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Nevin Manimala Statistics

Diagnostic performance of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma

Int Immunopharmacol. 2023 Oct 20;125(Pt A):111041. doi: 10.1016/j.intimp.2023.111041. Online ahead of print.

ABSTRACT

MAGEA family proteins are immunogenic and can produce corresponding autoantibodies, and we aim to evaluate the diagnostic value of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma (ESCC). Protein chip was used to detect the expression level of anti-MAGEA autoantibodies (IgG and IgM) in 20 mixed serum samples. Enzyme linked immunosorbent assay was adopted to determine the expression level of autoantibodies in 1019 serum samples (423 ESCC, 423 healthy control (HC), 173 benign esophageal disease (BED)), and stepwise logistic regression analysis was used for developing a diagnostic model. Eight anti-MAGEA autoantibodies were screened out based on the protein chip. The levels of 7 autoantibodies (MAGEA1-IgG, MAGEA3-IgG, MAGEA3-IgM, MAGEA4-IgG, MAGEA6-IgG, MAGEA10-IgG, MAGEA12-IgG) in ESCC were significantly higher than that in HC, and the levels of anti-MAGEA1 IgG, anti-MAGEA3-IgG, anti-MAGEA4-IgG, anti-MAGEA10-IgG and anti-MAGEA12-IgG autoantibodies in ESCC group were significantly higher than those in BED group. The area under curve (AUC), sensitivity and specificity of the logistic regression model (MAGEA1-IgG, MAGEA4-IgG, MAGEA6-IgG, MAGEA12-IgG) in the training set and the validation set were 0.725 and 0.698, 55.2% and 51.8%, 80.4% and 84.5%, respectively, in distinguishing ESCC and HC. The model also could distinguish between ESCC and BED, with the AUC of 0.743, sensitivity of 55.4% and specificity of 89.0%. The positive rate of the model combined with cytokeratin 19 fragment to diagnose ESCC reached 78.0%. The study identified anti-MAGEA autoantibodies with potential diagnostic value for ESCC, which may provide new promising for the detection of the disease.

PMID:37866309 | DOI:10.1016/j.intimp.2023.111041

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Nevin Manimala Statistics

Short-term predictor for COVID-19 severity from a longitudinal multi-omics study for practical application in intensive care units

Talanta. 2023 Oct 9;268(Pt 1):125295. doi: 10.1016/j.talanta.2023.125295. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic challenged the management of technical and human resources in intensive care units (ICU) across the world. Several long-term predictors for COVID-19 disease progression have been discovered. However, predictors to support short-term planning of resources and medication that can be translated to future pandemics are still missing. A workflow was established to identify a predictor for short-term COVID-19 disease progression in the acute phase of intensive care patients to support clinical decision-making.

METHODS: Thirty-two patients with SARS-CoV-2 infection were recruited on admission to the ICU and clinical data collected. During their hospitalization, plasma samples were acquired from each patient on multiple occasions, excepting one patient for which only one time point was possible, and the proteome (Inflammation, Immune Response and Organ Damage panels from Olink® Target 96), metabolome and lipidome (flow injection analysis and liquid chromatography-mass spectrometry) analyzed for each sample. Patient visits were grouped according to changes in disease severity based on their respiratory and organ function, and evaluated using a combination of statistical analysis and machine learning. The resulting short-term predictor from this multi-omics approach was compared to the human assessment of disease progression. Furthermore, the potential markers were compared to the baseline levels of 50 healthy subjects with no known SARS-CoV-2 or other viral infections.

RESULTS: A total of 124 clinical parameters, 271 proteins and 782 unique metabolites and lipids were assessed. The dimensionality of the dataset was reduced, selecting 47 from the 1177 parameters available following down-selection, to build the machine learning model. Subsequently, two proteins (C-C motif chemokine 7 (CCL7) and carbonic anhydrase 14 (CA14)) and one lipid (hexosylceramide 18:2; O2/20:0) were linked to disease progression in the studied SARS-CoV-2 infections. Thus, a predictor delivering the prognosis of an upcoming worsening of the patient’s condition up to five days in advance with a reasonable accuracy (79 % three days prior to event, 84 % four to five days prior to event) was found. Interestingly, the predictor’s performance was complementary to the clinicians’ capabilities to foresee a worsening of a patient.

CONCLUSION: This study presents a workflow to identify omics-based biomarkers to support clinical decision-making and resource management in the ICU. This was successfully applied to develop a short-term predictor for aggravation of COVID-19 symptoms. The applied methods can be adapted for future small cohort studies.

PMID:37866305 | DOI:10.1016/j.talanta.2023.125295

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Nevin Manimala Statistics

Spatial and temporal patterns of sarcoptic mange in wombats using the citizen science tool, WomSAT

Integr Zool. 2023 Oct 22. doi: 10.1111/1749-4877.12776. Online ahead of print.

ABSTRACT

There is currently limited information regarding the levels of infection and distribution of sarcoptic mange in the wombat population throughout Australia. We analyzed cases of sarcoptic mange in bare-nosed wombats reported into WomSAT, a website and mobile phone application where citizen scientists can upload sightings of wombats, burrows, and sarcoptic mange status. We used Maxent software to predict locations and the environmental factors associated with sarcoptic mange occurrence in bare-nosed wombats. A total of 1379 sarcoptic mange-infected and 3043 non-sarcoptic mange-infected wombats were reported by 674 and 841 citizen scientists, respectively. Of all the wombats reported to WomSAT from 2015 to 2019, 31.2% were infected with sarcoptic mange. Sarcoptic mange in bare-nosed wombats was reported in 502 suburbs across four states. New South Wales had the highest number of sarcoptic mange cases reported to WomSAT. There was no statistically significant seasonal variation of sarcoptic mange levels in bare-nosed wombats. The model showed that Euclidean distance to urban areas was the highest contributing factor for sarcoptic mange occurrence. As distance to urban areas decreased, the suitability for sarcoptic mange increased. Annual precipitation was the next contributing factor in the model, with higher rainfall of 400-700 mm correlating to an increase in sarcoptic mange occurrence. As the data collected to date have provided the largest-scale contemporary distribution of sarcoptic mange in wombats, data should continue to be collected by citizen scientists as it is an easy and low-cost method of collecting data over large areas. We suggest targeting the identified hotspot areas and more site-specific studies for studying and mitigating sarcoptic mange in bare-nosed wombats.

PMID:37865949 | DOI:10.1111/1749-4877.12776

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Impact of Surveillance Imaging in Detecting Local and Metastatic Lung Recurrences Among Patients with Sarcomas of the Extremities: A Systematic Review and Meta-analysis

Ann Surg Oncol. 2023 Oct 22. doi: 10.1245/s10434-023-14429-9. Online ahead of print.

ABSTRACT

BACKGROUND: The surveillance guidelines following treatment completion for patients with high-grade sarcomas of the extremities are based largely upon expert opinions and consensus. In the current meta-analysis, we aim to study the utility of surveillance imaging to diagnose local and metastatic pulmonary relapses among patients with extremity soft tissue sarcomas and primary bone sarcomas.

PATIENTS AND METHODS: A meta-analysis was performed to assess the sensitivity, specificity and diagnostic odds ratio (DOR) of surveillance imaging to diagnose local and metastatic pulmonary relapse among patients with sarcoma of the extremities. In addition, impact of surveillance imaging on overall survival was assessed. Heterogeneity among eligible studies was evaluated by I2 statistics. Sensitivity analysis was assessed using influence plots and Baujat plots.

RESULTS: Ten studies including 2160 patients with sarcoma were found eligible. For diagnoses of local recurrence based on surveillance imaging (nine studies, 1917 patients), the estimated sensitivity, specificity, and DOR were 13.6%, 99.5%, and 78.15, respectively. Only 16.7% of local recurrences were diagnosed based on imaging. For diagnoses of metastatic pulmonary recurrence (eight studies; 1868 patients), estimated sensitivity, specificity, and DOR were 76.1%, 99.3%, and 1059.9, respectively. A sensitivity analysis showed significant heterogeneity among included studies. None of the included studies showed an overall-survival benefit with the use of surveillance imaging.

CONCLUSION: The current meta-analysis challenges the notion of routine use of imaging to detect local relapse, while favoring chest imaging, using either chest radiography or computed tomography scan, for surveillance. Further studies are required to study the ideal surveillance strategy including timing and imaging modality.

PMID:37865942 | DOI:10.1245/s10434-023-14429-9

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Prognostic Impact of Mesenteric Lymph Node Status on Digestive Resection Specimens During Cytoreductive Surgery for Ovarian Peritoneal Metastases

Ann Surg Oncol. 2023 Oct 22. doi: 10.1245/s10434-023-14405-3. Online ahead of print.

ABSTRACT

BACKGROUND: The most common mode of ovarian cancer (OC) spread is intraperitoneal dissemination, with the peritoneum as the primary site of metastasis. Cytoreductive surgery (CRS) with chemotherapy is the primary treatment. When necessary, a digestive resection can be performed, but the role of mesenteric lymph nodes (MLNs) in advanced OC remains unclear, and its significance in treatment and follow-up evaluation remains to be determined. This study aimed to evaluate the prevalence of MLN involvement in patients who underwent digestive resection for OC peritoneal metastases (PM) and to investigate its potential prognostic value.

METHODS: This retrospective, descriptive study included patients who underwent CRS with curative intent for OC with PM between 1 January 2007 and 31 December 2020. The study assessed MLN status and other clinicopathologic features to determine their prognostic value in relation to overall survival (OS) and progression-free survival (PFS).

RESULTS: The study enrolled 159 women with advanced OC, 77 (48.4%) of whom had a digestive resection. For 61.1% of the patients who underwent digestive resection, MLNs were examined and found to be positive in 56.8%. No statistically significant associations were found between MLN status and OS (p = 0.497) or PFS ((p = 0.659).

CONCLUSIONS: In anatomopathologic studies, MLNs are not systematically investigated but are frequently involved. In the current study, no statistically significant associations were found between MLN status and OS or PFS. Further prospective studies with a systematic and standardized approach should be performed to confirm these findings.

PMID:37865938 | DOI:10.1245/s10434-023-14405-3

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Integrative Bioinformatics Analysis of The Cell Division Cycle and Ribosomal Pathways in The Rat Varicocele: Implications for Drug Discovery

Cell J. 2023 Oct 9;25(10):727-737. doi: 10.22074/cellj.2023.2004771.1329.

ABSTRACT

OBJECTIVE: Varicocele is a common cause of male infertility, affecting a substantial proportion of infertile men. Recent studies have employed transcriptomic analysis to identify candidate genes that may be implicated in the pathogenesis of this condition. Accordingly, this study sought to leverage rat gene expression profiling, along with protein-protein interaction networks, to identify key regulatory genes, related pathways, and potentially effective drugs for the treatment of varicocele.

MATERIALS AND METHODS: In this in-silico study, differentially expressed genes (DEGs) from the testicular tissue of 3 rats were screened using the edgeR package in R software and the results were compared to 3 rats in the control group. Data was obtained from GSE139447. Setting a -1<LogFC>1 and P<0.05 as cutoff points for statistical significance, up and down-regulated genes were identified. Based on Cytoscape plugins, protein-protein interaction (PPI) networks were drawn, and hub genes were highlighted. ShinyGO was used for pathway enrichment. Finally, effective drugs were identified from the drug database.

RESULTS: Among the 1277 DEGs in this study, 677 genes were up-regulated while 600 genes were down-regulated in rats with varicocele compared to the control group. Using protein-protein interaction networks, we identified the top five up-regulated genes and the top five down-regulated genes. Enrichment analysis showed that the up-regulated genes were associated with the cell division cycle pathway, while the down-regulated genes were linked to the ribosome pathway. Notably, our findings suggested that dexamethasone may be a promising therapeutic option for individuals with varicocele.

CONCLUSION: The current investigation indicates that in varicocele the cell division cycle pathway is up-regulated while the ribosome pathway is down-regulated compared to controls. Based on these findings, dexamethasone could be considered a future candidate drug for the treatment of individuals with varicocele.

PMID:37865881 | DOI:10.22074/cellj.2023.2004771.1329

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Nevin Manimala Statistics

Role of The circ-HIPK3, circ-PVT1, miR-25, and miR-149 in Response of Breast Cancer Cells to Ionizing Radiation

Cell J. 2023 Oct 1;25(10):688-695. doi: 10.22074/cellj.2023.1995943.1255.

ABSTRACT

OBJECTIVE: Determining cellular radiosensitivity of breast cancer (BC) patients through molecular markers before radiation therapy (RT) allows accurate prediction of individual’s response to radiation. The aim of this study was therefore to investigate the potential role of epigenetic biomarkers in breast cancer cellular radiosensitivity.

MATERIALS AND METHODS: In this experimental study, we treated two BC cell lines, MDA-MB 231 and MCF-7, with doses of 2, 4, and 8Gy of irradiation for 24 and 48 hours. Expression levels of circ-HIPK3, circ-PVT1, miR-25, and miR- 149 were quantified using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Significance of the observations was statistically verified using one-way ANOVA with a significance level of P<0.05. Annexin V-FITC/PI binding assay was utilized to measure cellular apoptosis.

RESULTS: The rate of cell apoptosis was significantly higher in MCF-7 cells compared to MDA-MB-231 cells at doses of 4Gy and 8Gy (P=0.013 and P=0.004, respectively). RNA expression analysis showed that circ-HIPK3 was increased in the MDA-MB-231 cell line compared to the MCF-7 cell line after exposure to 8Gy for 48 hours. Expression of circ-PVT1 was found to be higher in MDA-MB-231 cells compared to MCF-7 cells after exposure to 8Gy for 24 hours, likewise after exposure to 4Gy and 8Gy for 48 hours. After exposing 8Gy, expression of miR-25 was increased in MDA-MB-231 cells compared to MCF-7 cells at 24 and 48 hours. After exposing 8Gy dose, expression of miR-149 was increased in MCF-7 cells compared to MDA-MB-231 cells at 24 and 48 hours.

CONCLUSION: circ-HIPK3, circ-PVT1, and miR-25 played crucial roles in the mechanisms of radioresistance in breast cancer. Additionally, miR-149 was involved in regulating cellular radiosensitivity. Therefore, these factors provided predictive information about a tumor’s radiosensitivity or its response to treatment, which could be valuable in personalizing radiation dosage.

PMID:37865877 | DOI:10.22074/cellj.2023.1995943.1255

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LAENALS: epidemiological and clinical features of amyotrophic lateral sclerosis in Latin America

Amyotroph Lateral Scler Frontotemporal Degener. 2023 Oct 22:1-9. doi: 10.1080/21678421.2023.2271517. Online ahead of print.

ABSTRACT

OBJECTIVE: The Latin American Epidemiologic study of ALS (LAENALS) aims to gather data on ALS epidemiology, phenotype, and risk factors in Cuba, Chile, and Uruguay, to understand the impact of genetic and environmental factors on ALS.

METHODS: A harmonized data collection protocol was generated, and a Latin-American Spanish language Register was constructed. Patient data were collected in Uruguay in 2018, in Chile from 2017 to 2019, and in Cuba between 2017 and 2018. Statistical analysis was performed using SPSS 25.0.0 software. Crude cumulative incidence, standardized incidence, and prevalence were calculated in the population aged 15 years and older.

RESULTS: During 2017-2019, 90 people with ALS from Uruguay (55.6% men), 219 from Chile (54.6% men), and 49 from Cuba (55.1% men) were included. The cumulative crude incidence in 2018 was 1.73/100,000 persons in Uruguay, 1.08 in Chile and 0.195 in Cuba. Crude prevalence in 2018 was 2.19 per 100,000 persons in Uruguay, 1.39 in Chile and 0.55 in Cuba. Mean age at onset was 61.8 ± 11.96 SD years in Uruguay, 61.9 ± 10.4 SD years in Chile, and 60.21 ± 12.45 SD years in Cuba (p = 0.75). Median survival from onset was 32.43 months (21.93 – 42.36) in Uruguay, 24 months (13.5 – 33.5) in Chile, and 29 months (15 – 42.5) in Cuba (p = 0.006).

CONCLUSIONS: These preliminary data from LAENALS confirm the lower incidence and prevalence of ALS in counties with admixed populations. The LAENALS database is now open to other Latin American countries for harmonized prospective data collection.

PMID:37865869 | DOI:10.1080/21678421.2023.2271517

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Comparison of accuracy and reliability of CBCT and 3D laser scanner in the volumetric assessment of the root canal space

Am J Dent. 2023 Oct;36(5):246-250.

ABSTRACT

PURPOSE: To compare the accuracy and reliability of cone-beam computed tomography (CBCT) and laser scanner in measuring minor volume changes such as the root canal space.

METHODS: 35 maxillary incisors were endodontically prepared. A dimensionally stable silicone material was injected into the root canal space and scanned with CBCT. The root canal volume was measured using Romexis 3.0.1 R software. Replicas were carefully removed from the teeth and scanned using an extraoral laser scanner. These images were exported to the Rhinoceros software for volume measurement. The volume of each replica was also assessed using the gravimetric method. To determine the accuracy, the volume obtained from both devices was compared with the gravimetric method. Statistical analysis was done using a paired t-test. The reliability was assessed using the intraclass correlation coefficient.

RESULTS: There was no statistically significant difference between the mean volume of CBCT 27.04 ± 7.25 mm³ and the mean volume of the gravimetric method 27.87 ± 7.17 mm³ (P< 0.05). A statistically significant difference was seen with the laser scanner at 25.31 ± 6.89 mm³ and the gravimetric method at 27.87 ± 7.17 mm³ (P< 0.05). CBCT showed a good degree of agreement (ICC 0.899), while the laser scanner showed a moderate degree of agreement (ICC 0.644) with the gravimetric method. CBCT proved accurate and reliable in measuring minor volumes like the root canal space, ideally in the range of 20-25 mm³. The laser scanner presented acceptable reliability.

CLINICAL SIGNIFICANCE: The laboratory data showed satisfactory outcomes, providing an evidence-based approach and potentially motivating clinicians to integrate cone-beam computed tomography for volume analysis into clinical practice. The accuracy and reliability of laser scanners for small-volume analysis have not previously been evaluated. Consequently, the findings from this study warrant further clinical investigations.

PMID:37865812

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Shear bond strength of permanent 3D-printed resin and milled zirconia to primary teeth using different luting agents

Am J Dent. 2023 Oct;36(5):239-245.

ABSTRACT

PURPOSE: To evaluate the shear bond strengths (SBS) of permanent 3D-printed resin (PR) to primary dentin using different luting agents.

METHODS: 90 primary teeth were prepared. 45 cylinders (3 x 3 mm) were printed using PR, and 45 cylinders were milled using a Z block (to control). The cylinders were bonded to primary dentin by using three types of luting agent [glass-ionomer cement (GIC), resin-modified glass-ionomer cement (RMGIC), and self-adhesive resin cement (SRC)]. The SBS values of the specimens were calculated, and the fracture modes were examined.

RESULTS: There was a statistically significant difference between the three different luting agents that were used to lute the PR to primary dentin (P< 0.001). Changing the material (PR or Z) did not affect the SBS values of the luting agents (P> 0.05). The adhesive failure between cement and dentin in the PR-SRC group was significantly higher than the other groups (P< 0.001). The SBS values of the newly developed PR to primary dentin with RMGIC and SRC were similar, but GIC showed lower values than the others.

CLINICAL SIGNIFICANCE: This laboratory study suggests that bond strength of the permanent 3D-printed resin can be like that of zirconia. As the resin-modified glass-ionomer cement and self-adhesive resin cement showed higher bond strength to primary teeth making the 3D-printed resin a treatment option.

PMID:37865811