The effect of permeability on the rectilinear oscillations of two rigid spheres moving through an unbounded viscous fluid about their axis of symmetry with no slip is investigated. A collocation ...technique was employed to execute the conditions on the surfaces of the rigid spheres. The in-phase and out-phase forces are obtained and expressed graphically for various parameters. In addition, the streamlines are plotted for different relevant parameters. The limiting cases of Stokes and Darcy's flows are discussed.
Abstract Background In pediatric multi-system high risk organs (RO +) Langerhans cell histiocytosis (LCH), failing 1st line treatment has the highest mortality. We aim to present the outcome of ...failure of 1st line whether due to disease progression (DP) at end of induction or reactivation (REA) after initial better status response. Patients and methods Sixty-seven RO + LCH patients with hemopoietic, hepatic or splenic involvement, treated between 2007 and 2019 were retrospectively analyzed. The median follow-up (IQR) is 6 years (4–8.8 y).They were subjected to 2 eras of treatment; one with salvage by 2-Cda based regimen (2-CdABR) and another without. Results Of 67 patients, M/F 40/27, median age 1.74 y (0.2–10 y), 42 failed 1st line (62.7%). Of them DP n = 22 (52%) and REA n = 20 (48%). Of those with DP, 9/22 patients received 2-CdABR, where 5 survived in better status. While the remaining 13 did not receive 2-CdABR and all of them died. Otherwise, of those with REA, 12/20 reactivated on RO + mode. Of them, 8/12 received 2-CdABR, where only one survived in better status and the remaining 4 received vinblastine-based regimen,where 2 died and 2 were rescued. RO + 5-year overall survival (OS) was 65% (CI 95% 54 -78) while the event free survival (EFS) 36% (26.3—50.1). The OS of DP 27% (14–54) versus REA 67% (49–93) p 0.004. OS of DP with 2-CdABR 56% (31–97.7) versus 8% without (2–51), p < 0.001. While OS of REA with 2-CdABR 38% (13–100) versus 74% without (53–100) p 0.7. Conclusion Survival of RO + remains limited. Failure of 1st line in RO + due to DP carries worse prognosis in relation to REA. In DP those who were not salvaged by 2-CdABR, showed dismal outcome. This could not be shown when applied in REA.
Understanding pediatric brain tumor biology is essential to help on disease stratification, and to find novel markers for early diagnosis. MicroRNA (miRNA) expression has been linked to clinical ...outcomes and tumor biology. Here, we aimed to detect the expression of different miRNAs in different pediatric brain tumor subtypes to discover biomarkers for early detection and develop novel therapies. Expression of 82 miRNAs was detected in 120 pediatric brain tumors from fixed-formalin paraffin-embedded tissues, low-grade glioma, high-grade glioma, ependymoma, and medulloblastoma, using quantitative real-time PCR. Low-expression of miR-221, miR-9, and miR-181c/d and over-expression of miR-101, miR-222, miR-139, miR-1827, and miR-34c was found in medulloblastoma; low expression of miR-10a and over-expression of miR-10b and miR-29a in ependymoma; low expression of miR-26a and overexpression of miR-19a/b, miR-24, miR-27a, miR- 584, and miR-527 in low-grade glioma. Cox regression showed differential miRNA expression between responders and non-responders. The most specific were miR-10a and miR-29a low expression in LGG non-responders, miR-135a and miR-146b over-expression in ependymoma non-responders, and miR-135b overexpression in medulloblastoma non-responders. MicroRNAs are differentially expressed in subtypes of brain tumors suggesting that they may help diagnosis. A greater understanding of aberrant miRNA in pediatric brain tumors may support development of novel therapies.
Accurate breast tumor sizing is very important in treatment planning; as a result, ultrasound (US) plays an important role in diagnosing breast masses, due to its non-magnified image and its ...availability. The continuous change in the disease pathogenesis of breast cancer and tremendous advances in US imaging technology require the continuous evaluation of this imaging modality. In this study, our aim was to determine the accuracy of US in measuring the size of breast mass, and if there is an influence of the different pathological types on this accuracy.
This study contained 66 specimens of breast masses that underwent surgical excision and pathological examination of the resected masses; the mean difference between the size taken by US and the size taken by pathology was calculated to the patients as a whole and for each tumor type in this study.
The result was that US underestimates the size of the tumor by 0.5 cm for all pathological types, and the US size is in agreement with the pathology size.
US is an accurate method in measuring breast lesions with a degree of underestimation that may be related to many factors such as the tumor type, size, and margins. Complementary MRI is recommended in case of ILC and architectural distortion.
Purpose
Protein misfolding and aggregation result in proteotoxic stress and underlie the pathogenesis of many diseases. To overcome proteotoxicity, cells compartmentalize misfolded and aggregated ...proteins in different inclusion bodies. The aggresome is a paranuclear inclusion body that functions as a storage compartment for misfolded proteins. Choroid plexus tumors (CPTs) are rare neoplasms comprised of three pathological subgroups. The underlying mechanisms of their pathogenesis remain unclear. This study aims to elucidate the prognostic role and the biological effects of aggresomes in pediatric CPTs.
Methods
We examined the presence of aggresomes in 42 patient-derived tumor tissues by immunohistochemistry and we identified their impact on patients’ outcomes. We then investigated the proteogenomics signature associated with aggresomes using whole-genome DNA methylation and proteomic analysis to define their role in the pathogenesis of pediatric CPTs.
Results
Aggresomes were detected in 64.2% of samples and were distributed among different pathological and molecular subgroups. The presence of aggresomes with different percentages was correlated with patients’ outcomes. The ≥ 25% cutoff had the most significant impact on overall and event-free survival (p-value < 0.001) compared to the pathological and the molecular stratifications.
Conclusions
These results support the role of aggresome as a novel prognostic molecular marker for pediatric CPTs that was comparable to the molecular classification in segregating samples into two distinct subgroups, and to the pathological stratification in the prediction of patients’ outcomes. Moreover, the proteogenomic signature of CPTs displayed altered protein homeostasis, manifested by enrichment in processes related to protein quality control.
(1) Background: SARS-CoV-2 Omicron BA.1 is the most common variation found in most countries and is responsible for 99% of cases in the United States. To overcome this challenge, there is an urgent ...need to discover effective inhibitors to prevent the emerging BA.1 variant. Natural products, particularly flavonoids, have had widespread success in reducing COVID-19 prevalence. (2) Methods: In the ongoing study, fifteen compounds were annotated from Echium angustifolium and peach (Prunus persica), which were computationally analyzed using various in silico techniques. Molecular docking calculations were performed for the identified phytochemicals to investigate their efficacy. Molecular dynamics (MD) simulations over 200 ns followed by molecular mechanics Poisson–Boltzmann surface area calculations (MM/PBSA) were performed to estimate the binding energy. Bioactivity was also calculated for the best components in terms of drug likeness and drug score. (3) Results: The data obtained from the molecular docking study demonstrated that five compounds exhibited remarkable potency, with docking scores greater than −9.0 kcal/mol. Among them, compounds 1, 2 and 4 showed higher stability within the active site of Omicron BA.1, with ΔGbinding values of −49.02, −48.07, and −67.47 KJ/mol, respectively. These findings imply that the discovered phytoconstituents are promising in the search for anti-Omicron BA.1 drugs and should be investigated in future in vitro and in vivo research.
We aimed to study the clinical state and prognosis of patients with unilateral retinoblastoma who were being treated at a paediatric comprehensive cancer centre in a limited-resource country, to ...assess the different phases of treatment and the success of different, more complex real-life models.
In this retrospective study, we created a snapshot of our retinoblastoma database for the period between 2007 and 2015. Patients whose data were included in the study were followed up until 2016. Out of a total of 744 screened patients, we included data of 248 patients who had been diagnosed with unilateral retinoblastoma.
As classified as per the International Retinoblastoma Classification, 1 patient presented with group A, 21 with group B, 39 with group C, 104 with group D and 83 with group E retinoblastoma. Chemotherapy was the initial line of treatment in 115 patients and enucleation in 133 others. Later, 141 patients (56.9%) required further management. Patients had a mean ocular survival time of 20.8 months. Nine patients developed extraocular disease at a later stage of management: five after upfront enucleation and four after neoadjuvant chemotherapy. Mean overall survival time stood at 90.2 months. Four and three deaths were recorded in groups D and E, respectively. A single patient died in the initial chemotherapy arm, while six passed away in the initial enucleation arm.
Our study highlights the importance of initial chemotherapy and close follow-up after enucleation of classes D and E affected eyes even in absence of germline mutations.
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