Progression Of Lesions Research Articles

Effects of Helicobacter pylori and Moluodan on the Wnt/β-catenin signaling pathway in mice with precancerous gastric cancer lesions.

Helicobacter pylori (H. pylori) is the primary risk factor for gastric cancer (GC), the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis. GC has a high mortality rate and treatment cost, and there are no drugs to prevent the progression of gastric precancerous lesions to GC. Therefore, it is necessary to find a novel drug that is inexpensive and preventive to against GC. To explore the effects of H. pylori and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC (PLGC). Mice were divided into the control, N-methyl-N-nitrosourea (MNU), H. pylori + MNU, and Moluodan groups. We first created an H. pylori infection model in the H. pylori + MNU and Moluodan groups. A PLGC model was created in the remaining three groups except for the control group. Moluodan was fed to mice in the Moloudan group ad libitum. The general condition of mice were observed during the whole experiment period. Gastric tissues of mice were grossly and microscopically examined. Through quantitative real-time PCR (qRT-PCR) and Western blotting analysis, the expression of relevant genes were detected. Mice in the H. pylori + MNU group showed the worst performance in general condition, gastric tissue visual and microscopic observation, followed by the MNU group, Moluodan group and the control group. QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes, the results showed that the H. pylori + MNU group had the highest expression, followed by the MNU group, Moluodan group and the control group. H. pylori can activate the Wnt/β-catenin signaling pathway, thereby facilitating the development and progression of PLGC. Moluodan suppressed the activation of the Wnt/β-catenin signaling pathway, thereby decreasing the progression of PLGC.

B-cells in pulmonary arterial hypertension: friend, foe or bystander?

There is an unmet need for new therapeutic strategies that target alternative pathways to improve the prognosis of patients with pulmonary arterial hypertension (PAH). As immunity has been involved in the development and progression of vascular lesions in PAH, we review the potential contribution of B-cells in its pathogenesis and evaluate the relevance of B-cell-targeted therapies. Circulating B-cell homeostasis is altered in PAH patients, with total B-cell lymphopenia, abnormal subset distribution (expansion of naïve and antibody-secreting cells, reduction of memory B-cells) and chronic activation. B-cells are recruited to the lungs through local chemokine secretion, and activated by several mechanisms: 1) interaction with lung vascular autoantigens through cognate B-cell receptors; 2) costimulatory signals provided by T follicular helper cells (interleukin (IL)-21), type 2 T helper cells and mast cells (IL-4, IL-6 and IL-13); and 3) increased survival signals provided by B-cell activating factor pathways. This activity results in the formation of germinal centres within perivascular tertiary lymphoid organs and in the local production of pathogenic autoantibodies that target the pulmonary vasculature and vascular stabilisation factors (including angiotensin-II/endothelin-1 receptors and bone morphogenetic protein receptors). B-cells also mediate their effects through enhanced production of pro-inflammatory cytokines, reduced anti-inflammatory properties by regulatory B-cells, immunoglobulin (Ig)G-induced complement activation, and IgE-induced mast cell activation. Precision-medicine approaches targeting B-cell immunity are a promising direction for select PAH conditions, as suggested by the efficacy of anti-CD20 therapy in experimental models and a trial of rituximab in systemic sclerosis-associated PAH.

Successful multidisciplinary treatment for synchronous advanced esophageal and cecal cancers after total gastrectomy with reconstruction by jejunal interposition

BackgroundEsophageal squamous cell carcinoma is characterized by field cancerization, wherein multiple cancers occur in the esophagus, head and neck, and stomach. Synchronous esophageal and colorectal cancers are also encountered with a certain frequency. A good prognosis can be expected if the tumors in both locations can be safely and completely removed. For patients with multiple cancers that occur simultaneously with esophageal cancer, it is necessary to perform a staged operation, taking into consideration the associated surgical invasiveness. It is also necessary to select multidisciplinary treatment depending on the degree of progression of the multiple lesions. We report our rare experience with a staged operation for a patient with synchronous advanced cancers of the esophagus and cecum who had previously undergone total gastrectomy with reconstruction by jejunal interposition for gastric cancer.Case presentationA 71-year-old man with a history of reconstruction by jejunal interposition after total gastrectomy was diagnosed as having multiple synchronous esophageal and cecal cancers. After neoadjuvant chemotherapy, we performed a planned two-stage operation, with esophagectomy and jejunostomy in the first stage and ileocecal resection and jejunal reconstruction with vascular anastomosis in the second. Postoperatively, the patient was relieved without major complications, and both tumors were amenable to curative pathologic resection.ConclusionsOur procedure reported here may be recommended as an option for staged resection and reconstruction in patients with simultaneous advanced esophageal and cecal cancer after total gastrectomy.

Nutritional status as a predictive factor for paediatric tuberous sclerosis complex-associated kidney angiomyolipomas: a retrospective analysis

The purpose of this study is to determine the predictive factors of tuberous sclerosis complex (TSC)-associated kidney disease and its progression in children. Retrospective review of children with TSC in a tertiary children’s hospital was performed. Relevant data were extracted, and Cox proportional hazards regression was used to establish predictors of kidney lesions. Logistic regression was conducted to identify factors predicting chronic kidney disease (CKD) and high-risk angiomyolipomas (above 3 cm). Kidney imaging data were available in 145 children with TSC; of these, 79% (114/145) had abnormal findings. The only significant predictive factor for cyst development was being female (HR = 0.503, 95% CI 0.264–0.956). Being female (HR = 0.505, 95% CI 0.272–0.937) and underweight (HR = 0.092, 95% CI 0.011–0.800) both lowers the risk of having angiomyolipomas, but TSC2 mutations (HR = 2.568, 95% CI 1.101–5.989) and being obese (HR = 2.555, 95%CI 1.243–5.255) increases risks. Ten (12%) of 81 children with kidney function tested demonstrate CKD stages II–V, and only angiomyolipomas above 3 cm predict CKD. Additionally, 13/145 (9%) children had high-risk angiomyolipomas, whereby current age (adjusted odds ratio (aOR) 1.015, 95% CI 1.004–1.026) and being overweight/obese (aOR 7.129, 95% CI 1.940–26.202) were significantly associated with angiomyolipomas above 3 cm.Conclusions: While gender and genotype are known predictors, this study includes the novel finding of nutritional status as a predictor of TSC-associated kidney disease. This study sheds light on a possible complex interplay of hormonal influences, obesity, and kidney angiomyolipomas growth, and further investigations focusing on the impact of nutritional status on TSC-associated kidney disease are warranted.What is Known:• Gender and genotype are well-studied predictive factors in TSC kidney disease.What is New:• Nutritional status may influence the development and the progression of kidney lesions in children with TSC and should not be overlooked.• Management guidelines of TSC-associated kidney disease can address nutritional aspects.

Measuring coral disease lesions: a comparison of methodologies

The presence of stressors, particularly disease, on corals necessitates assessments of their severity in order to compare threat levels and to plan for impacts. Diseases in particular are often measured via the rate at which a lesion moves across a coral (lesion progression rate) to determine the impact of those lesions and also to compare virulence across species, regions, and disease types. Lesion progression can even be used as a field indicator for disease identification. Many different methodologies have been used to measure lesion progression rates. These may be field-based or photographic measurements, and they include linear progression rates as well as areal progression rates. All methods have pros and cons, including varying levels of accuracy and repeatability, variability with respect to colony and lesion sizes, and time and computational requirements. Additionally, not all metrics can be directly compared, and so experiments done with the intent to compare with previous work must consider methodologies used in former studies. Areal progression rates have high variability, but can provide impressive information on overall tissue loss. Overall, linear lesion progression rates provide more accurate and less variable assessments of loss, and are better used for comparisons. Using the average of multiple linear measurements may further increase precision. Measuring from photographs rather than direct field measurements provides a more permanent and repeatable record, but outside of directly planar surfaces is likely to yield inaccuracies. The emerging use of 3-D photogrammetry can overcome many of these limitations, but the methods require considerable time and computational power. The pros and cons of each methodology should be assessed during experimental design to best answer the hypotheses in question as well as consider whether comparisons to other studies are valid.

PHENOTYPIC CHARACTERIZATION OF PREDICTORS FOR DEVELOPMENT AND PROGRESSION OF GEOGRAPHIC ATROPHY USING OPTICAL COHERENCE TOMOGRAPHY.

To evaluate the impact of optical coherence tomography phenotypes preceding atrophy related to age-related macular degeneration on the progression of atrophic lesions. In this observational retrospective cohort study, a total of 70 eyes of 60 consecutive patients with intermediate age-related macular degeneration with a minimum follow-up of 24 months were included. The atrophy was quantified using fundus autofluorescence, also considering the directionality of atrophy as centrifugal and centripetal progression rates. The main outcome measures were geographic atrophy (GA) progression rate (mm 2 /year) and square root transformation of GA (mm 2 /year). The best-fit model for GA (odds ratio: 1.81, P < 0.001) and square root transformation of GA (odds ratio: 1.36, P < 0.001) areas revealed that the main baseline predictor was the presence of a retinal pigment epithelium-basal lamina-Bruch membrane splitting. Large drusen at baseline appeared protective for the GA area lesion expansion over time (odds ratio: 0.52, P < 0.001) when considered with other confounders. A thin retinal pigment epithelium-basal lamina-Bruch membrane splitting without evidence of neovascularization on optical coherence tomography angiography likely represents an optical coherence tomography signature for late basal laminar deposits. Identifying this phenotype can help identify individuals with a higher risk of rapid progression and atrophy expansion.

Simulation of cancer progression in bone by a virtual thermal flux with a case study on lumbar vertebrae with multiple myeloma

BackgroundTwo main problems examining the mechanism of cancer progression in the tissues using the computational models are lack of enough knowledge on the effective factors for such events in vivo environments and lack of specific parameters in the available computational models to simulate such complicated reactions. MethodsIn this study, it was tried to simulate the progression of cancerous lesions in the bone tissues by an independent parameter from the anatomical and physiological characteristics of the tissues, so to degrade the orthotropic mechanical properties of the bone tissues, a virtual temperature was determined to be used by a well-known framework for simulation of damages in the composite materials. First, the reliability of the FE model to simulate hyperelastic response in the intervertebral discs (IVDs) and progressive failure in the bony components were verified by simulation of some In-Vitro tests, available in the literature. Then, the progression of the osteolytic damage was simulated in a clinical case with multiple myeloma in the lumbar vertebrae. ResultsThe FE model could simulate stress-shielding and diffusion of lesion in the posterior elements of the damaged vertebra which led to spinal stenosis. The load carrying shares associated with the anterior half and the posterior half of the examined vertebral body and the posterior elements were estimated equal to 41 %, 47 % and 12 %, respectively for the intact condition, that changed to 14 %, 16 % and 70 %, when lesion occupied one third of the vertebral body. ConclusionCorrelation of the FE results with the deformation shapes, observed in the MRIs for the clinical case study, indicated appropriateness of the procedure, proposed for simulation of the progressive osteolytic damage in the vertebral segments. The future studies may follow simulation of tumor growth for various metastatic tissues using the method, established here.

Impact of Orthodontic Treatment on the Incidence of Dental Caries in Adolescents: A Prospective Cohort Study.

Orthodontic treatment is a widely embraced intervention aimed at enhancing dental aesthetics and correcting malocclusions among adolescents. However, concerns persist regarding its potential impact on oral health, particularly on the development of dental caries. This study aimed to systematically investigate the relationship between orthodontic treatment and the incidence of new carious lesions among adolescents. A prospective cohort design involving adolescents aged 12-18 years was employed. A total of 82 patients met the inclusion criteria. In addition, an age-matched control group of 82 participants who did not undergo orthodontic treatment was included. The study included both a treatment group undergoing orthodontic treatment (braces or aligners) and an age-matched control group that did not undergo any orthodontic intervention. Demographic characteristics, orthodontic treatment details, and oral hygiene practices were documented at baseline and throughout the study period. Dental examinations at six-month intervals post-treatment were conducted to track the incidence and progression of carious lesions. The demographic characteristics, baseline oral health status, orthodontic treatment details, and oral hygiene practices were comparable between the treatment and control groups. Post-orthodontic treatment assessment revealed a slightly higher incidence of new carious lesions in the treatment group (14.6%) than in the control group (9.8%), although this difference was not statistically significant (p = 0.15). Dental examinations at six-month intervals demonstrated a gradual increase in caries incidence over time in both groups, with no substantial disparities observed. This study provides a comprehensive examination of the relationship between orthodontic treatment and the incidence of new carious lesions among adolescents. While a trend towards higher caries incidence in the treatment group was observed, the difference was not statistically significant. These findings contribute to the existing body of knowledge and emphasize the need for ongoing research to guide clinical practice.

Distal Fibular Metastasis of Colorectal Carcinoma: A Case Report.

A 62-year-old woman presenting with ankle pain was initially treated for a non-displaced fracture. Persistent pain despite months of conservative management for her presumed injury prompted repeat radiographs which demonstrated the progression of a lytic lesion and led to an orthopedic oncology referral. Following a complete work-up, including biopsy and staging, she was diagnosed with colorectal carcinoma metastatic to the distal fibula. Secondary tumors of the fibula are uncommon but an important diagnosis to consider for intractable lower extremity pain especially in patients with history of malignancy or lack of age-appropriate cancer screening.

Time-frequency analysis reveals an association between the specific nuclear magnetic resonance (NMR) signal properties of serum samples and arteriosclerotic lesion progression in a diabetes mouse model.

Diabetes causes arteriosclerosis, primarily due to persistent hyperglycemia, subsequently leading to various cardiovascular events. No method has been established for directly detecting and evaluating arteriosclerotic lesions from blood samples of diabetic patients, as the mechanism of arteriosclerotic lesion formation, which involves complex molecular biological processes, has not been elucidated. "NMR modal analysis" is a technology that enables visualization of specific nuclear magnetic resonance (NMR) signal properties of blood samples. We hypothesized that this technique could be used to identify changes in blood status associated with the progression of arteriosclerotic lesions in the context of diabetes. The study aimed to assess the possibility of early detection and evaluation of arteriosclerotic lesions by NMR modal analysis of serum samples from diabetes model mice. Diabetes model mice (BKS.Cg db/db) were bred in a clean room and fed a normal diet. Blood samples were collected and centrifuged. Carotid arteries were collected for histological examination by hematoxylin and eosin staining on weeks 10, 14, 18, 22, and 26. The serum was separated and subjected to NMR modal analysis and biochemical examination. Mice typically show hyperglycemia at an early stage (8 weeks old), and pathological findings of a previous study showed that more than half of mice had atheromatous plaques at 18 weeks old, and severe arteriosclerotic lesions were observed in almost all mice after 22 weeks. Partial least squares regression analysis was performed, which showed that the mice were clearly classified into two groups with positive and negative score values within 18 weeks of age. The findings of this study revealed that NMR modal properties of serum are associated with arteriosclerotic lesions. Thus, it may be worth exploring the possibility that the risk of cardiovascular events in diabetic patients could be assessed using serum samples.

Helicobacter pylori components increase the severity of metabolic syndrome and its hepatic manifestations induced by a high fat diet

The metabolic syndrome, often accompanied by hepatic manifestations, is a high-risk factor for developing cardiovascular disease. Patients with metabolic dysfunction associated with steatohepatic disease (MASDL) are at significant risk of developing coronary artery disease. Atherosclerosis is a systemic inflammatory disorder in which several factors, including dietary or infectious factors, can cause an inflammatory response. Helicobacter pylori (HP) bacteria have been implicated in the progression of proatherogenic vascular endothelial lesions, moreover, our previous study in an experimental in vivo model of Cavia porcellus showed that HP components and high-fat substances acted synergistically in promoting vascular endothelial inflammation, leading to an early onset of a proatherogenic environment. In the present study, our goal was to determine the contribution of HP components to the development of hepatic manifestations of metabolic syndrome in an experimental model. Our results showed that HP infection in animals exposed to a high-fat diet increased oxidative stress and lipid peroxidation, followed by endothelial lipid deposition, impaired endothelial apoptosis, cell lysis, and increased vascular stiffness. Finally, histopathological analysis of liver tissue showed signs of MASLD development in HP-infected animals fed a high-fat diet.

A rare presentation of Nocardia Choroidal Abscess after Glioblastoma surgery.

to report the natural history of a rare ocular manifestation of endogenous Nocardia farcinica infection in an immunocompromised patient, with involvement observed in both the anterior and posterior segments of the eye. Given the patient's limited mobility, a handheld fundus camera was utilized for bedside anterior segment and ocular fundus examinations. The findings included visual acuity of hand motion, posterior synechiae, vitreal opacity, and a large choroidal abscess. We monitored the lesion's progression through a series of follow-ups. Despite not employing intravitreal drug therapy, we noted a significant reduction in the lesion's size until the patient's overall health deteriorated. This case contributes valuable information to our understanding of the natural history of a rare condition like Nocardia endophthalmitis. We highlighted the usefulness of a handheld fundus camera in aiding infectious disease specialists in assessing the immediate response to systemic treatment.

New-onset diabetes is a predictive risk factor for pancreatic lesions in high-risk individuals: An observational cohort study.

Pancreatic cancer (PC) is the third cause of cancer-related deaths. Early detection and interception of premalignant pancreatic lesions represent a promising strategy to improve outcomes. We evaluated risk factors of focal pancreatic lesions (FPLs) in asymptomatic individuals at hereditary high risk for PC. This is an observational single-institution cohort study conducted over a period of 5 years. Surveillance was performed through imaging studies (EUS or magnetic resonance imaging/magnetic resonance cholangiopancreatography) and serum biomarkers. We collected demographic characteristics and used univariate and multivariate logistic regression models to evaluate associations between potential risk factors and odd ratios (ORs) for FPL development. A total of 205 patients completed baseline screening. Patients were followed up to 53 months. We detected FPL in 37 patients (18%) at baseline; 2 patients had lesions progression during follow-up period, 1 of them to PC. Furthermore, 13 patients developed new FPLs during the follow-up period. Univariate and multivariate analyses revealed that new-onset diabetes (NOD) is strongly associated with the presence of FPL (OR, 10.94 [95% confidence interval, 3.01-51.79; P < 0.001]; OR, 9.98 [95% confidence interval, 2.15-46.33; P = 0.003]). Follow-up data analysis revealed that NOD is also predictive of lesions progression or development of new lesions during screening (26.7% vs. 2.6%; P = 0.005). In a PC high-risk cohort, NOD is significantly associated with presence of FPL at baseline and predictive of lesions progression or new lesions during surveillance.

LONGITUDINAL CHANGES OF POSTERIOR VORTEX VEINS IN HIGHLY MYOPIC EYES DETERMINED BY RETROSPECTIVE ANALYSES OF INDOCYANINE GREEN ANGIOGRAMS.

To assess the longitudinal changes of the posterior vortex veins (VVs) in highly myopic (HM) eyes. The medical records of 1,730 consecutive HM eyes that had undergone indocyanine green angiography were studied. Eyes that had posterior VVs and had undergone at least two indocyanine green angiography examinations with a minimum interval of 3 years were selected from this group. Ninety-one eyes of 78 patients met the inclusion criteria. A total of 124 posterior VVs were identified. Over an average interval of 7.8 ± 5.0 years, 41 (33.1%) of the 124 posterior VVs had marked changes consisting mainly of an attenuation of vessels in 36 posterior VVs (87.8%) and alterations in the drainage course in 16 posterior VVs (39.0%). Fifteen posterior VVs had both types of changes. Most of the attenuations of the vessels occurred for smaller branches, but a complete loss of the entire trunk was seen in three eyes. Additionally, four eyes had posterior VV changes in association with changes of peripheral VVs. Posterior VV in highly myopic eyes can undergo changes with increasing time. The associated factors included the development and progression of myopic maculopathy lesions. In some cases, the blood drainage shifted from posterior VV to peripheral VV by forming anastomotic channels.

Radiation therapy of renal cell carcinoma skeletal metastases – Does histologic subtype predict progression?: Renal cell histology and radiotherapy response

IntroductionThis investigation assessed whether the following factors were associated with radiographic local progression in bone metastases from renal cell carcinoma (RCC): (1) high-risk histologic features (2) lesional surgery (3) biologically effective dose (BED) of radiation therapy. Methods and materialsA single-institution database identified all patients who underwent surgery and radiation therapy for bone metastases from RCC to the appendicular skeleton and pelvis from 2006 to 2016. Thirty-six patients underwent radiotherapy for 80 metastases. While all patients had surgical stabilization, 17/36 also had lesional surgery to address the metastatic lesion. Progression of each individual lesion was determined using the application of RECIST criteria to imaging at last follow-up. ResultsThe rate of progressive disease was 8/25 (32%) in the high-risk group versus 5/55 (9%) in the standard-risk group (p ​= ​0.019). The rate of progression among high-risk metastases undergoing lesional surgery was 0/9 versus 8/16 (50%) having non-lesional surgery (p ​= ​0.0218). The rate of progression among standard-risk metastases undergoing lesional surgery was 1/16 (6%) versus 4/39 (10%) with non-lesional surgery (p ​= ​1.00). High-risk histologic features (OR: 10.592, 95% confidence interval: 1.347–83.271, p ​= ​0.025) and as well as a reduction in risk with every additional Gray of BED (OR: 0.902, 95% confidence interval: 0.827–0.984, p ​= ​0.021) were found to predict progressive disease. ConclusionsBone metastases from renal cell carcinoma with high-risk histologic features are associated with less favorable response to radiotherapy than those with standard-risk histology. Delivery of a higher BED was associated with lower odds of progression.

Edema progression in proximity to traumatic microbleeds: Evolution of cytotoxic and vasogenic edema on serial MRI

IntroductionAlthough cerebral edema is common following traumatic brain injury (TBI), its formation and progression are poorly understood. This is especially true for the mild TBI population, who rarely undergo magnetic resonance imaging (MRI) studies, which can pick up subtle structural details not visualized on computed tomography, in the first few days after injury. This study aimed to visually classify and quantitatively measure edema progression in relation to traumatic microbleeds (TMBs) in a cohort of primarily mild TBI patients up to 30 days after injury. Researchers hypothesized that hypointense lesions on Apparent Diffusion Coefficient (ADC) detected acutely after injury would evolve into hyperintense Fluid Attenuated Inversion Recover (FLAIR) lesions. MethodsThis study analyzed the progression of cerebral edema after acute injury using multimodal MRI to classify TMBs as potential edema-related biomarkers. ADC and FLAIR MRI were utilized for edema classification at three different timepoints: ≤48 h, ∼1 week, and 30 days after injury. Hypointense lesions on ADC (ADC+) suggested the presence of cytotoxic edema while hyperintense lesions on FLAIR (FLAIR+) suggested vasogenic edema. Signal intensity Ratio (SIR) calculations were made using ADC and FLAIR to quantitatively confirm edema progression. ResultsOur results indicated the presence of ADC+ lesions ≤48 h and ∼1 week were associated with FLAIR + lesions at ∼1 week and 30 days, respectively, suggesting some progression of cytotoxic edema to vasogenic edema over time. Ten out of 15 FLAIR + lesions at 30 days (67%) were ADC+ ≤48 h. However, ADC + lesions ≤48 h were not associated with FLAIR + lesions at 30 days; 10 out of 25 (40%) ADC + lesions ≤48 h were FLAIR + at 30 days, which could indicate that some lesions resolved or were not visualized due to associated atrophy or tissue necrosis. Quantitative analysis confirmed the visual progression of some TMB lesions from ADC + to FLAIR+. FLAIR SIRs at ∼1 week were significantly higher when lesions were ADC+ ≤48 h (1.22 [1.08–1.32] vs 1.03 [0.97–1.11], p = 0.002). ConclusionAwareness of how cerebral edema can evolve in proximity to TMBs acutely after injury may facilitate identification and monitoring of patients with traumatic cerebrovascular injury and assist in development of novel therapeutic strategies.

Enhancement Pattern Mapping for Early Detection of Hepatocellular Carcinoma in Patients with Cirrhosis.

Limited methods exist to accurately characterize the risk of malignant progression of liver lesions. Enhancement pattern mapping (EPM) measures voxel-based root mean square deviation (RMSD) of parenchyma and the contrast-to-noise (CNR) ratio enhances in malignant lesions. This study investigates the utilization of EPM to differentiate between HCC versus cirrhotic parenchyma with and without benign lesions. Patients with cirrhosis undergoing MRI surveillance were studied prospectively. Cases (n=48) were defined as patients with LI-RADS 3 and 4 lesions who developed HCC during surveillance. Controls (n=99) were patients with and without LI-RADS 3 and 4 lesions who did not develop HCC. Manual and automated EPM signals of liver parenchyma between cases and controls were quantitatively validated on an independent patient set using cross validation with manual methods avoiding parenchyma with artifacts or blood vessels. With manual EPM, RMSD of 0.37 was identified as a cutoff for distinguishing lesions that progress to HCC from background parenchyma with and without lesions on pre-diagnostic scans (median time interval 6.8 months) with an area under the curve (AUC) of 0.83 (CI: 0.73-0.94) and a sensitivity, specificity, and accuracy of 0.65, 0.97, and 0.89, respectively. At the time of diagnostic scans, a sensitivity, specificity, and accuracy of 0.79, 0.93, and 0.88 were achieved with manual EPM with an AUC of 0.89 (CI: 0.82-0.96). EPM RMSD signals of background parenchyma that did not progress to HCC in cases and controls were similar (case EPM: 0.22 ± 0.08, control EPM: 0.22 ± 0.09, p=0.8). Automated EPM produced similar quantitative results and performance. With manual EPM, a cutoff of 0.37 identifies quantifiable differences between HCC cases and controls approximately six months prior to diagnosis of HCC with an accuracy of 89%.

Identification of key biomarkers for predicting CAD progression in inflammatory bowel disease via machine-learning and bioinformatics strategies.

The study aimed to identify the biomarkers for predicting coronary atherosclerotic lesions progression in patients with inflammatory bowel disease (IBD). Related transcriptome datasets were seized from Gene Expression Omnibus database. IBD-related modules were identified via Weighted Gene Co-expression Network Analysis. The 'Limma' was applied to screen differentially expressed genes between stable coronary artery disease (CAD) and acute myocardial infarction (AMI). Subsequently, we employed protein-protein interaction (PPI) network and three machine-learning strategies to further screen for candidate hub genes. Application of the receiver operating characteristics curve to quantitatively evaluate candidates to determine key diagnostic biomarkers, followed by a nomogram construction. Ultimately, we performed immune landscape analysis, single-gene GSEA and prediction of target-drugs. 3227 IBD-related module genes and 570 DEGs accounting for AMI were recognized. Intersection yielded 85 shared genes and mostly enriched in immune and inflammatory pathways. After filtering through PPI network and multi-machine learning algorithms, five candidate genes generated. Upon validation, CTSD, CEBPD, CYP27A1 were identified as key diagnostic biomarkers with a superior sensitivity and specificity (AUC > 0.8). Furthermore, all three genes were negatively correlated with CD4+ T cells and positively correlated with neutrophils. Single-gene GSEA highlighted the importance of pathogen invasion, metabolism, immune and inflammation responses during the pathogenesis of AMI. Ten target-drugs were predicted. The discovery of three peripheral blood biomarkers capable of predicting the risk of CAD proceeding into AMI in IBD patients. These identified biomarkers were negatively correlated with CD4+ T cells and positively correlated with neutrophils, indicating a latent therapeutic target.

The expression analysis of human endogenous retrovirus-K Env, Np9, and Rec transcripts in cervical cancer.

While infection with high-risk human papillomavirus (HPV) types is necessary for cervical cancer (CC) development, it is not enough, and other risk factors are required. Several studies have reported the activation of HERV-K in different cancers; however, the investigation of HERV-K expression levels in CC is scarce. In this study, it was hypothesized that activation of HERV-K could play an essential role in CC development. In this order, the expression levels of HERV-K Env, Np9, and Rec transcripts were investigated on 147 normal to CC uterine cervical tissues using quantitative real-time PCR. The significantly higher levels of HERV-K Env and Np9 transcripts were found in patients with cervical intraepithelial neoplasia (CIN) II-III and CC groups compared to those in the normal/CIN I group. Expression of Rec transcript was also higher only in the CC group than normal/CIN I group. Among CC patients, meaningfully higher levels of HERV-K Env and Np9 transcripts were found in patients with squamous cell carcinoma rather than in adenocarcinoma. When only the HPV 16 positive samples were investigated, it was found that the mean difference in Env and Np9 mRNA levels was meaningfully higher among precancer lesions and the cancer group in comparison with the normal group. However, the Rec mRNA level showed no significant differences. The association between the expression of HERV-K genes was investigated, and a significant positive correlation of Env expression with Np9 transcript was found only in the group with precancer lesions (R = 0.6, p = 0.0037). Moreover, a significant positive correlation was found between Rec and Np9 transcripts in patients with normal cervix tissues (R = 0.26, p = 0.033). However, no correlations were observed between the expression of Env and Rec in the three groups. In conclusion, our results showed that HERV-K transcripts, especially Env and Np9, upregulated during cervical lesion progression. These findings highlight the potential use of HERV-K Env and Np9 as biomarkers for CC diagnosis and prognosis. Further investigation is needed to determine the clinical utility of these markers and whether targeting HERV-K oncogenes could be a viable therapeutic strategy for CC.

Caries in Primary Molars: Is Silver Diamine Fluoride Effective in Prevention and Treatment? A Systematic Review

In recent years, pediatric dentistry has evolved considerably in terms of both the techniques and materials used. A clear, odorless liquid called silver diamine fluoride (SDF) is recommended for molars affected by hypoplasia and dentinal hypersensitivity. In adults and children who are at a high risk of developing caries, it is also helpful to prevent the progression of carious lesions. Teeth too compromised to be reconstructed that are not accompanied by discomfort or infection can be treated with SDF. The current review aims to provide an overview of the most recent research over the last 10 years on the potential of SDF, focusing on the clinical evidence of professionally applied fluoride therapy to prevent and arrest caries in children’s primary molars. Research was conducted according to the guidelines of the PRISMA statement. “silver diamine fluoride”, “primary molar”, and “primary molars” were the search terms utilized on the databases Scopus, Web of Science, and PubMed, with the Boolean operator “AND” and “OR”. Of these 195 studies, 13 primary studies were included in this review. The quality of the included papers was assessed using the reputable Cochrane risk of bias assessment for randomized trials. The studies reviewed consistently support the effectiveness of SDF in stopping the progression of existing caries in deciduous molars; on the contrary, there is insufficient evidence to draw conclusions about SDF being effective for the prevention of carious lesions in deciduous molars.