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Nevin Manimala Statistics

The Role of Fascin-1 in Human Urologic Cancers: A Promising Biomarker or Therapeutic Target?

Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231175733. doi: 10.1177/15330338231175733.

ABSTRACT

Human cancer statistics show that an increased incidence of urologic cancers such as bladder cancer, prostate cancer, and renal cell carcinoma. Due to the lack of early markers and effective therapeutic targets, their prognosis is poor. Fascin-1 is an actin-binding protein, which functions in the formation of cell protrusions by cross-linking with actin filaments. Studies have found that fascin-1 expression is elevated in most human cancers and is related to outcomes such as neoplasm metastasis, reduced survival, and increased aggressiveness. Fascin-1 has been considered as a potential therapeutic target for urologic cancers, but there is no comprehensive review to evaluate these studies. This review aimed to provide an enhanced literature review, outline, and summarize the mechanism of fascin-1 in urologic cancers and discuss the therapeutic potential of fascin-1 and the possibility of its use as a potential marker. We also focused on the correlation between the overexpression of fascin-1 and clinicopathological parameters. Mechanistically, fascin-1 is regulated by several regulators and signaling pathways (such as long noncoding RNA, microRNA, c-Jun N-terminal kinase, and extracellular regulated protein kinases). The overexpression of fascin-1 is related to clinicopathologic parameters such as pathological stage, bone or lymph node metastasis, and reduced disease-free survival. Several fascin-1 inhibitors (G2, NP-G2-044) have been evaluated in vitro and in preclinical models. The study proved the promising potential of fascin-1 as a newly developing biomarker and a potential therapeutic target that needs further investigation. The data also highlight the inadequacy of fascin-1 to serve as a novel biomarker for prostate cancer.

PMID:37246525 | DOI:10.1177/15330338231175733

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Prospective assessment of platelet function in patients undergoing elective resection of glioblastoma multiforme

Platelets. 2023 Dec;34(1):2216802. doi: 10.1080/09537104.2023.2216802.

ABSTRACT

This prospective study was aimed to test changes in hemostasis in patients with GBM, occurring at baseline (before surgery, time 0, T0) and 2 (T2), 24 (T24), and 48-hour (T48) after surgery. We enrolled consecutive patients subjected to GBM resection (GBR group; N = 60), laparoscopic colon cancer resection (comparative CCR group; N = 40), and healthy blood donors (HBD group; N = 40). We performed 1. conventional coagulation tests 2. ROTEM (rotational thromboelastometry) parameters and 3. platelet function tests, including PFA-200 closure time when stimulated by collagen/epinephrine (COL-EPI) and ROTEM platelet, using three different activators (arachnoid acid in ARATEM, adenosine diphosphate in ADPTEM, and thrombin receptor-activating peptide-6 in TRAPTEM). Variables associated with unfavorable 1-year clinical outcome were investigated, too. We observed in GBR patients that platelet aggregometry, as assessed by ROTEM platelet parameters, was significantly impaired along with a shortened closure time. These changes were evident from T0 to T48. A decreased area under the aggregation curve in TRAPTEM was associated with improved survival (adjusted odd ratio (95% CI), 1.03 (1.01-1.06)). This study suggests that patients with GBM presented a decreased platelet aggregation from before surgery and thorough the postoperative period. Decreased platelet aggregation improved clinical outcome.

PMID:37246516 | DOI:10.1080/09537104.2023.2216802

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Epilepsy panel testing criteria: A clinical assessment

J Genet Couns. 2023 May 28. doi: 10.1002/jgc4.1732. Online ahead of print.

ABSTRACT

Epilepsy is a common, and often genetic, neurological disorder. Few guidelines exist to help medical providers or insurance companies decide when to order or cover epilepsy panels for patients with epilepsy. The most recent guidelines were published by NSGC after this study’s data collection. Since 2017, the Genetic Testing Stewardship Program (GTSP) at UPMC Children’s Hospital of Pittsburgh (CHP) has been utilizing a set of internally developed epilepsy panel (EP) testing criteria to facilitate appropriate EP ordering practices. The purpose of this study was to assess these testing criteria by determining their sensitivities and positive predictive values (PPV). Retrospective chart review of the electronic medical record (EMR) was performed for 1242 CHP Neurology patients that were evaluated for a primary diagnosis of epilepsy between 2016 and 2018. One hundred and nine patients had EPs at various testing laboratories. Of the patients that met criteria, 17 had diagnostic EPs and 54 had negative EPs. Criteria were organized into category groupings (C1-C4), and analyzed alone for C1, in pairs for C2, etc. The highest sensitivity and PPV results in each category grouping were: C1 (64.7%, 60%); C2, (88%, 30.3%); C3, (94.1%, 27.1%); C4, (94.1%, 25.4%). Family history was crucial to increasing sensitivity. Confidence intervals (CIs) narrowed as category grouping level increased, though this was not statistically significant due to the considerable CI overlap across category groupings. The PPV from C4 was applied to the untested population cohort and predicted 121 patients with unidentified positive EPs. This study presents data supporting the predictive capabilities of EP testing criteria and suggests the addition of a family history criterion. This study impacts public health by encouraging the adoption of evidence-driven insurance policies and by suggesting guidelines to ease EP ordering and coverage decisions, which could potentially improve patient access to EP testing.

PMID:37246482 | DOI:10.1002/jgc4.1732

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Investigation of the relationship between serum irisin level in the idiopathic restless legs syndrome: Could be a marker independent of physical activity?

Brain Behav. 2023 May 28:e3100. doi: 10.1002/brb3.3100. Online ahead of print.

ABSTRACT

INTRODUCTION: Restless legs syndrome (RLS) is a common but underdiagnosed neurological syndrome. It is characterized by the feeling of discomfort and desire to move, especially in the lower extremities, which often occurs at night, and the cure or relief of symptoms with movement. Irisin is a hormonelike polypeptide that was first identified in 2012, weighs 22 kDa, consists of 163 amino acids, and is mainly synthesized in muscle. Its synthesis increases with exercise. Here in this study, we planned to investigate the relationship among serum irisin level, physical activity, lipid profile, and RLS.

MATERIAL AND METHODS: A total of 35 patients with idiopathic RLS and 35 volunteers were included in the study. Then, venous blood was taken from the participants in the morning after 12 h of night fasting.

RESULTS: The mean value of serum irisin level was 16.9 ± 14.1 ng/mL in the case group and 5.1 ± 5.9 ng/mL in the control group, which was statistically quite significant (p < .001). A significant efficiency (under the curve area 0.886 [0.804-0.967]) of irisin value was observed in the differentiation of patients in the case and control groups.

DISCUSSION: Serum irisin level was significantly higher in the case group than in the control group. In conclusion, we suggest that irisin may play a role in the pathophysiology of RLS independently of the intensity and duration of physical activity and anthropometric data, such as body weight, body mass index, and waist/hip ratio.

PMID:37246480 | DOI:10.1002/brb3.3100

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Screening outcome for interpretation by the first and second reader in a population-based mammographic screening program with independent double reading

Acta Radiol. 2023 May 28:2841851231176272. doi: 10.1177/02841851231176272. Online ahead of print.

ABSTRACT

BACKGROUND: Double reading of screening mammograms is associated with a higher rate of screen-detected cancer than single reading, but different strategies exist regarding reader pairing and blinding. Knowledge about these aspects is important when considering strategies for future use of artificial intelligence in mammographic screening.

PURPOSE: To investigate screening outcome, histopathological tumor characteristics, and mammographic features stratified by the first and the second reader in a population based screening program for breast cancer.

MATERIAL AND METHODS: The study sample consisted of data from 3,499,048 screening examinations from 834,691 women performed during 1996-2018 in BreastScreen Norway. All examinations were interpreted independently by two radiologists, 272 in total. We analyzed interpretation score, recall, and cancer detection, as well as histopathological tumor characteristics and mammographic features of the cancers, stratified by the first and second readers.

RESULTS: For Reader 1, the rate of positive interpretations was 4.8%, recall 2.3%, and cancer detection 0.5%. The corresponding percentages for Reader 2 were 4.9%, 2.5%, and 0.5% (P < 0.05 compared with Reader 1). No statistical difference was observed for histopathological tumor characteristics or mammographic features when stratified by Readers 1 and 2. Recall and cancer detection were statistically higher and histopathological tumor characteristics less favorable for cases detected after concordant positive compared with discordant interpretations.

CONCLUSION: Despite reaching statistical significance, mainly due to the large study sample, we consider the differences in interpretation scores, recall, and cancer detection between the first and second readers to be clinically negligible. For practical and clinical purposes, double reading in BreastScreen Norway is independent.

PMID:37246466 | DOI:10.1177/02841851231176272

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Safety Profile and Effectiveness of Rivaroxaban for Patients With Venous Thromboembolism in Japan - Results From Post-Marketing Surveillance (XASSENT)

Circ J. 2023 May 27. doi: 10.1253/circj.CJ-23-0104. Online ahead of print.

ABSTRACT

BACKGROUND: The incidence of venous thromboembolism (VTE; pulmonary embolism [PE] and/or deep vein thrombosis [DVT]) in Japan is increasing, but relatively small numbers of patients from Japan have been included in studies investigating rivaroxaban (a direct factor Xa inhibitor) for the treatment of VTE and preventing its recurrence.Methods and Results: An open-label, prospective, observational study (XASSENT [NCT02558465]) investigated the safety profile and effectiveness of rivaroxaban for ≤2 years in the treatment of VTE and prevention of its recurrence in Japanese clinical practice. Primary outcomes were major bleeding and symptomatic recurrent VTE. Statistical analyses were exploratory and descriptive. Overall, 2,540 patients were enrolled (safety analysis population [SAP], n=2,387; effectiveness analysis population [EAP], n=2,386). In the SAP, >80% of patients received the approved rivaroxaban dose, the mean (standard deviation) age was 66.6 (15.0) years, ≈74% were >50 kg, and 43% had a creatinine clearance ≥80 mL/min. PE+DVT, PE only, and DVT only were reported in 42%, 8%, and 50% of patients, respectively, and active cancer in 17% of patients. Major bleeding was reported in 69 patients (2.89%; 3.60%/patient-year; SAP) and symptomatic PE/DVT recurrence in 26 patients (1.09%; 1.36%/patient-year; EAP) during the treatment period.

CONCLUSIONS: XASSENT provided information on the expected proportions of bleeding and VTE recurrence during rivaroxaban treatment in Japanese clinical practice; no new concerns of safety or effectiveness were found.

PMID:37245989 | DOI:10.1253/circj.CJ-23-0104

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Diagnostic Utility of an Adjusted DWI Lexicon Using Multiple b-values to Evaluate Breast Lesions in Combination with BI-RADS

Magn Reson Med Sci. 2023 May 26. doi: 10.2463/mrms.mp.2022-0056. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to investigate the diagnostic feasibility of an adjusted diffusion-weighted imaging (DWI) lexicon using multiple b values to assess breast lesions according to DWI-based breast imaging reporting and data system (BI-RADS).

METHODS: This Institutional Review Board (IRB)-approved prospective study included 127 patients with suspected breast cancer. Breast MRI was performed using a 3T scanner. Breast DW images were acquired using five b-values of 0, 200, 800, 1000, and 1500 s/mm2 (5b-value DWI) on 3T MRI. Two readers independently assessed lesion characteristics and normal breast tissue using DWI alone (5b-value DWI and 2b-value DWI with b = 0 and 800 s/mm2) according to DWI-based BI-RADS and in combination with the standard dynamic contrast-enhanced images (combined MRI). Interobserver and intermethod agreements were assessed using kappa statistics. The specificity and sensitivity of lesion classification were evaluated.

RESULTS: Ninety-five breast lesions (39 malignant and 56 benign) were evaluated. Interobserver agreement for lesion assessment on 5b-value DWI was very good (k ≥ 0.82) for DWI-based BI-RADS categories, lesion type, and mass characteristics; good (k = 0.75) in breast composition; and moderate (k ≥ 0.44) in background parenchymal signal (BPS) and non-mass distribution. Intermethod agreement between assessments performed using either 5b-value DWI or combined MRI was good-to-moderate (k = 0.52-0.67) for lesion type; moderate (k = 0.49-0.59) for DWI-based BI-RADS category and mass characteristics; and fair (k = 0.25-0.40) for mass shape, BPS, and breast composition. The sensitivity and positive predictive values (PPVs) for 5b-value DWI were 79.5%, 84.6% and 60.8%, 61.1% for each reader, respectively; 74.4%, 74.4% and 63.0%, 61.7% for 2b-value DWI; and 97.4%, 97.4% and 73.1%, 76.0% for combined MRI. The specificity and negative predictive values (NPVs) were 64.3%, 62.5% and 81.8%, 85.4% for 5b-value DWI; 69.6%, 67.9% and 79.6%, 79.2% for 2b-value DWI; and 75.0%, 78.6% and 97.7%, 97.8% for combined MRI.

CONCLUSION: Good observer agreement was observed in the 5b-value DWI. The 5b-value DWI based on multiple b-values might have the potential to complement the 2b-value DWI; however, their diagnostic performance tended to be inferior to that of combined MRI for the characterization of breast tumors.

PMID:37245964 | DOI:10.2463/mrms.mp.2022-0056

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Clinical performance of two onlay designs for molars after root canal treatment

J Oral Sci. 2023 May 29. doi: 10.2334/josnusd.22-0450. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the clinical performance of two proposed onlay designs.

METHODS: Molars with occlusal and/or mesial/distal defects after root canal treatment were classified by design into three groups. Onlays without shoulders were the control group (Group C, n = 50). The designed onlays were Group O (n = 50) and the designed mesio-occlusal/disto-occlusal onlays were Group MO/DO (n = 80). All onlays had an occlusal thickness of approximately 1.5-2.0 mm, and the designed onlays had a shoulder depth and width of approximately 1 mm. In Groups C and O, the box-shaped retention was 1.5 mm in depth. The proximal box was connected with a dovetail retention in Group MO/DO. Patients were examined every 6 months and followed for 36 months. Restorations were evaluated by using the modified United States Public Health Service Criteria. Statistical analysis was performed by using Kaplan-Meier analysis, the chi-square test, and Fisher’s exact test.

RESULTS: No tooth fracture, debonding, secondary caries, or gingivitis was observed in any group. Groups O and MO/DO had satisfactory survival and success rates, and there was no significant difference in performance characteristics among the three groups (P > 0.05).

CONCLUSION: The two proposed onlay designs were effective in protecting molars.

PMID:37245963 | DOI:10.2334/josnusd.22-0450

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A nested case-control study of factors contributing to the development of medication-related osteonecrosis of the jaw in patients using bone resorption inhibitors in Mishima City

J Oral Sci. 2023 May 29. doi: 10.2334/josnusd.23-0096. Online ahead of print.

ABSTRACT

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is characterized by necrosis of the jawbone with intraoral bacterial infection and has a significant negative impact on oral health-related quality of life. Risk factors for the onset are unknown, and definitive therapeutic approaches have not yet been defined. A case-control study at a single institution in Mishima City was conducted. The purpose of this study was to examine in detail the factors that contribute to the development of MRONJ.

METHODS: Medical records of MRONJ patients who visited Mishima Dental Center, Nihon University School of Dentistry, during the period 2015-2021 were extracted. Counter-matched sampling design was used to select participants matched for sex, age, and smoking for this nested case-control study. The incidence factors were statistically examined by logistic regression analysis.

RESULTS: Twelve MRONJ patients were used as cases and 32 controls were matched. After adjustment for potential confounders, injectable bisphosphonates (aOR = 24.5; 95% CI = 1.05, 575.0; P < 0.05) were significantly associated with the development of MRONJ.

CONCLUSION: High-dose bisphosphonates may be a risk factor for the development of MRONJ. Patients who use these products require careful prophylactic dental treatment against inflammatory diseases, and dentists and physicians should maintain close communication.

PMID:37245962 | DOI:10.2334/josnusd.23-0096

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Unsupervised learning

Am J Orthod Dentofacial Orthop. 2023 Jun;163(6):877-882. doi: 10.1016/j.ajodo.2023.04.001.

NO ABSTRACT

PMID:37245896 | DOI:10.1016/j.ajodo.2023.04.001