Nevin Manimala

Biogerontology. 2023 Aug 22. doi: 10.1007/s10522-023-10048-9. Online ahead of print.

ABSTRACT

Bone marrow mesenchymal stem cells (BM-MSCs) have a momentous function in the composition of the bone marrow microenvironment because of their many valuable properties and abilities, such as immunomodulation and hematopoiesis. The features and actions of MSCs are influenced by senescence, which may be affected by various factors such as nutritional/micronutrients status, e.g., vitamin D. This study aimed to examine the effects of a high-calorie diet (HCD) with/without vitamin D on BM-MSCs senescence. In the first phase, 48 middle-aged rats were fed a normal chow diet (NCD, n = 24) and an HCD (n = 24) for 26 weeks. Afterward, the rats in each group were randomly divided into three equal subgroups. Immediately, eight-rat from each diet group were sacrificed to assess the HCD effects on the first phase measurements. In the second phase, the remaining 4 groups of rats were fed either NCD or HCD with (6 IU/g) or without vitamin D (standard intake: 1 IU/g); in other words, in this phase, the animals were fed (a) NCD, (b) NCD plus vitamin D, (c) HCD, and (d) HCD plus vitamin D for 4 months. BM-MSCs were isolated and evaluated for P16^INK4a, P38 MAPK, and Bmi-1 gene expression, reactive oxygen species (ROS) levels, SA-β-gal activity, and cell cycle profile at the end of both phases. After 26 weeks (first phase), the ROS level, SA-β-gal-positive cells, and cells in the G1 phase were significantly higher in HCD-fed rats than in NCD-fed ones (P < 0.05). HCD prescription did not significantly affect cells in the S and G2 phases (p > 0.05). Compared with the NCD-fed animals, P16^INK4a and P38 MAPK gene expression were up-regulated in the HCD-fed animals; also, Bmi-1 gene expression was down-regulated (P < 0.05). BM-MSCs from vitamin D-treated rats (second phase) exhibited reduced mRNA levels of P16^INK4a and P38 MAPK genes and increased Bmi-1 mRNA levels (all P < 0.05). Vitamin D prescription also declined the percentage of SA-β-gal-positive cells, ROS levels, and the cells in the G1 phase and increased the cells in the S phase in both NCD and HCD-fed animals (P < 0.05). The reduction of the cells in the G2 phase in rats fed with an NCD plus vitamin D was statistically non-significant (P = 0.128) and significant in HCD plus vitamin D rats (P = 0.002). HCD accelerates BM-MSCs senescence, and vitamin D reduces BM-MSCs senescence biomarkers.

PMID:37606875 | DOI:10.1007/s10522-023-10048-9

Braz J Microbiol. 2023 Aug 22. doi: 10.1007/s42770-023-01106-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Candida tropicalis is a common non-albicans Candida (NAC) species that causes numerous fungal infections. Increasing antifungal resistance to azoles in NAC is becoming a major health problem worldwide; however, in Egypt, almost no data is available regarding fluconazole resistance mechanisms in C. tropicalis. The current study aims to investigate two possible important molecular mechanisms involved in fluconazole resistance in C. tropicalis isolates.

MATERIALS: Fifty-four clinical C. tropicalis isolates were included. Identification and antifungal susceptibility profiles of the isolates were carried out using the VITEK 2 compact system. The molecular investigation of fluconazole resistance included the expression of the CDR1 and MDR1 genes by quantitative real-time RT-PCR as well as the sequence analysis of the ERG11 gene.

RESULTS: Antifungal susceptibility testing identified 30 fluconazole-non-susceptible isolates. Statistically, CDR1 gene expression in fluconazole-non-susceptible isolates was significantly higher than that in fluconazole-susceptible isolates, with MDR1 gene expression levels that were similar in both non-susceptible and susceptible isolates. Sequence analysis of the ERG11 gene of 26 fluconazole-resistant isolates identified two missense mutations: A395T (Y132F) and G1390A (G464S).

CONCLUSIONS: This study has highlighted the role of overexpression of the CDR1 gene and ERG11 gene mutations in fluconazole non-susceptibility. Further studies in Egypt are required to investigate other possible molecular mechanisms involved in azole resistance.

PMID:37606863 | DOI:10.1007/s42770-023-01106-y

Childs Nerv Syst. 2023 Aug 22. doi: 10.1007/s00381-023-06115-8. Online ahead of print.

ABSTRACT

PURPOSE: The aim of the study was to compare the results of two surgical techniques for the treatment of isolated sagittal synostosis (ISS) by means of 3D stereophotogrammetry. One technique, the Renier’s “H” technique (RHT) comprised a biparietal expansion, the other, the total vault remodeling (TVR) included also a frontal remodeling.

METHODS: The two groups of operated children were compared with a third control group of normocephalic children. The 3D scanning was performed in all children between 12 and 245 months of age. On each 3D image six measurements and indices have been made, with the aim of evaluating not only length and width of the head, but also the height. The cranial index (CI) was measured in a plane parallel to the nasion-tragus plane, at the intersection with the opisthocranion.

RESULTS: Each of the three groups (RHT, TVR, control group) included 28 children. The measurements that were influenced by the correction of the frontal bossing, namely the CI and the sagittal length, were closer to normocephaly after TVR than after RHT. Lesser or no statistical difference was documented in the measurements evaluating the biparietal aspect and the height of the vertex, indicating that the biparietal expansion is effective in both procedures.

CONCLUSION: Based on our results TVR results in a better esthetical outcome, particularly in relation to the direct surgical remodeling of the frontal bossing.

PMID:37606834 | DOI:10.1007/s00381-023-06115-8

Childs Nerv Syst. 2023 Aug 22. doi: 10.1007/s00381-023-06134-5. Online ahead of print.

ABSTRACT

BACKGROUND: The epidemiology of central nervous system (CNS) tumors in pediatric patients worldwide continues to be defined. To date, there has been no evaluation of how national food availability may associate with the incidence and mortality of these tumors. Correspondingly, the aim of this study was to define if such associations exist.

METHODS: The most updated incidence and mortality rates of CNS tumors in pediatric patients were abstracted by country from the Global Burden of Disease database. Data regarding food availability parameters were identified and abstracted from the Food Systems Dashboard database. Associations were tested using univariate and multivariate regression analyses.

RESULTS: There were sufficient data in a total of 175 countries worldwide describing the required outcomes. Median incidence and mortality rates across these countries were 1.63 per 100,000 and 0.80 per 100,000, respectively. Higher incidence rates of pediatric CNS tumors were statistically associated with lower availability of fruit and vegetables (P = 0.02), higher average protein supply (P < 0.01), lower share of dietary energy from cereal and roots (P < 0.01), lower supply of meat (P < 0.01), lower supply of nuts and seeds (P < 0.01), lower supply of vegetable oils (P < 0.01), and higher supply of vegetables (P < 0.01). Higher mortality rates due to pediatric CNS tumors were statistically associated with lower availability of fruit and vegetables (P = 0.048), lower supply of fish (P = 0.046), and lower supply of nuts and seeds (P = 0.04). When categorizing countries based on income status, there was a decrease in significant associations found more pronounced in low-middle income countries.

CONCLUSIONS: There are many novel associations between national food availability and the incidence and mortality rates of pediatric CNS tumors across the world, which may be more pronounced and divergent in low-middle income countries. A greater understanding is needed to identify what specific components of the significant parameters influence these trends and how public health efforts may best address these associations to improve overall outcomes.

PMID:37606833 | DOI:10.1007/s00381-023-06134-5

Cell Oncol (Dordr). 2023 Aug 22. doi: 10.1007/s13402-023-00851-4. Online ahead of print.

ABSTRACT

PURPOSE: Collagen features in breast tumor microenvironment is closely associated with the prognosis of patients. We aim to explore the prognostic significance of collagen features at breast tumor border by combining multiphoton imaging and imaging analysis.

METHODS: We used multiphoton microscopy (MPM) to label-freely image human breast tumor samples and then constructed an automatic classification model based on deep learning to identify collagen signatures from multiphoton images. We recognized three kinds of collagen signatures at tumor boundary (CSTB I-III) in a small-scale, and furthermore obtained a CSTB score for each patient based on the combined CSTB I-III by using the ridge regression analysis. The prognostic performance of CSTB score is assessed by the area under the receiver operating characteristic curve (AUC), Cox proportional hazard regression analysis, as well as Kaplan-Meier survival analysis.

RESULTS: As an independent prognostic factor, statistical results reveal that the prognostic performance of CSTB score is better than that of the clinical model combining three independent prognostic indicators, molecular subtype, tumor size, and lymph nodal metastasis (AUC, Training dataset: 0.773 vs. 0.749; External validation: 0.753 vs. 0.724; HR, Training dataset: 4.18 vs. 3.92; External validation: 4.98 vs. 4.16), and as an auxiliary indicator, it can greatly improve the accuracy of prognostic prediction. And furthermore, a nomogram combining the CSTB score with the clinical model is established for prognosis prediction and clinical decision making.

CONCLUSION: This standardized and automated imaging prognosticator may convince pathologists to adopt it as a prognostic factor, thereby customizing more effective treatment plans for patients.

PMID:37606817 | DOI:10.1007/s13402-023-00851-4

Intern Emerg Med. 2023 Aug 22. doi: 10.1007/s11739-023-03392-8. Online ahead of print.

ABSTRACT

The current evidence suggests that higher levels of crowding in the Emergency Department (ED) have a negative impact on patient outcomes, including mortality. However, only limited data are available about the association between crowding and mortality, especially for patients discharged from the ED. The primary objective of this study was to establish the association between ED crowding and overall 10-day mortality for non-critical patients. The secondary objective was to perform a subgroup analysis of mortality risk separately for both admitted and discharged patients. An observational single-centre retrospective study was conducted in the Tampere University Hospital ED from January 2018 to February 2020. The ED Occupancy Ratio (EDOR) was used to describe the level of crowding and it was calculated both at patient’s arrival and at the maximum point during the stay in the ED. Age, gender, Emergency Medical Service transport, triage acuity, and shift were considered as confounding factors in the analyses. A total of 103,196 ED visits were included. The overall 10-day mortality rate was 1.0% (n = 1022). After controlling for confounding factors, the highest quartile of crowding was identified as an independent risk factor for 10-day mortality. The results were essentially similar whether using the EDOR at arrival (OR 1.31, 95% CI 1.07-1.61, p = 0.009) or the maximum EDOR (OR 1.27, 95% CI 1.04-1.56, p = 0.020). A more precise, mortality-associated threshold of crowding was identified at EDOR 0.9. The subgroup analysis did not yield any statistically significant findings. The risk for 10-day mortality increased among non-critical ED patients treated during the highest EDOR quartile.

PMID:37606803 | DOI:10.1007/s11739-023-03392-8

Ir J Med Sci. 2023 Aug 22. doi: 10.1007/s11845-023-03465-9. Online ahead of print.

ABSTRACT

Lung cancer is a major cause of death in Western countries, but survival had never been studied in Northern Ireland (NI) on a population basis prior to this study.

AIMS: The primary aims were to describe the survival of patients with primary lung cancer, evaluate the effect of treatment, identify patient characteristics influencing survival and treatment and describe current trends in survival.

METHODS: A population-based study identified all incident cases of primary lung cancer in NI during 1991-2 and followed them for 21 months. Their clinical notes were traced and relevant details abstracted. Survival status was monitored via the Registrar General’s Office, and ascertainment is thought to be near-complete. Appropriate statistical methods were used to analyse the survival data.

RESULTS: Some 855 incident cases were studied. Their 1-year survival was 24.5% with a median survival time of 4.7 months. Surgical patients had the best 1-year survival, 76.8%; however, adjustment suggested that about half of the benefit could be attributed to case-mix factors. Factors influencing treatment allocation were also identified, and a screening test showed the discordance between ‘model’ and ‘medic’: 210 patients were misclassified. Finally, the current trend in 1-year survival observed in the Republic of Ireland was best in the British Isles.

CONCLUSIONS: Overall, survival remains poor. The better survival of surgical patients is due, in part, to their superior case-mix profiles. Survival with other therapies is less good suggesting that the criteria for treatment might be relaxed with advantage using a treatment model to aid decision-making.

PMID:37606799 | DOI:10.1007/s11845-023-03465-9

J Cancer Res Clin Oncol. 2023 Aug 22. doi: 10.1007/s00432-023-05291-z. Online ahead of print.

ABSTRACT

PURPOSE: The prognosis of early-stage hepatocellular carcinoma (HCC) patients after radical resection has received widespread attention, but reliable prediction methods are lacking. Radiomics derived from enhanced computed tomography (CT) imaging offers a potential avenue for practical prognostication in HCC patients.

METHODS: We recruited early-stage HCC patients undergoing radical resection. Statistical analyses were performed to identify clinicopathological and radiomic features linked to recurrence. Clinical, radiomic, and combined models (incorporating clinicopathological and radiomic features) were built using four algorithms. The performance of these models was scrutinized via fivefold cross-validation, with evaluation metrics including the area under the curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE) being calculated and compared. Ultimately, an integrated nomogram was devised by combining independent clinicopathological predictors with the Radscore.

RESULTS: From January 2016 through December 2020, HCC recurrence was observed in 167 cases (64.5%), with a median time to recurrence of 26.7 months following initial resection. Combined models outperformed those solely relying on clinicopathological or radiomic features. Notably, among the combined models, those employing support vector machine (SVM) algorithms exhibited the most promising predictive outcomes (AUC: 0.840 (95% Confidence interval (CI): [0.696, 0.984]), ACC: 0.805, SEN: 0.849, SPE: 0.733). Hepatitis B infection, tumour size > 5 cm, and alpha-fetoprotein (AFP) > 400 ng/mL were identified as independent recurrence predictors and were subsequently amalgamated with the Radscore to create a visually intuitive nomogram, delivering robust and reliable predictive performance.

CONCLUSION: Machine learning models amalgamating clinicopathological and radiomic features provide a valuable tool for clinicians to predict postoperative HCC recurrence, thereby informing early preventative strategies.

PMID:37606762 | DOI:10.1007/s00432-023-05291-z

J Cancer Educ. 2023 Aug 22. doi: 10.1007/s13187-023-02355-z. Online ahead of print.

ABSTRACT

Pancreatic cancer is one of the most lethal diseases worldwide and incidence continues to rise, resulting in increased deaths each year. In the modern era, patients often turn to online sources like YouTube for information regarding their disease, which may be subject to a high degree of bias and misinformation; previous analyses have demonstrated low quality of other cancer-related YouTube videos. Thus, we sought to determine if patients can rely on educational YouTube videos for accurate and comprehensive information about pancreatic cancer diagnosis and treatment. We designed a search query and inclusion/exclusion criteria based on published studies evaluating YouTube user tendencies, which were used to identify videos most likely watched by patients. Videos were evaluated based on two well-known criteria, the DISCERN and JAMA tools, as well as a tool published by Sahin et al. to evaluate the comprehensiveness of YouTube videos. Statistical analyses were performed using Chi-square analysis to compare categorical variables. We used linear regression to assess for correlations between quantitative variables. Kruskal-Wallis and independent samples t-test were used to compare means between groups. We assessed inter-rater reliability using Cronbach’s alpha. After the initial search query, 39 videos were retrieved that met inclusion criteria. The comprehensiveness and quality of these materials was generally low to moderate, with only 7 videos being considered comprehensive. Pearson’s R demonstrated strong correlations between video length and both comprehensiveness and quality. Higher-quality videos also tended to be newer. YouTube videos regarding pancreatic cancer are generally of low to moderate quality and lack comprehensiveness, which could affect patients’ perceptions of their disease or understanding of treatment options. These videos, which have collectively been viewed over 6 million times, should be subject to some form of expert review before upload, and producers of this content should consider citing the sources used in the video.

PMID:37606727 | DOI:10.1007/s13187-023-02355-z

Cancer Chemother Pharmacol. 2023 Aug 22. doi: 10.1007/s00280-023-04573-0. Online ahead of print.

ABSTRACT

PURPOSE: Krebs von den Lungen-6 (KL-6) functions as a tumor marker, as well as a diagnostic tool for interstitial pneumonia (IP). However, the significance of KL-6 in the immune-checkpoint inhibitor (ICI) treatment of non-small cell lung cancer (NSCLC), especially in patients without IP, is unknown.

METHODS: This multicenter, retrospective study, which included patients with advanced NSCLC who received ICI therapy, analyzed the association between serum KL-6 values and ICI efficacy and the association between serum KL-6 values and ICI-induced interstitial lung disease (ILD) occurrence, focusing primarily on patients without IP.

RESULTS: In total, 322 patients had available KL-6 values before ICI therapy. Among 202 patients without IP who received ICI monotherapy, the high-KL-6 group (≥ 500 U/mL) showed significantly shorter progression-free survival (PFS) and overall survival (OS) than the low-KL-6 group (< 500 U/mL) (median: 2.1 vs. 3.6 months, p = 0.048; median: 9.2 vs. 14.5 months, p = 0.035). There was no significant difference in response rate between the KL-6 high and low groups (19% vs. 29%, p = 0.14). In the multivariate analysis, high KL-6 was a significant predictor of poor PFS (hazard ratio [HR], 1.52; 95% confidence interval [CI] 1.10-2.11, p = 0.012) and OS (HR, 1.51; 95% CI 1.07 – 2.13, p = 0.019) for patients treated with ICI monotherapy. There was no significant difference in the occurrence rate of ILD between the high KL-6 and low KL-6 groups in patients with (20% vs. 15%, p = 1.00) or without IP (12% vs. 12%, p = 1.00).

CONCLUSION: In ICI monotherapy for NSCLC without IP, elevated serum KL-6 levels were associated with poorer outcomes.

PMID:37606723 | DOI:10.1007/s00280-023-04573-0