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Nevin Manimala Statistics

Clinical trial protocol for PanDox: a phase I study of targeted chemotherapy delivery to non-resectable primary pancreatic tumours using thermosensitive liposomal doxorubicin (ThermoDox®) and focused ultrasound

BMC Cancer. 2023 Sep 23;23(1):896. doi: 10.1186/s12885-023-11228-z.

ABSTRACT

BACKGROUND: The dense stroma of pancreatic ductal adenocarcinomas is a major barrier to drug delivery. To increase the local drug diffusion gradient, high doses of chemotherapeutic agent doxorubicin can be released from thermally-sensitive liposomes (ThermoDox®) using ultrasound-mediated hyperthermia at the tumour target. PanDox is designed as a Phase 1 single centre study to investigate enhancing drug delivery to adult patients with non-operable pancreatic ductal adenocarcinomas. The study compares a single cycle of either conventional doxorubicin alone or ThermoDox® with focused ultrasound-induced hyperthermia for targeted drug release.

METHODS: Adults with non-resectable pancreatic ductal adenocarcinoma are allocated to receive a single cycle of either doxorubicin alone (Arm A) or ThermoDox® with focused ultrasound-induced hyperthermia (Arm B), based on patient- and tumour-specific safety conditions. Participants in Arm B will undergo a general anaesthetic and pre-heating of the tumour by extra-corporal focused ultrasound (FUS). Rather than employing invasive thermometry, ultrasound parameters are derived from a patient-specific treatment planning model to reach the 41 °C target temperature for drug release. ThermoDox® is then concurrently infused with further ultrasound exposure. Tumour biopsies at the targeted site from all patients are analysed post-treatment using high performance liquid chromatography to quantify doxorubicin delivered to the tumour. The primary endpoint is defined as a statistically significant enhancement in concentration of total intra-tumoural doxorubicin, comparing samples from patients receiving liposomal drug with FUS to free drug alone. Participants are followed for 21 days post-treatment to assess secondary endpoints, including radiological assessment to measure changes in tumour activity by Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST) criteria, adverse events and patient-reported symptoms.

DISCUSSION: This early phase study builds on previous work targeting tumours in the liver to investigate whether enhancement of chemotherapy delivery using ultrasound-mediated hyperthermia can be translated to the stroma-dense environment of pancreatic ductal adenocarcinoma. If successful, it could herald a new approach towards managing these difficult-to-treat tumours.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04852367 . Registered 21st April 2022. EudraCT number: 2019-003950-10 (Registered 2019) Iras Project ID: 272253 (Registered 2019) Ethics Number: 20/EE/0284.

PMID:37741968 | DOI:10.1186/s12885-023-11228-z

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Nevin Manimala Statistics

Evaluation of sympathetic skin response for early diagnosis and follow-up of diabetic peripheral neuropathy in children

BMC Pediatr. 2023 Sep 23;23(1):483. doi: 10.1186/s12887-023-04323-4.

ABSTRACT

BACKGROUND: The morbidity of type 1 diabetes mellitus (T1DM) in children is increasing and diabetic peripheral neuropathy (DPN) is one of the main microvascular complications of T1DM. The aim of this study was to explore sympathetic skin response (SSR) characteristics in children with T1DM and analyze the value of early diagnosis and follow-up in T1DM complicated with DPN.

METHODS: Our prospective study enrolling 85 participants diagnosed with T1DM and 30 healthy controls (HCs) in the Children’s Hospital of Hebei Province from 2017 to 2020. Compared the outcomes of SSR and nerve conduction study (NCS) in T1DM, and evaluated the variations in SSR and NCS of different durations, as well as changes after six months of therapy.

RESULTS: SSR latency of T1DM group showed statistical difference as compared to HCs (p < 0.05). The SSR test was more sensitive than the NCS test in the early diagnosis of T1DM with DPN (p < 0.05). The abnormal rates of SSR and NCS in long duration of disease were higher than those in short duration of disease (p < 0.05). Among 65 participants with diabetic neuropathy, the onset latencies of SSR were shortened and the NCS were improved after treatment (p < 0.05).

CONCLUSIONS: SSR could provide the accurate early diagnosis and follow-up of pediatric diabetic peripheral neuropathy.

PMID:37741963 | DOI:10.1186/s12887-023-04323-4

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Nevin Manimala Statistics

Value of placental virtual magnetic resonance elastography and intravoxel incoherent motion-based diffusion and perfusion in predicting adverse outcomes of small-for-gestational-age infants

Insights Imaging. 2023 Sep 23;14(1):153. doi: 10.1186/s13244-023-01503-9.

ABSTRACT

OBJECTIVE: It is critical to early monitor and manage small-for-gestational age (SGA) infants with truly adverse outcomes not detected by conventional methods. We aimed to explore the value of diffusion-weighted imaging (DWI)-based virtual magnetic resonance elastography (vMRE) and intravoxel incoherent motion (IVIM)-based biexponential and stretched exponential parameters in predicting adverse outcomes of SGA infants.

METHODS: Twenty SGA infants with adverse outcomes and forty without adverse outcomes were included in this prospective study. One DWI-based vMRE parameter [the stiffness value (μdiff)], five IVIM-based parameters [true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), diffusion distribution coefficient (DDC), and diffusion heterogeneity index (Alpha)] and apparent diffusion coefficient (ADC) were calculated and compared between groups. The predictive efficiency was compared by the logistic regression analysis and receiver operating characteristic curve analysis. The relationship between the μdiff value with gestational age was also evaluated.

RESULTS: The placental μdiff value was remarkably higher, and the f, DDC, and ADC values were considerably lower in the SGA infants with adverse outcomes compared with those without adverse outcomes. The μdiff and f value were predictive risk factors for SGA infants with adverse outcomes. A combined predictive model (μdiff and f) improved the predictive efficacy. Moreover, there was no statistically significant correlation between the placental stiffness value and gestational age.

CONCLUSIONS: Functional MRI parameters to quantify placenta elastography and microcirculation in SGA patients. This might be a useful tool to assess placental function and a vital non-invasive supplement for predicting adverse outcomes of SGA infants.

CRITICAL RELEVANCE STATEMENT: This prospective study shows DWI-based virtual magnetic resonance elastography and intravoxel incoherent motion-based functional parameters to quantify placenta elastography and microcirculation in small-for-gestational-age patients, which could complement existing non-invasive methods for monitoring and predicting neonatal perinatal adverse outcome.

KEY POINTS: • vMRE is an emerging non-invasive imaging technique for evaluating placenta stiffness. • SGA infants with adverse outcome have stiffer placental elasticity and lower microcirculation. • Risk factors combination displayed better efficacy in predicting adverse outcomes of SGA.

PMID:37741945 | DOI:10.1186/s13244-023-01503-9

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Nevin Manimala Statistics

Taguchi-TOPSIS based optimization of comfort in compression stockings for vascular disorders

Sci Rep. 2023 Sep 23;13(1):15888. doi: 10.1038/s41598-023-43268-7.

ABSTRACT

Compression stockings/socks are one of the most essential materials to treat vascular disorders in veins. However, the comfort of wearing such stockings over prolonged period of time is a major problem. There is limited research in the area of comfort optimization while retaining the compressional performance. The current work is carried out with an aim to determine the optimum level of the input factors e.g., knitting structure, plaiting yarn linear density and main yarn linear density for achieving desired stretch recovery percentage and thermo-physiological comfort properties of compression socks used in treatment of vascular disorders. Their optimum combination was determined by using Taguchi based techniques for order of preference by similarity to ideal solution i.e., TOPIS. In this study, thickness, areal density, air permeability, thermal resistance, over all moisture management capacity (OMMC), stretch and recovery % were optimized simultaneously by using Taguchi-TOPSIS method. The results showed that linear density of plaiting and main yarn has significant influence on all the comfort related properties for compression stockings/socks. The optimum sample had linear density 20 denier for Lycra covered by 70 denier of nylon 66 in the plaiting yarn. It also suggested 120 denier nylon 66 in the main yarn knitted into a plain single jersey structure. The percentage contribution of the factors i.e., structure, plaiting yarn linear density and main yarn linear density was obtained by using ANOVA which are 7%, 31% and 42% respectively. It is worth mentioning that in case of compression stockings, the main yarn linear density has more significant effect on comfort properties as compared to other independent parameters. The results were verified by experiment, and the accuracy was relatively high (maximum error 8.533%). This study helped to select suitable knit structure with the change of linear densities of plaiting yarn and main yarn for comfortable compression stocking/sock and will fulfill the potential requirement for treatment of venous/vascular disorders. The novel methodology involving TOPSIS method helped in analyzing the cumulative contribution of the input parameters to achieve optimum compression as well as comfort performance. This modern approach is based on contemporary scientific principles and statistical approximations. This study may provide benchmark solutions to complex problems involving multiple interdependent criteria.

PMID:37741942 | DOI:10.1038/s41598-023-43268-7

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Nevin Manimala Statistics

Nile red-based lipid fluorometry protocol and its use for statistical optimization of lipids in oleaginous yeasts

Appl Microbiol Biotechnol. 2023 Sep 23. doi: 10.1007/s00253-023-12786-9. Online ahead of print.

ABSTRACT

As lipogenic yeasts are becoming increasingly harnessed as biofactories of oleochemicals, the availability of efficient protocols for the determination and optimization of lipid titers in these organisms is necessary. In this study, we optimized a quick, reliable, and high-throughput Nile red-based lipid fluorometry protocol adapted for oleaginous yeasts and validated it using different approaches, the most important of which is using gas chromatography coupled to flame ionization detection and mass spectrometry. This protocol was applied in the optimization of the concentrations of ammonium chloride and glycerol for attaining highest lipid titers in Rhodotorula toruloides NRRL Y-6987 and Yarrowia lipolytica W29 using response surface central composite design (CCD). Results of this optimization showed that the optimal concentration of ammonium chloride and glycerol is 4 and 123 g/L achieving a C/N ratio of 57 for R. toruloides, whereas for Y. lipolytica, concentrations are 4 and 139 g/L with a C/N ratio of 61 for Y. lipolytica. Outside the C/N of 33 to 74 and 45 to 75, respectively, for R. toruloides and Y. lipolytica, lipid productions decrease by more than 10%. The developed regression models and response surface plots show the importance of the careful selection of C/N ratio to attain maximal lipid production. KEY POINTS: • Nile red (NR)-based lipid fluorometry is efficient, rapid, cheap, high-throughput. • NR-based lipid fluorometry can be well used for large-scale experiments like DoE. • Optimal molar C/N ratio for maximum lipid production in lipogenic yeasts is ~60.

PMID:37741936 | DOI:10.1007/s00253-023-12786-9

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Nevin Manimala Statistics

Prevalence and predictors of post-abortion modern contraceptive utilization among reproductive age women in Ethiopia

Sci Rep. 2023 Sep 23;13(1):15932. doi: 10.1038/s41598-023-42911-7.

ABSTRACT

The development of a post-abortion family plan is an integral part of comprehensive abortion care. In spite of this, it received insufficient attention as a means of breaking the cycle of repeated abortions, unintended pregnancies, and maternal deaths resulting from abortion. Therefore, this study examined post abortion modern contraceptive utilization among Ethiopian women as well as associated factors. The study was based on secondary data analysis of the Ethiopian Demographic and Health Survey 2016 data. A total weighted sample of 1236 reproductive age women was included. A multilevel mixed-effect binary logistic regression model was fitted to identify the significant associated factors of post abortion contraceptive use. Statistical significance was determined using Adjusted Odds Ratio (AOR) with 95% confidence interval. Overall prevalence of post abortion contraceptive use was observed to be 25.6% (95% CI: 23.24, 28.12). Women’s age 15-24 (AOR = 2.34; 95% CI: 1.11, 4.93), and 25-34 (AOR = 1.94; 95% CI: 1.27, 2.98), married women (AOR = 2.6; 95% CI: 1.43, 4.96), women who had 1-4 (AOR = 4.13; 95% CI: 1.79, 9.57) and ≥ 5 number of children (AOR = 8.80; 95% CI: 3.30, 13.49), Being in metropolitan region (AOR = 9.14; 95% CI: 1.79, 12.48), women being in urban area (AOR = 1.85; 95% CI: 1.32, 2.24), and community media exposure (AOR = 1.75; 95% CI: 1.11, 3.56) were associated with post abortion modern contraceptive use. Post abortion modern contraceptive use in this study was low. Women age, current marital status, number of living children, residency, community media exposure, and region were significantly associated with post abortion modern contraceptive utilization. Therefore, it is better to provide ongoing health information about post-abortion family planning and its benefits, especially for people who live in rural and small peripheral regions, and public health policymakers should take both individual and community level factors into account when designing family planning programmes.

PMID:37741903 | DOI:10.1038/s41598-023-42911-7

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Nevin Manimala Statistics

Serum Erythropoietin level in anemia of elderly with unclear etiology

Sci Rep. 2023 Sep 23;13(1):15902. doi: 10.1038/s41598-023-42806-7.

ABSTRACT

Anemia is a common condition, but its causes are often unclear, especially in elderly adults. Erythropoietin (EPO) levels are known to be elevated in myelodysplastic syndrome and hematologic malignancies, but decreased in chronic benign anemia. This study aimed to investigate whether EPO levels could be used to identify underlying bone marrow diseases including malignancies, among elderly anemic patients with unclear etiology. This single centered retrospective study included patients presented with isolated anemia and had their EPO levels measured at their first visit. Patients were divided into two groups: bone marrow disease and benign etiologic anemia, based on observation and bone marrow test results. Out of 1180 patients reviewed, 81 patients with anemia of unclear etiology were identified, including 67 with benign anemia and 14 with bone marrow disease. Statistically significant difference in EPO levels between these two groups (P < 0.001) were observed. The receiver operating characteristic curve analysis showed that an EPO cut-off value of 36.4 mU/mL had a sensitivity and specificity of 92.8% and 94.0% for detecting underlying bone marrow disease, respectively. We suggest measuring serum EPO levels can aid in the early detection of benign anemia from bone marrow disease, including malignancies, with high sensitivity and specificity.

PMID:37741889 | DOI:10.1038/s41598-023-42806-7

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Nevin Manimala Statistics

Assessing aerobic physical efficiency through temple surface temperature measurements during light, heavy exercise, and recovery

Sci Rep. 2023 Sep 23;13(1):15882. doi: 10.1038/s41598-023-43012-1.

ABSTRACT

The study was conducted to determine thecorrelation between the selected measures of aerobic physical efficiency and changes in the temple surface temperature in response to light and heavy exercise. 25 physically active men aged 19-25 were recruited for the study. They performed a graded exercise test on a cycle ergometer to measure maximum power (Pmax) and a test verifying the value of maximum oxygen uptake (VO2max). Then, two 3-min submaximal efforts with constant-intensity of 2.2 W·kgLBM-1 and 5 W·kgLBM-1, respectively were performed. During the constant-intensity efforts, the temperature of the temple surface was measured. Then, the difference between the temperature of the temple measured at the end of the exercise and the temperature measured at the beginning of the exercise was calculated (ΔT1-2.2, ΔT1-5, respectively). It was shown that ΔT1-2.2 correlated statistically significantly with VO2max (ml·min-1·kg-1) (r = 0.49; p = 0.01) and Pmax (W·kg-1) (r = 0.41, p = 0.04). Moreover, ΔT1-5 correlated statistically significantly with VO2max (l·min-1) (r = – 0.41; p = 0.04). Changes in body surface temperature in response to light exercise positively correlate with measurements of aerobic physical efficiency, such as VO2max and Pmax. When the exercise intensity is high (5 W·kgLBM-1), the correlation between exercise body temperature changes and VO2max becomes negative.

PMID:37741888 | DOI:10.1038/s41598-023-43012-1

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Nevin Manimala Statistics

Resistance-capacitance optimizer: a physics-inspired population-based algorithm for numerical and industrial engineering computation problems

Sci Rep. 2023 Sep 23;13(1):15909. doi: 10.1038/s41598-023-42969-3.

ABSTRACT

The primary objective of this study is to delve into the application and validation of the Resistance Capacitance Optimization Algorithm (RCOA)-a new, physics-inspired metaheuristic optimization algorithm. The RCOA, intriguingly inspired by the time response of a resistance-capacitance circuit to a sudden voltage fluctuation, has been earmarked for solving complex numerical and engineering design optimization problems. Uniquely, the RCOA operates without any control/tunable parameters. In the first phase of this study, we evaluated the RCOA’s credibility and functionality by deploying it on a set of 23 benchmark test functions. This was followed by thoroughly examining its application in eight distinct constrained engineering design optimization scenarios. This methodical approach was undertaken to dissect and understand the algorithm’s exploration and exploitation phases, leveraging standard benchmark functions as the yardstick. The principal findings underline the significant effectiveness of the RCOA, especially when contrasted against various state-of-the-art algorithms in the field. Beyond its apparent superiority, the RCOA was put through rigorous statistical non-parametric testing, further endorsing its reliability as an innovative tool for handling complex engineering design problems. The conclusion of this research underscores the RCOA’s strong performance in terms of reliability and precision, particularly in tackling constrained engineering design optimization challenges. This statement, derived from the systematic study, strengthens RCOA’s position as a potentially transformative tool in the mathematical optimization landscape. It also paves the way for further exploration and adaptation of physics-inspired algorithms in the broader realm of optimization problems.

PMID:37741875 | DOI:10.1038/s41598-023-42969-3

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Nevin Manimala Statistics

Predicting cancer stages from tissue energy dissipation

Sci Rep. 2023 Sep 23;13(1):15894. doi: 10.1038/s41598-023-42780-0.

ABSTRACT

Understanding cancer staging in order to predict its progression is vital to determine its severity and to plan the most appropriate therapies. This task has attracted interest from different fields of science and engineering. We propose a computational model that predicts the evolution of cancer in terms of the intimate structure of the tissue, considering that this is a self-organised structure that undergoes transformations governed by non-equilibrium thermodynamics laws. Based on experimental data on the dependence of tissue configurations on their elasticity and porosity, we relate the cancerous tissue stages with the energy dissipated, showing quantitatively that tissues in more advanced stages dissipate more energy. The knowledge of this energy allows us to know the probability of observing the tissue in its different stages and the probability of transition from one stage to another. We validate our results with experimental data and statistics from the World Health Organisation. Our quantitative approach provides insights into the evolution of cancer through its different stages, important as a starting point for new and integrative research to defeat cancer.

PMID:37741864 | DOI:10.1038/s41598-023-42780-0