Stages Of Dysplasia Research Articles

Evaluation of exo-long noncoding RNA MALAT1 in OSCC in comparison to dysplastic and normal: A cross-sectional study.

This study explores the role of MALAT1 as a valuable target for creating minimally-invasive diagnostic methods and personalized treatments in the management of OSCC. It focuses on evaluating the role of exosomal MALAT1 in the progression of dysplasia to OSCC by influencing the PI3K/AKT pathway. This cross-sectional study evaluated MALAT1 expression and PI3K/AKT pathway components in exosomes derived from plasma samples of patients with various stages of oral dysplasia, OSCC and compared with normal. RNA concentration was estimated, real-time polymerase chain reaction (qPCR) was used for quantitative analysis. Gene expression levels of MALAT1, PI3K, AKT1, and PTEN were analysed and compared across groups using one way ANOVA and Post-hoc Tukey analysis was performed for pairwise comparisons to assess correlations between MALAT1 expression and PI3K/AKT pathway components. MALAT1 was found to be overexpressed in OSCC in comparison to normal, significantly (p<0.001∗). There was no significant change in expression pattern of MALAT1 between dysplastic patients and normal, yet, significant association was found on corelation analysis between expression pattern of MALAT1 and PI3K/AKT/PTEN (p 0.001∗) among individuals of dysplasia and OSCC. As well pairwise comparisons of MALAT1 expression levels between all three stages of dysplasia showed significant association (p<0.001∗). MALAT1 stands out as a key player in the complex landscape of OSCC pathogenesis, impacting tumorigenesis, metastasis, and treatment outcomes through multifaceted molecular mechanisms. Continued research into MALAT1's regulatory roles and its interactions within the tumor microenvironment holds promise for uncovering novel therapeutic targets and biomarkers that could redefine the management of OSCC in the future.

Exploring the Clinical Signatures of Cervical Dysplasia Patients and Their Association With Vaginal Microbiota.

The vaginal microbiota plays a crucial role in women's health, and an imbalanced vaginal microbiota is linked to various diseases, including human papillomavirus (HPV) infection. However, most available data comes from Western countries and primarily focuses on HPV infection, with only a few studies considering detailed clinical factors to explore the relationship between vaginal microbiota and the development of cervical cancer, especially in China. Our study involved 266 women, including individuals at all stages of cervical dysplasia, and healthy controls with and without HPV infection. We assessed several aspects of the vaginal environment, including vaginal microbiota composition using 16S rRNA gene sequencing, HPV infection status using the standard Roche Cobas method, pH value, age, and H2O2 levels from clinical records, and partner numbers and contraceptive methods obtained through questionnaires. The association of these clinical signatures with cervical dysplasia stages and vaginal microbiota was analyzed. Our findings demonstrate a significant association between vaginal microbiota and cervical dysplasia stages. Patients with cervical dysplasia and cancer showed a substantial increase in HPV 16 infection, a higher prevalence of pH > 5, a lower H2O2 level, and older ages compared to healthy individuals. Additionally, these factors influence the beta diversity of the vaginal microbiota. These results underscore the importance of considering the vaginal microbiota within the cancer microenvironment and highlight the need to integrate all available data to aid in the current diagnosis and understanding of cervical dysplasia and the cervical cancer microenvironment.

A mathematical model for pancreatic cancer during intraepithelial neoplasia.

Cancer is the result of complex interactions of intrinsic and extrinsic cell processes, which promote sustained proliferation, resistance to apoptosis, reprogramming and reorganization. The evolution of any type of cancer emerges from the role of the microenvironmental conditions and their impact of some molecular complexes on certain signalling pathways. The understanding of the early onset of cancer requires a multiscale analysis of the cellular microenvironment. In this paper, we analyse a qualitative multiscale model of pancreatic adenocarcinoma by modelling the cellular microenvironment through elastic cell interactions and their intercellular communication mechanisms, such as growth factors and cytokines. We focus on the low-grade dysplasia (PanIN 1) and moderate dysplasia (PanIN 2) stages of pancreatic adenocarcinoma. To this end, we propose a gene-regulatory network associated with the processes of proliferation and apoptosis of pancreatic cells and its kinetics in terms of delayed differential equations to mimic cell development. Likewise, we couple the cell cycle with the spatial distribution of cells and the transport of growth factors to show that the adenocarcinoma evolution is triggered by inflammatory processes. We show that the oncogene RAS may be an important target for developing anti-inflammatory strategies that limit the emergence of more aggressive adenocarcinomas.

Identification of Stage-Specific microRNAs that Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Human Genetics with Epigenetics and Utilizing an Animal Model.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates reaching 60%, mainly due to its excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules exhibiting expressional dysregulation in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting seed-matching and the reverse interplay between miRNA levels and their target genes' expression. Incorporating gene-expression data from our group's experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia, and early invasion, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is under-expressed in dysplasia and early invasion. The malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p, and miR-34a-5p. The identification of stage-specific miRNAs may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Specificities in the Structure of the Cartilage of Patients with Advanced Stages of Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH) presents varying degrees of femoral head dislocation, with severe cases leading to the formation of a new articular surface on the external side of the iliac bone-the neoacetabulum. Despite conventional understanding suggesting otherwise, a tissue resembling hyaline cartilage is found in the neoacetabulum and acetabulum of Crowe III and IV patients, indicating a potential for hyaline cartilage development without mechanical pressure. To test this theory, acetabular and femoral head cartilage obtained from patients with DDH was stained with hematoxylin-eosin and toluidine blue. The immunohistochemical analysis for collagen types II and VI and aggrecan was performed, as well as delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) analysis on a 7.0 T micro-MRI machine. The results obtained from DDH patients were compared to those of the control groups. Hyaline cartilage was found in the neoacetabulum and the acetabulum of patients with DDH. The nature of the tissue was confirmed with both the histological and the MRI analyses. The results of this study proved the presence of hyaline cartilage in patients with DDH at anatomical regions genetically predisposed to be bone tissue and at regions that are not subjected to mechanical stress. This is the first time that the neoacetabular cartilage of patients with advanced stages of DDH has been characterized in detail.

Preoperative lymphocyte count, neutrophil to lymphocyte and platelet to lymphocyte ratio predict the recurrence with progression and cancerization in vocal fold lesions-retrospective study.

This study explored the contribution of peripheral blood markers in diagnosis and prognosis estimation of different stages of laryngeal dysplasia and early glottic cancer. Retrospective analysis of clinical, histopathological and laboratory data of 220 patients including hemoglobin, neutrophil, lymphocyte, monocyte and platelet counts, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR). The mean hemoglobin level and platelets count showed differences between histopathological stages of lesions (p=0.041 and 0.046, respectively). In patients with recurrent lesions mean level of lymphocyte count, NLR and PLR were significant in assessing progression and cancerization (p=0.005, 0.028 and 0.023, respectively). The univariate analysis recognized level of PLR ≥ 141.74 as significant risk factor of the recurrence of vocal fold hypertrophic lesions (OR = 1.963). The levels of blood cells and their ratios seem to be effective in predicting the recurrence of lesion and even more their potential role in indicating malignant progression.

Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy.

The immune checkpoint inhibitor (ICI), anti-programmed death-1 (anti-PD-1), has shown moderate efficacy in some patients with head and neck squamous cell carcinoma (HNSCC). Because of this, it is imperative to establish a mouse tumor model to explore mechanisms of antitumor immunity and to develop novel therapeutic options. Here, we examined the 4-nitroquinoline-1-oxide (4NQO)-induced oral squamous cell carcinoma (OSCC) model for genetic aberrations, transcriptomic profiles, and immune cell composition at different pathologic stages. Genomic exome analysis in OSCC-bearing mice showed conservation of critical mutations found in human HNSCC. Transcriptomic data revealed that a key signature comprised of immune-related genes was increased beginning at the moderate dysplasia stages. We first identified that macrophage composition in primary tumors differed across pathologic stages, leading to an oncogenic evolution through a change in the M1/M2 macrophage ratio during tumorigenesis. We treated the 4NQO-induced OSCC-bearing mice with anti-PD-1 and agonistic anti-CD40, which modulated multiple immune responses. The growth of tumor cells was significantly decreased by agonistic anti-CD40 by promoting an increase in the M1/M2 ratio. By examining cross-species genomic conservation in human and mouse tumors, our study demonstrates the molecular mechanisms underlying the development of OSCC and the regulation of contributing immune-related factors, and aims to facilitate the development of suitable ICI-based treatments for patients with HNSCC.

Developmental Dysplasia of the Hip - Part 1.

Developmental dysplasia of the hip (DDH) is a condition characterized by changes in joint formation within the last months of intrauterine life or the first months after birth. Developmental dysplasia of the hip presentation ranges from femoroacetabular instability to several stages of dysplasia up to complete dislocation. Early diagnosis is essential for successful treatment. Clinical screening, including appropriate maneuvers, is critical in newborns and subsequent examinations during the growth of the child. Infants with suspected DDH must undergo an ultrasound screening, especially those with a breech presentation at delivery or a family history of the condition. A hip ultrasound within the first months, followed by pelvic radiograph at 4 or 6 months, determines the diagnosis and helps follow-up. Treatment consists of concentric reduction and hip maintenance and stabilization with joint remodeling. The initial choices are flexion/abduction orthoses; older children may require a spica cast after closed reduction, with or without tenotomy. An open reduction also can be indicated. After 18 months, the choices include pelvic osteotomies with capsuloplasty and, eventually, acetabular and femoral osteotomies. The follow-up of treated children must continue throughout their growth due to the potential risk of late dysplasia.

PhD Project: Predictive and Functional Evaluation of Patients Derived Tumor Spheroids and Organoids-Investigating the Relationship between Size and Testing Performance

PhD Project: Predictive and Functional Evaluation of Patients Derived Tumor Spheroids and Organoids-Investigating the Relationship between Size and Testing Performance

Placental Findings in Infants Gestational Age < 34 Weeks and Impact on Short-Term Outcomes.

To analyse placental changes in infants' gestational age < 34 weeks and its correlation to short-term respiratory outcomes or death until hospital discharge. Information regarding all in-house born preterm infants born before 34 weeks gestation and born from January 2009 until December 2014 were collected and included among others, placental pathology and relevant data on demographics and outcomes of infants. Placental abnormalities was found in 157/253 (65.05%) cases. Acute placental inflammation was found to be the most common in both groups of premature neonates, followed by maternal vascular underperfusion. Maternal vascular underperfusion was significantly more common in GA ≤ 27 weeks compared to infants GA 28-33 weeks (35.2% vs. 13.7%; p = 0.018). Similarly, chronic placental inflammation was more common in infants GA ≤ 27 weeks compared to infants GA 28-33 weeks (14.3% vs. 3.3%; p = 0.014). Infants with placental pathology had a lower median birth weight (1460g vs. 1754g; p = 0.001, and were of shorter median GA at birth (31 vs. 32; p = 0.001). Infants with any placental disease had higher rates of death until hospital discharge (10.2% vs. 3.1%; p = 0.039) and higher rates of any stage of bronchopulmonary dysplasia (41.4% vs. 26.0%; p = 0.013). There were no significant differences in mechanical ventilation rates, duration of mechanical ventilation and duration of supplemental oxygen therapy. Identifiable placental abnormalities were found in most infants born < 34 weeks gestation. Placental pathology is associated with increased rates of bronchopulmonary dysplasia and death until hospital discharge.

Preliminary Study of the Cancer Stem Cells' Biomarker CD147 in Leukoplakia: Dysplasia and Squamous Cell Carcinoma of Oral Epithelial Origin.

Objectives Cancer stem cells (CSCs) are responsible for initiating the process of carcinogenesis de novo, as well as through the transformation of oral potential malignant disorders (OPMDs) to oral squamous cell carcinoma (OSCC). The aim of our study was to detect the expression of stemness-type CSC marker CD147 in oral leukoplakias (OLs), the most common OPMD, and OSCCs as well. Materials and methods This study focuses on the semiquantitative immunohistochemical pattern of the expression of the CSCprotein biomarker CD147 in paraffin-embedded samples of 20 OSCCs of different grades of differentiation and 30 cases of OLs without or with different grades of dysplasia, compared to the normal oral epithelium in terms of cells' stain positivity. Statistical analysis wasperformed through Statistical Package for Social Sciences (SPSS) version 25.0(IBM SPSS Statistics, Armonk, NY) with Pearson chi-square test, and the significance level was set at 0.05 (p=0.05). In addition, the study clarified the expression of the respective gene of CD147 through quantitative polymerase chain (qPCR), in paraffin-embedded samples of the two extreme graduations: OLs of mildly dysplastic or non-dysplastic cases (n=10 cases) andOSCCs of moderately/poorly differentiated cases(n=17). Statistical analysis wasthen performed through SPSS version 25.0 with an independent paired t-test, and the significance level was set at 0.05 (p=0.05). Results The gene CD147 was expressed in all cases, although no statistically significant correlations were established. Regarding its protein products, the characteristic membranous staining of CD147 was noticed in the majority of the samples, mostly in the basal and parabasal layers of the epithelium. CD147 was upregulated significantly in the moderately and severely dysplastic OLs than in the mildlydysplastic and non-dysplastic OLs (p=0.008). Also, CD147 was upregulated significantly in the mildly dysplastic and non-dysplastic OLs than in the normal oral epithelium (p=0.012). Discussion The characteristic expression of CD147 in OLs and OSCCs' lesions suggests the presence of stemlike cancer cells, illustrating an underlying effect on the early stages of oral dysplasia, in the OL stage. The clinical application of CD147 as prognostic factor requires the experimental evaluation in larger number of samples. Conclusion Stem cells play an important role in the process of carcinogenesis. A major goal in cancer researchis the identification of specific biomarkers for the detection of cancer stem cells. CD147 is considered as an innovative stem cell marker. Our findings in oral mucosal potentially malignant disorders showed that CD147 is expressed more intenselyin parallel with the progression of the grade of dysplasia in OL.On the other hand, in oral squamous cell carcinoma, CD147 expression remains stable regardless of the degree of differentiation.

Bile acid sequestrants in poor healing after endoscopic therapy of Barrett's esophagus.

Endoscopic therapy for neoplastic Barrett's esophagus (BE) has become the standard of care over the past two decades. In clinical practice, we regularly encounter patients who fail to achieve complete squamous epithelialization of the esophagus. Although the therapeutic strategies in the individual stages of BE, dysplasia, and esophageal adenocarcinoma are well studied and largely standardized, the problem of inadequate healing after endoscopic therapy is only marginally considered. This study aimed to shed light on the variables influencing inadequate wound healing after endoscopic therapy and the effect of bile acid sequestrants (BAS) on healing. Retrospective analysis of endoscopically treated neoplastic BE in a single referral center. In 12.1% out of 627 patients, insufficient healing was present 8 to 12 weeks after previous endoscopic therapy. The average follow-up duration was 38.8±18.4 months. Complete healing was achieved in 13 patients already after intensifying proton pump inhibitor therapy. Out of 48 patients under BAS, 29 patients (60.4%) showed complete healing. An additional eight patients (16.7%) improved, but only partial healing was achieved. Eleven (22.9%) patients showed no response to BAS augmented therapy. In cases of insufficient healing even under exhaustion of proton pump inhibitors, treatment with BAS can be an option as an ultimate healing attempt.

Lateral metabolome study reveals the molecular mechanism of cytoplasmic male sterility (CMS) in Chinese cabbage

BackgroundChinese cabbage is one of the most widely grown leafy vegetables in China. Cytoplasmic male sterility (CMS) is a maternally inherited trait that produces abnormal pollen during anther development, which is commonly seen in cruciferous vegetables. However, the molecular mechanism of Chinese cabbage CMS is not clear. In this study, the metabolome and hormone profiles of Chinese cabbage male sterile line (CCR20000) and sterile maintainer line (CCR20001) were analyzed in flower buds during normal stamen development and abnormal stamen development, respectively.ResultsA total of 556 metabolites were detected based on UPLC-MS/MS detection platform and database search, and the changes of hormones such as auxin, cytokinins, abscisic acid, jasmonates, salicylic acid, gibberellin acid and ethylene were analyzed. The results showed that compared with the male fertile line (MF), the male sterile line (MS) significantly decreased the content of flavonoids and phenolamides metabolites in the stamen dysplasia stage, accompanied by a large accumulation of glucosinolate metabolites. Meanwhile, the contents of GA9, GA20, IBA, tZ and other hormones in MS were significantly lower than those in MF strains. Further, by comparing the metabolome changes of MF and MS during stamen dysplasia, it was found that flavonoid metabolites and amino acid metabolites were distinctly different.ConclusionsThese results suggest that flavonoids, phenolamides and glucosinolate metabolites may be closely related to the sterility of MS strains. This study provides an effective basis for further research on the molecular mechanism of CMS in Chinese cabbage.

Stromal Changes in Colon Blastomogenesis Associated with Development of Hypoxia in the Foci of Dysplasia

We studied the features of reaction of the colon stromal cells (lymphohistiocytic population, fibroblasts, and blood vessels) to the appearance and progression of dysplasia in the colon epithelium against the background of increasing ischemia in the colon mucosa. The morphological material from 92 patients treated for benign processes and colon cancer in 2002-2016 was examined. Common histological methods and a complex immunohistochemical staining were used. The stromal cells of the colon mucosa, mainly lymphohistiocytic cells, undergo certain quantitative changes specific for each type of cells during progression of dysplasia and aggravation of ischemia in the mucosa. Some cells, e.g. plasma cells, presumably contribute to tissue hypoxia in the stroma. Most stromal cells, except interdigitating S100+ dendritic cells and CD10+ fibroblasts, decreased at the stage of grave dysplasia and cancer in situ. Low effectiveness of the immune defense can be partly explained by impairment of the function of stromal cells as a result of hypoxia in the microenvironment.

Abstract PR004: The role of NOTCH1 in bronchial pre-malignant lesions

Abstract Continuous carcinogen exposure through smoking creates a field of injury along the airway and resulting in mutations which promote remodeling of the bronchial epithelium. Over time lesions can form and exhibit increasing abnormalities progressing from goblet cell hyperplasia (GCH) which is the earliest detectable premalignant state through hyperplasia and squamous metaplasia to incremental stages of dysplasia, carcinoma in situ (CIS) and eventually to frank carcinoma. Unfortunately, more than half of all lung cancer patients are diagnosed with metastatic disease with a dismal 5-year survival rate of only 5.2%. However, when diagnosed at an early stage, the 5-year survival rate is more than 10 times as high. Our group has identified NOTCH1 as the most frequently mutated gene in progressive lung premalignant lesions (PMLs). However, these mutations are significantly less common in advanced lung squamous cell carcinoma (LUSC), indicating a role for NOTCH1 in the pre-tumorigenic environment rather than contributing to the actual tumor mass. Transcriptomic profiling of NOTCH1 mutated lesions identified up regulation of peri-goblet cells (PGC), a newly identified bronchial epithelial cell type that is associated with smoking, and a down regulation of immune components. Using highly multiplex Imaging Mass Cytometry (IMC) to analyze the epithelium of NOTCH1 mutated PMLs and its interplay with the immune system in situ. We identified a shift in epithelial composition with an increase in un- and de-differentiated cells. Interestingly, PGC appear to be an intermediate cell type on a previously undescribed path to goblet cell differentiation. In a parallel approach we are modeling NOTCH1 driven dysplasia in vitro to gain insight into the molecular mechanisms of lesion progression. Primary human bronchial epithelial cells (hBECs) grown at the air-liquid interface (ALI) into mature epithelia are exposed to cigarette smoke condensate (CSC) or IL-13 to model the early stages of bronchial airway dysplasia. Continuous exposure of these differentiating cultures to either stimulus increases the abundance of goblet cells and PGCs in a dose dependent manner with IL-13 additionally leading to the loss of baso-apical organization of the epithelium. After successfully modeling the first stage of bronchial epithelial dysplasia we are now advancing our model by co-culturing primary hBECs with NOTCH1 mutated cells and to disentangle the pathway of basal-PGC-goblet cell differentiation. Understanding driving forces in early lesion progression will further our ability to discern progressive lesions from those that regress naturally and facilitate interventions that force lesions into regression. Citation Format: Roxana Michaela Pfefferkorn, Darren Jianjhih Chiu, Divya Lakshmi Venkatraman, Jennifer Ellen Beane, Sarah Anne Mazzilli, Joshua David Campbell. The role of NOTCH1 in bronchial pre-malignant lesions. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr PR004.

Реакция нейроэндокринных клеток и макрофагов селезенки на развитие опухоли в толстой кишке

Introduction. High cancer incidence requires finding new ways for comprehensive studying car-cinogenesis. Therefore, it is crucial to understand immune organ cell response and cell interaction in tumor development. The aim of the research was to study Synaptophysin+-, CD68+-cells, and biogenic amines in rat spleens during tumor development in the colon during dysplasia stages and adenocarcinoma formation. Materials and methods. Spleen histological slides of 110 mature male rats were studied 1 and 4 months after 1,2-dimethylhydrazine carcinogen administration using immunohistochemical, morphometric, and luminescent histochemical methods. Results. We found imbalanced production of biogenic amines (serotonin, histamine, and catecholamines) in the spleen and, therefore, a decrease in the cellular activity of the germinal centers of the lymphoid nodules. We also observed activation of periarteriolar lymphoid sheath (PALS) and red pulp in rats with precancerous colon lesions (1 month after carcinogen administration). At the same time, there was an increase in the number of CD68+ macrophages and Synaptophysin+ cells in the red pulp. In animals with adenocarcinoma (4 months after carcinogen introduction), the level of catecholamines in the luminescent granular cells of the PALS and the functional activity of these cells increased significantly. Simultaneously, the number of macrophages decreased in all the studied spleen compartments. Amid the decreased level of all biogenic amines in the red pulp, the quantity of Synaptophysin+ cells grew even more. Conclusion. The cells of all spleen compartments react to colon carcinogenesis, with reactivity of PALS cells and the red pulp being the most pronounced. The population of spleen macrophages undergoes rapid changes: their number increases in the red pulp in animals with precancerous lesions, while it decreases in all the splenic structures of rats with adenocarcinoma. Synaptophysin+ neuroendocrine cells of the red pulp play an important role in the reaction of the spleen to tumor development, and the number of these cells rises over time. Biogenic amines participate in the interaction of spleen cells with each other and with tumor-associated cells. Keywords: spleen, biogenic amines, neuroendocrine cells, synaptophysin, carcinogenesis

Enhancing convolutional neural network model with spectral features for the identification of cervical dysplasia

AbstractCervical cell classification plays a key role in the computer‐based screening and diagnosis. This article focuses on cell classification and grading to differentiate the stages of cervical dysplasia. The proposed framework uses a unification of wavelet transform and convolutional neural network (CNN) for segregating spectral and spatial features from papanicolaou stained (pap) smear images. A correlation‐based feature selection is adopted to find relevant features from the CNN model. Random Forest classifier is then incorporated to identify cervical dysplasia from the extracted features. The proposed framework is verified on three publicly available datasets. Using the first dataset, the method obtained an average accuracy of 98.12% and area under curve (AUC) of 0.999. In the second (Sipakmed) and third (Herlev) dataset that consists of cell images of both normal and dysplastic condition, the method achieved an accuracy of 97.01%, 82.60% and AUC of 0.999 and 0.907, respectively. The observations of the study imply that spectral features with feature selection along with a proven machine learning model improves the detection rate of cervical dysplasia.

Operative treatment of the young cerebral palsy hip.

Hip dysplasia, subluxation, and eventual hip dislocation are commonly encountered in the cerebral palsy population secondary to spasticity and loss of motor control, especially in those patients with more severe neurologic involvement. The treatment of hip disorders in these patients should take into account the degree of limb and hip involvement, pain severity, and overall functioning. Conservative management focuses on mitigating spasticity and preserving range of motion in order to provide an environment in which the femoral head remains concentrically reduced in the acetabulum. However, operative management, consisting of soft tissue or tendon releases, femoral or pelvic osteotomies, or hip salvage procedures, is sometimes necessary to treat the painful, subluxated, or dislocated hip. Radiographic hip surveillance in the pediatric cerebral palsy population is used to guide operative treatment. Long term hip containment is generally improved when surgical intervention is performed in the earlier stages of dysplasia. Younger patients who demonstrate progressive hip subluxation despite conservative measures may be carefully selected to undergo soft tissue procedures. Bony reconstruction, with adjunctive soft tissue procedures, is often necessary to better contain the proximal femur in patients above the age of four years.

New Metabolic Alterations and A Predictive Marker Pipecolic Acid in Sera for Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increasing in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

DNA damage through oxidative stress is an important event in oral leukoplakia

To evaluate the oxidative DNA damage, through 8-hydroxy-2'-deoxyguanosine (8-OHdG), and its repair by base excision repair pathway [Redox factor-1 (Ref-1); X-ray Repair Cross Complementing-1 (XRCC-1)] in different epithelial dysplasia degrees in oral leukoplakia. Forty-four cases of oral leukoplakia and 10 normal oral mucosa were quantified for 8-OHdG, Ref-1, and XRCC-1 through immunohistochemistry. Cytoplasmic 8-OHdG and nuclear XRCC-1 were significantly associated with multiple synchronous lesions (p=0.048; p=0.034, respectively). Nuclear Ref-1 was significantly associated with oral leukoplakia on the tongue (p=0.027). A significantly gradual cytoplasmic 8-OHdG expression increase was observed between normal oral mucosa and epithelial dysplasia (p<0.05). Nuclear Ref-1 expression was significantly lower (p<0.01) in non-dysplasia/mild dysplasia, while its cytoplasmic expression was significantly higher in non-dysplasia/mild dysplasia compared to moderate/severe dysplasia and normal oral mucosa (p=0.03; p<0.0001, respectively). A significantly higher cytoplasmic XRCC-1 expression was observed in non-dysplasia/mild and moderate/severe dysplasia compared to normal oral mucosa (p<0.0001; p<0.0001, respectively). All epithelial dysplasia degrees showed a correlation between nuclear and cytoplasmic expression of these proteins (p<0.05). 8-OHdG formation may not play a role in the development of multiple synchronous oral leukoplakias. However, it is related to the severity of the epithelial dysplasia. The subcellular level of Ref-1 implies different roles according to the degree of epithelial dysplasia. Cytoplasmic XRCC-1 expression indicates a possible failure of the DNA repair mechanism and occurs in early morphological stages of epithelial dysplasia.