskal-Wallis test was used to compare the groups, and P < 0.05 was considered statistically significant., Results: The highest mean amount of residual debris (2.9 ± 1.13) was noted in XPF + saline group ( P < 0.05). XPF + saline and XPF + NaOCl (3.8 ± 0.60) had the lowest efficacy for smear layer removal ( P < 0.05) with no significant within-group difference. No significant difference was noted between Groups 2, 3, and 4 with the positive control group regarding debris removal. Groups 2 and 4 had no significant difference with the positive control group regarding smear layer removal., Conclusion: Use of XP-Endo finisher has no superiority to the standard protocol for the use of irrigating solutions (EDTA + NaOCl) for debris and smear layer removal, but in some cases, such as second appointment of regeneration treatment we cannot use NaOCl because of its destructive effects on stem cells; thus, we can benefit from the synergistic effects of XPF and EDTA for better smear layer removal., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or nonfinancial in this article.

The interrelations between inflammation and regeneration are of particular significance within the dental pulp tissue inextensible environment. Recent data have demonstrated the pulp capacity to respond to insults by initiating an inflammatory reaction and dentin pulp regeneration. Different study models have been developed in vitro and in vivo to investigate the initial steps of pulp inflammation and regeneration. These include endothelial cell interaction with inflammatory cells, stem cell interaction with pulp fibroblasts, migration chambers to study cell recruitment and entire human tooth culture model. Using these models, the pulp has been shown to possess an inherent anti-inflammatory potential and a high regeneration capacity in all teeth and at all ages. The same models were used to investigate the effects of tricalcium silicate-based pulp capping materials, which were found to modulate the pulp anti-inflammatory potential and regeneration capacity. Among these, resin-containing materials such as TheraCal ® shift the pulp response towards the inflammatory reaction while altering the regeneration process. On the opposite, resin-free materials such as Biodentine™ have an anti-inflammatory potential and induce the pulp regeneration capacity. This knowledge contradicts the new tendency of developing resin-based calcium silicate hybrid materials for direct pulp capping. Additionally, it would allow investigating the modulatory effects of newly released pulp capping materials on the balance between tissue inflammation and regeneration. It would also set the basis for developing future capping materials targeting these processes., (Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Infection of the dental pulp will result in inflammation and eventually tissue necrosis which is treated conventionally by pulpectomy and root canal treatment. Advances in regenerative medicine and tissue engineering along with the introduction of new sources of stem cells have led to the possibility of pulp tissue regeneration. This systematic review analyzes animal studies published since 2010 to determine the ability of stem cell therapy to regenerate the dentine-pulp complex (DPC) and the success of clinical protocols. In vitro and human clinical studies are excluded and only the experimental studies on animal models were included. Dental pulp stem cells constitute the most commonly used cell type. The majority of stem cells are incorporated into various types of scaffold and implanted into root canals. Some of the studies combine growth factors with stem cells in an attempt to improve the outcome. Studies of ectopic transplantation using small animal models are simple and non-systematic evaluation techniques. Stem cell concentrations have not been so far reported; therefore, the translational value of such animal studies remains questionable. Though all types of stem cells appear capable of regenerating a dentine-pulp complex, still several factors have been considered in selecting the cell type. Co-administrative factors are essential for inducing the systemic migration of stem cells, and their vascularization and differentiation into odontoblast-like cells. Scaffolds provide a biodegradable structure able to control the release of growth factors. To identify problems and reduce costs, novel strategies should be initially tested in subcutaneous or renal capsule implantation followed by root canal models to confirm results.

Introduction: A lack of information exists regarding the efficacy of RetroMTA (BioMTA, Seoul, Korea) directly applied on the pulp in vital pulp therapy. This study was designed to examine the clinical efficacy of RetroMTA compared with ProRoot mineral trioxide aggregate (MTA) (Dentsply Tulsa Dental, Tulsa, OK) for partial pulpotomy., Methods: Partial pulpotomy was performed in 22 healthy human maxillary and mandibular third molars planned for extraction. The teeth were randomly divided into 2 groups (n = 11) and underwent partial pulpotomy with RetroMTA and ProRoot MTA as the control. The teeth were then restored with glass ionomer cement. Clinical and electric pulp tests were performed after 1 and 8 weeks. The teeth were radiographed and extracted at 8 weeks. Histologic sections were prepared and analyzed for pulp inflammation and dentinal bridge formation. Data were analyzed using the Mann-Whitney U test., Results: Clinical examination after 1 and 8 weeks showed no sensitivity to heat, cold, or palpation in the ProRoot MTA and RetroMTA groups. Periapical radiographs taken before the extraction of teeth showed no evidence of periapical pathology. Electric pulp testing revealed no sensitivity. Data comparisons using the Mann-Whitney U test showed no significant difference between the materials with regard to the pulp inflammation type, intensity and extension (P = .3), or bridge continuity (P = .12). However, these data revealed a significant difference between the 2 materials in pulp morphology (P < .05) and bridge thickness (P < .01)., Conclusions: This is the first work to evaluate a RetroMTA histologic outcome in partial pulpotomy in human permanent teeth. It shows pulp disorganization, an absence of inflammation, and discontinuous mineralization, which may represent a potential drawback with RetroMTA in this indication., (Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Maintaining the original central canal path is an important parameter in efficient root canal preparation. Instruments causing minimal changes in original canal path are preferred for this purpose. This study sought to compare canal transportation and centering ability of ProTaper and SafeSider instruments in curved mesiobuccal root canals of mandibular first molars using cone beam computed tomography (CBCT)., Methods and Materials: In this experimental study, 30 mesiobuccal root canals of extracted human mandibular first molars with 20° to 40° curvature were randomly divided into two groups ( n =15). After mounting in putty, preoperative CBCT scans were obtained of teeth. Root canals in group A were shaped using S1, S2, F1 and F2 of ProTaper system. Root canals in group B were instrumented to size 25 using SafeSider system according to the manufacturers' instructions. Postoperative CBCT scans were then obtained. The distance between the external root surface and internal canal wall was measured at the mesial and distal at 1, 3 and 7 mm from the apex. The values measured on primary and secondary CBCT scans were compared to assess possible changes in original central canal path and canal transportation. Data were compared using the t -test and repeated measure ANOVA., Results: ProTaper and SafeSider were significantly different in terms of canal transportation and centering ability, and ProTaper was significantly superior to SafeSider in this respect ( P <0.001)., Conclusion: ProTaper (in contrast to SafeSider) is well capable of maintaining the original central canal path with the least amount of transportation., Competing Interests: ‘None declared’.

Introduction: Questions exist regarding the efficacy of resin-containing materials such as TheraCal directly applied on the pulp. This study sought to investigate the clinical efficacy of TheraCal as compared with Biodentine and ProRoot mineral trioxide aggregate (MTA) for partial pulpotomy., Methods: In this clinical trial, partial pulpotomy was performed for 27 sound human maxillary and mandibular third molars scheduled for extraction. The teeth were randomly divided into 3 groups (n = 9) and underwent partial pulpotomy with TheraCal, Biodentine, and ProRoot MTA. The teeth were then restored with glass ionomer cement. Clinical and electric pulp tests were performed after 1 and 8 weeks. The teeth were radiographed and extracted at 8 weeks. Histologic sections were prepared and analyzed for pulp inflammation and dentinal bridge formation. Data were analyzed by using one-way analysis of variance., Results: Clinical examination showed no sensitivity to heat, cold, or palpation in ProRoot MTA and Biodentine groups. Two patients in TheraCal group (20%) reported significant pain at 1 week. Periapical radiographs showed no periapical pathology, and electric pulp test revealed a normal pulp response with no hypersensitivity. Inflammation was absent with all materials at 8 weeks. Normal pulp organization was seen in 33.33% of the teeth in ProRoot MTA, 11.11% in TheraCal, and 66.67% in Biodentine group (P = .06). Biodentine group showed complete dentinal bridge formation in all teeth, whereas this rate was 11% and 56% in TheraCal and ProRoot MTA groups, respectively (P = .001)., Conclusions: Overall, Biodentine and MTA performed better than TheraCal when used as partial pulpotomy agent and presented the best clinical outcomes., (Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: The purpose of this case series was to report the clinical and radiographic results of a pulp regenerative procedure using platelet-rich fibrin (PRF), a second-generation platelet concentrate, in immature teeth with necrotic pulps., Methods: Root canal revascularization using PRF was performed on 4 immature teeth with necrotic pulps. After access cavity preparation, the root canals were irrigated with low concentration sodium hypochlorite solution (1.5% sodium hypochlorite [20 mL/canal, 5 minutes]) and then irrigated with saline (20 mL/canal, 5 minutes). Equal proportions (167 mg) of ciprofloxacin, metronidazole, and cefaclor were mixed and diluted to a final concentration of 1 g/mL. Finally, the canal was sealed with 3-4 mm of a temporary restorative material, and patients were dismissed for 2 to 3 weeks. At the second appointment, 9 mL of the patient's whole blood was obtained and centrifuged to prepare a PRF clot. Canals were irrigated with 17% EDTA, and a sharp spreader was inserted beyond the apex. Then, the PRF clot was placed inside the root canals, and Biodentine (Septodont, Saint-Maur, France) was placed directly over the PRF. The teeth were restored permanently with glass ionomer cement and composite resin., Results: Clinical examinations revealed that all cases were asymptomatic at the recall appointments at 1, 3, 6, 12, and 18 months. Radiographs revealed resolution of the periapical lesions, further root development, and apical closure in all cases., Conclusions: On the basis of the short-term results up to 12 months, PRF clots acted as successful scaffolds for the regeneration of pulpal contents in immature teeth with necrotic pulps., (Copyright © 2016 American Association of Endodontists. All rights reserved.)

The aim of this study was to perform a literature review of published in-vitro and ex-vivo studies, which evaluated microbial leakage in endodontics in the past 10 years. A comprehensive electronic literature search was carried out in PubMed database for English articles published from 2005 to 2016 using the keywords "endodontics," " in vitro ," " ex vivo ," "microbial leakage," "microbial penetration," "saliva," " Enterococcus faecalis ," " E. faecalis ," "endodontic sealers," "temporary filling material," "apical plug," "mineral trioxide aggregate," and "MTA." The keywords were combined using Boolean operators AND/OR. Based on our search strategy, 33 relevant articles were included in the study. There are three main methods for assessment of bacterial microleakage, namely, (A) the dual-chamber leakage model, (B) detection of bacteria using a scanning electron microscope (SEM), and (C) polymerase chain reaction. All bacterial leakage models have some limitations and may yield different results compared to other microleakage evaluation techniques (i.e., dye penetration, fluid filtration, or electrochemical tests). The results of SEM correlated with those of microbial leakage test in most studies. Microbial leakage test using saliva better simulates the clinical setting for assessment of the leakage of single or mixed bacterial species., Competing Interests: There are no conflicts of interest.