Tag: nevin manimala

J Neurooncol. 2023 Jul 4. doi: 10.1007/s11060-023-04347-x. Online ahead of print.

ABSTRACT

PURPOSE: H3K27 altered pediatric pontine diffuse midline gliomas (pDMG) have a poor prognosis, and conventional treatments offer limited benefits. However, recent advancements in molecular evaluations and targeted therapies have shown promise. The aim of this retrospective analysis was to evaluate the effectiveness of German-sourced ONC201, a selective antagonist of dopamine receptor DRD2, for the treatment of pediatric H3K27 altered pDMGs.

METHODS: Pediatric patients with H3K27 altered pDMG treated between January 2016 and July 2022 were included in this retrospective analysis. Tissue samples were acquired from all patients via stereotactic biopsy for immunohistochemistry and molecular profiling. All patients received radiation treatment with concurrent temozolomide, and those who could acquire GsONC201 received it as a single agent until progression. Patients who could not obtain GsONC201 received other chemotherapy protocols.

RESULTS: Among 27 patients with a median age of 5.6 years old (range 3.4-17.9), 18 received GsONC201. During the follow-up period, 16 patients (59.3%) had progression, although not statistically significant, the incidence of progression tended to be lower in the GsONC201 group. The median overall survival (OS) of the GsONC201 group was considerably longer than of the non-GsONC201 group (19.9 vs. 10.9 months). Only two patients receiving GsONC201 experienced fatigue as a side effect. 4 out of 18 patients in the GsONC201 group underwent reirradiation after progression.

CONCLUSION: In conclusion, this study suggests that GsONC201 may improve OS in pediatric H3K27-altered pDMG patients without significant side effects. However, caution is warranted due to retrospective design and biases, highlighting the need for further randomized clinical studies to validate these findings.

PMID:37402093 | DOI:10.1007/s11060-023-04347-x

J Neurooncol. 2023 Jul 4. doi: 10.1007/s11060-023-04385-5. Online ahead of print.

ABSTRACT

BACKGROUND: Corticosteroid is commonly used before surgery to control cerebral oedema in brain tumours and is frequently continued throughout treatment. Its long-term effect of on the recurrence of WHO-Grade 4 astrocytoma remains controversial. The interaction between corticosteroid, SRC-1 gene and cytotoxic T-cells has never been investigated.

METHODS: A retrospective cohort of 36 patients with WHO-Grade 4 astrocytoma were examined for CD8 + T-cell and SRC-1 gene expressions through IHC and qRT-PCR. The impact of corticosteroid on CD8⁺T-cells infiltration, SRC-1 expression, and tumour recurrence was analyzed.

RESULTS: The mean patients age was 47-years, with a male to female ratio 1.2. About 78% [n = 28] of the cases showed reduced or no CD8⁺T-cell expression while 22% [n = 8] of cases have showed medium to high CD8⁺T-cell expression. SRC-1 gene was upregulated in 5 cases [14%] and 31 cases [86%] showed SRC-1 downregulation. The average of total days and doses of administered corticosteroid from the preoperative period to the postoperative period was at range of 14-106 days and 41-5028 mg, respectively. There was no significant statistical difference in RFI among tumours expressing high or low CD8⁺T-cells when corticosteroid was administered in recommended or exceeded doses [p-value = 0.640]. There was a significant statistical difference in RFI between CD8⁺T-Cell expression and SRC-1 gene dysregulation [p-value = 002]. Tumours with high CD8⁺T T-cell expression and SRC-1 gene downregulation had late recurrence.

CONCLUSIONS: Corticosteroid treatment can directly affect the SRC-1 gene regulation but does not directly influence cytotoxic T-cells infiltration or tumor progression. However, SRC-1 gene downregulation can facilitate late tumor recurrence.

PMID:37402091 | DOI:10.1007/s11060-023-04385-5

J Patient Rep Outcomes. 2023 Jul 4;7(1):61. doi: 10.1186/s41687-023-00594-8.

ABSTRACT

BACKGROUND: As disease-modifying therapies do not reverse the course of multiple sclerosis (MS), assessment of therapeutic success involves documenting patient-reported outcomes (PROs) concerning health-related quality of life, disease and treatment-related symptoms, and the impact of symptoms on function. Interpreting PRO data involves going beyond statistical significance to calculate within-patient meaningful change scores. These thresholds are needed for each PRO in order to fully interpret the PRO data. This analysis of PRO data from the PROMiS AUBAGIO study, which utilized 8 PRO instruments in teriflunomide-treated relapsing-remitting MS (RRMS) patients, was designed to estimate clinically meaningful within-individual improvement thresholds in the same manner, for 8 PRO instruments.

RESULTS: The analytical approach followed a triangulation exercise that considered results from anchor- and distribution-based methods and graphical representations of empirical cumulative distribution functions in PRO scores in groups defined by anchor variables. Data from 8 PRO instruments (MSIS-29 v2, FSMC, MSPS, MSNQ, TSQM v1.4, PDDS, HRPQ-MS v2, and HADS) were assessed from 434 RRMS patients. For MSIS-29 v2, FSMC, MSPS, and MSNQ total scores, available anchor variables enabled both anchor- and distribution-based methods to be applied. For instruments with no appropriate anchor available, distribution-based methods were applied. A recommended value for meaningful within-individual improvement was defined by comparing mean change in PRO scores between participants showing improvement of one or two categories in the anchor variable or those showing no change. A “lower bound” estimate was calculated using distribution-based methods. An improvement greater than the lower-bound estimate was considered “clinically meaningful”.

CONCLUSION: This analysis produced estimates for assessing meaningful within-individual improvements for 8 PRO instruments used in MS studies. These estimates should be useful for interpreting scores and communicating study results and should facilitate decision-making by regulatory and healthcare authorities where these 8 PROs are commonly employed.

PMID:37402086 | DOI:10.1186/s41687-023-00594-8

Bull Math Biol. 2023 Jul 4;85(8):76. doi: 10.1007/s11538-023-01170-3.

ABSTRACT

The dynamics of a chemical reaction network (CRN) is often modeled under the assumption of mass action kinetics by a system of ordinary differential equations (ODEs) with polynomial right-hand sides that describe the time evolution of concentrations of chemical species involved. Given an arbitrarily large integer [Formula: see text], we show that there exists a CRN such that its ODE model has at least K stable limit cycles. Such a CRN can be constructed with reactions of at most second-order provided that the number of chemical species grows linearly with K. Bounds on the minimal number of chemical species and the minimal number of chemical reactions are presented for CRNs with K stable limit cycles and at most second order or seventh-order kinetics. We also show that CRNs with only two chemical species can have K stable limit cycles, when the order of chemical reactions grows linearly with K.

PMID:37402077 | DOI:10.1007/s11538-023-01170-3

J Immigr Minor Health. 2023 Jul 4. doi: 10.1007/s10903-023-01513-1. Online ahead of print.

ABSTRACT

Research on COVID-19 vaccine hesitancy has been sparse among Latino/a immigrants, a population at high risk for infection. This exploratory study examines rates of vaccine acceptance and its association with psychological antecedents of vaccination among Latino/a immigrants. A cross-sectional telephone survey on perceptions of COVID-19 was administered between October 2020 to February 2021 in South Florida to 200 adult Latino/a immigrants. Descriptive statistics, bivariate analysis, and logistic regression were employed to determine the influence of independent variables on vaccine acceptance. Most participants indicated a willingness to get vaccinated. Participants with higher confidence (aOR = 10.2, 95% CI: 4.8-21.8) and collective responsibility scores were (aOR = 3.1, 95%CI:1.3-6.9) more likely to report vaccine acceptance than those with lower scores. No other psychological antecedents or demographic variables were significantly associated with vaccine acceptance. Study results provide insights into motivating factors for vaccination that can inform culturally tailored education campaigns to increase vaccine acceptability in this population.

PMID:37402075 | DOI:10.1007/s10903-023-01513-1

Arch Virol. 2023 Jul 4;168(8):201. doi: 10.1007/s00705-023-05830-6.

ABSTRACT

Since 1987, infectious bursal disease virus (IBDV) has circulated and evolved in Vietnam, but little is known about the genotypes present. IBDV samples were collected in 1987, 2001-2006, 2008, 2011, 2015-2019, and 2021 in 18 provinces. We conducted phylogenotyping analysis based on an alignment of 143 VP2-HVR (hypervariable region) sequences from 64 Vietnamese isolates (26 previous and 38 additional sequences and two vaccines, and alignment of 82 VP1 B-marker sequences, including one vaccine and four Vietnamese field strains. The analysis identified three A-genotypes, A1, A3, and A7, and two B-genotypes, B1 and B3, among the Vietnamese IBDV isolates. The lowest average evolutionary distance (8.6%) was seen between the A1 and A3 genotypes, and the highest (21.7%) was between A5 and A7, while there was a distance of 14% between B1 and B3 and 17% between B3 and B2. Unique signature residues were observed for genotypes A2, A3, A5, A6, and A8, which could be used for genotypic discrimination. A timeline statistical summary revealed that the A3-genotype predominated (79.8% presence) in Vietnam from 1987 to 2021 and that it remained the dominant IBDV genotype over the last five years (2016-2021). The current study contributes to a better understanding of the circulating genotypes and evolution of IBDV in Vietnam and worldwide.

PMID:37402052 | DOI:10.1007/s00705-023-05830-6

Radiol Med. 2023 Jul 4. doi: 10.1007/s11547-023-01669-8. Online ahead of print.

ABSTRACT

PURPOSE: To assess the diagnostic accuracy of double inversion recovery (DIR) magnetic resonance imaging (MRI) sequences for synovitis of the wrist joints in patients with rheumatoid arthritis (RA).

MATERIAL AND METHODS: Participants with newly diagnosed RA were enrolled between November 2019 and November 2020. MRI examinations of the wrist joints were performed using a contrast-enhanced T1-weighted imaging sequence (CE-T1WI) and DIR sequence. We measured synovitis score, number of synovial areas, synovial volume, mean synovium-to-bone signal ratio (SBR), and synovial contrast-to-noise ratio (SNR). The inter-reviewer agreement rated on a four-point scale was evaluated by calculating the weighted k statistics. Two MRI sequences were assessed using Bland-Altman analyses, and the diagnostic performance of DIR images was calculated using the chi-square test.

RESULTS: A total of 47 participants were evaluated, and 282 joint regions in 5076 images were reviewed by two readers. There was no significant difference in synovitis scores (P = 0.67), number of synovial areas (P = 0.89), and synovial volume (P = 0.086) between the two MRI sequences. DIR images showed better SBR and SNR (all P < 0.01). There was good agreement between the two reviewers in terms of synovitis distribution (κ = 0.79). The synovitis was well agreed upon by the two readers according to Bland-Altman analyses. Using CE-T1WI as the reference standard, DIR imaging demonstrated a sensitivity of 94.1% and a specificity of 84.6% at the patient level.

CONCLUSION: The non-contrast DIR sequence showed good consistency with CE-T1WI and potential for evaluating synovitis in patients with RA.

PMID:37402026 | DOI:10.1007/s11547-023-01669-8

J Med Ultrason (2001). 2023 Jul 4. doi: 10.1007/s10396-023-01333-8. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to compare vibration-controlled transient elastography (VCTE) with shear wave elastography (SWE) without previous analysis and generate regression equations between VCTE and new point SWE using combination-elastography.

METHODS: Overall, 829 patients with chronic liver disease were enrolled in this study. Patients with a skin-liver capsule distance > 25 mm were excluded. The reproducibility of VCTE and SWE was confirmed in a phantom study and a clinical study. Considering that combination-elastography allows measurement based on strain elastography, a similar analysis was performed for the liver fibrosis index (LFI), which is a quantitative value for evaluation of liver fibrosis calculated using strain elastography image features. Regression equations between the VCTE and SWE values were obtained based on linear regression analysis.

RESULTS: In the phantom study and clinical study, there was a strong correlation between VCTE and SWE [r = 0.995 (p < 0.001) and r = 0.747 (p < 0.001), respectively). The regression equation between VCTE and SWE was VCTE (kPa) = 1.09 × point SWE (kPa) – 0.17. The Bland-Altman plots revealed no statistically significant bias. Meanwhile, there was no correlation between VCTE and LFI (r = 0.279). There was a statistically significant bias between VCTE and LFI in the Bland-Altman plots. The inter-operator reliability showed a good intraclass correlation coefficient of 0.760 (95% confidence interval: 0.720-0.779).

CONCLUSION: Liver stiffness measured using point SWE was comparable to that measured using VCTE.

PMID:37402022 | DOI:10.1007/s10396-023-01333-8

Int J Legal Med. 2023 Jul 4. doi: 10.1007/s00414-023-03055-5. Online ahead of print.

ABSTRACT

PURPOSE: To investigate prediction of age older than 18 years in sub-adults using tooth tissue volumes from MRI segmentation of the entire 1st and 2nd molars, and to establish a model for combining information from two different molars.

MATERIALS AND METHODS: We acquired T2 weighted MRIs of 99 volunteers with a 1.5-T scanner. Segmentation was performed using SliceOmatic (Tomovision©). Linear regression was used to analyse the association between mathematical transformation outcomes of tissue volumes, age, and sex. Performance of different outcomes and tooth combinations were assessed based on the p-value of the age variable, common, or separate for each sex, depending on the selected model. The predictive probability of being older than 18 years was obtained by a Bayesian approach using information from the 1st and 2nd molars both separately and combined.

RESULTS: 1st molars from 87 participants, and 2nd molars from 93 participants were included. The age range was 14-24 years with a median age of 18 years. The transformation outcome (high signal soft tissue + low signal soft tissue)/total had the strongest statistical association with age for the lower right 1st (p= 7.1*10^-4 for males) and 2nd molar (p=9.44×10^-7 for males and p=7.4×10^-10 for females). Combining the lower right 1st and 2nd molar in males did not increase the prediction performance compared to using the best tooth alone.

CONCLUSION: MRI segmentation of the lower right 1st and 2nd molar might prove useful in the prediction of age older than 18 years in sub-adults. We provided a statistical framework to combine the information from two molars.

PMID:37402013 | DOI:10.1007/s00414-023-03055-5

Int J Legal Med. 2023 Jul 4. doi: 10.1007/s00414-023-03050-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Due to its peculiar anatomy and physiology, the pericardial fluid is a biological matrix of particular interest in the forensic field. Despite this, the available literature has mainly focused on post-mortem biochemistry and forensic toxicology, while to the best of authors’ knowledge post-mortem metabolomics has never been applied. Similarly, estimation of the time since death or post-mortem interval based on pericardial fluids has still rarely been attempted.

OBJECTIVES: We applied a metabolomic approach based on ¹H nuclear magnetic resonance spectroscopy to ascertain the feasibility of monitoring post-mortem metabolite changes on human pericardial fluids with the aim of building a multivariate regression model for post-mortem interval estimation.

METHODS: Pericardial fluid samples were collected in 24 consecutive judicial autopsies, in a time frame ranging from 16 to 170 h after death. The only exclusion criterion was the quantitative and/or qualitative alteration of the sample. Two different extraction protocols were applied for low molecular weight metabolites selection, namely ultrafiltration and liquid-liquid extraction. Our metabolomic approach was based on the use of ¹H nuclear magnetic resonance and multivariate statistical data analysis.

RESULTS: The pericardial fluid samples treated with the two experimental protocols did not show significant differences in the distribution of the metabolites detected. A post-mortem interval estimation model based on 18 pericardial fluid samples was validated with an independent set of 6 samples, giving a prediction error of 33-34 h depending on the experimental protocol used. By narrowing the window to post-mortem intervals below 100 h, the prediction power of the model was significantly improved with an error of 13-15 h depending on the extraction protocol. Choline, glycine, ethanolamine, and hypoxanthine were the most relevant metabolites in the prediction model.

CONCLUSION: The present study, although preliminary, shows that PF samples collected from a real forensic scenario represent a biofluid of interest for post-mortem metabolomics, with particular regard to the estimation of the time since death.

PMID:37402012 | DOI:10.1007/s00414-023-03050-w